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1.
Exp Neurol ; 374: 114706, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38311020

RESUMO

Motor cortical circuit functions depend on the coordinated fine-tuning of two functionally diverse neuronal populations: glutamatergic pyramidal neurons providing synaptic excitation and GABAergic interneurons adjusting the response of pyramidal neurons through synaptic inhibition. Microglia are brain resident macrophages which dynamically refine cortical circuits by monitoring perineuronal extracellular matrix and remodelling synapses. Previously, we showed that colony-stimulating factor 1 receptor (CSF1R)-mediated myeloid cell depletion extended the lifespan, but impaired motor functions of MBP29 mice, a mouse model for multiple system atrophy. In order to better understand the mechanisms underlying these motor deficits we characterized the microglial involvement in the cortical balance of GABAergic interneurons and glutamatergic pyramidal neurons in 4-months-old MBP29 mice following CSF1R inhibition for 12 weeks. Lack of myeloid cells resulted in a decreased number of COUP TF1 interacting protein 2-positive (CTIP2+) layer V pyramidal neurons, however in a proportional increase of calretinin-positive GABAergic interneurons in MBP29 mice. While myeloid cell depletion did not alter the expression of important presynaptic and postsynaptic proteins, the loss of cortical perineuronal net area was attenuated by CSF1R inhibition in MBP29 mice. These cortical changes may restrict synaptic plasticity and potentially modify parvalbumin-positive perisomatic input. Collectively, this study suggests, that the lack of myeloid cells shifts the neuronal balance toward an increased inhibitory connectivity in the motor cortex of MBP29 mice thereby potentially deteriorating motor functions.


Assuntos
Córtex Motor , Atrofia de Múltiplos Sistemas , Camundongos , Animais , Neurônios , Células Piramidais/fisiologia , Interneurônios/fisiologia , Receptores Proteína Tirosina Quinases , Células Mieloides
2.
Acta Neuropathol Commun ; 12(1): 1, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167307

RESUMO

The growing recognition of a dichotomous role of astrocytes in neurodegenerative processes has heightened the need for unraveling distinct astrocytic subtypes in neurological disorders. In multiple system atrophy (MSA), a rare, rapidly progressing atypical Parkinsonian disease characterized by increased astrocyte reactivity. However the specific contribution of astrocyte subtypes to neuropathology remains elusive. Hence, we first set out to profile glial fibrillary acidic protein levels in astrocytes across the human post mortem motor cortex, putamen, and substantia nigra of MSA patients and observed an overall profound astrocytic response. Matching the post mortem human findings, a similar astrocytic phenotype was present in a transgenic MSA mouse model. Notably, MSA mice exhibited a decreased expression of the glutamate transporter 1 and glutamate aspartate transporter in the basal ganglia, but not the motor cortex. We developed an optimized astrocyte isolation protocol based on magnetic-activated cell sorting via ATPase Na+/K+ transporting subunit beta 2 and profiled the transcriptomic landscape of striatal and cortical astrocytes in transgenic MSA mice. The gene expression profile of astrocytes in the motor cortex displayed an anti-inflammatory signature with increased oligodendroglial and pro-myelinogenic expression pattern. In contrast, striatal astrocytes were defined by elevated pro-inflammatory transcripts accompanied by dysregulated genes involved in homeostatic functions for lipid and calcium metabolism. These findings provide new insights into a region-dependent, dichotomous astrocytic response-potentially beneficial in the cortex and harmful in the striatum-in MSA suggesting a differential role of astrocytes in MSA-related neurodegenerative processes.


