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1.
Nature ; 600(7888): 259-263, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34853468

RESUMO

Armoured dinosaurs are well known for their evolution of specialized tail weapons-paired tail spikes in stegosaurs and heavy tail clubs in advanced ankylosaurs1. Armoured dinosaurs from southern Gondwana are rare and enigmatic, but probably include the earliest branches of Ankylosauria2-4. Here we describe a mostly complete, semi-articulated skeleton of a small (approximately 2 m) armoured dinosaur from the late Cretaceous period of Magallanes in southernmost Chile, a region that is biogeographically related to West Antarctica5. Stegouros elengassen gen. et sp. nov. evolved a large tail weapon unlike any dinosaur: a flat, frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail. Stegouros shows ankylosaurian cranial characters, but a largely ancestral postcranial skeleton, with some stegosaur-like characters. Phylogenetic analyses placed Stegouros in Ankylosauria; specifically, it is related to Kunbarrasaurus from Australia6 and Antarctopelta from Antarctica7, forming a clade of Gondwanan ankylosaurs that split earliest from all other ankylosaurs. The large osteoderms and specialized tail vertebrae in Antarctopelta suggest that it had a tail weapon similar to Stegouros. We propose a new clade, the Parankylosauria, to include the first ancestor of Stegouros-but not Ankylosaurus-and all descendants of that ancestor.


Assuntos
Agressão , Dinossauros/anatomia & histologia , Dinossauros/fisiologia , Fósseis , Cauda/anatomia & histologia , Cauda/fisiologia , Animais , Regiões Antárticas , Chile , Comportamento Predatório , Esqueleto
2.
Nature ; 583(7816): 411-414, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555453

RESUMO

Egg size and structure reflect important constraints on the reproductive and life-history characteristics of vertebrates1. More than two-thirds of all extant amniotes lay eggs2. During the Mesozoic era (around 250 million to 65 million years ago), body sizes reached extremes; nevertheless, the largest known egg belongs to the only recently extinct elephant bird3, which was roughly 66 million years younger than the last nonavian dinosaurs and giant marine reptiles. Here we report a new type of egg discovered in nearshore marine deposits from the Late Cretaceous period (roughly 68 million years ago) of Antarctica. It exceeds all nonavian dinosaur eggs in volume and differs from them in structure. Although the elephant bird egg is slightly larger, its eggshell is roughly five times thicker and shows a substantial prismatic layer and complex pore structure4. By contrast, the new fossil, visibly collapsed and folded, presents a thin eggshell with a layered structure that lacks a prismatic layer and distinct pores, and is similar to that of most extant lizards and snakes (Lepidosauria)5. The identity of the animal that laid the egg is unknown, but these preserved morphologies are consistent with the skeletal remains of mosasaurs (large marine lepidosaurs) found nearby. They are not consistent with described morphologies of dinosaur eggs of a similar size class. Phylogenetic analyses of traits for 259 lepidosaur species plus outgroups suggest that the egg belonged to an individual that was at least 7 metres long, hypothesized to be a giant marine reptile, all clades of which have previously been proposed to show live birth6. Such a large egg with a relatively thin eggshell may reflect derived constraints associated with body shape, reproductive investment linked with gigantism, and lepidosaurian viviparity, in which a 'vestigial' egg is laid and hatches immediately7.


Assuntos
Dinossauros , Casca de Ovo/anatomia & histologia , Casca de Ovo/química , Fósseis , Dureza , Animais , Evolução Biológica , Dinossauros/classificação
3.
J Surg Res ; 300: 363-370, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843723

RESUMO

BACKGROUND: The surgery clerkship has a powerful impact on medical students' attitudes toward surgery. The primary aim of this study was to identify factors that influence current medical student experiences during the surgery clerkship and discern if they have shifted following the COVID pandemic and with a new generation of "Zillennial" students. MATERIALS AND METHODS: We conducted a qualitative content analysis of medical student surgery clerkship evaluations from 2018 to 2022 at three clinical training sites of our medical school (n = 596). The codes and themes that emerged from the data were then compared between the pre-COVID cohort (pre-March 2020) and post-COVID (post June 2020) cohorts. RESULTS: Our analysis revealed four themes: clerkship factors, educator qualities, surgical culture, and student expectations. Clerkship factors included the overall clerkship organization, preparatory sessions, and having schedule flexibility. The clinical educators had a significant impact on medical student experience by setting expectations and providing actionable feedback. Surgical culture included the team dynamic and professionalism or diversity issues. Students were expected to have clear guidance for their roles, opportunities to shine, and sought meaningful learning. While the themes were consistent between both cohorts, the frequency of codes varied, with more students commenting on flexibility, neglect, and long work hours in the post-COVID cohort. CONCLUSIONS: Numerous previously unreported factors impact surgical clerkship experiences, revealing a generational shift in medical student attitudes. These results suggest that educators and their institutions must be proactive in tracking student evaluations to adapt their clerkship curriculum for an optimal educational experience and evolving student expectations.


