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1.
Wound Repair Regen ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39376015

RESUMEN

The aim of this meta-analysis is to compare the clinical outcomes in patients with and without residual osteomyelitis (ROM) after surgical bone resection for diabetic foot osteomyelitis (DFO). We completed a systematic literature search using PubMed, Scopus, and Embase using keywords DFO, Residual OM (ROM), and positive bone margins. The study outcomes included wound healing, antibiotic duration, amputation, and re-infection. Five hundred and thirty patients were included in the analysis; 319 had no residual osteomyelitis (NROM), and 211 had ROM. There was not a significant difference in the proportion of wounds that healed 0.6 (p = 0.1, 95% confidence intervals [95% CI] 0.3-1.3). The risk of infection was 2.0 times higher (OR = 2.0, p = 0.02, 95% CI 1.1-3.4), and the risk of amputation was 4.3 times higher (OR = 4.3, p = 0.0001, 95% CI 2.4-7.6) in patients with ROM. Patients with ROM received antibiotics significantly longer. The mean difference was 16.3 days (p = 0.02, 95% CI 11.1-21.1).

2.
J Rural Health ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39363558

RESUMEN

PURPOSE: To create a model that predicts future financial distress among rural hospitals. METHODS: The sample included 14,116 yearly observations of 2311 rural hospitals recorded between 2013 and 2019. We randomly separated all sampled hospitals into a training set and test set at the start of our analysis. We used hospital financial performance, government reimbursement, organizational traits, and market characteristics to predict a given hospital's risk of experiencing one of three financial distress outcomes-negative cash flow margin, negative equity, or closure. FINDINGS: The model's area under the receiver operating characteristic curve (AUC) equaled 0.87 within the test set, indicating good predictive ability. We classified 30.55% of the observations in our sample as lowest risk of experiencing financial distress over the next 2 years. In comparison, we classified 32.52% of observations as mid-lowest risk of distress, 26.40% of observations as mid-highest risk, and 10.52% of observations as highest risk. Among test set observations classified as lowest-risk, 5.78% experienced negative cash flow margin within 2 years, 1.50% experienced negative equity within 2 years, and zero observations experienced closure within 2 years. Within the highest-risk group, 61.57% of observations experienced negative cash flow margin, 43.02% experienced negative equity, and 3.33% experienced closure. CONCLUSIONS: Given the ongoing challenges and consequences of rural hospital unprofitability, there is a clear need for accurate assessments of financial distress risk. The financial distress model can be used by researchers, policymakers, and rural health advocates as a screening tool to identify at-risk rural hospitals for closer monitoring.

3.
Sch Psychol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264659

RESUMEN

The dual-factor mental health (DFMH) model posits that mental health comprises two distinct yet interrelated dimensions: psychological distress and psychological well-being. This study used responses to a 10-item measure within a self-report risk survey to explore the prevalence rates and criterion validity of a DFMH screening model based on norm-referenced classifications with a nationally representative sample of U.S. children in Grades 5-10 (N = 5,949). Students' responses were classified into one of four possible DFMH statuses: complete mental health, troubled, symptomatic but content, or vulnerable. Results indicated most students were classified as complete mental health (71.2%), followed by symptomatic but content (13.2%), vulnerable (10.6%), and troubled (5.1%), respectively. Criterion validity findings showed students classified in the complete mental health group had the most beneficial concurrent outcomes across several academic, behavioral, and emotional indicators when compared with students in all other DFMH groups. Additionally, students in the symptomatic but content group demonstrated substantively better outcomes than both vulnerable and troubled students, whereas students in the vulnerable group had similar concurrent outcomes compared to those in the troubled group. Overall, results from this study provide further validity evidence supporting the interpretation and use of a DFMH screening model in schools with a nationally representative sample of elementary, middle, and high-school-aged youth. Implications and directions for future research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

4.
ACS Cent Sci ; 10(8): 1524-1536, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39220707

RESUMEN

Heme oxygenase-like domain-containing oxidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen Pseudomonas aeruginosa, catalyzes the excision of an oxime carbon in the biosynthesis of the copper-containing antibiotic fluopsin C. We show that FlcD is a dioxygenase that catalyzes a four-electron oxidation. Crystal structures of FlcD reveal a mononuclear iron in the active site, which is coordinated by two histidines, one glutamate, and the oxime of the substrate. Enzyme activity, Mössbauer spectroscopy, and electron paramagnetic resonance spectroscopy analyses support the usage of a mononuclear iron cofactor. This cofactor resembles that of mononuclear non-heme iron-dependent enzymes and breaks the paradigm of dinuclear HDO cofactors. This study begins to illuminate the catalytic mechanism of methine excision and indicates convergent evolution of different lineages of mononuclear iron-dependent enzymes.