Assuntos
Atrofia de Múltiplos Sistemas , Transtornos Parkinsonianos , Humanos , Camundongos , Animais , Atrofia de Múltiplos Sistemas/patologia , Astrócitos/metabolismo , Transtornos Parkinsonianos/patologia , Corpo Estriado/metabolismo , Substância Negra/metabolismo , Camundongos Transgênicos
3.
New Phytol ; 241(2): 747-763, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37964509

RESUMO

Land plants evolved multiple adaptations to restrict transpiration. However, the underlying molecular mechanisms are not sufficiently understood. We used an ozone-sensitivity forward genetics approach to identify Arabidopsis thaliana mutants impaired in gas exchange regulation. High water loss from detached leaves and impaired decrease of leaf conductance in response to multiple stomata-closing stimuli were identified in a mutant of MURUS1 (MUR1), an enzyme required for GDP-l-fucose biosynthesis. High water loss observed in mur1 was independent from stomatal movements and instead could be linked to metabolic defects. Plants defective in import of GDP-l-Fuc into the Golgi apparatus phenocopied the high water loss of mur1 mutants, linking this phenotype to Golgi-localized fucosylation events. However, impaired fucosylation of xyloglucan, N-linked glycans, and arabinogalactan proteins did not explain the aberrant water loss of mur1 mutants. Partial reversion of mur1 water loss phenotype by borate supplementation and high water loss observed in boron uptake mutants link mur1 gas exchange phenotypes to pleiotropic consequences of l-fucose and boron deficiency, which in turn affect mechanical and morphological properties of stomatal complexes and whole-plant physiology. Our work emphasizes the impact of fucose metabolism and boron uptake on plant-water relations.


Assuntos
Arabidopsis , Fucose , Fucose/metabolismo , Guanosina Difosfato Fucose/metabolismo , Boro/metabolismo , Arabidopsis/metabolismo , Polissacarídeos/metabolismo
4.
Acta Neurochir (Wien) ; 165(9): 2381-2387, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37460666

RESUMO

INTRODUCTION: Acute subdural hematoma (aSDH) is one of the main causes of high mortality and morbidity in traumatic brain injury. Prognosis is poor due to the rapid volume shift and mass effect. Cerebral perfusion is likely affected in this condition. This study quantifies perfusion changes in aSDH using early ER polytrauma CT with perfusion imaging (CTP). METHODS: Data of 54 patients with traumatic aSDH were retrospectively collected. Glasgow Coma scale (GCS), perfusion parameters, therapeutic decisions and imaging data including hematoma thickness, midline shift, and hematoma localization were analyzed. The cortical perfusion parameters of each hemisphere, the area anterior to the hematoma (AAH), area below the hematoma (ABH), area posterior to the hematoma (PAH), and corresponding mirrored contralateral regions were determined. RESULTS: We found a significant difference in Tmax in affected and unaffected whole-hemisphere data (mean 4.0 s vs. 3.3 s, p < 0.05) and a significantly different mean for Tmax in ABH and for the corresponding mirrored area (mABH) (mean 3.8 s vs. 3.1 s, p < 0.05). No significant perfusion changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were found. CONCLUSION: There was a significant elevation of time to maximum (Tmax) values in the underlying cortical area of aSDH. Possible pathophysiological explanations, the influence on immediate surgical decision-making and further therapeutic consequences have to be evaluated.


Assuntos
Hematoma Subdural Agudo , Humanos , Hematoma Subdural Agudo/diagnóstico por imagem , Hematoma Subdural Agudo/cirurgia , Estudos Retrospectivos , Hematoma , Perfusão , Circulação Cerebrovascular
5.
Hum Mol Genet ; 32(13): 2192-2204, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37010102

RESUMO

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. In contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations.


