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1.
Nature ; 590(7847): 566-570, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33627809

RESUMO

When a heavy atomic nucleus splits (fission), the resulting fragments are observed to emerge spinning1; this phenomenon has been a mystery in nuclear physics for over 40 years2,3. The internal generation of typically six or seven units of angular momentum in each fragment is particularly puzzling for systems that start with zero, or almost zero, spin. There are currently no experimental observations that enable decisive discrimination between the many competing theories for the mechanism that generates the angular momentum4-12. Nevertheless, the consensus is that excitation of collective vibrational modes generates the intrinsic spin before the nucleus splits (pre-scission). Here we show that there is no significant correlation between the spins of the fragment partners, which leads us to conclude that angular momentum in fission is actually generated after the nucleus splits (post-scission). We present comprehensive data showing that the average spin is strongly mass-dependent, varying in saw-tooth distributions. We observe no notable dependence of fragment spin on the mass or charge of the partner nucleus, confirming the uncorrelated post-scission nature of the spin mechanism. To explain these observations, we propose that the collective motion of nucleons in the ruptured neck of the fissioning system generates two independent torques, analogous to the snapping of an elastic band. A parameterization based on occupation of angular momentum states according to statistical theory describes the full range of experimental data well. This insight into the role of spin in nuclear fission is not only important for the fundamental understanding and theoretical description of fission, but also has consequences for the γ-ray heating problem in nuclear reactors13,14, for the study of the structure of neutron-rich isotopes15,16, and for the synthesis and stability of super-heavy elements17,18.

2.
Nature ; 582(7811): 294-297, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32523118

RESUMO

The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics1,2. Peptidoglycan is a single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor1,3. In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength4-6. Here we applied atomic force microscopy7-12 to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent; the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface13,14, providing information complementary to traditional structural biology approaches.


Assuntos
Bacillus subtilis/citologia , Bacillus subtilis/ultraestrutura , Parede Celular/química , Parede Celular/ultraestrutura , Microscopia de Força Atômica , Staphylococcus aureus/citologia , Staphylococcus aureus/ultraestrutura , Bacillus subtilis/química , Viabilidade Microbiana , Peptidoglicano/química , Peptidoglicano/isolamento & purificação , Peptidoglicano/ultraestrutura , Staphylococcus aureus/química
3.
PLoS Pathog ; 18(9): e1010851, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36174087

RESUMO

During infection, Bacillus anthracis bacilli encounter potent antimicrobial peptides (AMPs) such as defensins. We examined the role that B. anthracis capsule plays in protecting bacilli from defensins and other cationic AMPs by comparing their effects on a fully virulent encapsulated wild type (WT) strain and an isogenic capsule-deficient capA mutant strain. We identified several human defensins and non-human AMPs that were capable of killing B. anthracis. The human alpha defensins 1-6 (HNP-1-4, HD-5-6), the human beta defensins 1-4 (HBD-1-4), and the non-human AMPs, protegrin, gramicidin D, polymyxin B, nisin, and melittin were all capable of killing both encapsulated WT and non-encapsulated capA mutant B. anthracis. However, non-encapsulated capA mutant bacilli were significantly more susceptible than encapsulated WT bacilli to killing by nearly all of the AMPs tested. We demonstrated that purified capsule bound HBD-2, HBD-3, and HNP-1 in an electrophoretic mobility shift assay. Furthermore, we determined that the capsule layer enveloping WT bacilli bound and trapped HBD-3, substantially reducing the amount reaching the cell wall. To assess whether released capsule might also play a protective role, we pre-incubated HBD-2, HBD-3, or HNP-1 with purified capsule before their addition to non-encapsulated capA mutant bacilli. We found that free capsule completely rescued the capA mutant bacilli from killing by HBD-2 and -3 while killing by HNP-1 was reduced to the level observed with WT bacilli. Together, these results suggest an immune evasion mechanism by which the capsule, both that enveloping the bacilli and released fragments, contributes to virulence by binding to and inhibiting the antimicrobial activity of cationic AMPs.


