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1.
Cancers (Basel) ; 16(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38730631

RESUMO

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

2.
Opt Lett ; 49(8): 2061-2064, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621076

RESUMO

Controlling the properties of mid- and far-infrared radiation can provide a means to transiently alter the properties of materials for novel applications. However, a limited number of optical elements are available to control its polarization state. Here we show that a 15-µm thick liquid crystal cell containing 8CB (4-octyl-4'-cyanobiphenyl) in the ordered, smectic A phase can be used as a phase retarder or wave plate. This was tested using the bright, short-pulsed (∼1 ps) radiation centered at 16.5 µm (18.15 THz) that is emitted by a free electron laser at high repetition rate (13 MHz). These results demonstrate a possible tool for the exploration of the mid- and far-infrared range and could be used to develop novel metamaterials or extend multidimensional spectroscopy to this portion of the electromagnetic spectrum.

3.
Pathogens ; 13(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38535534

RESUMO

A previously unknown coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in the city of Wuhan, China, in December 2019 [...].

4.
Cardiovasc Diabetol ; 23(1): 89, 2024 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431644

RESUMO

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.


Assuntos
Doenças Cardiovasculares , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Rigidez Vascular , Humanos , Volume Plaquetário Médio , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Análise de Onda de Pulso , Fatores de Risco , Complicações do Diabetes/complicações , Fatores de Risco de Doenças Cardíacas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Homeostase , Glucose
5.
J Nutr ; 154(2): 638-647, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38181968

RESUMO

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity. OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity. METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs to enteral feeding of liquid formula (days 15-26), both groups were adapted to a solid high-fat diet (30% of the total diet) and sucrose (20% of the total diet) diet (days 27-33), which was fed until the end of the study (140 d). Body composition was measured by dual-energy X-ray absorptiometry at 14, 45, and 140 d. Serum biochemistry and glucose-insulin values (after a fasting intravenous glucose tolerance test) were obtained at 140 d. Liver and muscle were analyzed for insulin receptor signaling and triglycerides. RESULTS: Body weight was similar, but percent fat was higher, whereas percent lean and bone mineral density were lower in TPN than in EN pigs (P < 0.01) at 45 d of age but not at 140 d. At 140 d, there were no differences in serum markers of liver injury or lipidemia. Intravenous glucose tolerance test at 140 d showed a lower (P < 0.05) AUC for both glucose and insulin in TPN than in EN pigs, but the ratio of AUCs of insulin and glucose was not different between groups. CONCLUSIONS: Administration of TPN during the neonatal period increased adipose deposition that transiently persisted in early adolescence when challenged with a high-fat diet but was not sustained or manifested as glucose intolerance.


Assuntos
Diabetes Mellitus Tipo 2 , Animais , Feminino , Suínos , Animais Recém-Nascidos , Insulina , Glucose , Obesidade , Fenótipo
6.
Sci Rep ; 14(1): 2602, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297106

RESUMO

Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n = 10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14 post-surgery. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE + BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 alone caused cystic-like regeneration with incomplete defect closure. HE + BMP2 showed virtually complete bone fusion. Collagen fibril birefringence pattern (red color) under polarized light indicated high organization in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p < 0.05). Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE-treated rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p < 0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE had a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.


Assuntos
Hesperidina , Ratos , Animais , Ratos Sprague-Dawley , Hesperidina/farmacologia , Microtomografia por Raio-X , Regeneração Óssea , Osteogênese , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/genética , Colágeno/farmacologia , Inflamação
7.
Materials (Basel) ; 17(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38255612