Assuntos
Epilepsia , Deficiência Intelectual , Epilepsia/genética , Deficiência Intelectual/genética , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Canal de Sódio Disparado por Voltagem NAV1.2/metabolismo , Neurônios/metabolismo , Convulsões , Sódio/metabolismo , Canais de Sódio/genética , Humanos
6.
Eur Rev Med Pharmacol Sci ; 27(6): 2605-2618, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013778

RESUMO

OBJECTIVE: The aim of this study was to investigate the influence of obstructive sleep apnea and continuous positive airway pressure on the nasal microbiome. PATIENTS AND METHODS: Endonasal swabs from the olfactory groove of 22 patients with moderate and severe obstructive sleep apnea (OSA) and a control group of 17 healthy controls were obtained at the Department of Otorhinolaryngology of the Friedrich-Alexander-Universität Erlangen-Nürnberg. 16S rRNA gene sequencing was performed to further evaluate the endonasal microbiome. In a second step, the longitudinal influence of continuous positive airway pressure (CPAP) therapy on the nasal microbiome was investigated (3-6 and 6-9 months). RESULTS: Analysis of the bacterial load and ß-diversity showed no significant differences between the groups, although patients with severe OSA showed increased α-diversity compared to the control group, while those with moderate OSA showed decreased α-diversity. The evaluation of longitudinal changes in the nasal microbiota during CPAP treatment showed no significant difference in α- or ß-diversity. However, the number of bacteria for which a significant difference between moderate and severe OSA was found in the linear discriminant analysis decreased during CPAP treatment. CONCLUSIONS: Long-term CPAP treatment showed an alignment of the composition of the nasal microbiome in patients with moderate and severe OSA as well as an alignment of biodiversity with that of the healthy control group. This change in the composition of the microbiome could be both part of the therapeutic effect in CPAP therapy and a promoting factor of the adverse side effects of the therapy. Further studies are needed to investigate whether the endonasal microbiome is related to CPAP compliance and whether CPAP compliance can be positively influenced in the future by therapeutic modification of the microbiome.


Assuntos
Microbiota , Apneia Obstrutiva do Sono , Humanos , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , RNA Ribossômico 16S/genética , Apneia Obstrutiva do Sono/terapia , Nariz , Cooperação do Paciente
8.
BMC Psychiatry ; 23(1): 38, 2023 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639626

RESUMO

BACKGROUND: Most studies agree that the Covid-19 pandemic and the subsequent lockdown had a negative impact on mental health. On the other hand, international studies have shown that psychiatric emergency departments (pED) experienced a decrease in presentations and admissions. METHODS: Retrospective chart review of all pED presentations and admissions during the first wave of Covid-19 pandemic in Germany (Covid-19 period: 3/2/20 to 05/24/20) in a psychiatric hospital in Berlin compared to 1 year earlier (pre-Covid-19 period). Descriptive statistics and logistic regression were performed. RESULTS: We observed no statistical significant changes in overall pED presentations and overall hospital admissions during the Covid-19 period compared to the pre-Covid-19 period (813 vs. 894, - 9.1%, p = 0.064 and (363 vs. 437, - 16.9%, p = 0.080 respectively). In the subgroup analysis, less patients with depressive disorders (p = 0.035) and with personality disorders (p = 0.002) presented to the pED, a larger number of presentations with schizophrenia was observed (p = 0.020). In the Covid-19 period, less patients with substance use disorder and paranoid schizophrenia were admitted to the hospital via the pED than in the pre-Covid-19 period (p = 0.035 and p = 0.006, respectively). Bed capacity was reduced in the Covid-19 period by - 32.8% (p <  0.001). Presentations in police custody were 13.7% (p = 0.029) higher during the Covid-19 compared to pre-Covid-19 period, with higher rates in female presentations (p = 0.008) and suicide attempts (p = 0.012) and less hospital admissions (p = 0.048). Logistic regression analyses revealed that positive predictors for pED presentation during Covid-19 period were police custody (p <  0.001), being redirected from another hospital (p <  0.001), suicide attempt (p = 0.038), suicidal thoughts (p = 0.004), presentation with paranoid schizophrenia (p = 0.001) and bipolar and manic disorders (p = 0.004), negative predictors were hospital admission (p <  0.001), depressive disorders (p = 0.021) and personality disorders (p <  0.001). CONCLUSIONS: A larger number of presentations in police custody during the Covid-19 period may represent untreated medical needs. This was seen predominantly in female patients, suggesting this subgroup might have suffered particularly under lockdown measures. Patients with paranoid schizophrenia were the only subgroup, which increased in absolute numbers, also suggesting a particular lockdown effect. Reduced bed capacity due to infection curbing measures is suggestive to have played an important role in augmenting the threshold for hospital admissions.


