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OBJECTIVES: This national survey aimed to explore how existing pandemic preparedness plans (PPP) accounted for the demands placed on infection prevention and control (IPC) services in acute and community settings in England during the first wave of the COVID-19 pandemic. STUDY DESIGN: This was a cross-sectional survey of IPC leaders working within National Health Service Trusts or clinical commissioning groups/integrated care systems in England. METHODS: The survey questions related to organisational COVID-19 preparedness pre-pandemic and the response provided during the first wave of the pandemic (January to July 2020). The survey ran from September to November 2021, and participation was voluntary. RESULTS: In total, 50 organisations responded. Seventy-one percent (n = 34/48) reported having a current PPP in December 2019, with 81% (n = 21/26) indicating their plan was updated within the previous 3 years. Around half of IPC teams were involved in previous testing of these plans via internal and multi-agency tabletop exercises. Successful aspects of pandemic planning were identified as command structures, clear channels of communication, COVID-19 testing, and patient pathways. Key deficiencies were lack of personal protective equipment, difficulties with fit testing, keeping up to date with guidance, and insufficient staffing. CONCLUSIONS: Pandemic plans need to consider the capability and capacity of IPC services to ensure they can contribute their critical knowledge and expertise to the pandemic response. This survey provides a detailed evaluation of how IPC services were impacted during the first wave of the pandemic and identifies key areas, which need to be included in future PPP to better manage the impact on IPC services.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Teste para COVID-19 , Estudos Transversais , Medicina Estatal , Controle de InfecçõesRESUMO
Background: Data are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up. Materials and methods: We retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy. Results: Follow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit. Conclusion: There was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy.
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OBJECTIVES: The aim of the study was to systematically review current studies reporting on clinical outcomes in people living with HIV (PLHIV) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search was conducted in Global Health, SCOPUS, Medline and EMBASE using pertinent key words and Medical Subject Headings (MeSH) terms relating to coronavirus disease 2019 (COVID-19) and HIV. A narrative synthesis was undertaken. Articles are summarized in relevant sections. RESULTS: Two hundred and eighty-five articles were identified after duplicates had been removed. After screening, eight studies were analysed, totalling 70 HIV-infected patients (57 without AIDS and 13 with AIDS). Three themes were identified: (1) controlled HIV infection does not appear to result in poorer COVID-19 outcomes, (2) more data are needed to determine COVID-19 outcomes in patients with AIDS and (3) HIV-infected patients presenting with COVID-19 symptoms should be investigated for superinfections. CONCLUSIONS: Our findings suggest that PLHIV with well-controlled disease are not at risk of poorer COVID-19 disease outcomes than the general population. It is not clear whether those with poorly controlled HIV disease and AIDS have poorer outcomes. Superimposed bacterial pneumonia may be a risk factor for more severe COVID-19 but further research is urgently needed to elucidate whether PLHIV are more at risk than the general population.
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Síndrome da Imunodeficiência Adquirida/complicações , COVID-19/complicações , Coinfecção , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/patologia , Síndrome da Imunodeficiência Adquirida/virologia , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Progressão da Doença , Feminino , Humanos , MEDLINE , Masculino , Aplicações da Informática Médica , Fatores de RiscoRESUMO
Males employed in the construction industry are at greater risk of suicide than other employed males. It is plausible that a high level of stigma against mental health problems explains the elevated rates of suicide among this group. This study sought to test the effectiveness of an electronic mental health stigma intervention on suicide ideation, communication about suicide and attempts. Participants were randomly assigned to receive either a series of brief contact interventions over a 6-week period or a wait list control. Suicidal ideation, communication about suicide and suicide attempts were assessed using the Suicidal Behaviors Questionnaire-Revised at post-intervention. We used linear regression to assess effectiveness at post-intervention, adjusting for relevant covariates using both conventional methods and a propensity score approach. Results indicate that the intervention had no significant impact on suicidal thoughts, communication or suicide attempts. There was some indication that individuals in the intervention group reported a slight increase in attempts and communication about suicide. These observations underscore an urgent need for more research to understand the complex and nuanced relationship between stigma and suicide in non-clinical populations.
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Promoção da Saúde/métodos , Smartphone , Estigma Social , Prevenção do Suicídio , Adulto , Indústria da Construção , Humanos , Masculino , Pessoa de Meia-Idade , Ideação Suicida , Tentativa de Suicídio/prevenção & controle , Tentativa de Suicídio/psicologia , Inquéritos e Questionários , VitóriaRESUMO
The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg(-1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r=-0.78, P=0.023), but no other measures.