RESUMO

Inconel 718 is a Ni superalloy with superior mechanical properties, even at high temperatures. However, due to its high hardness and low thermal conductivity, it is considered a difficult-to-machine material. This material is widely used in applications that require good dimensional stability, making the milling process the most used in machining this alloy. The wear resulting from this process and the quality of the machined surface are still challenging factors when it comes to Inconel 718. TiAlN-based coating has been used on cutting tools with Yttrium as a doping element to improve the process performance. Based on this, this work evaluated the machined surface integrity and wear resistance of cutting tools coated using Physical Vapor Deposition (PVD) HiPIMS with TiAlYN in the end milling of Inconel 718, varying the process parameters such as cutting speed (vc), feed per tooth (fz), and cutting length (Lcut). It was verified that the Lcut is the parameter that exerts the most significant influence since, even at small distances, Inconel 718 already generates high tool wear (TW). Furthermore, the main wear mechanisms were abrasive and adhesive wear, with the development of a built-up edge (BUE) under a125 m/min feed rate (f) and a Lcut = 15 m. Chipping, cracking, and delamination of the coating were also observed, indicating a lack of adhesion between the coating and the substrate, suggesting the need for a good interlayer or the adjustment of the PVD parameters.

8.
J Nutr ; 154(2): 505-515, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38141773

RESUMO

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 µmol Leu·kg-1·h-1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle. OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm. METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 d and then assigned to 1 of the following 4 treatments for 28 h: 1) ALA (continuous feeding; pulsed with 800 µmol alanine·kg-1·h-1 every 4 h; n = 8); 2) L1× (continuous feeding; pulsed with 800 µmol Leu·kg-1·h-1 every 4 h; n = 7); 3) L2× (continuous feeding; pulsed with 1600 µmol Leu·kg-1·h-1 every 4 h; n = 8); and 4) INT (intermittent feeding every 4 h; supplied with 800 µmol alanine·kg-1 per feeding; n = 7). Muscle protein synthesis rates were determined with L-[2H5-ring]Phenylalanine. The activation of insulin, amino acid, and translation initiation signaling pathways were assessed by Western blot. RESULTS: Peak plasma Leu concentrations were 134% and 420% greater in the L2× compared to the L1× and ALA groups, respectively (P < 0.01). Protein synthesis was greater in the L2× than in the ALA and L1× groups in both the longissimus dorsi and gastrocnemius muscles (P < 0.05) but not different from the INT group (P > 0.10). Amino acid signaling upstream and translation initiation signaling downstream of mTORC1 largely corresponded to the differences in protein synthesis. CONCLUSIONS: Intravenous Leu pulses potentiate mTORC1 activity and protein synthesis in the skeletal muscles of continuously fed preterm pigs, but the amount required is greater than in pigs born at term.


Assuntos
Nutrição Enteral , Recém-Nascido Prematuro , Animais , Suínos , Recém-Nascido , Humanos , Leucina , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Animais Recém-Nascidos , Músculo Esquelético/metabolismo , Aminoácidos/metabolismo , Alanina/metabolismo
9.
J Surg Res ; 294: 16-25, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37857139

RESUMO

INTRODUCTION: An ultrasound (US)-first approach for evaluating appendicitis is recommended by the American College of Radiology. We sought to assess the access to and utilization of an US-first approach for children with acute appendicitis in United States Emergency Departments. METHODS: Utilizing the 2019 Nationwide Emergency Department Sample, we performed a retrospective cohort study of patients <18 y with a primary diagnosis of acute appendicitis based on International Classification of Disease 10th Edition Diagnosis codes. Our primary outcome was the presentation to a hospital that does not perform US for children with acute appendicitis. Our secondary outcome was the receipt of a US at US-capable hospital. We developed generalized linear models with inverse-probability weighting to determine the association between patient characteristics and outcomes. RESULTS: Of 49,703 total children, 24,102 (48%) received a US evaluation. The odds of presenting at a hospital with no US use were significantly higher for patients aged 11-17 compared to patients <6 y (adjusted odds ratio [aOR] [95% confidence interval (CI)]: 1.59, [1.19- 2.13], P = 0.002); lowest median household income quartile compared to highest (aOR [95% CI]: 2.50, [1.52-4.10], P < 0.001); rural locations compared to metropolitan (aOR [95% CI]: 8.36 [5.54-12.6], P < 0.001), and Hispanic compared to non-Hispanic White (aOR [95% CI]: 0.63 [0.45-0.90], P = 0.01). The odds of receiving a US at US-capable hospitals were significantly lower for patients >6 y, lowest median household income quartiles, and rural locations (P < 0.05). CONCLUSIONS: Rural, older, and poorer children are more likely to present to hospitals that do not utilize US in the diagnosis of acute appendicitis and are less likely to undergo US at US-capable hospitals.