Assuntos
Transtorno Bipolar , COVID-19 , Humanos , Feminino , Estudos Retrospectivos , Berlim/epidemiologia , Pandemias , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Alemanha/epidemiologia , Serviço Hospitalar de Emergência
10.
Oecologia ; 197(4): 903-919, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33880635

RESUMO

Climate change is increasing the frequency and intensity of warming and drought periods around the globe, currently representing a threat to many plant species. Understanding the resistance and resilience of plants to climate change is, therefore, urgently needed. As date palm (Phoenix dactylifera) evolved adaptation mechanisms to a xeric environment and can tolerate large diurnal and seasonal temperature fluctuations, we studied the protein expression changes in leaves, volatile organic compound emissions, and photosynthesis in response to variable growth temperatures and soil water deprivation. Plants were grown under controlled environmental conditions of simulated Saudi Arabian summer and winter climates challenged with drought stress. We show that date palm is able to counteract the harsh conditions of the Arabian Peninsula by adjusting the abundances of proteins related to the photosynthetic machinery, abiotic stress and secondary metabolism. Under summer climate and water deprivation, these adjustments included efficient protein expression response mediated by heat shock proteins and the antioxidant system to counteract reactive oxygen species formation. Proteins related to secondary metabolism were downregulated, except for the P. dactylifera isoprene synthase (PdIspS), which was strongly upregulated in response to summer climate and drought. This study reports, for the first time, the identification and functional characterization of the gene encoding for PdIspS, allowing future analysis of isoprene functions in date palm under extreme environments. Overall, the current study shows that reprogramming of the leaf protein profiles confers the date palm heat- and drought tolerance. We conclude that the protein plasticity of date palm is an important mechanism of molecular adaptation to environmental fluctuations.


Assuntos
Phoeniceae , Secas , Fotossíntese , Folhas de Planta , Arábia Saudita , Estresse Fisiológico
11.
Plant Cell Physiol ; 62(3): 502-514, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-33544865

RESUMO

Plants are constantly exposed to stressful environmental conditions. Plant stress reactions were mainly investigated for single stress factors. However, under natural conditions plants may be simultaneously exposed to different stresses. Responses to combined stresses cannot be predicted from the reactions to the single stresses. Flavonoids accumulate in Arabidopsis thaliana during exposure to UV-A, UV-B or cold, but the interactions of these factors on flavonoid biosynthesis were unknown. We therefore investigated the interaction of UV radiation and cold in regulating the expression of well-characterized stress-regulated genes, and on transcripts and metabolites of the flavonoid biosynthetic pathway in 52 natural Arabidopsis accessions that differ widely in their freezing tolerance. The data revealed interactions of cold and UV on the regulation of stress-related and flavonoid biosynthesis genes, and on flavonoid composition. In many cases, plant reactions to a combination of cold and UV were unique under combined stress and not predictable from the responses to the single stresses. Strikingly, all correlations between expression levels of flavonoid biosynthesis genes and flavonol levels were abolished by UV-B exposure. Similarly, correlations between transcript levels of flavonoid biosynthesis genes or flavonoid contents, and freezing tolerance were lost in the presence of UV radiation, while correlations with the expression levels of cold-regulated genes largely persisted. This may indicate different molecular cold acclimation responses in the presence or absence of UV radiation.


