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1.
bioRxiv ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38746372

RESUMEN

The fruit fly Drosophila melanogaster is a model for understanding how hosts and their microbial partners interact as the host adapts to wild environments. These interactions are readily interrogated because of the low taxonomic and numeric complexity of the flies' bacterial communities. Previous work has established that host genotype, the environment, diet, and interspecies microbial interactions can all influence host fitness and microbiota composition, but the specific processes and characters mediating these processes are incompletely understood. Here, we compared the variation in microbiota composition between wild-derived fly populations when flies could choose between the microorganisms in their diets and when flies were reared under environmental perturbation (different humidities). We also compared the colonization of the resident and transient microorganisms. We show that the ability to choose between microorganisms in the diet and the environmental condition of the flies can influence the relative abundance of the microbiota. There were also key differences in the abundances of the resident and transient microbiota. However, the microbiota only differed between populations when the flies were reared at humidities at or above 50% relative humidity. We also show that elevated humidity determined the penetrance of a gradient in host genetic selection on the microbiota that is associated with the latitude the flies were collected from. Finally, we show that the treatment-dependent variation in microbiota composition is associated with variation in host stress survival. Together, these findings emphasize that host genetic selection on the microbiota composition of a model animal host can be patterned with the source geography, and that such variation has the potential to influence their survival in the wild. Importance: The fruit fly Drosophila melanogaster is a model for understanding how hosts and their microbial partners interact as hosts adapt in wild environments. Our understanding of what causes geographic variation in the fruit fly microbiota remains incomplete. Previous work has shown that the D. melanogaster microbiota has relatively low numerical and taxonomic complexity. Variation in the fly microbiota composition can be attributed to environmental characters and host genetic variation, and variation in microbiota composition can be patterned with the source location of the flies. In this work we explored three possible causes of patterned variation in microbiota composition. We show that host feeding choices, the host niche colonized by the bacteria, and a single environmental character can all contribute to variation in microbiota composition. We also show that penetrance of latitudinally-patterned host genetic selection is only observed at elevated humidities. Together, these results identify several factors that influence microbiota composition in wild fly genotypes and emphasize the interplay between environmental and host genetic factors in determining the microbiota composition of these model hosts.

2.
Curr Probl Diagn Radiol ; 53(3): 341-345, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38309990

RESUMEN

BACKGROUND: Computed tomography (CT) imaging has become a first line investigation for most cases of febrile neutropenia (FN) which can be the only sign of infection in oncology patients undergoing active chemotherapy and bone marrow transplants. The utility of routine non-targeted imaging remains unclear. OBJECTIVE: To assess and compare the diagnostic rate between targeted, non-targeted and pan-scan CT in identifying an acute source of infection in adult oncology patients with FN. MATERIALS AND METHODS: A retrospective observational study was conducted between February 2019 and March 2023 on 417 consecutive CT examinations for the clinical indication of source identification in FN. Scans were noted for the anatomical regions that were imaged and reports were classified as positive, negative or equivocal for infection. Pre-existing pathology was also noted. Results were tabulated and statistical analyses for comparison between groups of scans was performed using chi-square test. RESULTS: All targeted regional scans had statistically significant difference in positive rate compared to non-targeted scans of the respective region; chest (Χ²(1)=18.11, P<.001); sinus (Χ²(1)=15.36, P<.001); abdomen and pelvis (Χ²(1)=5.95, P=.01). Pneumonia (41.3 %) was much more likely to be the diagnosis compared to sinusitis (16.2 %) in concomitant CT chest to sinus examinations (Χ²(1)=45.3, P<.001). Pan-scans had a higher incidence of positive diagnosis compared to all-targeted scans (Χ²(1)=4.91, P=.03) but when compared to higher yield targeted scans (abdomen and chest), there was no statistical difference (Χ²(1)=2.43, P=.12). 20/54 patients had pan-scans despite having localising symptoms. CONCLUSION: Imaging guided by presenting signs and symptoms can help to reduce unnecessary imaging and promote more judicious use of non-targeted and pan-scan CT in current practices.