Assuntos
Bacillus anthracis , Nisina , alfa-Defensinas , beta-Defensinas , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos , Defensinas/genética , Defensinas/farmacologia , Gramicidina , Humanos , Meliteno , Polimixina B , alfa-Defensinas/farmacologia
4.
Brain ; 146(8): 3484-3499, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36811945

RESUMO

Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.


Assuntos
Concussão Encefálica , Lesões Encefálicas , Síndrome Pós-Concussão , Humanos , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Síndrome Pós-Concussão/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Emoções , Imageamento por Ressonância Magnética , Encéfalo
5.
Gen Comp Endocrinol ; 354: 114519, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677339

RESUMO

Estrogen receptors (ERs) are thought to be the ancestor of all steroid receptors and are present in most lophotrochozoans studied to date, including molluscs, annelids, and rotifers. A number of studies have investigated the functional role of estrogen receptors in invertebrate species, although most are in molluscs, where the receptor is constitutively active. In vitro experiments provided evidence for ligand-activated estrogen receptors in annelids, raising important questions about the role of estrogen signalling in lophotrochozoan lineages. Here, we review the concordant and discordant evidence of estradiol receptor signalling in lophotrochozoans, with a focus on annelids and rotifers. We explore the de novo synthesis of estrogens, the evolution and expression of estrogen receptors, and physiological responses to activation of estrogen receptors in the lophotrochozoan phyla Annelida and Rotifera. Key data are missing to determine if de novo biosynthesis of estradiol in non-molluscan lophotrochozoans is likely. For example, an ortholog for the CYP11 gene is present, but confirmation of substrate conversion and measured tissue products is lacking. Orthologs CYP17 and CYP19 are lacking, yet intermediates or products (e.g. estradiol) in tissues have been measured. Estrogen receptors are present in multiple species, and for a limited number, in vitro data show agonist binding of estradiol and/or transcriptional activation. The expression patterns of the lophotrochozoan ERs suggest developmental, reproductive, and digestive roles but are highly species dependent. E2 exposures suggest that lophotrochozoan ERs may play a role in reproduction, but no strong dose-response relationship has been established. Therefore, we expect most lophotrochozoan species, outside of perhaps platyhelminths, to have an ER but their physiological role remains elusive. Mining genomes for orthologs gene families responsible for steroidogenesis, coupled with in vitro and in vivo studies of the steroid pathway are needed to better assess whether lophotrochozoans are capable of estradiol biosynthesis. One major challenge is that much of the data are divided across a diversity of species. We propose that the polychaetes Capitella teleta or Platyneris dumerilii, and rotifer Brachionus manjavacas may be strong species choices for studies of estrogen receptor signalling, because of available genomic data, established laboratory culture techniques, and gene knockout potential.


Assuntos
Transdução de Sinais , Animais , Transdução de Sinais/fisiologia , Transdução de Sinais/genética , Receptores de Estradiol/metabolismo , Receptores de Estradiol/genética , Anelídeos/metabolismo , Anelídeos/genética , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Rotíferos/metabolismo , Rotíferos/genética , Estradiol/metabolismo
6.
Anaesthesia ; 79(7): 748-758, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38508699