Assuntos
COVID-19 , Estágio Clínico , Cirurgia Geral , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , COVID-19/epidemiologia , Cirurgia Geral/educação , Pesquisa Qualitativa , Atitude do Pessoal de Saúde , Educação de Graduação em Medicina/métodos
4.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38949279

RESUMO

Magnetometer cell wall coat molecules play an important role in preserving the lifetime of pumped alkali metal atoms for use in magnetometers that are capable of measuring very small magnetic fields. The goal of this study is to help rationalize the design of the cell coat molecules. Rubidium-87 is studied in terms of its interaction with three template cell coat molecules: ethane, ethene, and methyltrichlorosilane (MeTS). Ab initio electronic structure methods are applied to investigate the effect that the coat molecules have on the 2S ground state and 2P excited state of 87Rb. We find that, from the ab initio results, the three template molecules have differing effects, with MeTS having the largest effect on the ground state and ethane or ethene having the largest effect on the non-degenerate excited states.

5.
BMC Public Health ; 24(1): 1010, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605388

RESUMO

BACKGROUND: Workplace social isolation and loneliness have been found to result in a decline in job satisfaction and an increase in burnout among working individuals. The COVID-19 pandemic exacerbated feelings of loneliness and social isolation among healthcare workers. The majority of research on healthcare worker experiences is conducted in siloes which does not reflect the shared experiences of interprofessional teams. The purpose of this study is to understand stress from social isolation or loneliness across the entire clinical and non-clinical healthcare team over the course of the pandemic. METHODS: Data was acquired using a cross-sectional survey distributed to healthcare workers once a year at a large academic medical center in the Southeastern United States during the COVID-19 pandemic (2020-2022). Information pertaining to job role, work location, and demographic factors was collected. Participants were also asked to assess individual well-being and resilience, in addition to reporting stress derived from various sources including job demands and social isolation or loneliness. Descriptive statistics and bivariate analyses were conducted to assess the association between stress from social isolation or loneliness and individual characteristics. RESULTS: Stress from social isolation or loneliness was found to decrease over the survey period across all measured variables. Trainees and physician-scientists were found to report the highest rates of this stressor compared to other job roles, while Hospital-Based ICU and Non-ICU work locations reported the highest rates of loneliness and social isolation stress. Younger workers and individuals from marginalized gender and racial groups were at greater risk for stress from social isolation or loneliness. CONCLUSIONS: Given the importance of social connections for well-being and job performance, organizations have a responsibility to create conditions and mechanisms to foster social connections. This includes establishing and reinforcing norms of behavior, and developing connection mechanisms, particularly for groups at high risk of loneliness and social isolation.


Assuntos
COVID-19 , Solidão , Humanos , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Isolamento Social , Pessoal de Saúde
6.
Chemistry ; 29(16): e202202503, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36534955

RESUMO

The site-selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, those that generate C(sp3 )-C(sp3 ) bonds are significantly underrepresented despite affording proteolytically stable, biogenic linkages. Herein, a visible-light-mediated reaction is described that enables the site-selective modification of peptides and proteins via desulfurative C(sp3 )-C(sp3 ) bond formation. The reaction is rapid and high yielding in peptide systems, with comparable translation to proteins. Using this chemistry, a range of moieties is installed into model systems and an effective PTM-mimic is successfully integrated into a recombinantly expressed histone.