Asunto(s)
Neutropenia Febril , Neoplasias , Sinusitis , Adulto , Humanos , Tomografía Computarizada por Rayos X/métodos , Sinusitis/complicaciones , Oncología Médica , Estudios Retrospectivos , Neutropenia Febril/diagnóstico por imagen , Neutropenia Febril/complicaciones
3.
PLoS Genet ; 19(9): e1010906, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37703303

RESUMEN

Fluctuating environments threaten fertility and viability. To better match the immediate, local environment, many organisms adopt alternative phenotypic states, a phenomenon called "phenotypic plasticity." Natural populations that predictably encounter fluctuating environments tend to be more plastic than conspecific populations that encounter a constant environment, suggesting that phenotypic plasticity can be adaptive. Despite pervasive evidence of such "adaptive phenotypic plasticity," gene regulatory mechanisms underlying plasticity remains poorly understood. Here we test the hypothesis that environment-dependent phenotypic plasticity is mediated by epigenetic factors. To test this hypothesis, we exploit the adaptive reproductive arrest of Drosophila melanogaster females, called diapause. Using an inbred line from a natural population with high diapause plasticity, we demonstrate that diapause is determined epigenetically: only a subset of genetically identical individuals enter diapause and this diapause plasticity is epigenetically transmitted for at least three generations. Upon screening a suite of epigenetic marks, we discovered that the active histone marks H3K4me3 and H3K36me1 are depleted in diapausing ovaries. Using ovary-specific knockdown of histone mark writers and erasers, we demonstrate that H3K4me3 and H3K36me1 depletion promotes diapause. Given that diapause is highly polygenic, that is, distinct suites of alleles mediate diapause plasticity across distinct genotypes, we also investigated the potential for genetic variation in diapause-determining epigenetic marks. Specifically, we asked if these histone marks were similarly depleted in diapause of a genotypically distinct line. We found evidence of divergence in both the gene expression program and histone mark abundance. This study reveals chromatin determinants of phenotypic plasticity and suggests that these determinants may be genotype-dependent, offering new insight into how organisms may exploit and evolve epigenetic mechanisms to persist in fluctuating environments.


Asunto(s)
Diapausa , Drosophila melanogaster , Femenino , Animales , Drosophila melanogaster/genética , Metilación , Histonas/genética , Procesamiento Proteico-Postraduccional
4.
SAGE Open Med Case Rep ; 11: 2050313X231191899, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37654547

RESUMEN

A female in her 60s presented to the allergy and immunology clinic for further investigation of ongoing dermatitis. She presented with chronic acrocyanosis, mainly in her left lower extremity, extending distally from her mid thigh with concurrent ulcerations in her foot resulting in immobility secondary to pain. She experienced these symptoms for years without a definitive diagnosis. The lack of diagnosis was due, in part, to her atypical symptoms and laboratory findings that required a high level of clinical suspicion to diagnose. Extensive autoimmune workup was largely unrevealing with the exception of a cold agglutinin titer of 1:250 and a positive anticomplement C3b direct antiglobulin test. A diagnosis of cold agglutinin disease was made and treatment with rituximab monotherapy was initiated.