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Aminoácidos/metabolismo , Antidepressivos/uso terapêutico , Encéfalo/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/uso terapêutico , Neurotransmissores/metabolismo , Adulto , Antidepressivos/sangue , Encéfalo/efeitos dos fármacos , Feminino , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Ketamina/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Espectroscopia de Prótons por Ressonância Magnética , Escalas de Graduação Psiquiátrica , Trítio/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Spontaneous age-related lesions of laboratory rabbits are not well documented in the contemporary scientific literature. A retrospective study of diagnostic necropsies of 36 rabbits >2 years of age found a number of common lung lesions. Fibromuscular intimal hyperplasia affected medium and to a lesser extent large pulmonary arteries and was present to a variable extent in all 36 rabbits >2 years of age. The lesions were characterized by fragmentation and/or reduplication of the internal elastic lamina (IEL), proliferation of smoothelin+/alpha-smooth muscle actin (α-SMA)+/vimentin- smooth muscle cells and fewer smoothelin-/α-SMA+/vimentin+ myofibroblasts, and intimal deposition of collagen without thrombosis, embolism, or evidence of pulmonary hypertension. Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of alveolar septa; most affected rabbits did not have clinical signs of respiratory disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a unique syndrome of granulomatous pneumonia containing hyaline brown to gray, globular to ring-like acellular material that was Alcian blue and periodic acid-Schiff positive. The material was immunoreactive for surfactant protein-A and had the ultrastructural appearance of multilamellar vesicles, suggesting a genetic defect in surfactant metabolism. Additionally, we found small benign primary lung tumors (fibropapillomas, 5 rabbits) not previously described. Other findings included heterotopic bone (5 rabbits), subacute to chronic suppurative bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary artifacts from barbiturate euthanasia solution.
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Pulmão/patologia , Coelhos/fisiologia , Envelhecimento/patologia , Animais , Feminino , Masculino , Pneumonia/patologia , Pneumonia/veterinária , Artéria Pulmonar/patologia , Coelhos/anatomia & histologia , Estudos RetrospectivosRESUMO
This study compares how different cow genotyping strategies increase the accuracy of genomic estimated breeding values (EBV) in dairy cattle breeds with low numbers. In these breeds, few sires have progeny records, and genotyping cows can improve the accuracy of genomic EBV. The Guernsey breed is a small dairy cattle breed with approximately 14,000 recorded individuals worldwide. Predictions of phenotypes of milk yield, fat yield, protein yield, and calving interval were made for Guernsey cows from England and Guernsey Island using genomic EBV, with training sets including 197 de-regressed proofs of genotyped bulls, with cows selected from among 1,440 genotyped cows using different genotyping strategies. Accuracies of predictions were tested using 10-fold cross-validation among the cows. Genomic EBV were predicted using 4 different methods: (1) pedigree BLUP, (2) genomic BLUP using only bulls, (3) univariate genomic BLUP using bulls and cows, and (4) bivariate genomic BLUP. Genotyping cows with phenotypes and using their data for the prediction of single nucleotide polymorphism effects increased the correlation between genomic EBV and phenotypes compared with using only bulls by 0.163±0.022 for milk yield, 0.111±0.021 for fat yield, and 0.113±0.018 for protein yield; a decrease of 0.014±0.010 for calving interval from a low base was the only exception. Genetic correlation between phenotypes from bulls and cows were approximately 0.6 for all yield traits and significantly different from 1. Only a very small change occurred in correlation between genomic EBV and phenotypes when using the bivariate model. It was always better to genotype all the cows, but when only half of the cows were genotyped, a divergent selection strategy was better compared with the random or directional selection approach. Divergent selection of 30% of the cows remained superior for the yield traits in 8 of 10 folds.