Assuntos
Arabidopsis/genética , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Variação Genética/genética , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Temperatura Baixa , Congelamento , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Estresse Fisiológico , Raios Ultravioleta
12.
Hautarzt ; 71(2): 101-108, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31965207

RESUMO

BACKGROUND: Since the establishment of dermoscopy as a routine examination procedure in dermatology, the spectrum of noninvasive, optical devices has further expanded. In difficult-to-diagnose clinical cases, these systems may support dermatologists to arrive at a correct diagnosis without the need for a surgical biopsy. OBJECTIVE: To give an overview about technical background, indications and diagnostic performance regarding four new optical procedures: reflectance confocal microscopy, in vivo multiphoton tomography, dermatofluoroscopy, and systems based on image analysis by artificial intelligence (AI). MATERIALS AND METHODS: This article is based on a selective review of the literature, as well as the authors' personal experience from clinical studies relevant for market approval of the devices. RESULTS: In contrast to standard histopathological slides with vertical cross sections, reflectance confocal microscopy and in vivo multiphoton tomography allow for "optical biopsies" with horizontal cross sections. Dermatofluoroscopy and AI-based image analyzers provide a numerical score, which helps to correctly classify a skin lesion. The presented new optical procedures may be applied for the diagnosis of skin cancer as well as inflammatory skin diseases. CONCLUSION: The presented optical procedures provide valuable additional information that supports dermatologists in making the correct diagnosis. However, a surgical biopsy followed by dermatohistopathological examination remains the diagnostic gold standard in dermatology.


Assuntos
Dermatologia , Dermatopatias , Neoplasias Cutâneas , Dermoscopia , Humanos , Microscopia Confocal , Pele , Dermatopatias/diagnóstico , Neoplasias Cutâneas/diagnóstico
13.
Glob Chang Biol ; 26(3): 1908-1925, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957145

RESUMO

Warming occurs in the Arctic twice as fast as the global average, which in turn leads to a large enhancement in terpenoid emissions from vegetation. Volatile terpenoids are the main class of biogenic volatile organic compounds (VOCs) that play crucial roles in atmospheric chemistry and climate. However, the biochemical mechanisms behind the temperature-dependent increase in VOC emissions from subarctic ecosystems are largely unexplored. Using 13 CO2 -labeling, we studied the origin of VOCs and the carbon (C) allocation under global warming in the soil-plant-atmosphere system of contrasting subarctic heath tundra vegetation communities characterized by dwarf shrubs of the genera Salix or Betula. The projected temperature rise of the subarctic summer by 5°C was realistically simulated in sophisticated climate chambers. VOC emissions strongly depended on the plant species composition of the heath tundra. Warming caused increased VOC emissions and significant changes in the pattern of volatiles toward more reactive hydrocarbons. The 13 C was incorporated to varying degrees in different monoterpene and sesquiterpene isomers. We found that de novo monoterpene biosynthesis contributed to 40%-44% (Salix) and 60%-68% (Betula) of total monoterpene emissions under the current climate, and that warming increased the contribution to 50%-58% (Salix) and 87%-95% (Betula). Analyses of above- and belowground 12/13 C showed shifts of C allocation in the plant-soil systems and negative effects of warming on C sequestration by lowering net ecosystem exchange of CO2 and increasing C loss as VOCs. This comprehensive analysis provides the scientific basis for mechanistically understanding the processes controlling terpenoid emissions, required for modeling VOC emissions from terrestrial ecosystems and predicting the future chemistry of the arctic atmosphere. By changing the chemical composition and loads of VOCs into the atmosphere, the current data indicate that global warming in the Arctic may have implications for regional and global climate and for the delicate tundra ecosystems.


Assuntos
Aquecimento Global , Compostos Orgânicos Voláteis , Regiões Árticas , Ecossistema , Tundra
14.
Ann Oncol ; 31(1): 137-143, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31912788

RESUMO

BACKGROUND: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. MATERIALS AND METHODS: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists' management decisions. Secondary endpoints included the dermatologists' diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). RESULTS: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866-0.970), respectively. In level I, the dermatologists' management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists' management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. CONCLUSIONS: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.


