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1.
Phys Rev Lett ; 131(22): 221801, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101357

RESUMO

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

2.
Front Cardiovasc Med ; 10: 1190513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37288254

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Currently, cardiovascular disease risk algorithms play a role in primary prevention. However, this is complicated by a lack of powerfully predictive biomarkers that could be observed in individuals before the onset of overt symptoms. A key potential biomarker for heart disease is the vascular endothelial growth factor (VEGF-A), a molecule that plays a pivotal role in blood vessel formation. This molecule has a complex biological role in the cardiovascular system due to the processes it influences, and its production is impacted by various CVD risk factors. Research in different populations has shown single nucleotide polymorphisms (SNPs) may affect circulating VEGF-A plasma levels, with some variants associated with the development of CVDs, as well as CVD risk factors. This minireview aims to give an overview of the VEGF family, and of the SNPs reported to influence VEGF-A levels, cardiovascular disease, and other risk factors used in CVD risk assessments.

3.
Phys Rev Lett ; 130(5): 051803, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36800477

RESUMO

The COHERENT Collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220 MeV/c^{2} using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9 keV_{nr}. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6 kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants α_{D}<0.64, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios.

4.
Phys Rev Lett ; 129(8): 081801, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36053683

RESUMO

We measured the cross section of coherent elastic neutrino-nucleus scattering (CEvNS) using a CsI[Na] scintillating crystal in a high flux of neutrinos produced at the Spallation Neutron Source at Oak Ridge National Laboratory. New data collected before detector decommissioning have more than doubled the dataset since the first observation of CEvNS, achieved with this detector. Systematic uncertainties have also been reduced with an updated quenching model, allowing for improved precision. With these analysis improvements, the COHERENT Collaboration determined the cross section to be (165_{-25}^{+30})×10^{-40} cm^{2}, consistent with the standard model, giving the most precise measurement of CEvNS yet. The timing structure of the neutrino beam has been exploited to compare the CEvNS cross section from scattering of different neutrino flavors. This result places leading constraints on neutrino nonstandard interactions while testing lepton flavor universality and measures the weak mixing angle as sin^{2}θ_{W}=0.220_{-0.026}^{+0.028} at Q^{2}≈(50 MeV)^{2}.

5.
Science ; 372(6539)2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33859004

RESUMO

Quantum computing hardware technologies have advanced during the past two decades, with the goal of building systems that can solve problems that are intractable on classical computers. The ability to realize large-scale systems depends on major advances in materials science, materials engineering, and new fabrication techniques. We identify key materials challenges that currently limit progress in five quantum computing hardware platforms, propose how to tackle these problems, and discuss some new areas for exploration. Addressing these materials challenges will require scientists and engineers to work together to create new, interdisciplinary approaches beyond the current boundaries of the quantum computing field.

6.
Phys Rev Lett ; 126(1): 012002, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33480779

RESUMO

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

7.
Acta Biomater ; 120: 116-123, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32711083

RESUMO

Various material-strengthening strategies have evolved in the cuticle and the feeding tools of arthropods. Of particular interest is the crustacean mandible, which is frequently reinforced with calcium phosphate, giving a minerology similar to that of human bones and teeth. We report here a biological strengthening method of apatite by Zn substitution, found in the incisor teeth of the freshwater prawn Macrobrachium rosenbergii. Nanoindentation measurements show a clear positive correlation between the Zn/Ca ratio and the stiffness and hardness of the composite. In the incisor, Zn-substituted apatite forms an internal vertical axis, extending from the sharp outer edges of the tooth to its basal segment. The substitution level in this zone (up to 40%) is very high compared with the levels achieved in synthetic ceramics (<20%). Finite element simulation suggests that the high-Zn axis acts as a unique internal load transfer element, directing stress from the biting cusps to the more compliant underlying layers. In light of the considerable research being invested in developing synthetic calcium phosphate derivatives for human bone and tooth grafts, the innovative mineralogy of the M. rosenbergii incisor may inspire beneficial biomimetic applications. STATEMENT OF SIGNIFICANCE: The controlled incorporation of impurities into biominerals is a widespread phenomenon in biomineralization that may pave the way to new classes of biomimetic materials. The present study reveals a biogenic mineral of zinc-substituted apatite found in the incisor teeth of a prawn. A clear correlation between zinc substitution level and stiffness and hardness, suggests that zinc substitution serves to mechanically reinforce the bioapatite. The spatial arrangement of the high-zinc apatite unveils a material-level adaptation strategy for tooth fortification, in which the rigid high-Zn structure servs as an internal load-transfer element that transmits the stress directly from the tooth's sharp cusps to the more compliant underlying layers.


