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1.
Mol Cell Proteomics ; 22(9): 100576, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37209813

RESUMEN

Imaging mass spectrometry (IMS) is a molecular technology utilized for spatially driven research, providing molecular maps from tissue sections. This article reviews matrix-assisted laser desorption ionization (MALDI) IMS and its progress as a primary tool in the clinical laboratory. MALDI mass spectrometry has been used to classify bacteria and perform other bulk analyses for plate-based assays for many years. However, the clinical application of spatial data within a tissue biopsy for diagnoses and prognoses is still an emerging opportunity in molecular diagnostics. This work considers spatially driven mass spectrometry approaches for clinical diagnostics and addresses aspects of new imaging-based assays that include analyte selection, quality control/assurance metrics, data reproducibility, data classification, and data scoring. It is necessary to implement these tasks for the rigorous translation of IMS to the clinical laboratory; however, this requires detailed standardized protocols for introducing IMS into the clinical laboratory to deliver reliable and reproducible results that inform and guide patient care.


Asunto(s)
Reproducibilidad de los Resultados , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
2.
J Am Chem Soc ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922296

RESUMEN

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized in situ forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((NPhe)4GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated. After subcutaneous injection, a hydrogel depot forms from the solubilized peptoid-peptide-drug formulation in response to phosphatase enzymes present within the skin space. This system is able to deliver clinically relevant concentrations of a model drug, the antiretroviral zidovudine (AZT), for 35 days in Sprague-Dawley rats. Oscillatory rheology demonstrated that hydrogel formation began within ∼30 s, an important characteristic of in situ systems for reducing initial drug bursts. Gel formation continued for up to ∼90 min. Small-angle neutron scattering data reveal narrow-radius fibers (∼0.78-1.8 nm) that closely fit formation via a flexible cylinder elliptical model. The inclusion of non-native peptoid monomers and D-variant amino acids confers protease resistance, enabling enhanced biostability to be demonstrated in vitro. Drug release proceeds via hydrolysis of an ester linkage under physiological conditions, releasing the drug in an unmodified form and further reducing the initial drug burst. Subcutaneous administration of (NPhe)4GGGGk(AZT)y(p)-OH to Sprague-Dawley rats resulted in zidovudine blood plasma concentrations within the 90% maximal inhibitory concentration (IC90) range (30-130 ng mL-1) for 35 days.

3.
New Phytol ; 242(3): 1333-1347, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38515239

RESUMEN

Warming and elevated CO2 (eCO2) are expected to facilitate vascular plant encroachment in peatlands. The rhizosphere, where microbial activity is fueled by root turnover and exudates, plays a crucial role in biogeochemical cycling, and will likely at least partially dictate the response of the belowground carbon cycle to climate changes. We leveraged the Spruce and Peatland Responses Under Changing Environments (SPRUCE) experiment, to explore the effects of a whole-ecosystem warming gradient (+0°C to 9°C) and eCO2 on vascular plant fine roots and their associated microbes. We combined trait-based approaches with the profiling of fungal and prokaryote communities in plant roots and rhizospheres, through amplicon sequencing. Warming promoted self-reliance for resource uptake in trees and shrubs, while saprophytic fungi and putative chemoorganoheterotrophic bacteria utilizing plant-derived carbon substrates were favored in the root zone. Conversely, eCO2 promoted associations between trees and ectomycorrhizal fungi. Trees mostly associated with short-distance exploration-type fungi that preferentially use labile soil N. Additionally, eCO2 decreased the relative abundance of saprotrophs in tree roots. Our results indicate that plant fine-root trait variation is a crucial mechanism through which vascular plants in peatlands respond to climate change via their influence on microbial communities that regulate biogeochemical cycles.


Asunto(s)
Microbiota , Micorrizas , Tracheophyta , Ecosistema , Dióxido de Carbono/farmacología , Plantas , Árboles , Suelo , Microbiología del Suelo , Raíces de Plantas
4.
Nature ; 563(7732): 522-526, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30464262

RESUMEN

Limited DNA end resection is the key to impaired homologous recombination in BRCA1-mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase. Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination. Concurrent decreases in DYNLL1 expression in carcinomas with low BRCA1 expression reduced genomic alterations and increased homology at lesions. In cells, DYNLL1 limits nucleolytic degradation of DNA ends by associating with the DNA end-resection machinery (MRN complex, BLM helicase and DNA2 endonuclease). In vitro, DYNLL1 binds directly to MRE11 to limit its end-resection activity. Therefore, we infer that DYNLL1 is an important anti-resection factor that influences genomic stability and responses to DNA-damaging chemotherapy.