5.
Nat Cardiovasc Res ; 3(5): 500-514, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-39185387

RESUMEN

The mitochondrial calcium (mCa2+) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca2+ to enter the mitochondrial matrix. The mtCU is essential for cellular function, as mCa2+ regulates metabolism, bioenergetics, signaling pathways and cell death. mCa2+ uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca2+-sensing proteins, which respond to cytosolic Ca2+ concentrations to modulate mtCU activity. Considering that mitochondrial function and Ca2+ signaling are ubiquitously disrupted in cardiovascular disease, mtCU function has been a hot area of investigation for the last decade. Here we provide an in-depth review of MICU-mediated regulation of mtCU structure and function, as well as potential mtCU-independent functions of these proteins. We detail their role in cardiac physiology and cardiovascular disease by highlighting the phenotypes of different mutant animal models, with an emphasis on therapeutic potential and targets of interest in this pathway.


Asunto(s)
Canales de Calcio , Enfermedades Cardiovasculares , Humanos , Animales , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Canales de Calcio/metabolismo , Canales de Calcio/genética , Mitocondrias Cardíacas/metabolismo , Señalización del Calcio , Calcio/metabolismo , Activación del Canal Iónico , Relación Estructura-Actividad
6.
Lupus ; 33(10): 1116-1129, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39148457

RESUMEN

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE. METHODS: This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6 months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected. RESULTS: Thirteen patients with active major NPSLE, 13 age/sex/kidney function matched SLE controls without active major NPSLE, and 13 age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6 years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3 pg/ml (p = .42) and 1.2 pg/ml higher (p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2 pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy. CONCLUSIONS: Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting.


Asunto(s)
Biomarcadores , Proteína Ácida Fibrilar de la Glía , Vasculitis por Lupus del Sistema Nervioso Central , Proteínas de Neurofilamentos , Humanos , Femenino , Biomarcadores/sangre , Estudios de Casos y Controles , Adulto , Masculino , Vasculitis por Lupus del Sistema Nervioso Central/sangre , Proteína Ácida Fibrilar de la Glía/sangre , Proteínas de Neurofilamentos/sangre , Adulto Joven , Adolescente , Persona de Mediana Edad , Niño , Neuroglía/patología , Neuroglía/metabolismo , Neuronas/patología
7.
Artículo en Inglés | MEDLINE | ID: mdl-38884838

RESUMEN

Brief, school-based mental health interventions hold promise for reducing barriers to mental health support access, a critical endeavor in light of increasing rates of mental health concerns among youth. However, there is no consensus on whether or not brief school-based interventions are effective at reducing mental health concerns or improving well-being. This systematic review and meta-analysis aims to provide consensus and determine directions for future work. Articles were included if they examined a brief (≤ four sessions or 240 min of intervention time) psychosocial intervention, were conducted within a Pre-K through 12th-grade school setting, included at least one treatment outcome evaluating mental health or well-being, and were published since 2000. A total of 6,702 papers were identified through database searching, of which 81 papers (k studies = 75) were ultimately selected for inclusion. A total of 40,498 students were included across studies and a total of 75 unique interventions were examined. A total of 324 effect sizes were extracted. On average, interventions led to statistically significant improvements in mental health/well-being outcomes versus control conditions up to one-month (g = .18, p = .004), six-month (g = .15, p = .006), and one-year (g = .10, p = .03) post-intervention. There may be benefits to brief school-based interventions from a preventative public health standpoint; future research may focus on how to optimize their real-world utility. Prospero pre-registration: CRD42021255079.