Assuntos
Melanoma , Neoplasias Cutâneas , Dermatologistas , Dermoscopia , Alemanha , Humanos , Masculino , Melanoma/diagnóstico por imagem , Redes Neurais de Computação
15.
Hum Vaccin Immunother ; 16(2): 436-444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31361179

RESUMO

Including dental health providers in human papillomavirus (HPV) vaccination could reduce rising rates in HPV-associated oropharyngeal cancer (HPV-OPC). This study assessed Utah dentists' perspectives on providing HPV vaccination education and services in the dental setting. A cross-sectional, 70-item self-administered survey was conducted among a convenience sample of N = 203 practicing Utah dentists. Statistical analyses included Chi Square tests of independence, scaled scores and Cronbach's alpha coefficients. Majority of Utah dentists surveyed perceived that discussing the link between HPV and OPC and recommending the HPV vaccine is within their scope of practice, but not administration of the HPV vaccine. Dentists with >10 minutes of patient education per week were less likely to be concerned about the cultural, social norms or religious ideology of discussing HPV with their patients (p = .024). Rural dentists were more concerned about the safety and liability of the HPV vaccine (p = .011). Good internal consistency was observed survey items regarding barriers and willing to engage in HPV vaccination practices. Dental providers were interested in HPV training and patient education brochures as strategies, but less interested in administering the HPV vaccine. Dental associations support dentists' engagement in HPV education and HPV-OPC prevention. This is the first study in Utah to examine dentists' perspectives on HPV vaccination. Findings have implications for program planning, intervention development, and future research.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Estudos Transversais , Odontólogos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Infecções por Papillomavirus/prevenção & controle , Inquéritos e Questionários , Utah , Vacinação
16.
J Eur Acad Dermatol Venereol ; 34(6): 1355-1361, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31856342

RESUMO

BACKGROUND: Deep learning convolutional neural networks (CNN) may assist physicians in the diagnosis of melanoma. The capacity of a CNN to differentiate melanomas from combined naevi, the latter representing well-known melanoma simulators, has not been investigated. OBJECTIVE: To assess the diagnostic performance of a CNN when used to differentiate melanomas from combined naevi in comparison with dermatologists. METHODS: In this study, a CNN with regulatory approval for the European market (Moleanalyzer-Pro, FotoFinder Systems GmbH, Bad Birnbach, Germany) was used. We attained a dichotomous classification (benign, malignant) in dermoscopic images of 36 combined naevi and 36 melanomas with a mean Breslow thickness of 1.3 mm. Primary outcome measures were the CNN's sensitivity, specificity and the diagnostic odds ratio (DOR) in comparison with 11 dermatologists with different levels of experience. RESULTS: The CNN revealed a sensitivity, specificity and DOR of 97.1% (95% CI [82.7-99.6]), 78.8% (95% CI [62.8-89.1.3]) and 34 (95% CI [4.8-239]), respectively. Dermatologists showed a lower mean sensitivity, specificity and DOR of 90.6% (95% CI [84.1-94.7]; P = 0.092), 71.0% (95% CI [62.6-78.1]; P = 0.256) and 24 (95% CI [11.6-48.4]; P = 0.1114). Under the assumption that dermatologists use the CNN to verify their (initial) melanoma diagnosis, dermatologists achieve an increased specificity of 90.3% (95% CI [79.8-95.6]) at an almost unchanged sensitivity. The largest benefit was observed in 'beginners', who performed worst without CNN verification (DOR = 12) but best with CNN verification (DOR = 98). CONCLUSION: The tested CNN more accurately classified combined naevi and melanomas in comparison with trained dermatologists. Their diagnostic performance could be improved if the CNN was used to confirm/overrule an initial melanoma diagnosis. Application of a CNN may therefore be of benefit to clinicians.