Asunto(s)
Proteína BRCA1/deficiencia , Dineínas Citoplasmáticas/metabolismo , ADN/metabolismo , Genes BRCA1 , Proteína Homóloga de MRE11/metabolismo , Reparación del ADN por Recombinación , Proteína BRCA1/genética , Sistemas CRISPR-Cas/genética , Línea Celular Tumoral , Aberraciones Cromosómicas , Daño del ADN/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Edición Génica , Inestabilidad Genómica/efectos de los fármacos , Recombinación Homóloga/efectos de los fármacos , Humanos , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Platino (Metal)/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Unión Proteica , Reparación del ADN por Recombinación/efectos de los fármacos , Factores de Transcripción/metabolismo
5.
J Proteome Res ; 22(11): 3401-3417, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37877579

RESUMEN

Imaging mass spectrometry is a well-established technology that can easily and succinctly communicate the spatial localization of molecules within samples. This review communicates the recent advances in the field, with a specific focus on matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) applied on tissues. The general sample preparation strategies for different analyte classes are explored, including special considerations for sample types (fresh frozen or formalin-fixed,) strategies for various analytes (lipids, metabolites, proteins, peptides, and glycans) and how multimodal imaging strategies can leverage the strengths of each approach is mentioned. This work explores appropriate experimental design approaches and standardization of processes needed for successful studies, as well as the various data analysis platforms available to analyze data and their strengths. The review concludes with applications of imaging mass spectrometry in various fields, with a focus on medical research, and some examples from plant biology and microbe metabolism are mentioned, to illustrate the breadth and depth of MALDI IMS.


Asunto(s)
Formaldehído , Péptidos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Formaldehído/química , Polisacáridos , Manejo de Especímenes
6.
New Phytol ; 240(1): 412-425, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37148190

RESUMEN

Drainage-induced encroachment by trees may have major effects on the carbon balance of northern peatlands, and responses of microbial communities are likely to play a central mechanistic role. We profiled the soil fungal community and estimated its genetic potential for the decay of lignin and phenolics (class II peroxidase potential) along peatland drainage gradients stretching from interior locations (undrained, open) to ditched locations (drained, forested). Mycorrhizal fungi dominated the community across the gradients. When moving towards ditches, the dominant type of mycorrhizal association abruptly shifted from ericoid mycorrhiza to ectomycorrhiza at c. 120 m from the ditches. This distance corresponded with increased peat loss, from which more than half may be attributed to oxidation. The ectomycorrhizal genus Cortinarius dominated at the drained end of the gradients and its relatively higher genetic potential to produce class II peroxidases (together with Mycena) was positively associated with peat humification and negatively with carbon-to-nitrogen ratio. Our study is consistent with a plant-soil feedback mechanism, driven by a shift in the mycorrhizal type of vegetation, that potentially mediates changes in aerobic decomposition during postdrainage succession. Such feedback may have long-term legacy effects upon postdrainage restoration efforts and implication for tree encroachment onto carbon-rich soils globally.


Asunto(s)
Micorrizas , Micorrizas/fisiología , Árboles , Suelo , Plantas , Carbono , Microbiología del Suelo
7.
Stud Fam Plann ; 54(3): 523-538, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37464575

RESUMEN

Globally, there is a need for more family planning method options as currently, available options do not adequately meet the needs of women, specifically those who have infrequent sex. Levonorgestrel (LNG) 1.5 mg is widely available as emergency contraception pills (ECP), and recent research has shown that certain women take it as their main form of contraception. Furthermore, limited studies have found repeat, on-demand use safe and efficacious. This 12-month prospective, single-arm, interventional study in Ghana tested whether a single LNG 1.5 mg on-demand or pericoital ("around the time of sex") dose contraceptive was acceptable to women who have infrequent sex and if pharmacy provision was feasible. The study sample (1,890) comprised women of reproductive age recruited from urban areas, having infrequent sex (i.e., coital frequency ≤ 6× per month), and not using any other modern methods except condoms or ECP at the time of study inclusion. Results indicated that there is demand and acceptability for a pericoital pill and that pharmacy provision is feasible. Furthermore, precoital use of the pill had high levels of satisfaction and was popular with new users. Adding LNG 1.5 mg for pericoital use to the family planning method mix has the potential to address an important segment of the population currently underserved, decrease unwanted pregnancies, and increase modern contraceptive prevalence rates.