8.
Neurosurgery ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38899908

RESUMEN

BACKGROUND AND OBJECTIVES: Penetrating ballistic cranial trauma (PBCT) carries significant mortality when compared with blunt trauma. The development of coagulopathy in PBCT is a strong predictor of mortality. The goal of the study was to describe the incidence and risk factors of coagulopathy in PBCT and to report the value of tranexamic acid administration in PBCT. METHODS: We retrospectively analyzed 270 patients who presented with PBCT to a single, Level 1 trauma center between 2016 and 2023. RESULTS: A total of 47% (127/270) of patients with PBCT developed coagulopathy at presentation. Fifty-seven patients received tranexamic acid at presentation, which did not affect the development of coagulopathy. Coagulopathic patients were more likely to have more serious injury patterns (bihemispheric [adjusted odds ratio, aOR: 2.6 CI: 1.4-4.9, P = .004] or transventricular trajectories [aOR: 4.9 CI: 1.9-19.6, P = .03]). In addition, they presented with a larger base deficit (aOR: 0.9 CI: 1.002-1.2 per mEq/L, P = .006) which negatively correlated with the international normalized ratio (ρ: -0.46, P < .0001, Spearman correlation). Using thromboelastography helped to identify an additional 20% of patients who presented with normal coagulation on conventional testing. CONCLUSION: Coagulopathy is prevalent in approximately 50% of patients with PBCT and is persistent despite treatment in a substantial subset of patients. The addition of thromboelastography with its increased coagulopathy sensitivity can potentially guide treatment more efficiently than traditional coagulopathy laboratory tests and fibrinogen alone. Patients with a significant base deficit on arterial blood gas are at higher risk for coagulopathy.

9.
Adv Exp Med Biol ; 1441: 1057-1090, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884769

RESUMEN

Arrhythmias account for over 300,000 annual deaths in the United States, and approximately half of all deaths are associated with heart disease. Mechanisms underlying arrhythmia risk are complex; however, work in humans and animal models over the past 25 years has identified a host of molecular pathways linked with both arrhythmia substrates and triggers. This chapter will focus on select arrhythmia pathways solved by linking human clinical and genetic data with animal models.


Asunto(s)
Arritmias Cardíacas , Modelos Animales de Enfermedad , Animales , Humanos , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/metabolismo , Transducción de Señal/genética
10.
Theor Appl Genet ; 137(5): 117, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700534

RESUMEN

KEY MESSAGE: A large-effect QTL was fine mapped, which revealed 79 gene models, with 10 promising candidate genes, along with a novel inversion. In commercial maize breeding, doubled haploid (DH) technology is arguably the most efficient resource for rapidly developing novel, completely homozygous lines. However, the DH strategy, using in vivo haploid induction, currently requires the use of mutagenic agents which can be not only hazardous, but laborious. This study focuses on an alternative approach to develop DH lines-spontaneous haploid genome duplication (SHGD) via naturally restored haploid male fertility (HMF). Inbred lines A427 and Wf9, the former with high HMF and the latter with low HMF, were selected to fine-map a large-effect QTL associated with SHGD-qshgd1. SHGD alleles were derived from A427, with novel haploid recombinant groups having varying levels of the A427 chromosomal region recovered. The chromosomal region of interest is composed of 45 megabases (Mb) of genetic information on chromosome 5. Significant differences between haploid recombinant groups for HMF were identified, signaling the possibility of mapping the QTL more closely. Due to suppression of recombination from the proximity of the centromere, and a newly discovered inversion region, the associated QTL was only confined to a 25 Mb region, within which only a single recombinant was observed among ca. 9,000 BC1 individuals. Nevertheless, 79 gene models were identified within this 25 Mb region. Additionally, 10 promising candidate genes, based on RNA-seq data, are described for future evaluation, while the narrowed down genome region is accessible for straightforward introgression into elite germplasm by BC methods.


Asunto(s)
Mapeo Cromosómico , Haploidia , Sitios de Carácter Cuantitativo , Zea mays , Zea mays/genética , Mapeo Cromosómico/métodos , Fitomejoramiento , Genoma de Planta , Fenotipo , Alelos , Cromosomas de las Plantas/genética , Genes de Plantas
11.
J Am Chem Soc ; 146(21): 14856-14863, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38717994

RESUMEN

Uranyl fluoride (UO2F2) particles (<20 µm) were subjected to first-of-its-kind analysis via simultaneous laser-induced breakdown spectroscopy (LIBS) and laser ablation multi-collector inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS). Briefly, a nanosecond pulsed high-energy laser was focused onto the sample (particle) surface. In a single laser pulse, the UO2F2 particle was excited/ionized within the microplasma volume, and the emission of light was collected via fiber optics such that emission spectroscopy could be employed for the detection of uranium (U) and fluorine (F). The ablated particle was simultaneously transported into the MC-ICP-MS for high precision isotopic (i.e., 234U, 235U, and 238U) analysis. This method, LIBS/LA-MC-ICP-MS was optimized and employed to rapidly measure 80+ UO2F2 particles, which were subjected to different calcination processes, which results in varying degrees of F loss from the individual particles. In measuring the particles, the average F/U ratios for the populations treated at 100 and 500 °C were 2.78 ± 1.28 and 1.01 ± 0.50, respectively, confirming loss of F through the calcination process. The average 235U/238U on the particle populations for the 100 and 500 °C were 0.007262 (22) and 0.007231 (23), which was determined to be <0.2% from the expected value. The 234U/238U ratios on the same particles were 0.000053 (11) and 0.000050 (10) for the 100 and 500 °C, respectively, <10% from the expected value. Notably, each population was analyzed in under 5 min, demonstrating the truly rapid analysis technique presented here.