5.
Poult Sci ; 102(7): 102688, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37141814

RESUMEN

Mechanical loading has been used increasingly in recent years alongside the manual loading of broilers. The aim of this study was to analyze the influence of various factors on the behavior of broilers and the impacts occurring to broilers during loading with a loading machine in order to identify risk factors and thus improve animal welfare. During 32 loadings we assessed escape behavior, wing flapping, flip, bumping into an animal, and bumping against the machine or container by evaluation of video recordings. The parameters were analyzed for influences of rotation speed, container type (GP container vs. SmartStack container), husbandry system ("Indoor Plus" vs. "Outdoor Climate"), and season. In addition, the behavior and impact parameters were correlated with the loading-related injuries. The results showed that an increase in rotation and conveyor belt speed was associated with an elevated risk of all behaviors or impacts, except for a lower risk of escape behavior. The seasonal influence showed that the risk of wing flapping, bumping into an animal, and bumping against the machine or container was highest in fall. The comparison of the container types showed that the risk of escape behavior, wing flapping, and bumping into an animal was increased when loading with the SmartStack container, but the risk of bumping against the machine or container was reduced. For animals of the husbandry system "Outdoor Climate," the risk of bumping into an animal and bumping against the machine or container was reduced. In addition, we found an influence of the examined parameters on the loading-related injuries. Increased escape behavior reduced the risk of severe injuries (fractures, dislocations, epiphysiolyses). Wing flapping and bumping against the machine or container increased the risk of hematomas and abrasions. The risk of hematomas was increased if broilers bumped into conspecifics. In summary, our analysis revealed that the behavior and impacts on the animals during loading are influenced by each of the analyzed factors and that they in turn can affect loading-related injuries.


Asunto(s)
Bienestar del Animal , Pollos , Animales , Estaciones del Año , Factores de Riesgo , Alas de Animales
6.
Mol Biol Evol ; 40(6)2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37220650

RESUMEN

Since the pioneering work of Dobzhansky in the 1930s and 1940s, many chromosomal inversions have been identified, but how they contribute to adaptation remains poorly understood. In Drosophila melanogaster, the widespread inversion polymorphism In(3R)Payne underpins latitudinal clines in fitness traits on multiple continents. Here, we use single-individual whole-genome sequencing, transcriptomics, and published sequencing data to study the population genomics of this inversion on four continents: in its ancestral African range and in derived populations in Europe, North America, and Australia. Our results confirm that this inversion originated in sub-Saharan Africa and subsequently became cosmopolitan; we observe marked monophyletic divergence of inverted and noninverted karyotypes, with some substructure among inverted chromosomes between continents. Despite divergent evolution of this inversion since its out-of-Africa migration, derived non-African populations exhibit similar patterns of long-range linkage disequilibrium between the inversion breakpoints and major peaks of divergence in its center, consistent with balancing selection and suggesting that the inversion harbors alleles that are maintained by selection on several continents. Using RNA-sequencing, we identify overlap between inversion-linked single-nucleotide polymorphisms and loci that are differentially expressed between inverted and noninverted chromosomes. Expression levels are higher for inverted chromosomes at low temperature, suggesting loss of buffering or compensatory plasticity and consistent with higher inversion frequency in warm climates. Our results suggest that this ancestrally tropical balanced polymorphism spread around the world and became latitudinally assorted along similar but independent climatic gradients, always being frequent in subtropical/tropical areas but rare or absent in temperate climates.


Asunto(s)
Inversión Cromosómica , Drosophila melanogaster , Animales , Drosophila melanogaster/genética , Adaptación Fisiológica/genética , Polimorfismo de Nucleótido Simple , América del Norte
7.
Animals (Basel) ; 13(3)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36766418

RESUMEN

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness of local anesthetics. In this study, we investigated the efficacy of four local anesthetics in terms of pain relief during and after surgical castration in three sequential study parts. To do so, we filmed 178 piglets before the applied procedures, after injection of the local anesthetic, and up to 24 h after castration (five observation times in total) in an observation arena and compared their behavior before and after castration and between treatments and control groups. The results showed significant differences in the behavior of the piglets before and after castration and between the sham-castrated control group and the control group castrated without anesthesia. The different local anesthesia treatment groups showed diverging differences to the control groups. The most frequently shown pain-associated behaviors of the piglets were changes in tail position and hunched back posture. We observed a reduction but no complete elimination of the expressed pain-associated behaviors after local anesthesia. Several behavioral changes-such as changes in tail position, hunched back posture or tail wagging-persisted until the day after castration. Owing to the limited duration of the effects of the local anesthetics, local anesthesia did not influence long-term pain.