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Genótipo , Seleção Genética , Animais , Cruzamento , Bovinos , Feminino , Genoma , Genômica , Masculino , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Dietary methionine restriction (MR) improves healthspan in part by reducing adiposity and by increasing insulin sensitivity in rodent models. The purpose of this study was to determine whether MR inhibits tumor progression in breast cancer xenograft model and breast cancer cell lines. METHODS: Athymic nude mice were injected with MCF10AT1 cells in Matrigel® and fed a diet containing either 0.86 % methionine (control fed, CF), or 0.12 % methionine (MR) for 12 weeks. Plasma amino acid concentrations were measured by UPLC, and proliferation and apoptosis were examined using RT-PCR, immunohistochemistry, and Cell Titer 96® Aqueous One Solution Cell Proliferation assay. RESULTS: Mice on the MR diet had reduced body weight and decreased adiposity. They also had smaller tumors when compared to the mice bearing tumors on the CF diet. Plasma concentrations of the sulfur amino acids (methionine, cysteine, and taurine) were reduced, whereas ornithine, serine, and glutamate acid were increased in mice on the MR diet. MR mice exhibited decreased proliferation and increased apoptosis in cells that comprise the mammary glands and tumors of mice. Elevated expression of P21 occurred in both MCF10AT1-derived tumor tissue and endogenously in mammary gland tissue of MR mice. Breast cancer cell lines MCF10A and MDA-MB-231 grown in methionine-restricted cysteine-depleted media for 24 h also up-regulated P21 and P27 gene expression, and MDA-MB-231 cells had decreased proliferation. CONCLUSION: MR hinders cancer progression by increasing cell cycle inhibitors that halt cell cycle progression. The application of MR in a clinical setting may provide a delay in the progression of cancer, which would provide more time for conventional cancer therapies to be effective.
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Dieta , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Metionina/metabolismo , Animais , Ciclo Celular/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Endocardiosis or myxomatous degeneration of the cardiac valves is a well-described age-related change in humans and dogs. Lesions consist of polypoid nodular proliferations of loose extracellular matrix and valvular interstitial cells, most commonly affecting the mitral valve. This entity has not been previously described in fish. Herein we report the appearance, location, and occurrence of valvular and mural endocardiosis in a retrospective survey of aging laboratory zebrafish. Endocardiosis was present in 59 of 777 fish (7.59%), most commonly affecting the sinoatrial (34 fish; 57.6%) and atrioventricular (33 fish; 55.9%) valves. Lesions were more common in fish raised in recirculating water systems and fed commercial diets (52/230 fish; 22.6%) versus flow-through systems with fish fed semi-purified diets (4/234; 1.71%). Lesions were overrepresented in fish heterozygous for a mutant smoothened allele (34/61 fish, 55.7% vs 17/168, 10.1% wild type). There was no association between endocardiosis and intestinal carcinoids. Valvular endocardiosis is a significant age- and husbandry-related background finding in zebrafish and should be considered in the design and interpretation of research studies.
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Envelhecimento/patologia , Endocardite/veterinária , Doenças dos Peixes/patologia , Peixe-Zebra , Animais , Modelos Animais de Doenças , Endocardite/patologia , Matriz Extracelular/patologia , Feminino , Masculino , Valva Mitral/patologia , Estudos RetrospectivosRESUMO
Inbred mice are a unique model system for studying aging because of the genetic homogeneity within inbred strains, the short life span of mice relative to humans, and the rich array of analytic tools that are available. A large-scale aging study was conducted on 28 inbred strains representing great genetic diversity to determine, via histopathology, the type and diversity of spontaneous diseases that aging mice develop. A total of 20 885 different diagnoses were made, with an average of 12 diagnoses per mouse in the study. Eighteen inbred strains have had their genomes sequenced, and many others have been partially sequenced to provide large repositories of data on genetic variation among the strains. This vast amount of genomic information can be utilized in genome-wide association studies to find candidate genes that are involved in the pathogenesis of spontaneous diseases. As an illustration, this article presents a genome-wide association study of the genetic associations of age-related intestinal amyloidosis, which implicated 3 candidate genes: translocating chain-associated membrane protein 1 (Tram1); splicing factor 3b, subunit 5 (Sf3b5); and syntaxin 11 (Stx11). Representative photomicrographs are available on the Mouse Tumor Biology Database and Pathbase to serve as a reference when evaluating inbred mice used in other genetic or experimental studies to rule out strain background lesions. Many of the age-related mouse diseases are similar, if not identical, to human diseases; therefore, the genetic discoveries have direct translational benefit.