12.
Urology ; 191: 193-199, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38735441

RESUMEN

OBJECTIVE: To provide a framework for diversifying the urologic workforce through residency recruitment by integrating principles of diversity, equity, and inclusion (DEI) into program mission and values, application review, and interview process. MATERIALS AND METHODS: For this narrative review, the Society of Women in Urology Advancing DEI in Urology Residency Recruitment Task Force identified 4 areas for incorporating DEI into residency recruitment: defining a residency program's mission and values, holistic application review, an objective interview process, and implementing DEI principles into a program. Using PubMed and Google Scholar, we performed a non-systematic literature search of articles from January 2014 to January 2024. Search terms included combinations of "diversity", "equity", "inclusion", "residency", "holistic review", "applications", "interviews", and "initiatives". Additional resources were identified through citations of selected articles. Based on findings from these articles, Task Force members made recommendations for best practices. RESULTS: The diversity of practicing urologists is disproportionate to that of the United States population. Emerging evidence demonstrates that DEI efforts in healthcare are associated with better outcomes and reduction in healthcare inequities. We offer strategies for residency programs to integrate DEI initiatives into their recruitment, application review, and interview process. Furthermore, we address extending DEI principles into a program's mission and culture to create an inclusive environment conducive to training and supporting individuals from unique backgrounds. CONCLUSION: It is critical to recruit and retain diverse talent in urology to improve patient care. We urge residency programs and their supporting institutions to adopt DEI principles into their recruitment efforts.


Asunto(s)
Diversidad Cultural , Internado y Residencia , Selección de Personal , Sociedades Médicas , Urología , Femenino , Humanos , Internado y Residencia/organización & administración , Internado y Residencia/normas , Selección de Personal/normas , Médicos Mujeres/estadística & datos numéricos , Sociedades Médicas/normas , Estados Unidos , Urología/educación , Urología/normas
13.
Appl Spectrosc ; 78(8): 815-824, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38693875

RESUMEN

Raman spectroscopy is an emerging technique for rapid and nondestructive analysis of nuclear materials for forensic and nonproliferation applications as it is a powerful tool for distinguishing multiple chemical forms of materials with similar stoichiometries. Recent developments in spectroscopic software have enabled rapid data collection with high-speed Raman spectroscopic mapping capabilities. However, some uranium-rich materials are susceptible to degradation in humid air and/or laser-induced phase transformations. To mitigate environmental or measurement-related sample degradation of potential samples of interest, we have taken a systematic approach to define optimized data collection parameters for high-throughput measurements of uranyl fluoride (UO2F2), which is an important intermediate material in the nuclear fuel cycle. First, we systematically describe the influence of optical magnification (5× to 100×), laser power, and exposure time on obtained signal for identical particles of UO2F2 and find that at low laser power and exposure times, comparable signal is obtained regardless of optical magnification. Second, we ensure sample integrity during data collection, and third, collect spectroscopic maps that employ optimized parameters to reduce the time required to obtain spatially resolved spectroscopic information. Reductions of 90% and 99% in measurement times are discussed as they relate to differences in resolving spectroscopic features of particles in identical mapping areas. During this work, we found that additional data processing options were needed and thus developed a customized Python script for importing, processing, analyzing, and visualizing Raman spectroscopic map data.

14.
Nat Med ; 30(8): 2303-2310, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38760584

RESUMEN

Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system. The primary composite effectiveness endpoint was evaluated through 1 year and included freedom from acute procedural failure and repeat ablation at any time, plus arrhythmia recurrence, drug initiation or escalation or cardioversion after a 3-month blanking period. The primary safety endpoint was freedom from a composite of serious procedure-related or device-related adverse events. The primary effectiveness endpoint was observed for 73.8% and 65.8% of patients in the investigational and control arms, respectively (P < 0.0001 for non-inferiority). Major procedural or device-related complications occurred in three patients in the investigational arm and in two patients in the control arm (P < 0.0001 for non-inferiority). In a secondary analysis, procedural times were shorter in the investigational arm as compared to the control arm (P < 0.0001). These results demonstrate non-inferior safety and effectiveness of the dual-energy catheter for the treatment of persistent AF. Future large-scale studies are needed to gather real-world evidence on the impact of the focal dual-energy lattice catheter on the broader population of patients with AF. ClinicalTrials.gov identifier: NCT05120193 .