Assuntos
Materiais Biomiméticos , Dente , Ácidos , Apatitas , Humanos , Incisivo , Zinco
8.
J Antimicrob Chemother ; 74(11): 3352-3361, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31325313

RESUMO

BACKGROUND: Diagnostic uncertainty and a high prevalence of viral infections present unique challenges for antimicrobial prescribing for respiratory tract infections (RTIs). Procalcitonin (PCT) has been shown to support prescribing decisions and reduce antimicrobial use safely in patients with RTIs, but recent study results have been variable. METHODS: We conducted a feasibility study of the introduction of PCT testing in patients admitted to hospital with a lower RTI to determine if PCT testing is an effective and worthwhile intervention to introduce to support the existing antimicrobial stewardship (AMS) programme and safely decrease antimicrobial prescribing in patients admitted with RTIs. RESULTS: A total of 79 patients were randomized to the intervention PCT-guided treatment group and 40 patients to the standard care respiratory control group. The addition of PCT testing led to a significant decrease in duration of antimicrobial prescriptions (mean 6.8 versus 8.9 days, P = 0.012) and decreased length of hospital stay (median 7 versus 8 days, P = 0.009) between the PCT and respiratory control group. PCT did not demonstrate a significant reduction in antimicrobial consumption when measured as DDDs and days of therapy. CONCLUSIONS: PCT testing had a positive effect on antimicrobial prescribing during this feasibility study. The successful implementation of PCT testing in a randomized controlled trial requires an ongoing comprehensive education programme, greater integration into the AMS programme and delivery of PCT results in a timely manner. This feasibility study has shown that a larger randomized controlled trial would be beneficial to further explore the positive aspects of these findings.


Assuntos
Gestão de Antimicrobianos/métodos , Prescrições de Medicamentos/estatística & dados numéricos , Pró-Calcitonina/sangue , Infecções Respiratórias/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Viabilidade , Feminino , Hospitais Universitários , Humanos , Irlanda , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Distribuição Aleatória , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia
9.
Rev Sci Instrum ; 90(5): 053305, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31153225

RESUMO

The Neutron Scatter Camera (NSC) is a neutron spectrometer and imager that has been developed and improved by the Sandia National Laboratories for several years. Built for special nuclear material searches, the instrument was configured by the design to reconstruct neutron sources within the fission energy range 1-10 MeV. In this work, we present modifications that attempt to extend the NSC sensitivity to neutron energies in the range ∼10-200 MeV and discuss the corresponding consequences for the event processing. We present simulation results that manifest important aspects of the NSC response to those intermediate energy neutrons. The simulation results also evidence that the instrument's spectroscopic capabilities severely deteriorate at those energies, mainly due to the uncertainties in measuring energy, time, and distance between the two neutron scattering interactions. This work is motivated by the need to characterize neutron fluxes at particle accelerators as they may represent important backgrounds for neutrino experiments.