Assuntos
Aprendizado Profundo , Dermatologistas , Diagnóstico por Computador/métodos , Melanoma/diagnóstico por imagem , Nevo Pigmentado/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Competência Clínica , Dermoscopia , Feminino , Humanos , Masculino , Melanócitos/patologia , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/patologia , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Adulto Jovem
18.
Atmos Sci Lett ; 20(3): e888, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31191173

RESUMO

Low-level jets (LLJs) are relatively fast-moving streams of air that form in the lower troposphere and are a common phenomenon across the Great Plains (GP) of the United States. LLJs play an important role in moisture transport and the development of nocturnal convection in the spring and summer. Alterations to surface moisture and energy fluxes can influence the planetary boundary layer (PBL) development and thus LLJs. One important anthropogenic process that has been shown to affect the surface energy budget is irrigation. In this study, we investigate the effects of irrigation on LLJ development across the GP by incorporating a dynamic and realistic irrigation scheme into the Weather Research and Forecasting (WRF) model. WRF simulations were conducted with and without the irrigation scheme for the exceptionally dry summer of 2012 over the GP. The results show irrigation-introduced changes to LLJ features both over and downstream of the most heavily irrigated regions in the GP. There were statistically significant increases to LLJ speeds in the simulation with the irrigation parameterization. Decreases to the mean jet core height on the order of 50 m during the overnight hours were also simulated when irrigation was on. The overall frequency of jet occurrences increased over the irrigated regions by 5-10%; however, these differences were not statistically significant. These changes were weaker than those reported in earlier studies based on simple representations of irrigation that unrealistically saturate the soil columns over large areas over a long period of time, which highlights the importance and necessity to represent human activity more accurately in modeling studies.

19.
Plant Methods ; 14: 109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568721

RESUMO

BACKGROUND: Climate change represents a grand challenge for agricultural productivity. Understanding complex plant traits such as stress tolerance, disease resistance or crop yield is thus essential for breeding and the development of sustainable agriculture strategies. When screening for the most robust plant phenotypes, fast, high-throughput phenotyping represents the means of choice. RESULTS: We have developed a plant phenotyping platform to measure the emission of volatile organic compounds (VOCs), photosynthetic gas exchange and transpiration under ambient, or abiotic and biotic stress conditions. These parameters are highly suitable markers to non-invasively and dynamically study plant growth and plant stress status, making them perfect test variables for long-term, online plant monitoring. Here we introduce the new phenotyping platform, termed VOC-SCREEN, and present results of a first case study with three barley cultivars, demonstrating that the plant's volatilome can be successfully applied to discriminate different barley varieties. CONCLUSION: Volatilomics is a promising technique to non-invasively screen for plant phenotypic traits.

20.
Genes Dev ; 32(19-20): 1332-1343, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30254107

RESUMO

Plants have evolved complex photoreceptor-controlled mechanisms to sense and respond to seasonal changes in day length. This ability allows plants to optimally time the transition from vegetative growth to flowering. UV-B is an important part intrinsic to sunlight; however, whether and how it affects photoperiodic flowering has remained elusive. Here, we report that, in the presence of UV-B, genetic mutation of REPRESSOR OF UV-B PHOTOMORPHOGENESIS 2 (RUP2) renders the facultative long day plant Arabidopsis thaliana a day-neutral plant and that this phenotype is dependent on the UV RESISTANCE LOCUS 8 (UVR8) UV-B photoreceptor. We provide evidence that the floral repression activity of RUP2 involves direct interaction with CONSTANS, repression of this key activator of flowering, and suppression of FLOWERING LOCUS T transcription. RUP2 therefore functions as an essential repressor of UVR8-mediated induction of flowering under noninductive short day conditions and thus provides a crucial mechanism of photoperiodic flowering control.


Assuntos
Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Proteínas Cromossômicas não Histona/metabolismo , Flores/crescimento & desenvolvimento , Fotoperíodo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Raios Ultravioleta
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