RESUMO

Post-intensive care syndrome describes the physical, cognitive and emotional symptoms which persist following critical illness. At present there is limited understanding of the pathological mechanisms contributing to the development of post-intensive care syndrome. The aim of this systematic review was to synthesise current evidence exploring the association between inflammation and features of post-intensive care syndrome in survivors of critical illness. Relevant databases were systematically searched for studies of human participants exposed to critical illness. We sought studies that reported results for biomarkers with an identified role in the pathophysiology of inflammation obtained at any time-point in the patient journey and an outcome measure of any feature of post-intensive care syndrome at any point following hospital discharge. We included 32 studies, with 23 in the primary analysis and nine in a brain injury subgroup analysis. In the primary analysis, 47 different biomarkers were sampled and 44 different outcome measures were employed. Of the biomarkers which were sampled in five or more studies, interleukin-8, C-reactive protein and interleukin-10 most frequently showed associations with post-intensive care syndrome outcomes in 71%, 62% and 60% of studies, respectively. There was variability in terms of which biomarkers were sampled, time-points of sampling and outcome measures reported. Overall, there was mixed evidence of a potential association between an inflammatory process and long-term patient outcomes following critical illness. Further high-quality research is required to develop a longitudinal inflammatory profile of survivors of critical illness over the recovery period and evaluate the association with outcomes.


Assuntos
Biomarcadores , Cuidados Críticos , Estado Terminal , Inflamação , Humanos , Inflamação/sangue , Biomarcadores/sangue
7.
J Clin Microbiol ; 61(8): e0043823, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37395662

RESUMO

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related Ochrobactrum spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic Ochrobactrum spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or Ochrobactrum; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and Ochrobactrum genera separate to avoid further bewilderment and harm.


Assuntos
Brucella , Ochrobactrum , Ochrobactrum/classificação , Ochrobactrum/genética , Ochrobactrum/patogenicidade , Ochrobactrum/fisiologia , Brucella/classificação , Brucella/genética , Brucella/patogenicidade , Brucella/fisiologia , Terminologia como Assunto , Filogenia , Brucelose/tratamento farmacológico , Brucelose/microbiologia , Humanos , Infecções Oportunistas/microbiologia
8.
Theor Appl Genet ; 136(3): 44, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36897387

RESUMO

KEY MESSAGE: Breeding target traits can be broadened to include nutritive value and plant breeder's rights traits in perennial ryegrass by using in-field regression-based spectroscopy phenotyping and genomic selection. Perennial ryegrass breeding has focused on biomass yield, but expansion into a broader set of traits is needed to benefit livestock industries whilst also providing support for intellectual property protection of cultivars. Numerous breeding objectives can be targeted simultaneously with the development of sensor-based phenomics and genomic selection (GS). Of particular interest are nutritive value (NV), which has been difficult and expensive to measure using traditional phenotyping methods, resulting in limited genetic improvement to date, and traits required to obtain varietal protection, known as plant breeder's rights (PBR) traits. In order to assess phenotyping requirements for NV improvement and potential for genetic improvement, in-field reflectance-based spectroscopy was assessed and GS evaluated in a single population for three key NV traits, captured across four timepoints. Using three prediction approaches, the possibility of targeting PBR traits using GS was evaluated for five traits recorded across three years of a breeding program. Prediction accuracy was generally low to moderate for NV traits and moderate to high for PBR traits, with heritability highly correlated with GS accuracy. NV did not show significant or consistent correlation between timepoints highlighting the need to incorporate seasonal NV into selection indexes and the value of being able to regularly monitor NV across seasons. This study has demonstrated the ability to implement GS for both NV and PBR traits in perennial ryegrass, facilitating the expansion of ryegrass breeding targets to agronomically relevant traits while ensuring necessary varietal protection is achieved.


Assuntos
Lolium , Lolium/genética , Biomassa , Melhoramento Vegetal , Fenótipo , Genômica , Seleção Genética
9.
Am J Respir Crit Care Med ; 205(12): 1419-1428, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35349397

RESUMO

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).