8.
Neuroimage Clin ; 37: 103311, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36623350

RESUMEN

BACKGROUND: Lesions in the periventricular, (juxta)cortical, and infratentorial region, as visible on brain MRI, are part of the diagnostic criteria for Multiple sclerosis (MS) whereas lesions in the subcortical region are currently only a marker of disease activity. It is unknown whether MS lesions follow individual spatial patterns or whether they occur in a random manner across diagnostic regions. AIM: First, to describe cross-sectionally the spatial lesion patterns in patients with MS. Second, to investigate the spatial association of new lesions and lesions at baseline across diagnostic regions. METHODS: Experienced neuroradiologists analyzed brain MRI (3D, 3T) in a cohort of 330 early MS patients. Lesions at baseline and new solitary lesions after two years were segmented (manually and by consensus) and classified as periventricular, (juxta)cortical, or infratentorial (diagnostic regions) or subcortical-with or without Gadolinium-enhancement. Gadolinium enhancement of lesions in the different regions was compared by Chi square test. New lesions in the four regions served as dependent variable in four zero-inflated Poisson models each with the six independent variables of lesions in the four regions at baseline, age and gender. RESULTS: At baseline, lesions were most often observed in the subcortical region (mean 13.0 lesions/patient), while lesion volume was highest in the periventricular region (mean 2287 µl/patient). Subcortical lesions were less likely to show gadolinium enhancement (3.1 %) than juxtacortical (4.3 %), periventricular (5.3 %) or infratentorial lesions (7.2 %). Age was inversely correlated with new periventricular, juxtacortical and subcortical lesions. New lesions in the periventricular, juxtacortical and infratentorial region showed a significant autocorrelative behavior being positively related to the number of lesions in the respective regions at baseline. New lesions in the subcortical region showed a different behavior with a positive association with baseline periventricular lesions and a negative association with baseline infratentorial lesions. CONCLUSION: Across regions, new lesions do not occur randomly; instead, new lesions in the periventricular, juxtacortical and infratentorial diagnostic region are associated with that at baseline. Lesions in the subcortical regions are more closely related to periventricular lesions. Moreover, subcortical lesions substantially contribute to lesion burden in MS but are less likely to show gadolinium enhancement (than lesions in the diagnostic regions).


Asunto(s)
Esclerosis Múltiple , Humanos , Esclerosis Múltiple/patología , Gadolinio , Medios de Contraste , Imagen por Resonancia Magnética , Neuroimagen , Encéfalo
9.
Theor Appl Genet ; 136(1): 18, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36680594

RESUMEN

To assess the efficiency of genetic improvement programs, it is essential to assess the genetic trend in long-term data. The present study estimates the genetic trends for grain yield of rice varieties released between 1970 and 2020 by the Bangladesh Rice Research Institute. The yield of the varieties was assessed from 2001-2002 to 2020-2021 in multi-locations trials. In such a series of trials, yield may increase over time due to (i) genetic improvement (genetic trend) and (ii) improved management or favorable climate change (agronomic/non-genetic trend). In both the winter and monsoon seasons, we observed positive genetic and non-genetic trends. The annual genetic trend for grain yield in both winter and monsoon rice varieties was 0.01 t ha-1, while the non-genetic trend for both seasons was 0.02 t ha-1, corresponding to yearly genetic gains of 0.28% and 0.18% in winter and monsoon seasons, respectively. The overall percentage yield change from 1970 until 2020 for winter rice was 40.96%, of which 13.91% was genetic trend and 27.05% was non-genetic. For the monsoon season, the overall percentage change from 1973 until 2020 was 38.39%, of which genetic and non-genetic increases were 8.36% and 30.03%, respectively. Overall, the contribution of non-genetic trend is larger than genetic trend both for winter and monsoon seasons. These results suggest that limited progress has been made in improving yield in Bangladeshi rice breeding programs over the last 50 years. Breeding programs need to be modernized to deliver sufficient genetic gains in the future to sustain Bangladeshi food security.