Assuntos
Cisteína , Proteínas , Cisteína/química , Proteínas/química , Peptídeos/química
7.
J Microsc ; 291(3): 248-255, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37433616

RESUMO

Soft X-ray tomography (SXT) is an imaging technique to visualise whole cells without fixation, staining, and sectioning. For SXT imaging, cells are cryopreserved and imaged at cryogenic conditions. Such 'near-to-native' state imaging is in high demand and initiated the development of the laboratory table-top SXT microscope. As many laboratories do not have access to cryogenic equipment, we asked ourselves whether SXT imaging is feasible on dry specimens. This paper shows how the dehydration of cells can be used as an alternative sample preparation to obtain ultrastructure information. We compare different dehydration processes on mouse embryonic fibroblasts in terms of ultrastructural preservation and shrinkage. Based on this analysis, we chose critical point (CPD) dried cells for SXT imaging. In comparison to cryopreserved and air-dried cells, CPD dehydrated cells show high structural integrity although with about 3-7 times higher X-ray absorption for cellular organelles. As the difference in X-ray absorption values between organelles is preserved, 3D anatomy of CPD-dried cells can be segmented and analysed, demonstrating the applicability of CPD-dried sample preparation for SXT imaging. LAY DESCRIPTION: Soft X-ray tomography (SXT) is an imaging technique that allows to see the internal structures of cells without the need for special treatments like fixation or staining. Typically, SXT imaging involves freezing and imaging cells at very low temperatures. However, since many labs lack the necessary equipment, we explored whether SXT imaging could be done on dry samples instead. We compared different dehydration methods and found that critical point drying (CPD) was the most promising for SXT imaging. CPD-dried cells showed high structural integrity, although they absorbed more X-rays than hydrated cells, demonstrating that CPD-dried sample preparation is a viable alternative for SXT imaging.


Assuntos
Desidratação , Imageamento Tridimensional , Animais , Camundongos , Imageamento Tridimensional/métodos , Fibroblastos , Tomografia por Raios X/métodos , Microscopia
8.
J Chem Inf Model ; 63(23): 7330-7337, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37988325

RESUMO

Quantitative structure-odor relationships are critically important for studies related to the function of olfaction. Current literature data sets contain expert-labeled molecules but lack feature data. This paper introduces QuantumScents, a quantum mechanics augmented derivative of the Leffingwell data set. QuantumScents contains 3.5k structurally and chemically diverse molecules ranging from 2 to 30 heavy atoms (CNOS) and their corresponding 3D coordinates, total PBE0 energy, molecular dipole moment, and per-atom Hirshfeld charges, dipoles, and ratios. The authors demonstrate that Hirshfeld charges and ratios contain sufficient information to perform molecular classification by training a Message Passing Neural Network with chemprop (Heid, E.; et al. ChemRxiv, 2023, DOI: 10.26434/chemrxiv-2023-3zcfl) to predict scent labels. The QuantumScents data set is freely available on Zenodo along with the authors' code, example models, and data set generation workflow (https://zenodo.org/doi/10.5281/zenodo.8239853).


Assuntos
Odorantes , Relação Estrutura-Atividade
9.
Prehosp Emerg Care ; 27(3): 297-302, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35412382

RESUMO

OBJECTIVE: Identify if prehospital patient encounters can predict SARS-CoV-2 (COVID-19) related hospital utilization. METHODS: EMS data from COVID-19-related prehospital encounters was pulled from NEMSIS systems in Minnesota. This data was plotted against hospital general medical-surgical bed and ICU bed usage during the initial COVID-19 surge and again during a second surge. A validation dataset from 2019 was also utilized. RESULTS: There was a total of 6,460 influenza-like-illness calls, and 2,161 COVID-19-specific calls during the studied timeframe. A total of 24,806 medical-surgical bed-days and 20,208 ICU bed-days were analyzed. During initial COVID surge (April-July 2020), EMS encounters best correlated with medical-surgical bed utilization 10 days in the future (r2 = 0.85, N = 113, p = <0.001), with each encounter correlating with a utilization of 7.1 beds. ICU bed utilization was best predicted 16 days in the future (r2 = 0.86, N = 107, p = <0.001) with each encounter correlating with the use of 4.5 ICU beds. Similarly strong and clinically significant correlations were found during the second surged during July and August. There was no significant correlation when comparing to a similar dataset using 2019 ILI calls. CONCLUSION: Minnesota prehospital COVID-19-related prehospital encounters are shown to accurately predict hospital bed utilization 1-2 weeks in advance. This was reproducible across two COVID-19 surges. Trends in EMS patient encounters could serve as a valuable data point in predicting COVID-19 surges and their effects on hospital utilization.