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/terapia , Masculino , Femenino , Persona de Mediana Edad , Ablación por Catéter/métodos , Anciano , Resultado del Tratamiento , Método Simple Ciego , Recurrencia
15.
Nat Commun ; 15(1): 3324, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637512

RESUMEN

CRISPR-Cas are adaptive immune systems in bacteria and archaea that utilize CRISPR RNA-guided surveillance complexes to target complementary RNA or DNA for destruction1-5. Target RNA cleavage at regular intervals is characteristic of type III effector complexes6-8. Here, we determine the structures of the Synechocystis type III-Dv complex, an apparent evolutionary intermediate from multi-protein to single-protein type III effectors9,10, in pre- and post-cleavage states. The structures show how multi-subunit fusion proteins in the effector are tethered together in an unusual arrangement to assemble into an active and programmable RNA endonuclease and how the effector utilizes a distinct mechanism for target RNA seeding from other type III effectors. Using structural, biochemical, and quantum/classical molecular dynamics simulation, we study the structure and dynamics of the three catalytic sites, where a 2'-OH of the ribose on the target RNA acts as a nucleophile for in line self-cleavage of the upstream scissile phosphate. Strikingly, the arrangement at the catalytic residues of most type III complexes resembles the active site of ribozymes, including the hammerhead, pistol, and Varkud satellite ribozymes. Our work provides detailed molecular insight into the mechanisms of RNA targeting and cleavage by an important intermediate in the evolution of type III effector complexes.


Asunto(s)
Proteínas Asociadas a CRISPR , ARN Catalítico , ARN/metabolismo , ARN Catalítico/metabolismo , Sistemas CRISPR-Cas/genética , ADN/metabolismo , Dominio Catalítico , Proteínas Asociadas a CRISPR/genética , Proteínas Asociadas a CRISPR/metabolismo , División del ARN
16.
Nat Commun ; 15(1): 3663, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38688943

RESUMEN

CRISPR-Cas9 is a powerful tool for genome editing, but the strict requirement for an NGG protospacer-adjacent motif (PAM) sequence immediately next to the DNA target limits the number of editable genes. Recently developed Cas9 variants have been engineered with relaxed PAM requirements, including SpG-Cas9 (SpG) and the nearly PAM-less SpRY-Cas9 (SpRY). However, the molecular mechanisms of how SpRY recognizes all potential PAM sequences remains unclear. Here, we combine structural and biochemical approaches to determine how SpRY interrogates DNA and recognizes target sites. Divergent PAM sequences can be accommodated through conformational flexibility within the PAM-interacting region, which facilitates tight binding to off-target DNA sequences. Nuclease activation occurs ~1000-fold slower than for Streptococcus pyogenes Cas9, enabling us to directly visualize multiple on-pathway intermediate states. Experiments with SpG position it as an intermediate enzyme between Cas9 and SpRY. Our findings shed light on the molecular mechanisms of PAMless genome editing.


Asunto(s)
Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , ADN , Edición Génica , Streptococcus pyogenes , Proteína 9 Asociada a CRISPR/metabolismo , Proteína 9 Asociada a CRISPR/genética , Edición Génica/métodos , ADN/metabolismo , ADN/genética , Streptococcus pyogenes/genética , Streptococcus pyogenes/metabolismo , Streptococcus pyogenes/enzimología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , ARN Guía de Sistemas CRISPR-Cas/metabolismo , ARN Guía de Sistemas CRISPR-Cas/genética
17.
Wound Repair Regen ; 32(4): 366-376, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566503