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Envelhecimento/genética , Amiloidose/genética , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Genoma/genética , Camundongos Endogâmicos , Animais , Causas de Morte , Estudos de Coortes , Estudos Transversais , Modelos Animais de Doenças , Feminino , Estudos Longitudinais , Masculino , Camundongos , Camundongos Endogâmicos/genética , Fenótipo , Análise de Sequência de DNARESUMO
The objectives of this paper were to briefly review progress in the genetic evaluation of novel traits in Canada and the United States, assess methods to predict selection accuracy based on cow reference populations, and illustrate how the use of indicator traits could increase genomic selection accuracy. Traits reviewed are grouped into the following categories: udder health, hoof health, other health traits, feed efficiency and methane emissions, and other novel traits. The status of activities expected to lead to national genetic evaluations is indicated for each group of traits. For traits that are more difficult to measure or expensive to collect, such as individual feed intake or immune response, the development of a cow reference population is the most effective approach. Several deterministic methods can be used to predict the reliability of genomic evaluations based on cow reference population size, trait heritability, and other population parameters. To provide an empirical validation of those methods, predicted accuracies were compared with observed accuracies for several cow reference populations and traits. Reference populations of 2,000 to 20,000 cows were created through random sampling of genotyped Holstein cows in Canada and the United States. The effects of single nucleotide polymorphisms (SNP) were estimated from those cow records, after excluding the dams of validation bulls. Bulls that were first progeny tested in 2013 and 2014 were then used to carry out a validation and estimate the observed accuracy of genomic selection based on those SNP effects. Over the various cow population sizes and traits considered in the study, even the best prediction methods were found, on average, to either under-evaluate observed accuracy by 0.20 or over-evaluate it by 0.22, depending on the approach used to estimate the number of independently segregating chromosome segments. In some instances, differences between observed and predicted accuracies were as large as 0.47. Indicator traits can be very useful for the selection of novel traits. To illustrate this, protein yield, body weight, and mid-infrared data were used as indicator traits for feed efficiency. Using those traits in conjunction with 5,000 cow records for dry matter intake increased the reliability of genomic predictions for young animals from 0.20 to 0.50.
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Cruzamento , Bovinos/genética , Genômica/métodos , Fenótipo , Seleção Genética , Animais , Canadá , Indústria de Laticínios , Feminino , América do Norte , Reprodutibilidade dos TestesRESUMO
GeneSeek (Neogen Corp., Lexington, KY) designed a new version of the GeneSeek Genomic Profiler HD BeadChip for Dairy Cattle, which originally had >77,000 single nucleotide polymorphisms (SNP). A set of >140,000 SNP was selected that included all SNP on the existing GeneSeek chip, all SNP used in US national genomic evaluations, SNP that were possible functional mutations, and other informative SNP. Because SNP with a lower minor allele frequency might track causative variants better, 30,000 more SNP were selected from the Illumina BovineHD Genotyping BeadChip (Illumina Inc., San Diego, CA) by choosing SNP to maximize differences in minor allele frequency between a SNP being considered for the new chip and the 2 SNP that flanked it. Single-gene tests were included if their location was known and bioinformatics indicated relevance for dairy cattle. To determine which SNP from the new chip should be included in genomic evaluations, genotypes available from chips already in use were used to impute and evaluate the SNP set. Effects for 134,511 usable SNP were estimated for all breed-trait combinations; SNP with the largest absolute values for effects were selected (5,000 for Holsteins, 1,000 for Jerseys, and 500 each for Brown Swiss and Ayrshires for each trait). To increase overlap with the 60,671 SNP currently used for genomic evaluation, 12,094 more SNP with the largest effects were added. After removing SNP with many parent-progeny conflicts, 84,937 SNP remained. Three cutoff studies were conducted with 3 SNP sets to determine reliability gain over that for parent average when evaluations based on August 2011 data were used to predict December 2014 performance. Across all traits, mean Holstein reliability gains were 32.5, 33.4, and 32.0 percentage points for 60,671, 84,937, and 134,511 SNP, respectively. After genotypes from the new chip became available, the proposed set was reduced from 84,937 to 77,321 SNP to remove SNP that were not included during manufacture, reduce computing time, and improve imputation performance. The set of 77,321 SNP was evaluated using August 2011 data to predict April 2015 performance. Reliability gain over 60,671 SNP was 1.4 percentage points across traits for Holsteins. Improvement over 84,937 SNP was partially the result of 4mo of additional data and genotypes from the new chip. Revision of the SNP set used for genomic evaluation is expected to be an ongoing process to increase evaluation accuracy.