Assuntos
Estado Terminal , Sepse , Adulto , Teorema de Bayes , Estado Terminal/terapia , Soluções Cristaloides/uso terapêutico , Hidratação/métodos , Humanos , Solução Salina
10.
Public Health ; 217: 89-94, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36867987

RESUMO

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.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Teste para COVID-19 , Estudos Transversais , Medicina Estatal , Controle de Infecções
11.
Sensors (Basel) ; 23(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36679580

RESUMO

Driver identification refers to the process whose primary purpose is identifying the person behind the steering wheel using collected information about the driver him/herself. The constant monitoring of drivers through sensors generates great benefits in advanced driver assistance systems (ADAS), to learn more about the behavior of road users. Currently, there are many research works that address the subject in search of creating intelligent models that help to identify vehicle users in an efficient and objective way. However, the different methodologies proposed to create these models are based on data generated from sensors that include different vehicle brands on routes established in real environments, which, although they provide very important information for different purposes, in the case of driver identification, there may be a certain degree of bias due to the different situations in which the route environment may change. The proposed method seeks to intelligently and objectively select the most outstanding statistical features from motor activity generated in the main elements of the vehicle with genetic algorithms for driver identification, this process being newer than those established by the state-of-the-art. The results obtained from the proposal were an accuracy of 90.74% to identify two drivers and 62% for four, using a Random Forest Classifier (RFC). With this, it can be concluded that a comprehensive selection of features can greatly optimize the identification of drivers.


Assuntos
Condução de Veículo , Humanos , Masculino , Acidentes de Trânsito , Algoritmo Florestas Aleatórias , Aprendizagem , Atividade Motora
12.
J Fish Biol ; 103(1): 155-171, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37189303

RESUMO

Two new miniature species of the trichomycterid genus Tridens are described from the Madeira River drainage, Acre and Rondônia States, Brazil. Until this work, Tridens was a monotypic genus composed solely of Tridens melanops, from the Putumayo/Içá River drainage, upper Amazonas River basin. Tridens vitreus sp.n. is known from upper and middle Madeira River drainage and differs from all other congeners by the lack of pelvic fins and girdle and by vertebra and dorsal-fin ray counts. Tridens chicomendesi sp.n. is known from Abunã River, middle Madeira River drainage and is distinguished from all other congeners by the number of vertebrae, dorsal-fin ray count and anal-fin base colouration pattern. Tr. chicomendesi sp.n. is further distinguished from T. vitreus by a combination of character states regarding the position of urogenital opening, dorsal-fin position, anal-fin position, maxillary barbel length, number of premaxillary teeth, number of dorsal-fin rays, number of anal-fin rays, number of lateral-line system pores, frontal bone anatomy, degree of ossification of maxilla, anatomy of quadrate-hyomandibular joint, size of posterodorsal process of hyomandibula, length of opercular patch of odontodes, number of interopercular odontodes, proportion of upper hypural plate cartilage relative to its area ; by the absence of a proximal, distal and ventral cartilages on ventral hypohyal; by the absence of a lateral process on basibranchial 4; by the presence of a cartilage block on the lateral process of autopalatine, the presence of a well-developed ossification on proximal margin of ventral hypohyal, the presence of hypobranchial foramen; and by the presence of an anterior cartilaginous joint between quadrate and base of posterodorsal process of hyomandibula. This work represents the first species description for the subfamily Tridentinae in more than 30 years and for the genus Tridens since its original description in 1889.


Assuntos
Peixes-Gato , Animais , Brasil , Rios , Cabeça , Coluna Vertebral
13.
Circulation ; 143(24): 2395-2405, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34125564

RESUMO

In the United States, race-based disparities in cardiovascular disease care have proven to be pervasive, deadly, and expensive. African American/Black, Hispanic/Latinx, and Native/Indigenous American individuals are at an increased risk of cardiovascular disease and are less likely to receive high-quality, evidence-based medical care as compared with their White American counterparts. Although the United States population is diverse, the cardiovascular workforce that provides its much-needed care lacks diversity. The available data show that care provided by physicians from racially diverse backgrounds is associated with better quality, both for minoritized patients and for majority patients. Not only is cardiovascular workforce diversity associated with improvements in health care quality, but racial diversity among academic teams and research scientists is linked with research quality. We outline documented barriers to achieving workforce diversity and suggest evidence-based strategies to overcome these barriers. Key strategies to enhance racial diversity in cardiology include improving recruitment and retention of racially diverse members of the cardiology workforce and focusing on cardiovascular health equity for patients. This review draws attention to academic institutions, but the implications should be considered relevant for nonacademic and community settings as well.