10.
Haemophilia ; 24(6): 896-901, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30004617

RESUMO

INTRODUCTION: Factor VIII inhibitor development is currently the most serious complication of the treatment of haemophilia A. Differences in manufacturing and the molecular structure of brands of recombinant factor VIII have led to speculation that concentrates may differ in immunogenicity. This has led to a regulatory focus on the immunogenicity of factor VIII concentrates both before and after licensure. AIM: To investigate the immunogenicity of ReFacto AF post licensure in a real-world setting in previously untreated patients (PUPs) treated exclusively with this product until at least 50 exposure days (EDs). METHODS: The United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO) National Haemophilia Database (NHD) identified a consecutive cohort of patients with severe haemophilia A (<0.01 IU/L) whose first treatment was with ReFacto AF, monitored time to inhibitor development and described associated risk factors. RESULTS: One hundred and three boys reached 50 EDs within the study period, of whom 35 developed an inhibitor (P(t ≤ 50) = 0.33, [95% CI: 0.25-0.43]), of which 15 (P(t ≤ 50) = 0.16, [95% CI: 0.10-0.25]) were high titre. Inhibitors arose after a median (interquartile range) 11 (7-16) EDs. Inhibitors were significantly associated with high-risk mutations and non-significantly associated with non-white ethnicity. Inhibitors were negatively associated with a family history of haemophilia A. High-titre inhibitors were significantly associated with a family history of inhibitors. CONCLUSION: Inhibitor incidence in a single country population of ReFacto AF PUPs was similar to that previously described. Low- and high-titre inhibitors were detected after a similar number of EDs, contrasting with previous data, probably reflecting standardized inhibitor monitoring within the United Kingdom.


Assuntos
Fator VIII/imunologia , Hemofilia A/imunologia , Adolescente , Criança , Pré-Escolar , Fator VIII/uso terapêutico , Feminino , Genótipo , Hemofilia A/tratamento farmacológico , Hemofilia A/genética , Humanos , Lactente , Masculino , Fatores de Tempo , Reino Unido
11.
Haemophilia ; 24(4): 641-647, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29635852

RESUMO

INTRODUCTION: Intracranial haemorrhage in children with inherited bleeding disorders is a potentially life-threatening complication and presents a significant therapeutic challenge. AIM: To define the characteristics, management and outcomes of intracranial haemorrhage presenting in UK children ≤16 years of age with inherited bleeding disorders from 2003 to 2015. METHOD: Retrospective analysis of children treated at UK haemophilia centres. RESULTS: Of 66 children presenting with Intracranial haemorrhage (ICH), 82% had haemophilia A or B, 3% VWD and 15% a rare IBD. The IBD was a severe phenotype in 91%. The rates of ICH were 6.4 and 4.2 per 1000 patient years for haemophilia A and B, respectively. Median age at presentation was 4 months (33% neonates; 91% children <2 years of age). In neonates, delivery was spontaneous vaginal (SV) in 11, instrumental in 6, caesarean in 4 and unknown in 1. In children with haemophilia, the risk of ICH after instrumental delivery was 10.6 times greater than after SV delivery. Trauma was more common in children >2 years (67%) than in children 1 month to 2 years (18%; P = .027). Prior to ICH, only 4.5% of children were on prophylaxis. 6% of haemophiliacs had an inhibitor. The median duration of initial replacement therapy was 15 days. Mortality was 13.5%. Neurological sequelae occurred in 39% of survivors, being more common following intracerebral bleeding. In haemophilia survivors, 52% subsequently developed a FVIII inhibitor. CONCLUSION: Intracranial haemorrhage occurs most frequently in children with severe IBDs, during the first 2 years of life and in children not receiving prophylaxis. Intracranial haemorrhage often occurs without documented trauma.


Assuntos
Hemofilia A/complicações , Hemofilia B/complicações , Hemorragias Intracranianas/complicações , Estudos de Coortes , Parto Obstétrico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Recidiva , Fatores de Risco , Reino Unido
12.
J Pediatr Urol ; 14(2): 157.e1-157.e8, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29398588

RESUMO

INTRODUCTION: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. OBJECTIVE: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. STUDY DESIGN: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. RESULTS: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. DISCUSSION: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. CONCLUSION: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management.