Asunto(s)
Anticoncepción Postcoital , Anticonceptivos Femeninos , Embarazo , Femenino , Humanos , Levonorgestrel , Anticonceptivos , Ghana , Estudios Prospectivos , Estudios de Factibilidad
8.
Ann Vasc Surg ; 97: 8-17, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37004920

RESUMEN

BACKGROUND: Intraoperative dextran infusion has been associated with reduction of an embolic risk in patients undergoing carotid endarterectomy (CEA). Nonetheless, dextran has been associated with adverse reactions, including anaphylaxis, hemorrhage, cardiac, and renal complications. Herein, we aimed to compare the perioperative outcomes of CEA stratified by the use of intraoperative dextran infusion using a large multiinstitutional dataset. METHODS: Patients undergoing CEA between 2008 and 2022 from the Vascular Quality Initiative database were reviewed. Patients were categorized by use of intraoperative dextran infusion, and demographics, procedural data, and in-hospital outcomes were compared. Logistic regression analysis was utilized to adjust for differences in patients while assessing the association between postoperative outcomes and intraoperative infusion of dextran. RESULTS: Of 140,893 patients undergoing CEA, 9,935 (7.1%) patients had intraoperative dextran infusion. Patients with intraoperative dextran infusion were older with lower rates of symptomatic stenosis (24.7% vs. 29.3%; P < 0.001) and preoperative use of antiplatelets, anticoagulants and statins. Additionally, they were more likely to have severe carotid stenosis (>80%; 49% vs. 45%; P < 0.001) and undergo CEA under general anesthesia (96.4% vs. 92.3%; P < 0.001), with a more frequent use of shunt (64.4% vs. 49.5%; P < 0.001). After adjustment, multivariable analysis showed that intraoperative dextran infusion was associated with higher odds of in-hospital major adverse cardiac events (MACE), including myocardial infarction [MI] (odds ratio [OR], 1.76, 95% confidence interval [CI]: 1.34-2.3, P < 0.001), congestive heart failure [CHF] (OR, 2.15, 95% CI: 1.67-2.77, P = 0.001), and hemodynamic instability requiring vasoactive agents (OR, 1.08, 95% CI: 1.03-1.13, P = 0.001). However, it was not associated with decreased odds of stroke (OR, 0.92, 95% CI: 0.74-1.16, P = 0.489) or death (OR, 0.88, 95% CI: 0.58-1.35, P = 0.554). These trends persisted even when stratified by symptomatic status and degree of stenosis. CONCLUSIONS: Intraoperative infusion of dextran was associated with increased odds of MACE, including MI, CHF, and persistent hemodynamic instability, without decreasing the risk of stroke perioperatively. Given these results, judicious use of dextran in patients undergoing CEA is recommended. Furthermore, careful perioperative cardiac management is warranted in select patients receiving intraoperative dextran during CEA.


Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Endarterectomía Carotidea/efectos adversos , Dextranos/efectos adversos , Constricción Patológica/etiología , Factores de Riesgo , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Infarto del Miocardio/etiología , Estudios Retrospectivos , Medición de Riesgo
9.
New Phytol ; 234(6): 1914-1918, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35098533

RESUMEN

The rapidly growing industry of crop biostimulants leverages the application of plant growth promoting rhizobacteria (PGPR) to promote plant growth and health. However, introducing nonnative rhizobacteria may impact other aspects of ecosystem functioning and have legacy effects; these potential consequences are largely unexplored. Nontarget consequences of PGPR may include changes in resident microbiomes, nutrient cycling, pollinator services, functioning of other herbivores, disease suppression, and organic matter persistence. Importantly, we lack knowledge of whether these ecosystem effects may manifest in adjacent ecosystems. The introduced PGPR can leave a functional legacy whether they persist in the community or not. Legacy effects include shifts in resident microbiomes and their temporal dynamics, horizontal transfer of genes from the PGPR to resident taxa, and changes in resident functional groups and interaction networks. Ecosystem functions may be affected by legacies PGPR leave following niche construction, such as when PGPR alter soil pH that in turn alters biogeochemical cycling rates. Here, we highlight new research directions to elucidate how introduced PGPR impact resident microbiomes and ecosystem functions and their capacity for legacy effects.