Asunto(s)
Oryza , Oryza/genética , Bangladesh , Fitomejoramiento , Grano Comestible/genética , Agricultura , Estaciones del Año
10.
Animals (Basel) ; 12(19)2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-36230380

RESUMEN

The objective of this study was to describe the ontogeny of the severe feather pecking (SFP), gentle feather pecking (GFP), aggressive pecking (AP), and enrichment pecking (EP) of non-beak-trimmed Lohmann Brown (LB)-pullets during the first 4 weeks of life (observation on 1st, 8th, 15th, 22nd, and 29th days of life) while they were kept within the compartments of a commercial rearing aviary (without access to a litter area). All chicks were placed into compartments of the middle tier of the aviary on the 1st day of life. On the 10th day of life, half of the chicks of each compartment were moved into the compartments of the lower tier. The aviary floor was covered with chick paper before the placement of the chicks and fully or partially removed from the 15th day of life onwards. The pecking behavior patterns were observed in three experimental groups (EG): NE (not enriched): group size until/after 10th day of life: 230/115; 120.8/60.4 birds/m2, no enrichment; EL (enriched, low stocking rate): group size until/after 10th day of life: 203/101, 106.6/53.6 birds/m2; and EH (enriched, high stocking rate): group size until/after 10th day of life: 230/115;120.8/60.4 birds/m2, both pecking stones and blocks as enrichment) in two rearing periods. For each pecking behavior pattern, an independent regression model with the parameters EG, chick paper, observation day, and functional area was estimated. GFP, SFP, and EP increased with age during the observation. The AP rate was highest in all EGs on the first day of life and decreased during the observation period. A pairwise comparison of NE (high stocking rate without enrichment) with EH (high stocking rate with enrichment and with EL (low stocking rate with enrichment) showed a significant effect of the EG on pecking behavior, with more SFP, AP, and GFP in NE. There were no differences between EL and EH, indicating that the provision of pecking materials had more influence than the stocking rate. However, we presumed that the difference between the stocking rates were too small to observe an effect. AP, SFP, and GFP were significantly higher on wired slats, as compared to the perches and the vicinity of the enrichment materials. The enrichment materials were suitable and intensely used by the pullets. The provision of pecking blocks and pecking stones was recommended as a preventive measure from the first day of life onwards for pullets housed in commercial rearing aviaries. There was no effect of reduced stocking rate, most likely due to the low variation in stocking rates.

11.
Poult Sci ; 101(10): 102093, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36055026

RESUMEN

Various plumage and integument scoring methods are commonly used to deduce the occurrence of severe feather pecking and cannibalism in laying hens. The aim of our study was to provide evidence of correlations between the occurrence of severe feather pecking and our individual plumage scoring system used under practical conditions on commercial farms with non-beak-trimmed and beak-trimmed layers (study I). In second step, we aimed to verify whether the results of the elaborate individual scoring may be predicted with a visual scoring method based on the total body scores of groups of birds (study II). For study I we observed the pecking behavior and performed an individual plumage scoring at the beginning, in the middle, and at the end of a laying period on 8 commercial farms. For study II we performed both an individual and a visual plumage scoring on 49 flocks on 45 farms at the beginning of the laying period and on 43 flocks on 41 farms at the end of the laying period. Spearman's Rho revealed a correlation of the mean feather pecking rate with the total plumage score, the neck-back plumage score, and the total cannibalism score in all observation periods. A high feather pecking rate was correlated with severe plumage damage and the frequent occurrence of skin injuries. We conclude that both the total plumage score and the neck-back plumage score constitute a reliable indicator of the occurrence of severe feather pecking in the flocks assessed in this study. The results of study II suggest that the percental assessment of plumage damage on flock level in 3 categories ("visual score") leads to a good prognosis of the actual, individually assessed plumage score. Therefore, the application (and documentation) of the visual score on a regular basis can provide a good evaluation of the development of the plumage condition of the flock. The visual score presented in this study is suggested as a suitable instrument for self-evaluation programs on farms.


