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1.
Artigo em Inglês | MEDLINE | ID: mdl-32052225

RESUMO

Right atrial (RA) and right ventricular (RV) parameters assessed by traditional echocardiography lack sensitivity to identify pulmonary embolism (PE). We sought to determine if alterations in RV free wall longitudinal strain (FWS) would be present in PE patients and improve evaluation. This retrospective study comprised of 84 consecutive PE patients from 2 centres, with adequate transthoracic echocardiography (TTE) images for RV FWS analysis. PE patients were compared to 66 healthy controls. Compared to controls, PE patients had increased RV parasternal long-axis diameter (RVPLAX) (33.4 ± 5.8 mm vs 39.9 ± 4.1 mm) and RA area (17.4 ± 5.6 cm2 vs 14.5 ± 3.1 cm2) (p < 0.001 for both). RV function was reduced in PE patients (RV fractional area change 31.1 ± 13.2% vs 41.7 ± 9.1%, TAPSE 17.0 ± 4.5 vs 21.3 ± 2.2 mm; p < 0.001 for both). RV FWS was reduced in PE patients (-14.4 ± 7.2% vs - 26.0 ± 4.4%, p < 0.001). RV FWS was the best discriminator for PE (AUC 0.912). In comparative multiple logistic regression models for PE, the model which included traditional measures of RV size and function and RV FWS, produced a powerful classifier (AUC 0.966, SE 0.013) with significantly better performance (p < 0.022) than the model without RV FWS (AUC 0.921, SE 0.024). RV FWS is a discriminator of PE patients; addition of RV FWS to existing parameters of RV size and function, significantly improves sensitivity and specificity for diagnosis of PE, and may play a role in diagnosis and guiding therapy. Validation in other PE groups is required to confirm these observations and its prognostic value needs evaluation.

2.
Exp Neurol ; 324: 113112, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31730762

RESUMO

Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration leading to severe cognitive decline and eventual death. AD pathophysiology is complex, but neurotoxic accumulation of amyloid-ß (Aß) and hyperphosphorylation of Tau are believed to be main drivers of neurodegeneration in AD. The formation and deposition of Aß plaques occurs in the brain parenchyma as well as in the cerebral vasculature. Thus, proper blood-brain barrier (BBB) and cerebrovascular functioning are crucial for clearance of Aß from the brain, and neurovascular dysfunction may be a critical component of AD development. Further, neuroinflammation and dysfunction of angiogenesis, neurogenesis, and neurorestorative capabilities play a role in AD pathophysiology. Currently, there is no effective treatment to prevent or restore loss of brain tissue and cognitive decline in patients with AD. Based on multifactorial and complex pathophysiological cascades in multiple Alzheimer's disease stages, effective AD therapies need to focus on targeting early AD pathology and preserving cerebrovascular function. Neural stem cells (NSCs) participate extensively in mammalian brain homeostasis and repair and exhibit pleiotropic intrinsic properties that likely make them attractive candidates for the treatment of AD. In the review, we summarize the current advances in knowledge regarding neurovascular aspects of AD-related neurodegeneration and discuss multiple actions of NSCs from preclinical studies of AD to evaluate their potential for future clinical treatment of AD.

3.
AIDS Care ; 32(2): 193-201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31104481

RESUMO

The rate of HIV infection for Latinx men who have sex with men (LMSM) increased by 20% from 2008 to 2014 even as rates stabilized among MSM of other racial and ethnic backgrounds. We hypothesize that this disparity is partially attributable to individual and structural factors associated with HIV testing, including substance use practices, among LMSM. In this retrospective study, we examined data from 502 LMSM to determine whether (a) hypothesized relationships exist between individual factors (perceived HIV susceptibility, experiences with HIV prevention, condom use, sex under the influence, sexual identity development status, heterosexual self-presentation, and traditional Latinx gender norms) and structural factors (access to healthcare resources and social support) and HIV testing for LMSM. We also tested whether (b) substance use practices moderate relations between individual and structural factors and HIV testing. Findings indicate that (a) relationships exist between several individual and structural factors and HIV testing and that (b) substance use moderated these relationships to HIV testing in a number of hypothesized ways. Practice and prevention implications are discussed.

4.
BJOG ; 127(1): 28-35, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31541614

RESUMO

BACKGROUND: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh-related complications. OBJECTIVE: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline 'Urinary incontinence (update) and pelvic organ prolapse in women: management'. SEARCH STRATEGY: Search strategies were developed for each indication for referral. SELECTION CRITERIA: Relevant interventions included complete or partial mesh removal, mesh division, and non-surgical treatments such as vaginal estrogen. DATA COLLECTION AND ANALYSIS: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted. MAIN RESULTS: Twenty-four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely. CONCLUSIONS: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh-related complications. Robust data are needed so that mesh complications can be managed effectively in the future. TWEETABLE ABSTRACT: Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.