Assuntos
COVID-19 , Serviços Médicos de Emergência , Humanos , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Hospitais
10.
J Med Internet Res ; 25: e47629, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37314842

RESUMO

Understanding the impact of caregiving responsibilities on women in medicine is crucial for ensuring a healthy and intact workforce, as caregiving responsibilities have the potential to affect the careers of women in health care along the entire pipeline, from students and trainees to physicians, physician-scientists, and biomedical researchers.


Assuntos
Medicina , Médicos , Feminino , Humanos , Fadiga , Nível de Saúde , Pesquisadores
11.
J Healthc Manag ; 68(6): 427-451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37944174

RESUMO

GOAL: Research has highlighted psychological distress resulting from the COVID-19 pandemic on healthcare workers (HCWs), including the development of posttraumatic stress symptoms (PTSS). However, the degree to which these conditions have endured beyond the pandemic and the extent to which they affect the entire healthcare team, including both clinical and nonclinical workers, remain unknown. This study aims to identify correlates of PTSS in the entire healthcare workforce with the goal of providing evidence to support the development of trauma-informed leadership strategies. METHODS: Data were collected from June to July 2022 using a cross-sectional anonymous survey in a large academic medical center setting. A total of 6,466 clinical and nonclinical employees completed the survey (27.3% response rate). Cases with at least one missing variable were omitted, for a total sample size of 4,806, the evaluation of which enabled us to understand individual, organizational, and work-related and nonwork-related stressors associated with PTSS. Data were analyzed using ordinal logistic regression and dominance analyses to identify predictors of PTSS specific to clinical and nonclinical workers. PRINCIPAL FINDINGS: While previous studies have shown that HCWs in different job roles experience unique stressors, our data indicate that the top correlates of PTSS among both clinical and nonclinical HCWs are the same: burnout, moral distress, and compassion fatigue. These three factors alone explained 45% and 44.4% of the variance in PTSS in clinical and nonclinical workers, respectively. PTSS was also associated with a lower sense of recognition and feeling mistreated by other employees at work in the clinical workforce. Concerningly, women and sexual minorities in the clinical sample exhibited a higher incidence of PTSS. In nonclinical workers, social isolation or loneliness and lower trust and confidence in senior leadership were associated with PTSS. Nonwork-related factors, such as exhaustion from caregiving responsibilities and financial strain, were also significantly associated with PTSS. Even after controlling for discrimination at and outside of work in both samples, we found that non-White populations were more likely to experience PTSS, highlighting a deeply concerning issue in the healthcare workforce. PRACTICAL APPLICATIONS: The primary objective of this article is to help healthcare leaders understand the correlates of PTSS across the entire healthcare team as organizations recover from the COVID-19 pandemic. Understanding which factors are associated with PTSS will help healthcare leaders develop best practices that aim to reduce HCW distress and strategies to circumvent trauma derived from future crises. Our data indicate that leaders must address the correlates of PTSS in the workforce, focusing attention on both those who work on the frontlines and those who work behind the scenes. We urge leaders to adopt a trauma-informed leadership approach to ensure that the entire healthcare workforce is recognized, supported, and cared for as each HCW plays a unique role in the care of patients.


Assuntos
Esgotamento Profissional , COVID-19 , Fadiga de Compaixão , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Fadiga de Compaixão/complicações , Fadiga de Compaixão/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Pessoal de Saúde/psicologia , Princípios Morais
12.
Ophthalmology ; 129(10): 1120-1128, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35660415

RESUMO

PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.