Assuntos
Hiperplasia Suprarrenal Congênita/cirurgia , Transtornos do Desenvolvimento Sexual/cirurgia , Anormalidades Urogenitais/cirurgia , Hiperplasia Suprarrenal Congênita/diagnóstico , Pré-Escolar , Estudos de Coortes , Transtornos do Desenvolvimento Sexual/diagnóstico , Estética , Feminino , Genitália Feminina/anormalidades , Genitália Feminina/cirurgia , Genitália Masculina/anormalidades , Genitália Masculina/cirurgia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias , Estudos Prospectivos , Qualidade de Vida , Procedimentos de Cirurgia Plástica/métodos , Medição de Risco , Cirurgia Plástica/métodos , Resultado do Tratamento , Anormalidades Urogenitais/diagnóstico , Procedimentos Cirúrgicos Urogenitais/efeitos adversos , Procedimentos Cirúrgicos Urogenitais/métodos
13.
Science ; 357(6356): 1123-1126, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28775215

RESUMO

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.

14.
Obes Rev ; 18(8): 819-831, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28547916

RESUMO

Currently, there is a significant percentage of the population who are or will be classified as obese, necessitating novel strategies to facilitate sustainable weight loss. Reductions in basal metabolic rate occur in the face of weight loss and pose formidable barriers to individuals attempting to sustain meaningful weight reductions. Here, we discuss the mechanisms by which non-shivering thermogenesis may provide insight into metabolic pathways that can become druggable targets to facilitate sustainable weight loss. Specifically, we highlight the fact that non-shivering thermogenesis results in activation and expansion of brown and beige adipose tissues as well as activates pathways in skeletal muscle which increase metabolic flux and activity of muscle fibres through futile calcium cycling across the endoplasmic reticulum all facilitating an increase in metabolism. Finally, we highlight the fact there are sexual dimorphisms with respect to these metabolic processes in keeping with the National Institutes of Health mandate of treating sex as a biologic variable.


Assuntos
Tecido Adiposo Marrom/metabolismo , Obesidade/metabolismo , Termogênese/fisiologia , Redução de Peso/fisiologia , Animais , Metabolismo Energético/fisiologia , Humanos
15.
J Pediatr Urol ; 13(5): 489.e1-489.e5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28284732

RESUMO

INTRODUCTION: The adoption of robot-assisted laparoscopic (RAL) procedures in the field of urology has occurred rapidly, but is, to date, without pediatric-specific instrumentation. Surgical fog is a significant barrier to safe and efficient laparoscopy. This appears to be a significant challenge when adapting three-dimensional 8.5-mm scopes to use in pediatric RAL surgery. The objective of the present study was to compare matched controls from a prospectively collected database to procedures that were performed utilizing special equipment and a protocol to minimize surgical fog in pediatric RAL procedures. METHODS: A prospectively collected database of all patients who underwent RAL pediatric urology procedures was used to compare: procedure, age, sex, American Society of Anesthesiologists score, weight, console time, number of times the camera was removed to clean the lens during a procedure, length of hospital stay, and morphine equivalents required in the postoperative period. A uniquely developed protocol was used, it consisted of humidified (95% relative humidity) and warmed CO2 gas (95 °F) insufflation via Insuflow® on a working trocar, with active smoke evacuation via PneuVIEW®XE on the opposite working trocar with a gas pass through of 3.5-5 l/min. The outcomes were compared with matched controls (Summary Fig). RESULTS: The novel gas protocol was utilized in 13 procedures (five pyeloplasties, two revision pyeloplasties, three ureteroureterostomies (UU), three nephrectomies) and compared with 13 procedures (six pyeloplasties, one revision pyeloplasty, three UU, three nephrectomies) prior to the protocol development. There was no statistical difference in age (P = 0.78), sex (P = 0.11), ASA score (P = 1.00) or weight (P = 0.69). There were no open conversions, ≥Grade 2 Clavien complications, or readmissions within 30 days in either group. CONCLUSIONS: This novel gas protocol yielded a statistically significant reduction in procedure time, by decreasing the number of times the camera was required to be pulled during the case by more than five occurrences, and saved approximately 35 min on average per case.