Asunto(s)
Pollos , Plumas , Animales , Conducta Animal , Granjas , Femenino , Pronóstico
12.
Poult Sci ; 101(11): 102127, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36087442

RESUMEN

The aim of this study was to compare the 2 manual catching methods in terms of injuries and behavior. Throughout 12 loadings on practical farms with the same standard, 1 container each was caught using the one-legged (1LCM) and 1 using the two-legged catching method (2LCM). The animals were filmed during loading to evaluate their behavior and subsequently examined regarding injuries. Wing flapping was observed more frequently in broilers caught with the 1LCM than 2 LCM. Carrying animals with neighbors (1 neighbor: P < 0.001; 2 neighbors: P < 0.001) and a grasping position at or above the tarsal joint (P < 0.001; P < 0.054) reduced wing flapping in both methods. A short grasping duration (P = 0.004), settling the broilers into the crate (P = 0.005) and avoiding striking the broilers against the crate (P < 0.001) reduced the occurrence of wing flapping. About 1.1% of 1LCM and 0.43% of 2LCM broilers were diagnosed with an epiphysiolysis. Catching with the 1LCM (P = 0.042), loading in lower crates (low vs. middle: P = 0.005; low vs. high: P = 0.008), a longer catching duration (p = 0.025) and female broilers (P = 0.007) had a higher chance for epiphysiolysis. Broilers loaded in lower crates (P = 0.007) and ones which showed more wing flapping (P = 0.015) had a higher chance for hematomas. A higher loading duration led to a higher risk of hematomas (prevalence: 1.5%) and a prevalence of 1.0% of broilers with severe injury in 2LCM in a simultaneously performed study (mechanical loading vs. 2LCM), in which manual loadings of entire barns were evaluated. This may be caused by fatigue of the workers. In summary, the catching method or number of grasped legs is not the decisive factor, but the compliance and implementation of the identified risks and careful handling of the animals are determining factors to reduce wing injuries caused by loading and wing flapping.


Asunto(s)
Pollos , Epífisis Desprendida , Animales , Femenino , Alas de Animales , Epífisis Desprendida/veterinaria , Hematoma/veterinaria , Vuelo Animal
13.
Poult Sci ; 101(9): 102025, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35901651

RESUMEN

This study aimed to develop and validate a camera vision score that could detect macroscopic alterations of the hock, to identify errors and to assess possible factors that could influence the assessment. Two hundred hocks in the first (calibration) phase and 500 hocks in the second (validation) phase were collected at slaughter, visually assessed, placed back into the evisceration line and assessed by a camera system with 2 software systems. The size of the alteration in percent (%) measured by the camera system was evaluated ("camera score", CS). Additionally, temperature, humidity, and light intensities were measured. In the calibration phase, threshold values of camera scores for respective macro scores were defined and performance measures evaluated. In the validation phase, the generated threshold values were validated, occurring errors, as well as possible impacts of climatic factors analyzed. The results showed that the generated thresholds predict the camera score values at which the respective macro score has the highest probability of appearance. Small hock burn lesions ≤0.5 cm have the highest probability at a camera score of ≥0.2 (original CS) or ≥0.1 (updated CS), and lesions >0.5 cm have the highest probability at a camera score of ≥0.7 (original CS) or ≥1.1 (updated CS). Large lesions (>0.5 cm) are more reliably identified by the system than small lesions. The risks of errors in assessing reference areas and lesions showed a correct identification of lesions to be the most probable result even if the reference area is not correctly identified. The probability of a correct identification of lesions by the camera system was slightly higher (not significant) with the updated software (risk = 0.66 [0.62-0.70]) than with the original software (risk = 0.63 [0.58-0.67]). Automatic assessment systems at slaughter could be adjusted to the presented threshold values to classify hock burn lesions. Software adaptations can improve the performance measures of diagnosis and reduce the probability of errors.