Assuntos
Cardiologistas/estatística & dados numéricos , Feminino , Equidade em Saúde , Humanos , Masculino , Grupos Raciais , Estados Unidos , Recursos Humanos
14.
Mol Genet Metab ; 135(3): 215-220, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35034844

RESUMO

BACKGROUND: Erythropoietic protoporphyria (EPP) patients suffer from painful phototoxicity. Sunlight-avoiding behaviour has not yet been quantified objectively in EPP patients. OBJECTIVE: To study total white light exposure obtained with an actigraph device, before and during afamelanotide treatment, in EPP patients compared to healthy controls. Effects on circadian rhythm, pain and sleep were also investigated. METHODS: Adult EPP patients visiting the Porphyria Center Rotterdam of the Erasmus MC were included in this single-center longitudinal case-control open-label intervention study. Controls were age and place of residence matched. Participants wore an actigraph (Actiwatch Pro) during two weeks for multiple periods. Afamelanotide was given to EPP patients as part of standard care. RESULTS: Twenty-six EPP patients and 23 matched controls participated. Controls were statistically significantly more exposed to white light than EPP patients off treatment during autumn (95.4%), spring (69.9%), and summer (105.4%; p = 0.01). EPP patients on afamelanotide treatment had 71.6% more light exposure during spring compared to EPP patients off treatment (p < 0.01). Afamelanotide treatment resulted in a reduction of painful moments in the morning (6.5% decrease) and the evening (8.1% decrease; p < 0.05). Bedtime differed between EPP patients off treatment, controls and EPP patients on treatment (23:45 h ± 1:51 versus 23:02 ± 1:41 and 23:14 ± 1:29, respectively; p < 0.0001). CONCLUSION: Actigraphy is a useful method to objectively measure white light exposure and treatment effects in EPP. In EPP patients afamelanotide treatment is associated with increased white light exposure during spring, and overall less pain. Treatment with afamelanotide is also associated with normalization of circadian rhythm.


Assuntos
Dermatite Fototóxica , Protoporfiria Eritropoética , Adulto , Estudos de Casos e Controles , Ritmo Circadiano , Humanos , Dor/tratamento farmacológico , Protoporfiria Eritropoética/terapia
15.
Phys Rev Lett ; 128(3): 033201, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35119888

RESUMO

Neutral atom qubits with Rydberg-mediated interactions are a leading platform for developing large-scale coherent quantum systems. In the majority of experiments to date, the Rydberg states are not trapped by the same potential that confines ground state atoms, resulting in atom loss and constraints on the achievable interaction time. In this Letter, we demonstrate that the Rydberg states of an alkaline earth atom, ytterbium, can be stably trapped by the same red-detuned optical tweezer that also confines the ground state, by leveraging the polarizability of the Yb^{+} ion core. Using the previously unobserved ^{3}S_{1} series, we demonstrate trapped Rydberg atom lifetimes exceeding 100 µs, and observe no evidence of auto- or photoionization from the trap light for these states. We measure a coherence time of T_{2}=59 µs between two Rydberg levels, exceeding the 28 µs lifetime of untrapped Rydberg atoms under the same conditions. These results are promising for extending the interaction time of Rydberg atom arrays for quantum simulation and computing, and are vital to capitalize on the extended Rydberg lifetimes in circular states or cryogenic environments.