Assuntos
Apendicite , Serviço Hospitalar de Emergência , Disparidades em Assistência à Saúde , Ultrassonografia , Criança , Humanos , Apendicite/diagnóstico por imagem , Apendicite/epidemiologia , Apendicite/etnologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos/epidemiologia , Ultrassonografia/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Adolescente , Brancos/estatística & dados numéricos , Fatores Etários , População Rural
10.
J Surg Res ; 295: 820-826, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160493

RESUMO

INTRODUCTION: Emergency Department (ED) visits for gastrostomy tube complications in children represent a substantial health-care burden, and many ED visits are potentially preventable. The number and nature of ED visits to community hospitals for pediatric gastrostomy tube complications is unknown. METHODS: Using the 2019 Nationwide Emergency Department Sample, we performed a retrospective cross-sectional analysis of pediatric patients (<18 y) with a primary diagnosis of gastrostomy tube complication. Our primary outcome was a potentially preventable ED visit, defined as an encounter that did not result in any imaging, procedures, or an inpatient admission. Univariate and multivariable logistic regression analyses were used to determine the associations between patient factors and our primary outcome. RESULTS: We observed 32,036 ED visits at 535 hospitals and 15,165 (47.3%) were potentially preventable. The median (interquartile range) age was 2 (1, 6) years and 17,707 (55%) were male. Compared to White patients, patients with higher odds of potentially preventable visits were Black (adjusted odds ratio (aOR) [95% confidence interval {CI}]: 1.07 [1.05-1.11], P < 0.001) and Hispanic (aOR [95% CI]: 1.05 [1.02-1.08], P = 0.004). Patients with residential zip codes in the first (aOR [95% CI]: 1.08 [1.04, 1.12], P < 0.001), second (aOR [95% CI]: 1.07 [1.03, 1.11], P < 0.001), and third (aOR [95% CI]: 1.09 [1.05, 1.13], P < 0.001) median household income quartiles had higher odds of potentially preventable visits compared to the highest. CONCLUSIONS: In a nationally representative sample of EDs, 47.3% of visits for pediatric gastrostomy tubes were potentially preventable. Efforts to improve outpatient management are warranted to reduce health-care utilization for these patients.


Assuntos
Serviço Hospitalar de Emergência , Gastrostomia , Criança , Humanos , Masculino , Estados Unidos , Feminino , Gastrostomia/efeitos adversos , Estudos Retrospectivos , Estudos Transversais , Hospitalização
11.
Sci Rep ; 13(1): 21678, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38065993

RESUMO

Large high pressure die castings (HPDC), recently referred to as mega-castings, can replace plenty of steel metal sheets usually employed for body-in-white (BIW) structures. They can save manufacturing expense and unleash additional lightweight potential thanks to additional design freedom and material properties. The BIW plays a major role in automotive design since it must fulfill numerous structural targets ranging from stiffness for vehicle dynamics, dynamic responses for NVH (noise, vibration, harshness), driving comfort standards and several passive safety requirements. The use of mega-casting structures leads to additional requirements with respect to castability and material quality. Achieving a lightweight design considering requirements related to crash or castability is a challenge on its own, due to the high computational cost of related simulation techniques. Considering multiple requirements simultaneously, therefore often leads to non-weight-optimal structures. To exploit the full lightweight potential, we present a generative multidisciplinary optimization pipeline for the structural design of automotive mega-casting parts in this paper. The approach combines established methods in automotive industry such as topology optimization and response-surface-based (RSM) optimization and enhances the latter by machine learning (ML) based clustering and classification. In a first step topology optimization is employed to derive optimal load-paths for multidisciplinary loading conditions. For this purpose, casting manufacturing constraints as well as more than hundred linearized loads are used to incorporate NVH and passive safety requirements. In a next step the optimal thickness distribution and rib orientation of the structure is achieved using RSM optimization algorithms for the computationally expensive nonlinear crash and casting simulations. Performance indicators are treated by unsupervised learning based on clustering. This enables classification constraints based on simulation field results from hundreds of samples to be included into RSM optimization. It resolves a typical risk of pure scalar, regression-type targets, where supposed optimal results fail when domain experts examine the full field result of the corresponding simulation. It is shown how this approach is superior in achieving a weight-optimal design and turnaround time compared to a design workflow classically used for BIW structures.