Assuntos
Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos , Incontinência Urinária por Estresse/cirurgia , Adolescente , Adulto , Idoso , Perda Sanguínea Cirúrgica , Dispareunia/etiologia , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Recidiva , Disfunções Sexuais Fisiológicas/etiologia , Resultado do Tratamento , Adulto Jovem
5.
J Am Chem Soc ; 141(50): 19594-19599, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31791121

RESUMO

The discovery of catalytic systems based on earth-abundant transition metals for the functionalization of C-H bonds enables streamlined and sustainable solutions to problems in synthetic organic chemistry. In this Communication, we disclose an iron-based catalytic system for the functionalization of propargylic and allylic C-H bonds. Inexpensive and readily available cyclopentadienyliron(II) dicarbonyl complexes were employed as catalysts for a novel deprotonative activation mode for C-H functionalization, an approach that allows for the direct union of unsaturated building blocks with aryl aldehydes and other carbonyl electrophiles to deliver a range of unsaturated alcohol coupling products under operationally simple and functional group tolerant reaction conditions.

6.
Neuron ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31810839

RESUMO

Paravascular drainage of solutes, including ß-amyloid (Aß), appears to be an important process in brain health and diseases such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the major driving force for clearance remains largely unknown. Here we used in vivo two-photon microscopy in awake head-fixed mice to assess the role of spontaneous vasomotion in paravascular clearance. Vasomotion correlated with paravascular clearance of fluorescent dextran from the interstitial fluid. Increasing the amplitude of vasomotion by means of visually evoked vascular responses resulted in increased clearance rates in the visual cortex of awake mice. Evoked vascular reactivity was impaired in mice with CAA, which corresponded to slower clearance rates. Our findings suggest that low-frequency arteriolar oscillations drive drainage of solutes. Targeting naturally occurring vasomotion in patients with CAA or AD may be a promising early therapeutic option for prevention of Aß accumulation in the brain.

7.
Phys Rev Lett ; 123(23): 231107, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31868462

RESUMO

The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).

9.
Org Lett ; 21(23): 9658-9662, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31763859

RESUMO

We report our iterative efforts toward the divergent total syntheses of curcusones A-D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment.

10.
Phys Rev Lett ; 123(16): 161102, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31702344

RESUMO

We present a search for subsolar mass ultracompact objects in data obtained during Advanced LIGO's second observing run. In contrast to a previous search of Advanced LIGO data from the first observing run, this search includes the effects of component spin on the gravitational waveform. We identify no viable gravitational-wave candidates consistent with subsolar mass ultracompact binaries with at least one component between 0.2 M_{⊙}-1.0 M_{⊙}. We use the null result to constrain the binary merger rate of (0.2 M_{⊙}, 0.2 M_{⊙}) binaries to be less than 3.7×10^{5} Gpc^{-3} yr^{-1} and the binary merger rate of (1.0 M_{⊙}, 1.0 M_{⊙}) binaries to be less than 5.2×10^{3} Gpc^{-3} yr^{-1}. Subsolar mass ultracompact objects are not expected to form via known stellar evolution channels, though it has been suggested that primordial density fluctuations or particle dark matter with cooling mechanisms and/or nuclear interactions could form black holes with subsolar masses. Assuming a particular primordial black hole (PBH) formation model, we constrain a population of merging 0.2 M_{⊙} black holes to account for less than 16% of the dark matter density and a population of merging 1.0 M_{⊙} black holes to account for less than 2% of the dark matter density. We discuss how constraints on the merger rate and dark matter fraction may be extended to arbitrary black hole population models that predict subsolar mass binaries.

11.
Acta Neuropathol Commun ; 7(1): 171, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703739

RESUMO

The detection of amyloid beta deposits and neurofibrillary tangles, both hallmarks of Alzheimer's disease (AD), is key to understanding the mechanisms underlying these pathologies. Luminescent conjugated oligothiophenes (LCOs) enable fluorescence imaging of these protein aggregates. Using LCOs and multiphoton microscopy, individual tangles and amyloid beta deposits were labeled in vivo and imaged longitudinally in a mouse model of tauopathy and cerebral amyloidosis, respectively. Importantly, LCO HS-84, whose emission falls in the green region of the spectrum, allowed for the first time longitudinal imaging of tangle dynamics following a single intravenous injection. In addition, LCO HS-169, whose emission falls in the red region of the spectrum, successfully labeled amyloid beta deposits, allowing multiplexing with other reporters whose emission falls in the green region of the spectrum. In conclusion, this method can provide a new approach for longitudinal in vivo imaging using multiphoton microscopy of AD pathologies as well as other neurodegenerative diseases associated with protein aggregation in mouse models.