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Bovinos/genética , Genoma , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Polimorfismo de Nucleotídeo Único , Animais , Indústria de Laticínios , Feminino , Genômica , Análise de Sequência com Séries de Oligonucleotídeos/métodosRESUMO
As of December 2015, 2,376 Guernsey bulls and cows had genotypes from collaboration between the United States, Canada, the United Kingdom, and the Isle of Guernsey. Of those, 439 bulls and 504 cows had traditional US evaluations, which provided sufficient data to justify investigation of the possible benefits of genomic evaluation for the Guernsey breed. Evaluation accuracy was assessed using a traditional 4-yr cutoff study. Twenty-two traits were analyzed (5 yield traits, 3 functional traits, and 14 conformation traits). Mean reliability gain over that for parent average was 16.8 percentage points across traits, which compares with 8.2, 18.5, 20.0, and 32.6 percentage points reported for Ayrshires, Brown Swiss, Jerseys, and Holsteins, respectively. Highest Guernsey reliability gains were for rump width (44.5 percentage points) and dairy form (40.5 percentage points); lowest gains were for teat length (1.9 percentage points) and rear legs (side view) (2.3 percentage points). Slight reliability losses (1.5 to 4.5 percentage points) were found for udder cleft, final score, and udder depth as well as a larger loss (13.6 percentage points) for fore udder attachment. Twenty-one single nucleotide polymorphisms were identified for Guernsey breed determination and can be used in routine genotype quality control to confirm breed and identify crossbreds. No haplotypes that affect fertility were identified from the current data set. Principal component analysis showed some divergence of US and Isle of Guernsey subpopulations. However, the overlap of US, Canadian, UK, and Isle of Guernsey subpopulations indicated the presence of gene flow, and the similarities in the subpopulations supports a common genomic evaluation system across the regions.
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Bovinos/classificação , Bovinos/genética , Animais , Cruzamento , Canadá , Bovinos/anatomia & histologia , Feminino , Fertilidade/genética , Genômica , Genótipo , Guernsey , Haplótipos , Lactação/genética , Masculino , América do Norte , Fenótipo , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Reprodutibilidade dos Testes , Reprodução/genética , Especificidade da Espécie , Reino Unido , Estados UnidosRESUMO
Thermochemical CO2-splitting via redox cycling of Ca, Sr and Al-doped La-Mn perovskites induces irreversible changes in the texture and chemical composition of these oxides. Though the crystal structure is mostly preserved after high-temperature redox cycling, the chemical stability is detrimentally affected by sintering and by the formation and eventual segregation of a carbonate phase during oxidation by CO2. Carbonation of the Ca and Sr phase was diminished by Al-substitution of the Mn-cation in the B-position.
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OBJECTIVE: While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. METHOD: Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. RESULTS: Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 µg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. CONCLUSION: The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.
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Adjuvantes Imunológicos/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Doenças Vaginais/tratamento farmacológico , Doenças da Vulva/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Administração Intravaginal , Adulto , Idoso , Atrofia/complicações , Atrofia/tratamento farmacológico , Desidroepiandrosterona/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Dispareunia/tratamento farmacológico , Dispareunia/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Resultado do Tratamento , Doenças Vaginais/complicações , Doenças da Vulva/complicaçõesRESUMO
Chordomas are uncommon neoplasms arising from notochord remnants, most commonly occurring in the axial skeleton. Extraskeletal soft tissue chordomas are rare primary tumors, and primary alimentary tract chordomas have not been reported. Herein we report 24 cases of spontaneous primary intestinal chordomas in zebrafish, as well as 9 spontaneous vertebral chordomas. Both intestinal and vertebral tumors showed invasive behavior, although more commonly in the latter. In all cases of primary intestinal chordomas, there was no axial or peripheral skeletal or other nonvisceral involvement. Although uncommon, intestinal chordomas represent a unique background lesion in aged zebrafish.
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Cordoma/veterinária , Doenças dos Peixes/patologia , Neoplasias Intestinais/veterinária , Neoplasias da Coluna Vertebral/veterinária , Animais , Cordoma/patologia , Feminino , Neoplasias Intestinais/patologia , Masculino , Neoplasias da Coluna Vertebral/patologia , Peixe-ZebraRESUMO
Seven male Hartley guinea pigs, 3 to 18 months old, died or had to be euthanized because of nonspecific clinical signs unresponsive to supportive treatment. Gross necropsy and histopathology findings in all animals included severe soft tissue calcification affecting the myocardium, kidneys, and occasionally the liver.