13.
Neurosurg Focus ; 55(4): E2, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37778038

RESUMO

OBJECTIVE: Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation. METHODS: The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis. RESULTS: Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001). CONCLUSIONS: Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.


Assuntos
Lesões Encefálicas Traumáticas , Hemorragia Intracraniana Traumática , Adulto , Humanos , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Hemorragia Intracraniana Traumática/complicações , Hemorragia Intracraniana Traumática/tratamento farmacológico , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/complicações , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fatores de Risco , Vitamina K
14.
Polymers (Basel) ; 15(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37835981

RESUMO

Due to chlorine's ability to kill bacteria and fungi through a chemical reaction, chlorine solutions are commonly used to clean and disinfect numerous public facilities, although these actions are also dependent to the equipment present in those facilities. Accordingly, the interest in studying its effect when in contact with different materials is obvious. This study was carried out through accelerated degradation tests and various analysis methods (optical microscope, scanning electron microscope, and tensile tests). The objective was to observe the wear presented by three polymeric materials, polyvinyl chloride (PVC), high-density polyethylene (HDPE), and polypropylene (PP), when exposed to chlorine's action in swimming pools and drinking water treatment plants. The resulting effect depends on the chlorine content and the type of contact between the chemical agent and the material. The aim was to select the material less likely to be affected by chlorine through tests and analyses, allowing a longer component life. The use of certain more resistant polymeric materials can drastically reduce maintenance, reducing fundamental factors such as costs, the downtime of municipal facilities, and also the risk to public health. It was concluded that PVC has the most stable behaviour overall when in contact with chlorine solutions.

15.
Int J Mol Sci ; 24(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37686257

RESUMO

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10-2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p-value = 1.3 × 10-3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10-4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10-2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.


Assuntos
Aterosclerose , Isquemia Encefálica , COVID-19 , AVC Embólico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , COVID-19/complicações , COVID-19/genética , AVC Isquêmico/genética , Artérias
16.
J Dent Educ ; 87(12): 1718-1724, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37740716

RESUMO

INTRODUCTION: As part of curriculum innovation, the University of North Carolina (UNC) Adams School of Dentistry identified core entrustable professional activities (EPAs) that graduates must demonstrate for practice readiness. This paper describes the development of the UNC EPAs and the perceptions of the general dentistry faculty. METHODS: Upon establishing a blueprint of knowledge, skills, and attitudes of UNC graduates, using a distributed leadership approach, faculty teams developed EPAs focused on the patient care process. The American Dental Education Association Compendium of Clinical Competency Assessments and Commission on Dental Accreditation Standards informed the team's work. Perceptions of the assessment framework were examined using a questionnaire completed by 13 general dentistry faculty considering the importance, accuracy, and agreement of each EPA, associated domains of competence, and encounter management on a 6-point rating scale. RESULTS: Distributed leadership was a useful strategy in EPA development to disperse decision-making and build ownership. Through multiple iterations, four EPAs (assessment, plan of care, collaborative care, and provision of care) with associated sub-EPAs emerged. EPAs included a description, required knowledge and skills, and rubrics for assessment. The general dentistry faculty reported a high level of importance, accuracy, and agreement with EPAs, domains of competence, and encounter management. DISCUSSION: EPAs provide a standardized manner to describe the comprehensive work dentists perform, shifting away from individual competencies. The UNC EPAs provide the foundation for longitudinal measures of competence preparing graduates for independent practice. With limited EPAs frameworks available in dentistry, we aim to inform the development and implementation of EPAs across dental education.