16.
Phys Rev Lett ; 128(5): 050602, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35179942

RESUMO

Repeated local measurements of quantum many-body systems can induce a phase transition in their entanglement structure. These measurement-induced phase transitions (MIPTs) have been studied for various types of dynamics, yet most cases yield quantitatively similar critical exponents, making it unclear how many distinct universality classes are present. Here, we probe the properties of the conformal field theories governing these MIPTs using a numerical transfer-matrix method, which allows us to extract the effective central charge, as well as the first few low-lying scaling dimensions of operators at these critical points for (1+1)-dimensional systems. Our results provide convincing evidence that the generic and Clifford MIPTs for qubits lie in different universality classes and that both are distinct from the percolation transition for qudits in the limit of large on-site Hilbert space dimension. For the generic case, we find strong evidence of multifractal scaling of correlation functions at the critical point, reflected in a continuous spectrum of scaling dimensions.

17.
J Gen Intern Med ; 37(10): 2521-2525, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35076857

RESUMO

BACKGROUND: Inpatient addiction medicine consultation services (AMCS) have grown rapidly, but there is limited research of their impact on patient outcomes. OBJECTIVE: To examine whether AMCS is associated with all-cause mortality and hospital utilization post-discharge. DESIGN: This was a propensity-score-matchedcase-control study from 2018 to 2020. PARTICIPANTS: The intervention group included patients referred to the AMCS from October 2018 to March 2020. Matched control participants included patients hospitalized from October 2017 to September 2018 at an urban academic hospital with a large suburban and rural catchment area. MAIN MEASURES: The effect of treatment was estimated as the difference between the proportion of subjects experiencing the event (7-day and 30-day readmission, emergency department visits, and mortality within 90 days) for each group in the matched sample. KEY RESULTS: There were 711 patients in the intervention group and 2172 patients in the control group. The most common substance use disorders among the intervention group were primary alcohol use disorder (n=181; 25.5%) and primary opioid use disorder (n=175, 24.6%) with over a third with polysubstance use (n=257, 36.1%). Intervention patients showed a reduction in 90-day mortality post-hospital discharge (average treatment effect [ATE]: -2.35%, 95% CI: -3.57, -1.13; p-value <0.001) compared to propensity-matched controls. We found a statistically significant reduction in 7-day hospital readmission by 2.15% (95% CI: -3.65, -0.65; p=0.005) and a nonsignificant reduction in 30-day readmission (ATE: -2.38%, 95% CI: -5.20, 0.45; p=0.099). There was a statistically significant increase in 30-day emergency department visits (ATE: 5.32%, 95% CI: 2.19, 8.46; 0.001) compared to matched controls. CONCLUSIONS: There was a reduction in 90-day all-cause mortality for the AMCS intervention group compared to matched controls, although the impact on hospital utilization was mixed. AMCS are systems interventions that are effective tools to improve patient health and reduce all-cause mortality.


Assuntos
Medicina do Vício , Transtornos Relacionados ao Uso de Opioides , Assistência ao Convalescente , Serviço Hospitalar de Emergência , Humanos , Pacientes Internados , Alta do Paciente , Readmissão do Paciente , Encaminhamento e Consulta
18.
J Gen Intern Med ; 37(16): 4080-4087, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35230623