Assuntos
Retinopatia da Prematuridade , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Injeções Intravítreas , Fotocoagulação a Laser , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos
13.
Am J Bot ; 109(12): 1991-2005, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36254552

RESUMO

PREMISE: Numerous processes influence plant distributions and co-occurrence patterns, including ecological sorting, limiting similarity, and stochastic effects. To discriminate among these processes and determine the spatial scales at which they operate, we investigated how functional traits and phylogenetic relatedness influence the distribution of temperate forest herbs. METHODS: We surveyed understory plant communities across 257 forest stands in Wisconsin and Michigan (USA) and applied Bayesian phylogenetic linear mixed-effects models (PGLMMs) to quantify how functional traits and phylogenetic relatedness influence the environmental distribution of 139 herbaceous plant species along broad edaphic, climatic, and light gradients. These models also allowed us to test how functional and phylogenetic similarity affect species co-occurrence within microsites. RESULTS: Leaf height, specific leaf area, and seed mass all influenced individualistic plant distributions along landscape-scale gradients in soil texture, soil fertility, light availability, and climate. In contrast, phylogenetic relationships did not consistently predict species-environment relationships. Neither functionally similar nor phylogenetically related herbs segregated among microsites within forest stands. CONCLUSIONS: Trait-mediated ecological sorting appears to drive temperate-forest community assembly, generating individualistic plant distributions along regional environmental gradients. This finding links classic studies in plant ecology and prior research in plant physiological ecology to current trait-based approaches in community ecology. However, our results fail to support the common assumption that limiting similarity governs local plant co-occurrences. Strong ecological sorting among forest stands coupled with stochastic fine-scale interactions among species appear to weaken deterministic, niche-based assembly processes at local scales.


Assuntos
Ecologia , Florestas , Filogenia , Teorema de Bayes , Plantas
14.
Proteins ; 89(9): 1134-1144, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33864655

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused substantially more infections, deaths, and economic disruptions than the 2002-2003 SARS-CoV. The key to understanding SARS-CoV-2's higher infectivity lies partly in its host receptor recognition mechanism. Experiments show that the human angiotensin converting enzyme 2 (ACE2) protein, which serves as the primary receptor for both CoVs, binds to the receptor binding domain (RBD) of CoV-2's spike protein stronger than SARS-CoV's spike RBD. The molecular basis for this difference in binding affinity, however, remains unexplained from X-ray structures. To go beyond insights gained from X-ray structures and investigate the role of thermal fluctuations in structure, we employ all-atom molecular dynamics simulations. Microseconds-long simulations reveal that while CoV and CoV-2 spike-ACE2 interfaces have similar conformational binding modes, CoV-2 spike interacts with ACE2 via a larger combinatorics of polar contacts, and on average, makes 45% more polar contacts. Correlation analysis and thermodynamic calculations indicate that these differences in the density and dynamics of polar contacts arise from differences in spatial arrangements of interfacial residues, and dynamical coupling between interfacial and non-interfacial residues. These results recommend that ongoing efforts to design spike-ACE2 peptide blockers will benefit from incorporating dynamical information as well as allosteric coupling effects.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Simulação de Dinâmica Molecular , SARS-CoV-2/química , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Regulação Alostérica , Humanos , Mutação , Ligação Proteica , Receptores Virais/química , Receptores Virais/metabolismo , Termodinâmica
15.
PLoS Biol ; 16(11): e2005066, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30419022

RESUMO

Genome-wide sequence divergence between populations can cause hybrid sterility through the action of the anti-recombination system, which rejects crossover repair of double strand breaks between nonidentical sequences. Because crossovers are necessary to ensure proper segregation of homologous chromosomes during meiosis, the reduced recombination rate in hybrids can result in high levels of nondisjunction and therefore low gamete viability. Hybrid sterility in interspecific crosses of Saccharomyces yeasts is known to be associated with such segregation errors, but estimates of the importance of nondisjunction to postzygotic reproductive isolation have been hampered by difficulties in accurately measuring nondisjunction frequencies. Here, we use spore-autonomous fluorescent protein expression to quantify nondisjunction in both interspecific and intraspecific yeast hybrids. We show that segregation is near random in interspecific hybrids. The observed rates of nondisjunction can explain most of the sterility observed in interspecific hybrids through the failure of gametes to inherit at least one copy of each chromosome. Partially impairing the anti-recombination system by preventing expression of the RecQ helicase SGS1 during meiosis cuts nondisjunction frequencies in half. We further show that chromosome loss through nondisjunction can explain nearly all of the sterility observed in hybrids formed between two populations of a single species. The rate of meiotic nondisjunction of each homologous pair was negatively correlated with chromosome size in these intraspecific hybrids. Our results demonstrate that sequence divergence is not only associated with the sterility of hybrids formed between distantly related species but may also be a direct cause of reproductive isolation in incipient species.