Asunto(s)
Microbiota , Microbiología del Suelo , Desarrollo de la Planta , Rizosfera , Suelo
10.
J Surg Res ; 280: 114-122, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35964483

RESUMEN

INTRODUCTION: The rate of mastectomy in lumpectomy-eligible patients with unilateral breast cancer is increasing. We sought to investigate the association between magnetic resonance imaging (MRI) and surgical management of patients with early-stage breast cancer by comparing the rate of mastectomy as first surgery in patients with and without preoperative MRI. METHODS: A bi-institutional retrospective study included patients diagnosed between 2016 and 2020. Lumpectomy-eligible patients with in situ and invasive cancer were included. Those receiving preoperative therapy, MRI before diagnosis, or with known bilateral cancer were excluded. The risk factors for bilateral and multicentric disease were accounted for. Fisher's exact and chi-square tests compared categorical variables, Wilcoxon two-sample test analyzed continuous variables, and multivariate analyses were performed with Poisson regression. RESULTS: Four hundred twenty-eight participants met inclusion criteria. Patients who received MRI were younger (58 versus 67 y; P < 0.001) and had denser breasts (group 3 or 4; 61% versus 25%; P < 0.001). Mastectomy rate was twice as high in patients undergoing MRI (32% versus 15%, rate ratio 2.16; P < 0.001), which remained significant in multivariate analysis (rate ratio 2.0; P < 0.001). Contralateral mastectomy (12% versus 4%; P = 0.466) and reexcision (13% versus 12%; P = 0.519) rates were similar. Time to surgery was greater in those receiving MRI alone and MRI biopsy (34 [no MRI] versus 45 [MRI] versus 62 [MRI biopsy]; P < 0.001 for both). CONCLUSIONS: MRI receipt is associated with a doubled rate of mastectomy in lumpectomy-eligible patients. Future work is needed to standardize patient selection for MRI to those with the highest likelihood of having additional undiagnosed disease.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Humanos , Femenino , Mastectomía/métodos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Mastectomía Segmentaria , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Cuidados Preoperatorios
11.
Ann Clin Psychiatry ; 34(3): 176-182, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35849766

RESUMEN

BACKGROUND: A systematic diagnostic mental health assessment was conducted with first-year students at Paul Quinn College, a small historically Black college/university (HBCU) in Dallas, Texas. METHODS: A sample of 128 students was assessed with the Mini-International Neuropsychiatric Interview for DSM-5 and the Childhood Trauma Questionnaire. RESULTS: Nearly one-third of students were diagnosed with a current psychiatric disorder, most commonly substance use disorders (17%) and major depressive disorder (9%). Despite these findings, few students had ever received psychiatric treatment, and considering their substantial trauma histories, few developed posttraumatic stress disorder, reflecting protective factors in the HBCU. CONCLUSIONS: The prevalence of psychiatric disorders in this HBCU study is consistent with findings of studies conducted at predominately White institutions. However, the relatively low access to treatment of these HBCU students suggests relevant mental health care disparities in this population. Further research is needed to develop interventions designed to help connect HBCU students to mental health care.