RESUMEN

The aim of this study was to evaluate the diagnostic characteristics of biomarker for diabetic foot osteomyelitis (DFO). We searched PubMed, Scopus, Embase and Medline for studies who report serological markers and DFO before December 2022. Studies must include at least one of the following diagnostic parameters for biomarkers: area under the curve, sensitivities, specificities, positive predictive value, negative predictive value. Two authors evaluated quality using the Quality Assessment of Diagnostic Accuracy Studies tool. We included 19 papers. In this systematic review, there were 2854 subjects with 2134 (74.8%) of those patients being included in the meta-analysis. The most common biomarkers were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and procalcitonin (PCT). A meta-analysis was then performed where data were evaluated with Forrest plots and receiver operating characteristic curves. The pooled sensitivity and specificity were 0.72 and 0.75 for PCT, 0.72 and 0.76 for CRP and 0.70 and 0.77 for ESR. Pooled area under the curves for ESR, CRP and PCT were 0.83, 0.77 and 0.71, respectfully. Average diagnostic odds ratios were 16.1 (range 3.6-55.4), 14.3 (range 2.7-48.7) and 6.7 (range 3.6-10.4) for ESR, CRP and PCT, respectfully. None of the biomarkers we evaluated could be rated as 'outstanding' to diagnose osteomyelitis. Based on the areas under the curve, ESR is an 'excellent' biomarker to detect osteomyelitis, and CRP and PCT are 'acceptable' biomarkers to diagnose osteomyelitis. Diagnostic odds ratios indicate that ESR, CRP and PCT are 'good' or 'very good' tools to identify osteomyelitis.


Asunto(s)
Biomarcadores , Pie Diabético , Osteomielitis , Humanos , Pie Diabético/diagnóstico , Pie Diabético/sangre , Osteomielitis/diagnóstico , Osteomielitis/sangre , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Polipéptido alfa Relacionado con Calcitonina/sangre , Sedimentación Sanguínea , Sensibilidad y Especificidad , Curva ROC
19.
J Neurol Sci ; 459: 122946, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38493733

RESUMEN

BACKGROUND: The ability to recognize and address bias is an important communication skill not typically addressed during training. We describe the design of an educational curriculum that aims to identify and change behavior related to diversity, equity, and inclusion (DEI). "DEI at the Bedside" uses the existing infrastructure of bedside teaching and provides a tool to normalize DEI discussions and develop skills to address bias during a neurology inpatient rotation. METHODS: As part of traditional clinical rounds, team members on an inpatient service shared experiences with DEI topics, including bias. The team developed potential responses should they encounter a similar situation in the future. We report the results of our needs assessment and curriculum development to evaluate the feasibility of incorporating a DEI educational curriculum in the neurology inpatient setting. RESULTS: Forty-two DEI experiences were recorded. Medical students were the most frequent discussants (44%). Direction of bias occurred between healthcare team members (33%), against patients (31%), and patients against healthcare team members (28%). Experiences ranged from microaggressions to explicit comments of racism, sexism, and homophobia. CONCLUSIONS: Based on needs assessment data, we developed a DEI educational curriculum for the inpatient neurology setting aimed to improve knowledge and skills related to DEI topics as well as to normalize conversation of DEI in the clinical setting. Additional study will demonstrate whether this initiative translates into measurable and sustained improvement in knowledge of how bias and disparity show up in the clinical setting and behavioral intent to discuss and address them.


Asunto(s)
Educación Médica , Neurología , Humanos , Diversidad, Equidad e Inclusión , Pacientes Internos , Comunicación
20.
ACS Omega ; 9(9): 10979-10991, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38463331

RESUMEN

Voloxidation is a potential alternative reprocessing scheme for spent nuclear fuel that uses gas-solid reactions to minimize aqueous wastes and to separate volatile fission products from the desired actinide phase. The process uses NO2(g) as an oxidant for uranium dioxide (UO2) fuel, ideally producing soluble uranium powders which can then be processed for full recycle. To continue development of the process flowsheet for voloxidation, ongoing examination of the process chemistry and associated process materials is required: discrepancies in the proposed chemical reactions that occur when spent nuclear fuel is exposed to NO2(g) atmospheres must be addressed. The objective of this work is to analyze the intermediate solid phases produced during voloxidation to support verification of the proposed NO2(g) voloxidation reaction mechanisms. This objective was achieved through using (1) powder X-ray diffraction and Raman spectroscopy to identify bulk uranium phases and (2) scanning electron microscopy to describe the morphology and microstructure of the powders at each reaction stage. The initial oxidation of UO2 under NO2(g) reactions produced ε-UO3. Further exposure to NO2(g) did not nitrate the solid to produce uranyl nitrate, as reported in some literature. However, after the powder was hydrated with steam and then further exposed to NO2(g), some traces of uranyl nitrate hexahydrate were found. The results of this study suggest that surface hydration of powders plays a vital role in uranyl nitrate formation under voloxidation conditions and raises questions about the kinetics of the oxide-to-nitrate voloxidation conversion process. Future chemical and engineering design decisions for the voloxidation process may benefit from an improved understanding of these chemical mechanisms.

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