Asunto(s)
Enfermedades de las Aves de Corral , Tarso Animal , Animales , Pollos , Enfermedades de las Aves de Corral/patología , Tarso Animal/patología
14.
BMJ Open ; 12(6): e063424, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35697438

RESUMEN

INTRODUCTION: Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality. METHODS AND ANALYSIS: PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation. ETHICS AND DISSEMINATION: The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ISRCTN54006056.


Asunto(s)
Infecciones Bacterianas , Sepsis , Adulto , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Servicio de Urgencia en Hospital , Humanos , Estudios Multicéntricos como Asunto , Polipéptido alfa Relacionado con Calcitonina , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico
15.
J Vet Med Educ ; : e20220011, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35617609

RESUMEN

Surgical skills are an important competency for new graduates. Simulators offer a means to train and assess veterinary students prior to their first surgical performance. A simulated ovariohysterectomy (OVH) rubric's validity was evaluated using a framework of content evidence, internal structure evidence, and evidence of relationship with other variables, specifically subsequent live surgical performance. Clinically experienced veterinarians (n = 13) evaluated the utility of each rubric item to collect evidence; each item's content validity index was calculated to determine its inclusion in the final rubric. After skills training, veterinary students (n = 57) were assessed using the OVH model rubric in March and August. Internal structure evidence was collected by video-recording 14 students' mock surgeries, each assessed by all five raters to calculate inter-rater reliability. Relationship with other variables evidence was collected by assessing 22 students performing their first live canine OVH in November. Experienced veterinarians included 22 items in the final rubric. The rubric generated scores with good to excellent internal consistency; inter-rater reliability was fair. Students' performance on the March model assessment was moderately correlated with their live surgical performance (ρ = 0.43) and moderately negatively correlated with their live surgical time (ρ = -0.42). Students' performance on the August model assessment, after a summer without surgical skills practice, was weakly correlated with their live surgical performance (ρ = 0.17). These data support validation of the simulated OVH rubric. The continued development of validated assessment instruments is critical as veterinary medicine seeks to become competency based.

16.
Science ; 375(6586): eabj7484, 2022 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-35298245

RESUMEN

Direct observation of evolution in response to natural environmental change can resolve fundamental questions about adaptation, including its pace, temporal dynamics, and underlying phenotypic and genomic architecture. We tracked the evolution of fitness-associated phenotypes and allele frequencies genome-wide in 10 replicate field populations of Drosophila melanogaster over 10 generations from summer to late fall. Adaptation was evident over each sampling interval (one to four generations), with exceptionally rapid phenotypic adaptation and large allele frequency shifts at many independent loci. The direction and basis of the adaptive response shifted repeatedly over time, consistent with the action of strong and rapidly fluctuating selection. Overall, we found clear phenotypic and genomic evidence of adaptive tracking occurring contemporaneously with environmental change, thus demonstrating the temporally dynamic nature of adaptation.


Asunto(s)
Aclimatación , Evolución Biológica , Drosophila melanogaster/fisiología , Selección Genética , Animales , Drosophila melanogaster/genética , Ecosistema , Ambiente , Evolución Molecular , Frecuencia de los Genes , Aptitud Genética , Genoma de los Insectos , Fenotipo , Estaciones del Año
17.
Diagnostics (Basel) ; 12(1)2022 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-35054358