Asunto(s)
Trastorno Depresivo Mayor , Negro o Afroamericano/psicología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Humanos , Salud Mental , Estudiantes/psicología , Universidades
12.
Pediatr Emerg Care ; 38(7): 312-316, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35696301

RESUMEN

OBJECTIVE: The objective of the current study was to examine (1) physician trainee interventions when confronted with a situation in which corporal punishment (CP) occurs in a simulated medical setting and (2) their knowledge, comfort, and experiences shared during a semistructured debriefing. METHODS: Themes were developed from simulation sessions from 2018 to 2019, where a convenience sample of training physicians was invited to participate. The simulation involved a medical visit where a caregiver becomes increasingly aggravated, eventually striking her child on the back of the head. There were a total of 7 simulations with one trainee participating while others observed. All trainees subsequently participated in a debriefing and educational session. RESULTS: A total of 37 physician trainees participated. Themes of not having the wording to address CP, not knowing the distinction between CP and physical abuse, previous negative experiences discussing discipline with families, and fear of offending families negatively impacted trainees' ability to intervene during the simulation. Trainees were interested in future education including simulated medical encounters to improve their responses to CP in the future. CONCLUSIONS: Trainees felt uncomfortable with intervening when CP was observed and did not know how to provide appropriate guidance to families on discipline. Moreover, performance during the simulation and discussions during the debriefings revealed knowledge gaps regarding the difference between CP and physical abuse, how to word recommendations about CP to caregivers, and what resources should be provided. These data suggest the need for education on CP and discipline to be integrated into pediatric training.


Asunto(s)
Médicos , Castigo , Niño , Femenino , Humanos , Abuso Físico
13.
Pediatr Emerg Care ; 38(12): e1678-e1683, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36355046

RESUMEN

OBJECTIVES: This study aimed to describe which infants with a skull fracture (1) receive a child abuse pediatrician (CAP) consultation, (2) receive a skeletal survey, and (3) re-present to medical care before age 3 years with concerns for physical abuse. METHODS: We conducted a retrospective chart review of infants younger than 12 months who presented to the emergency department between January 1, 2005, and December 30, 2015, with a skull fracture. Medical records were reviewed for the skull fracture presentation and for all future medical evaluations at the same institution with concerns for physical abuse until 3 years of age. RESULTS: Of 366 infants with a skull fracture, a CAP was contacted for 272 (74%) and 76 (20.8%) infants who received a skeletal survey. Factors associated with skeletal survey acquisition included younger age (<6 months), no history to explain the skull fracture, other injuries on examination, and social risk factors. Six children (1.6%) re-presented to medical care with concerns of physical abuse before age 3 years. Five of these infants did not have a skeletal survey at the time of their skull fracture, and 1 was likely a case of missed physical abuse at the time of the skull fracture. DISCUSSION: Most skull fractures in infancy occur accidentally, and a skeletal survey may not be necessary for every infant. Obtaining a thorough history including social risk factors, performing a complete physical examination, and consulting with a CAP is an effective first step in the evaluation of physical abuse in infants with skull fractures.


Asunto(s)
Maltrato a los Niños , Fracturas Óseas , Fracturas Craneales , Lactante , Niño , Humanos , Preescolar , Abuso Físico , Estudios Retrospectivos , Fracturas Craneales/epidemiología , Fracturas Craneales/terapia , Fracturas Craneales/diagnóstico , Fracturas Óseas/complicaciones , Maltrato a los Niños/diagnóstico , Cráneo
14.
Minim Invasive Ther Allied Technol ; 31(4): 620-627, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33555217

RESUMEN

INTRODUCTION: Color Doppler ultrasonography (CDU) is widely used to diagnose adnexal torsion (AT). However, its validity remains questionable due to its low sensitivity. Our study aimed to evaluate the accuracy of CDU for the preoperative diagnosis of AT. MATERIAL AND METHODS: The electronic medical records of patients who were taken to the operating room with the diagnosis of suspected AT were reviewed. Patients having surgically/pathologically-proven AT were compared with patients who were found to have a different pathology at the time of surgery. CDU validity was assessed using a 2 × 2 table and compared with a diagnostic model that consists of the Doppler findings, patient's age, and previous surgical history. RESULTS: AT was diagnosed correctly in 74.6% of cases. Absent Doppler flow was seen in only 18.6% of cases. Although its specificity and positive predictive value were high, CDU had very low sensitivity and negative predictive value. The combined diagnostic model exceeded CDU alone in terms of diagnostic accuracy. CONCLUSIONS: The use of CDU alone is not a reliable modality to exclude AT. Absent Doppler flow is a sign of ovarian necrosis. Clinical correlation between CDU findings and the patient's symptoms makes the diagnosis of AT more timely and accurate.