Assuntos
Segregação de Cromossomos/fisiologia , Hibridização Genética/genética , Infertilidade/genética , Quimera/genética , Segregação de Cromossomos/genética , Cromossomos , DNA Helicases/metabolismo , Imunofluorescência/métodos , Meiose/genética , Meiose/fisiologia , Não Disjunção Genética/genética , Não Disjunção Genética/fisiologia , Processamento de Proteína Pós-Traducional , RecQ Helicases/genética , RecQ Helicases/metabolismo , Recombinação Genética/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Esporos Fúngicos/genética
16.
J Surg Res ; 268: 263-266, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34392179

RESUMO

INTRODUCTION: Coronavirus Disease-19 (COVID-19) was declared a pandemic in March 2020. States issued stay-at-home orders and hospitals cancelled non-emergent surgeries. During this time, we anecdotally noticed more admissions for perforated appendicitis. Therefore, we hypothesized that during the months following the COVID-19 pandemic declaration, more children were presenting with perforated appendicitis. MATERIALS AND METHODS: This is a retrospective cohort study reviewing pediatric patients admitted at a single institution with acute and/or perforated appendicitis between October 2019 to May 2020. Interval appendectomies were excluded. COVID-19 months were designated as March, April, and May 2020. Additional analysis of March, April, and May 2019 was performed for comparison purposes. Analyzed data included demographics, symptoms, white blood cell count, imaging findings, procedures performed, and perforation status. Statistical analysis was performed. RESULTS: During the study period, 285 patients were admitted with the diagnosis of acute appendicitis with 95 patients being perforated. We identified a significant increase in perforated appendicitis cases in the three COVID-19 months compared with the preceding five months (45.6% vs 26.4%; P <0.001). In addition, a similar significant increase was identified when comparing to the same months a year prior (P = 0.003). No significant difference in duration of pain was identified (P=0.926). CONCLUSION: The COVID-19 pandemic and its associated stay-at-home orders have had downstream effects on healthcare. Our review has demonstrated a significant increase in the number of children presenting with perforated appendicitis following these stay-at-home ordinances. These results demonstrate that further investigations into the issues surrounding access to healthcare, especially during this pandemic, are warranted.


Assuntos
Apendicite , COVID-19 , Apendicite/epidemiologia , Apendicite/cirurgia , Criança , Humanos , Pandemias , Estudos Retrospectivos
17.
Org Biomol Chem ; 19(5): 1133-1144, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33443507

RESUMO

The development of new approaches toward chemo- and regioselective functionalization of polycyclic aromatic hydrocarbon (PAH) scaffolds will provide opportunities for the synthesis of novel biologically active small molecules that exploit the high degree of lipophilicity imparted by the PAH unit. Herein, we report a new synthetic method for C-X bond substitution that is speculated to operate via a N-centered radical (NCR) mechanism according to experimental observations. A series of PAH sulfonamides have been synthesized and their biological activity has been evaluated against Gram-negative and Gram-positive bacterial strains (using a BacTiter-Glo assay) along with a series of mammalian cell lines (using CellTiter-Blue and CellTiter-Glo assays). The viability assays have resulted in the discovery of a number of bactericidal compounds that exhibit potency similar to other well-known antibacterials such as kanamycin and tetracycline, along with the discovery of a luciferase inhibitor. Additionally, the physicochemical and drug-likeness properties of the compounds were determined experimentally and using in silico approaches and the results are presented and discussed within.


Assuntos
Acetatos/química , Iodo/química , Iodobenzenos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Catálise , Linhagem Celular Tumoral , Técnicas de Química Sintética , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Sulfonamidas/química
18.
Nature ; 522(7556): 331-4, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-25915021

RESUMO

Theropod dinosaurs were the dominant predators in most Mesozoic era terrestrial ecosystems. Early theropod evolution is currently interpreted as the diversification of various carnivorous and cursorial taxa, whereas the acquisition of herbivorism, together with the secondary loss of cursorial adaptations, occurred much later among advanced coelurosaurian theropods. A new, bizarre herbivorous basal tetanuran from the Upper Jurassic of Chile challenges this conception. The new dinosaur was discovered at Aysén, a fossil locality in the Upper Jurassic Toqui Formation of southern Chile (General Carrera Lake). The site yielded abundant and exquisitely preserved three-dimensional skeletons of small archosaurs. Several articulated individuals of Chilesaurus at different ontogenetic stages have been collected, as well as less abundant basal crocodyliforms, and fragmentary remains of sauropod dinosaurs (diplodocids and titanosaurians).