Assuntos
Laparoscopia/métodos , Duração da Cirurgia , Segurança do Paciente , Pneumoperitônio Artificial/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Umidade/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Laparoscopia/efeitos adversos , Masculino , Pneumoperitônio Artificial/efeitos adversos , Prognóstico , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Doenças Urológicas/diagnóstico , Doenças Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Procedimentos Cirúrgicos Urológicos/métodos
16.
Nat Commun ; 8: 14148, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-28128205

RESUMO

The deterministic generation of non-classical states of light, including squeezed states, Fock states and Bell states, plays an important role in quantum information processing and exploration of the physics of quantum entanglement. Preparation of these non-classical states in resonators is non-trivial due to their inherent harmonicity. Here we use stimulated Raman adiabatic passage to generate microwave photon Fock states in a superconducting circuit quantum electrodynamics system comprised of a fixed-frequency transmon qubit in a three-dimensional microwave cavity at 20 mK. A two-photon process is employed to overcome a first order forbidden transition and the first, second and third Fock states are demonstrated. We also demonstrate how this all-microwave technique can be used to generate an arbitrary superposition of Fock states. Simulations of the system are in excellent agreement with the data and fidelities of 89%, 68% and 43% are inferred for the first three Fock states respectively.

17.
J Pediatr Urol ; 13(1): 28.e1-28.e6, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27887913

RESUMO

INTRODUCTION: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center. OBJECTIVE: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery. STUDY DESIGN: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings. DISCUSSION: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life. CONCLUSION: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.


Assuntos
Doenças dos Genitais Femininos/cirurgia , Doenças dos Genitais Masculinos/cirurgia , Genitália/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Urogenitais , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
18.
Clin Pharmacol Ther ; 99(6): 600-11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26940481

RESUMO

Human immunodeficiency virus (HIV) infection is associated with an altered gut microbiome that is not consistently restored with effective antiretroviral therapy (ART). Interpretation of the specific microbiome changes observed during HIV infection is complicated by factors like population, sample type, and ART-each of which may have dramatic effects on gut bacteria. Understanding how these factors shape the microbiome during HIV infection (which we refer to as the HIV-associated microbiome) is critical for defining its role in HIV disease, and for developing therapies that restore gut health during infection.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Disbiose/microbiologia , Microbioma Gastrointestinal , Infecções por HIV/tratamento farmacológico , Infecções por HIV/microbiologia , Animais , Fármacos Anti-HIV/uso terapêutico , Disbiose/imunologia , Humanos , Microbiota
19.
Int J Obes (Lond) ; 40(2): 206-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26073655

RESUMO

In this review, we discuss the observations that, following chronic high-fat diet (HFD) exposure, male mice have higher levels of saturated fatty acids (FAs) and total sphingolipids, whereas lower amounts of polyunsaturated FAs in the central nervous system (CNS) than females. Furthermore, males, when compared with female mice, have higher levels of inflammatory markers in the hypothalamus following exposure to HFD. The increase in markers of inflammation in male mice is possibly due to the reductions in proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and estrogen receptor alpha (ERα), which is not recapitulated in female mice. Consistently, hypothalamic inflammation is induced both in male and female ERα total-body knockout mice when exposed to a HFD, thus confirming the key role of ERα in the regulation of HFD-induced hypothalamic inflammation. Finally, the HFD-induced depletion of hypothalamic ERα is associated with dysregulation in metabolic homeostasis, as evidenced by reductions in glucose tolerance and decrements in myocardial function.


Assuntos
Hipotálamo/patologia , Inflamação/metabolismo , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Receptor alfa de Estrogênio/metabolismo , Feminino , Hipotálamo/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/patologia , Ácido Palmítico/metabolismo , Fatores Sexuais , Esfingolipídeos/metabolismo , Fatores de Transcrição/metabolismo
20.
Transl Psychiatry ; 5: e689, 2015 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-26645624

RESUMO

The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.


Assuntos
Transtorno Bipolar/sangue , Transtornos do Humor/sangue , Proteômica/métodos , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
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