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Calcinose/veterinária , Insuficiência Cardíaca/veterinária , Animais , Calcinose/patologia , Diagnóstico Diferencial , Cobaias , Insuficiência Cardíaca/patologia , Masculino , Miocárdio/patologiaRESUMO
Increased computing time for the ever-growing predictor population and linkage decay between the ancestral population and current animals have become concerns for genomic evaluation systems. The effects on reliability of US genomic evaluations from including cows and bulls in the Holstein predictor population and also from excluding older bulls from the predictor population were examined. Holstein data collected for December 2013 US genomic evaluations were used in cutoff studies to determine reliability gains, regression coefficients, and bias for 5 yield, 3 fitness, 2 fertility, and 18 conformation traits. Three predictor populations were examined based on animal sex: 30,852 cows with traditional evaluations as of August 2012, 21,883 bulls with traditional evaluations as of August 2012, and a combined group of all bulls and cows. Three subsets of the bull predictor population were examined to determine effect of age: bulls born before 1996 excluded (25% of bulls excluded), bulls born before 2001 excluded (50%), and bulls born before 2005 excluded (75%). The validation set for all predictor populations was either bulls or cows first receiving a traditional evaluation between August 2012 and December 2013. Across all traits, the addition of cows to the bull predictor population increased reliability gains by 0.4 percentage points for validation bulls and 4.4 points for validation cows. Across all traits, excluding bulls born before 1996 from the bull-only predictor population decreased gains in genomic reliability by 1.8 percentage points. For 19 of 28 traits, excluding bulls born before 2005 from the predictor population resulted in lower bias in genomic evaluations of validation bulls. Although the contribution of cows and older bulls to improved accuracy of US genomic evaluations is small, a plateau of achievable gain has not yet been reached.
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Envelhecimento , Bovinos/genética , Genômica/métodos , Genótipo , Animais , Comunicação , Feminino , Ligação Genética , Genoma , Masculino , Parto/genética , Fatores Sexuais , Estados UnidosRESUMO
A method was developed to calculate preliminary genomic evaluations daily or weekly before the release of official monthly evaluations by processing only newly genotyped animals using estimates of single nucleotide polymorphism effects from the previous official evaluation. To minimize computing time, reliabilities and genomic inbreeding are not calculated, and fixed weights are used to combine genomic and traditional information. Correlations of preliminary and September official monthly evaluations for animals with genotypes that became usable after the extraction of genotypes for August 2014 evaluations were >0.99 for most Holstein traits. Correlations were lower for breeds with smaller population size. Earlier access to genomic evaluations benefits producers by enabling earlier culling decisions and genotyping laboratories by making workloads more uniform across the month.
Assuntos
Bovinos/genética , Indústria de Laticínios/métodos , Genômica , Animais , Feminino , Genoma/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Estações do Ano , Fatores de TempoRESUMO
The effect on prediction accuracy for Jersey genomic evaluations of Danish and US bulls from using a larger reference population was assessed. Each country contributed genotypes from 1,157 Jersey bulls to the reference population of the other. Data were separated into reference (US only, Danish only, and combined US-Danish) and validation (US only and Danish only) populations. Depending on trait (milk, fat, and protein yields and component percentages; productive life; somatic cell score; daughter pregnancy rate; 14 conformation traits; and net merit), the US reference population included 2,720 to 4,772 bulls and cows with traditional evaluations as of August 2009; the Danish reference population included 635 to 996 bulls. The US validation population included 442 to 712 bulls that gained a traditional evaluation between August 2009 and December 2013; the Danish validation population included 105 to 196 bulls with multitrait across-country evaluations on the US scale by December 2013. Genomic predicted transmitting abilities (GPTA) were calculated on the US scale using a selection index that combined direct genomic predictions with either traditional predicted transmitting ability for the reference population or traditional parent averages (PA) for the validation population and a traditional evaluation based only on genotyped animals. Reliability for GPTA was estimated from the reference population and August 2009 traditional PA and PA reliability. For prediction of December 2013 deregressed daughter deviations on the US scale, mean August 2009 GPTA reliability for Danish validation bulls was 0.10 higher when based on the combined US-Danish reference population than when the reference population included only Danish bulls; for US validation bulls, mean reliability increased by 0.02 when Danish bulls were added to the US reference population. Exchanging genotype data to increase the size of the reference population is an efficient approach to increasing the accuracy of genomic prediction when the reference population is small.