Asunto(s)
Torsión Ovárica , Ultrasonografía Doppler en Color , Estudios de Cohortes , Humanos
15.
Glob Chang Biol ; 27(7): 1349-1364, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33159820

RESUMEN

Fungal decomposition of soil organic matter depends on soil nitrogen (N) availability. This ecosystem process is being jeopardized by changes in N inputs that have resulted from a tripling of atmospheric N deposition in the last century. Soil fungi are impacted by atmospheric N deposition due to higher N availability, as soils are acidified, or as micronutrients become increasingly limiting. Fungal communities that persist with chronic N deposition may be enriched with traits that enable them to tolerate environmental stress, which may trade-off with traits enabling organic matter decomposition. We hypothesized that fungal communities would respond to N deposition by shifting community composition and functional gene abundances toward those that tolerate stress but are weak decomposers. We sampled soils at seven eastern US hardwood forests where ambient N deposition varied from 3.2 to 12.6 kg N ha-1  year-1 , five of which also have experimental plots where atmospheric N deposition was simulated through fertilizer application treatments (25-50 kg N ha-1  year-1 ). Fungal community and functional responses to fertilizer varied across the ambient N deposition gradient. Fungal biomass and richness increased with simulated N deposition at sites with low ambient deposition and decreased at sites with high ambient deposition. Fungal functional genes involved in hydrolysis of organic matter increased with ambient N deposition while genes involved in oxidation of organic matter decreased. One of four genes involved in generalized abiotic stress tolerance increased with ambient N deposition. In summary, we found that the divergent response to simulated N deposition depended on ambient N deposition levels. Fungal biomass, richness, and oxidative enzyme potential were reduced by N deposition where ambient N deposition was high suggesting fungal communities were pushed beyond an environmental stress threshold. Fungal community structure and function responses to N enrichment depended on ambient N deposition at a regional scale.


Asunto(s)
Micobioma , Nitrógeno , Ecosistema , Nitrógeno/análisis , Suelo , Microbiología del Suelo , Árboles
16.
J Cutan Pathol ; 48(12): 1455-1462, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34151458

RESUMEN

BACKGROUND: The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by imaging mass spectrometry (IMS). METHODS: Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine classification model. RESULTS: We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, 2 misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations. CONCLUSION: This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists.


Asunto(s)
Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Humanos , Sensibilidad y Especificidad
17.
Regul Toxicol Pharmacol ; 123: 104934, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33872740

RESUMEN

Systemic toxicity assessments for oral or parenteral drugs often utilize the concentration of drug in plasma to enable safety margin calculations for human risk assessment. For topical drugs, there is no standard method for measuring drug concentrations in the stratum basale of the viable epidermis. This is particularly important since the superficial part of the epidermis, the stratum corneum (SC), is nonviable and where most of a topically applied drug remains, never penetrating deeper into the skin. We investigated the relative concentrations of a prototype kinase inhibitor using punch biopsy, laser capture microdissection, and imaging mass spectrometry methods in the SC, stratum basale, and dermis of minipig skin following topical application as a cream formulation. The results highlight the value of laser capture microdissection and mass spectrometry imaging in quantifying the large difference in drug concentration across the skin and even within the epidermis, and supports use of these methods for threshold-based toxicity risk assessments in specific anatomic locations of the skin, like of the stratum basale.


Asunto(s)
Preparaciones Farmacéuticas/metabolismo , Absorción Cutánea/fisiología , Piel/metabolismo , Animales , Epidermis , Humanos , Espectrometría de Masas , Medición de Riesgo , Porcinos , Porcinos Enanos/fisiología
18.
Pediatr Emerg Care ; 37(4): e159-e162, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30870343

RESUMEN

ABSTRACT: Substance use and abuse have been documented as both a risk factor in and consequence of involvement in domestic minor sex trafficking (DMST). Domestic minor sex trafficking is defined as the commercial sexual exploitation of children in exchange for money, food, shelter, or any other valued entity. The current investigation sought to describe substance use in a cohort of DMST patients who present for medical evaluation. Findings revealed that 68 patients referred for DMST involvement reported high rates of alcohol/substance use and parental substance abuse. Further, many patients who had a urine toxicology screen had a positive result, most often identifying the presence of cannabinoids. Our data may inform the importance of comprehensive assessments and specialized interventions for substance abuse in this unique patient population.