Assuntos
Dinossauros/fisiologia , Fósseis , Herbivoria , Animais , Osso e Ossos/anatomia & histologia , Chile , Dinossauros/anatomia & histologia , Dinossauros/classificação , Filogenia , Dente/anatomia & histologia
19.
BMC Musculoskelet Disord ; 22(1): 155, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557821

RESUMO

BACKGROUND: Lower-limb osteoarthritis (OA) causes high levels of pain and disability. Physiotherapists are the primary healthcare provider of non-pharmacological treatments, and incorporate strategies to optimise physical activity (PA) to aid patients with lower-limb OA to moderate their clinical symptoms. However, patients with lower-limb OA have low adherence to PA recommendations both during treatment and after discharge. This study aimed to use knowledge of identified barriers and facilitators to physiotherapy prescribed PA (during treatment and post-discharge) to develop a theoretically informed intervention to optimise adherence to PA for patients with lower-limb OA during treatment and post-discharge. METHODS: 1) A purposive sample of 13 patients with lower-limb OA participated in semi-structured interviews following physiotherapy treatment. Inductive analysis identified themes/subthemes reflecting barriers and facilitators to physiotherapist prescribed PA, which were organised deductively according to personal factors, treatment and post-discharge phases. 2) Themes/subthemes were mapped onto the theoretical domains framework (TDF). 3) Behaviour change techniques (BCTs) were coded from the key identified domains and a theoretically informed physiotherapy intervention addressing barriers and using facilitators, was developed. RESULTS: Themes of patient confidence, mind-set, motivation, OA symptoms and PA experiences were primary personal factors that influenced PA adherence; with the TDF domain 'Beliefs about capabilities' most important to target. During treatment, the theme of routine formation was the major driver of personal factors; and primarily influenced by developing a positive physiotherapist-patient relationship. Post-discharge, physical factors, psychosocial factors and ongoing access to resources were important themes influencing PA maintenance. 'Environmental context and resources' and 'social influences' emerged as the key TDF domains to target during treatment and post-discharge. The proposed theoretically informed intervention included 26 BCTs delivered across conceptual phases of adoption, routine formation, and maintenance. CONCLUSION: A theoretically informed physiotherapy intervention was proposed to optimise PA adherence in patients with lower-limb OA. The included BCTs primarily target patients' perceived beliefs about their capabilities, by developing a PA routine during treatment and facilitating appropriate psychosocial support and access to resources for PA maintenance post-discharge. The feasibility of delivering the intervention in clinical practice will now be evaluated.


Assuntos
Assistência ao Convalescente , Osteoartrite , Exercício Físico , Humanos , Alta do Paciente , Modalidades de Fisioterapia
20.
J Dual Diagn ; 17(4): 304-312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34699336

RESUMO

OBJECTIVES: We aimed to evaluate the impact of the Pathways to Comorbidity Care (PCC) training program for alcohol and other drugs (AOD) clinicians to improve the management of comorbidity. METHODS: A controlled before-and-after study using PCC training was conducted across 6 matched sites in Australia including 35 clinicians. Controls received standard workplace training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined (a) identification (screening, assessment) and treatment (treatment, referral) of comorbidity in practice (N = 10 clinical files per clinician), (b) self-efficacy, knowledge, and attitudes of clinicians. RESULTS: Significant improvements were observed in the PCC group but not the control sites with regards to the rate of clinical files showing identification of comorbidity (+50% v -12% change from baseline, respectively; [X2 (1, N = 340) = 35.29, p = .01] with only a trend for improvements in the rate of files demonstrating treatment of comorbidity [X2 (1, N = 340) = 10.45, p = .06]. There were significant improvements in the PCC relative to the control group for clinician self-efficacy, F(1,33) = 6.40, p = .02 and knowledge and attitudes of comorbidity monitoring, F(1,33) = 8.745, p = .01. CONCLUSIONS: The PCC training package may help improve identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity in drug and alcohol settings.


Assuntos
Transtornos Mentais , Preparações Farmacêuticas , Austrália , Comorbidade , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia
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