12.
PLoS Pathog ; 15(11): e1007928, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725799

RESUMO

Type 3 secretion systems (T3SSs) are conserved bacterial nanomachines that inject virulence proteins (effectors) into eukaryotic cells during infection. Due to their ability to inject heterologous proteins into human cells, these systems are being developed as therapeutic delivery devices. The T3SS assembles a translocon pore in the plasma membrane and then docks onto the pore. Docking activates effector secretion through the pore and into the host cytosol. Here, using Shigella flexneri, a model pathogen for the study of type 3 secretion, we determined the molecular mechanisms by which host intermediate filaments trigger docking and enable effector secretion. We show that the interaction of intermediate filaments with the translocon pore protein IpaC changed the pore's conformation in a manner that was required for docking. Intermediate filaments repositioned residues of the Shigella pore protein IpaC that are located on the surface of the pore and in the pore channel. Restricting these conformational changes blocked docking in an intermediate filament-dependent manner. These data demonstrate that a host-induced conformational change to the pore enables T3SS docking and effector secretion, providing new mechanistic insight into the regulation of type 3 secretion.

13.
Org Lett ; 21(22): 8962-8965, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31663754

RESUMO

A versatile thermal Overman rearrangement of enantioenriched, cyclic allylic alcohols providing tertiary allylic amines has been developed. The vinyl bromide used to control enantioselectivity in a preceding CBS reduction is utilized as a synthetic handle for the preparation of tertiary α-amino ketones and related derivatives in an asymmetric fashion.

14.
Heart ; 2019 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-31611326

RESUMO

OBJECTIVE: Low levels of total cholesterol (TC) are associated with adverse outcomes in older populations. Whether this phenomenon is independent of statin use is unknown. We investigated the association between low TC levels and long-term major adverse cardiovascular events (MACE) in a prospective study of men aged ≥70 years without ischaemic heart disease (IHD) and whether this was influenced by statin use. METHODS: The CHAMP (Concord Health and Ageing in Men Project) cohort is a prospective cohort study of community-dwelling men aged ≥70 years. The relationship between TC and long-term MACE was analysed using Cox-regression modelling adjusted for comorbidities and stratified by statin use. RESULTS: The study cohort comprised 1289 men (mean (±SD) age, 77.0±5.5 years; mean follow-up, 6.4±2.7 years). Decreasing TC level was associated with increased comorbidity burden, frailty and MACE (linear trend p<0.001). In men not on statin therapy (n=731), each 1 mmol/L decrease in TC was associated with increased MACE (HR 1.27, 95% CI 1.10 to 1.45, p=0.001) and mortality (HR 1.22, 95% CI 1.03 to 1.44, p=0.02) adjusted for comorbidities. In contrast, low TC in men on statins (n=558) was not associated with MACE (HR 0.91, 95% CI 0.74 to 1.11) or mortality (HR 0.86, 95% CI 0.68 to 1.09). CONCLUSION: Low TC is associated with increased risk of MACE in older men without IHD who are not taking statin therapy but not in those on statins.

15.
Plast Reconstr Surg ; 144(4): 801-807, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568276

RESUMO

BACKGROUND: The development of acellular dermal matrices has revolutionized implant-based breast reconstruction. The most recent development has been the introduction of prepectoral breast reconstruction. However, concerns have been expressed related to the quality of soft-tissue coverage and infectious complications. Thus, the authors felt it prudent to perform a matched-pair analysis of clinical outcomes following prepectoral and subpectoral tissue expander placement. METHODS: A retrospective study of patients who underwent immediate breast reconstruction by means of prepectoral (group 1) and dual-plane subpectoral (group 2) tissue expander placement was performed. Patients in each group were matched for age, body mass index, history of radiotherapy, and type of acellular dermal matrix. Of note, patients in group 1 received perioperative antibiotic prophylaxis for less than 24 hours, whereas patients in group 2 received antibiotic prophylaxis for at least 1 week. RESULTS: A total of 80 patients (138 breast reconstructions) were included in the study (group 1, n = 40; group 2, n = 40). No difference in total postoperative complication rate (p = 0.356) and mastectomy skin necrosis rate (p = 1.0) was noted. Observed differences in major complications (p = 0.06), major infection (p = 0.09), and loss of reconstruction (p = 0.09) were not found to be significant. CONCLUSION: Immediate prepectoral tissue expander insertion with anterior acellular dermal matrix coverage and less than 24 hours of antibiotic prophylaxis is safe and compares favorably to subpectoral tissue expander placement with an inferior acellular dermal matrix sling and a prolonged course of antibiotics. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Derme Acelular , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Complicações Pós-Operatórias/epidemiologia , Expansão de Tecido , Adulto , Feminino , Humanos , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Am Board Fam Med ; 32(5): 746-748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31506371