Asunto(s)
Abuso Sexual Infantil , Maltrato a los Niños , Trata de Personas , Trastornos Relacionados con Sustancias , Niño , Humanos , Conducta Sexual , Trastornos Relacionados con Sustancias/epidemiología
19.
Pediatr Emerg Care ; 37(5): 269-272, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32530835

RESUMEN

OBJECTIVES: No studies have evaluated how training physicians intervene when corporal punishment (CP) is observed in a simulated hospital setting. The pilot study examined physician trainee performance in a simulation where hitting is observed between caregiver and child during a medical visit and to assess physician self-reported experiences, opinions, and comfort when observing CP in a simulation. METHODS: We ran 7 simulations where one pediatric resident, emergency medicine resident, or pediatric emergency medicine fellow participated in the simulation while a group of similar trainees observed. All participants were given a postsurvey, followed by a semistructured debriefing led by a child abuse pediatrician. RESULTS: Thirty-seven physician trainees participated; 7 engaged in the simulation while 30 observed. The majority (6/7) did not de-escalate the increasingly aggravated parent prior to hitting, 4 of 7 did not recommend that the caregiver refrain from CP, and most (5/7) did not provide education to the parent about more appropriate discipline. The majority (91.4%) believe that a physician should intervene when a parent hits or spanks his/her child in the hospital setting, highlighting the incongruity between this belief and their performance in/knowledge of intervening. All participants stated they would benefit from additional education and training on CP. CONCLUSIONS: The educational experience provided physicians in training with the opportunity to participate in or observe a situation in which CP occurs in the medical setting. The simulation and debriefing were an innovative approach to providing an educational opportunity for physicians to learn from difficult situations and discussions surrounding CP with caregivers.


Asunto(s)
Médicos , Castigo , Niño , Femenino , Humanos , Masculino , Relaciones Padres-Hijo , Padres , Proyectos Piloto
20.
Pediatr Emerg Care ; 37(12): e1409-e1415, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32371752

RESUMEN

OBJECTIVE: The objective of this study was to determine the prevalence of rib fractures (RFs) identified by chest x-ray (CXR) among children younger than 2 years who sustained accidental versus nonaccidental injuries. It is hypothesized that RFs are uncommon among all accidental pediatric trauma mechanisms (eg, falls, motor vehicle crashes) as compared with the prevalence of RFs in the setting of nonaccidental trauma (NAT). METHODS: A retrospective chart review of sequential CXRs of children younger than 2 years evaluated at a pediatric level 1 trauma center for accidental trauma and possible NAT was conducted from January 1, 2011, to October 31, 2016. Data collected included demographics, CXR indication and findings, history of cardiopulmonary resuscitation, trauma mechanism, associated injuries, final diagnoses, and outcomes. RESULTS: Two (<1%) of 226 CXRs obtained to evaluate accidental trauma demonstrated acute RFs. Ten (19.6%) of 51 CXRs obtained in the setting of concern for NAT revealed RFs (9/10 identified only healing RFs and 1/10 identified acute RFs). Among patients with a final diagnosis of NAT (ie, not neglect, accidental trauma, etc; n = 38), the overall prevalence increased to 26.3%. CONCLUSIONS: The presence of RFs in pediatric accidental trauma is uncommon even in the setting of high-force mechanisms, and when identified, these RFs are acute. Comparatively, the overall prevalence of RFs identified on CXR among cases with a final diagnosis of NAT was much higher and almost exclusively healing RFs. These data provide support that identification of RFs is highly concerning for NAT even if an accidental mechanism is provided. When RFs are identified, a full NAT work-up should be considered.


Asunto(s)
Maltrato a los Niños , Fracturas de las Costillas , Accidentes por Caídas , Niño , Maltrato a los Niños/diagnóstico , Humanos , Lactante , Estudios Retrospectivos , Fracturas de las Costillas/diagnóstico por imagen , Fracturas de las Costillas/epidemiología , Fracturas de las Costillas/etiología , Centros Traumatológicos
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