RESUMEN

BACKGROUND: Multiple sclerosis patients often develop neurogenic lower urinary tract dysfunction with a potential risk of upper urinary tract damage. Diagnostic tools are urodynamics, bladder diary, uroflowmetry, and post-void residual, but recommendations for their use are controversial. OBJECTIVE: We aimed to identify clinical parameters indicative of neurogenic lower urinary tract dysfunction in multiple sclerosis patients. METHODS: 207 patients were prospectively assessed independent of the presence of lower urinary tract symptoms. We analyzed Expanded Disability Status Scale scores, uroflowmetry, post-void residual, rate of urinary tract infections, standardized voiding frequency, and voided volume in correlation with urodynamic findings. RESULTS: We found a significant correlation between post-void residual (odds ratio (OR) 4.17, confidence interval (CI) 1.20-22.46), urinary tract infection rate (OR 3.91, CI 1.13-21.0), voided volume (OR 4.53, CI 1.85-11.99), increased standardized voiding frequency (OR 7.40, CI 2.15-39.66), and urodynamic findings indicative of neurogenic lower urinary tract dysfunction. Expanded Disability Status Scale shows no correlation. Those parameters (except post-void residual) are also associated with reduced bladder compliance, as potential risk for kidney damage. CONCLUSION: Therefore, bladder diary and urinary tract infection rate should be routinely assessed to identify patients who require urodynamics.

18.
Animals (Basel) ; 11(8)2021 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-34438853

RESUMEN

Feather pecking and cannibalism are behavioral disorders that cause animal-welfare-relevant and economic problems. To mitigate these problems, the beaks of conventionally reared turkeys are usually already trimmed in the hatcheries. To find an alternative to beak trimming, we conducted this study with male turkeys of three breeds: B.U.T. 6, B.U.T. Premium and, Auburn (200 turkeys per breed). Half of the birds had infrared-trimmed beaks; the other half had intact beaks. For each treatment combination (breed, beak status), 25 turkeys were housed in one section. A screed grinding wheel was installed in each feed pan of the non-beak-trimmed turkeys as of week six to facilitate natural beak abrasion until slaughter. Eight randomly selected turkeys per section were regularly examined to record injuries, plumage condition, and beak dimensions. In addition, 96 beaks from randomly slaughtered birds were examined macroscopically and histologically. The results concerning injuries and plumage condition showed in most cases no differences between the beak-trimmed turkeys and the ones provided with the blunting disks. The histological examinations revealed alterations in only the beak-trimmed birds. We can conclude that the blunting method smoothens the beak during feeding and thus may be a possible alternative to beak trimming.

19.
Elife ; 102021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34155971

RESUMEN

To advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions, and we find a broad concordance between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. Our results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation in Drosophila.


Asunto(s)
Adaptación Biológica , Inversión Cromosómica , Drosophila melanogaster/fisiología , Frecuencia de los Genes , Polimorfismo Genético , Animales , Austria , Drosophila melanogaster/genética , Masculino , Ontario , Estaciones del Año , Selección Genética , España , Ucrania , Estados Unidos
20.
Mol Ecol ; 30(12): 2817-2830, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33914989

RESUMEN

The insulin/insulin-like growth factor signalling pathway has been hypothesized as a major determinant of life-history profiles that vary adaptively in natural populations. In Drosophila melanogaster, multiple components of this pathway vary predictably with latitude; this includes foxo, a conserved gene that regulates insulin signalling and has pleiotropic effects on a variety of fitness-associated traits. We hypothesized that allelic variation at foxo contributes to genetic variance for size-related traits that vary adaptively with latitude. We first examined patterns of variation among natural populations along a latitudinal transect in the eastern United States and show that thorax length, wing area, wing loading, and starvation tolerance exhibit significant latitudinal clines for both males and females but that development time does not vary predictably with latitude. We then generated recombinant outbred populations and show that naturally occurring allelic variation at foxo, which exhibits stronger clinality than expected, is associated with the same traits that vary with latitude in the natural populations. Our results suggest that allelic variation at foxo contributes to adaptive patterns of life-history variation in natural populations of this genetic model.


Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster , Aclimatación , Adaptación Fisiológica/genética , Alelos , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Femenino , Factores de Transcripción Forkhead/genética , Variación Genética , Masculino , Polimorfismo Genético , Estados Unidos
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