RESUMO

BACKGROUND: Baseline depressive symptoms are associated with subsequent adverse cardiovascular (CV) events in subjects with and without diabetes but the impact of persistent symptoms vs. improvement remains controversial. OBJECTIVE: Examine long-term changes in depressive symptoms in individuals with and without diabetes and the associated risk for adverse CV events. DESIGN: REGARDS is a prospective cohort study of CV risk factors in 30,000 participants aged 45 years and older. PARTICIPANTS: N = 16,368 (16.5% with diabetes mellitus) who remained in the cohort an average of 11.1 years later and who had complete data. MAIN MEASURES: Depressive symptoms were measured using the 4-item Centers for Epidemiologic Study of Depression (CES-D) questionnaire at baseline and again at a mean follow-up of 5.07 (SD = 1.66) years. Adjudicated incident stroke, coronary heart disease (CHD), CV mortality, and a composite outcome were assessed in a subsequent follow-up period of 6.1 (SD = 2.6) years. METHODS: The association of changes in depressive symptoms (CES-D scores) across 5 years with incident CV events was assessed using Cox proportional hazards modeling. KEY RESULTS: Compared to participants with no depressive symptoms at either time point, participants without diabetes but with persistently elevated depressive symptoms at both baseline and follow-up demonstrated a significantly increased risk of incident stroke (HR (95% CI) = 1.84 (1.03, 3.30)), a pattern which was substantially more prevalent in blacks (HR (95% CI) = 2.64 (1.48, 4.72)) compared to whites (HR (95% CI) = 1.06 (0.50, 2.25)) and in those not taking anti-depressants (HR (95% CI) = 2.01 (1.21, 3.35)) in fully adjusted models. CONCLUSIONS: The persistence of depressive symptoms across 5 years of follow-up in participants without diabetes identifies individuals at increased risk for incident stroke. This was particularly evident in black participants and among those not taking anti-depressants.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Fatores de Risco , Diabetes Mellitus/epidemiologia , Depressão/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Modelos de Riscos Proporcionais , Incidência
19.
Biol Lett ; 18(2): 20210583, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35104429

RESUMO

Puffer and porcupine fishes (families Diodontidae and Tetraodontidae, order Tetradontiformes) are known for their extraordinary ability to triple their body size by swallowing and retaining large amounts of seawater in their accommodating stomachs. This inflation mechanism provides a defence to predation; however, it is associated with the secondary loss of the stomach's digestive function. Ingestion of alkaline seawater during inflation would make acidification inefficient (a potential driver for the loss of gastric digestion), paralleled by the loss of acid-peptic genes. We tested the hypothesis of stomach inflation as a driver for the convergent evolution of stomach loss by investigating the gastric phenotype and genotype of four distantly related stomach inflating gnathostomes: sargassum fish, swellshark, bearded goby and the pygmy leatherjacket. Strikingly, unlike in the puffer/porcupine fishes, we found no evidence for the loss of stomach function in sargassum fish, swellshark and bearded goby. Only the pygmy leatherjacket (Monochanthidae, Tetraodontiformes) lacked the gastric phenotype and genotype. In conclusion, ingestion of seawater for inflation, associated with loss of gastric acid secretion, is restricted to the Tetraodontiformes and is not a selective pressure for gastric loss in other reported gastric inflating fishes.


Assuntos
Perciformes , Estômago , Animais , Digestão , Peixes/genética , Humanos , Água do Mar
20.
Environ Sci Technol ; 56(17): 12137-12147, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35973096

RESUMO

Pesticides are critical for invasive species management but often have negative effects on nontarget native biota. Tolerance to pesticides should have an evolutionary basis, but this is poorly understood. Invasive sea lamprey (Petromyzon marinus) populations in North America have been controlled with a pesticide lethal to them at lower concentrations than native fishes. We addressed how interspecific variation in gene expression and detoxification gene diversity confer differential pesticide sensitivity in two fish species. We exposed sea lamprey and bluegill (Lepomis macrochirus), a tolerant native species, to 3-trifluoromethyl-4-nitrophenol (TFM), a pesticide commonly used in sea lamprey control. We then used whole-transcriptome sequencing of gill and liver to characterize the cellular response in both species. Comparatively, bluegill exhibited a larger number of detoxification genes expressed and a larger number of responsive transcripts overall, which likely contributes to greater tolerance to TFM. Understanding the genetic and physiological basis for pesticide tolerance is crucial for managing invasive species.


Assuntos
Praguicidas , Petromyzon , Animais , Peixes/metabolismo , Brânquias/metabolismo , Praguicidas/metabolismo , Praguicidas/toxicidade , Petromyzon/metabolismo , Transcriptoma
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