RESUMO

BACKGROUND: Although there have been analyses on the qualities associated with individuals who chose to repeatedly donate blood, there is little known about national blood donation rates in the United States. To address this lack of information, this article uses data from the National Health and Nutrition Examination Surveys (NHANES) to assess changes in the national rates of blood donation among adults aged 20 years and older. METHODS: Data was collected from 49,512 US adults aged 20 years and older who were surveyed from 1999 to 2016 through the NHANES. Individuals selected for inclusion in NHANES underwent an in-home interview, where they were asked whether or not they participated in blood donation in the past 12 months. Data were analyzed with SAS and Wald-chi square tests were used to assess trends in recent blood donations. RESULTS: The overall recent blood donation rate has hovered around 6% since 1999, with no significant change during that time period. Over the last 2 decades, the percentage of individuals aged 20 to 29 years with a recent blood donation has increased significantly. During the same time period, the percentage of individuals aged 30 to 39 years and individuals with a 4-year college degree or greater with a recent blood donation decreased significantly. CONCLUSIONS: Although the national blood donation rate has not changed significantly, significant changes in donation rates have occurred among a number of US subpopulations.

17.
J Am Med Dir Assoc ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31548109

RESUMO

OBJECTIVES: An increasing number of post-acute care patients are admitted to skilled nursing facilities (SNFs) with behavioral symptoms such as wandering and rejecting care, which can interfere with care and place a patient at risk of social isolation or injury. This study examines whether increasing the qualifications of social service staff through using a greater proportion of qualified social workers (QSWs) instead of paraprofessionals improves patients' behavioral symptoms and reduces the use of antipsychotic medications. DESIGN: Secondary data analysis of national data drawn from the Minimum Data Set, Medicare Beneficiary Summary File, and Certification and Survey Provider Enhanced Reporting surveys. SETTING AND PARTICIPANTS: Newly admitted, Medicare fee-for-service patients aged ≥65 years who received post-acute care after a hospitalization from 2011-2015 (1,201,096 patient admissions in 5383 unique SNFs). METHODS: A regression discontinuity approach is used to identify how changes in the qualifications of social service staffing affect changes in patient outcomes, through exploiting a federal regulation that requires 1 full-time QSW for SNFs with at least 121 beds. RESULTS: SNFs with a greater proportion of QSWs improved behavioral symptoms that affected residents or others and reduced the use of antipsychotic medications. Marginally significant improvements were also found in patients' rejecting care, wandering, and having any behavioral symptoms. There was no statistically significant change in delusions. CONCLUSIONS AND IMPLICATIONS: Although the focus of most research and effects on improving patient outcomes in SNFs has focused on nursing staff, our results underscore the importance of staffing in social services. Specifically, social service staff with higher qualifications are integral to improving care through reducing patients' behavioral symptoms and avoiding the use of antipsychotic medications. It may be time for SNFs to revisit efforts to improve staffing in social services.

18.
J Phys Act Health ; : 1-9, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31476736

RESUMO

BACKGROUND: This study sought to determine the impact of an acute prior bout of high-intensity interval aerobic exercise on attenuating the vascular dysfunction associated with a prolonged sedentary bout. METHODS: Ten young (24 ± 1 y) healthy males completed two 3-hour sessions of prolonged sitting with (SIT-EX) and without (SIT) a high-intensity interval aerobic exercise session performed immediately prior. Prior to and 3 hours into the sitting bout, leg vascular function was assessed with the passive leg movement technique, and blood samples were obtained from the lower limb to evaluate changes in oxidative stress (malondialdehyde and superoxide dismutase) and inflammation (interleukin-6). RESULTS: No presitting differences in leg vascular function (assessed via passive leg movement technique-induced hyperemia) were revealed between conditions. After 3 hours of prolonged sitting, leg vascular function was significantly reduced in the SIT condition, but unchanged in the SIT-EX. Lower limb blood samples revealed no alterations in oxidative stress, antioxidant capacity, or inflammation in either condition. CONCLUSIONS: This study revealed that lower limb vascular dysfunction was significantly attenuated by an acute presitting bout of high-intensity interval aerobic exercise. Further analysis of lower limb blood samples revealed no changes in circulating oxidative stress or inflammation in either condition.

19.
J Org Chem ; 84(17): 11258-11260, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31403294

RESUMO

A modified procedure for dehydrative ketal protections is disclosed, which serves as an alternative to the classic Dean-Stark protocol. Studies show that this new procedure can outperform the Dean-Stark apparatus on small scales and thus serves as a complementary approach to effect dehydrative ketalizations. A detailed procedure for this apparatus is presented.

20.
Phys Rev Lett ; 123(1): 011102, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31386391

RESUMO

The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

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