Assuntos
Educação Baseada em Competências , Internato e Residência , Humanos , Avaliação Educacional , Currículo , Competência Clínica , Odontologia
17.
Mol Biochem Parasitol ; 256: 111590, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37652239

RESUMO

Previous work has shown that the TbFUT1 and LmjFUT1 genes encode essential fucosyltransferases located inside the single mitochondria of the protozoan parasites Trypanosoma brucei and Leishmania major, respectively. However, nothing was known about the orthologous gene TcFUT1 or its gene product in Trypanosoma cruzi, aetiological agent of Chagas disease. In this study, we describe the overexpression of TcFUT1 with a C-terminal 6xMyc epitope tag in T. cruzi epimastigote cells. Overexpressed and immunoprecipitated TcFUT1-6xMyc was used to demonstrate enzymatic activity and to explore substrate specificity. This defined TcFUT1 as a GDP-Fuc : ßGal α1-2 fucosyltransferase with a strict requirement for acceptor glycans with non-reducing terminal Galß1-3GlcNAc structures. This differs from the specificity of the T. brucei orthologue TbFUT1, which can also tolerate non-reducing terminal Galß1-4GlcNAc and Galß1-4Glc acceptor sites. Immunofluorescence microscopy using α-Myc tag antibodies also showed a mitochondrial location for TcFUT1 in T. cruzi epimastigote cells. Collectively, these results are like those described for TbFUT1 and LmjFUT1 from T. brucei and L. major, suggesting that FUT1 gene products have conserved function for across the trypanosomatids and may share therapeutic target potential.


Assuntos
Doença de Chagas , Leishmania major , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/genética , Fucosiltransferases/genética , Leishmania major/genética , Mitocôndrias
18.
J Chem Phys ; 159(7)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37581421

RESUMO

Multiphoton ionization (MPI) of alkyl iodides (RI, R = CnH2n+1, n = 1-4) has been investigated with femtosecond laser pulses centered at 800 and 400 nm along with photoelectron imaging detection. In addition, the ultraviolet (UV)-vacuum ultraviolet (VUV) absorption spectra of gas-phase RIs have been measured in the photon energy range of 5-11 eV using the VUV Fourier transform spectrometer at the VUV DESIRS beamline of the synchrotron SOLEIL facility. The use of high-laser-field strengths in matter-radiation interaction generates highly non-linear phenomena, such as the Stark shift effect, which distorts the potential energy surfaces of molecules by varying both the energy of electronic and rovibrational states and their ionization energies. The Stark shift can then generate resonances between intermediate states and an integer number of laser photons of a given wavelength, which are commonly known as Freeman resonances. Here, we study how the molecular structure of linear and branched alkyl iodides affects the UV-VUV absorption spectrum, the MPI process, and the generation of Freeman resonances. The obtained results reveal a dominant resonance in the experiments at 800 nm, which counter-intuitively appears at the same photoelectron kinetic energy in the whole alkyl iodide series. The ionization pathways of this resonance strongly involve the 6p(2E3/2) Rydberg state with different degrees of vibrational excitation, revealing an energy compensation effect as the R-chain complexity increases.

19.
J Alzheimers Dis ; 95(2): 477-491, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37574730

RESUMO

BACKGROUND: Sleep disruption in elderly has been associated with an increased risk of cognitive impairment and its transition into Alzheimer's disease (AD). High arousal indices (AIs) during sleep may serve as an early-stage biomarker of cognitive impairment non-dementia (CIND). OBJECTIVE: Using full-night polysomnography (PSG), we investigated whether CIND is related to different AIs between NREM and REM sleep stages. METHODS: Fourteen older adults voluntarily participated in this population-based study that included Mini-Mental State Examination, Neuropsi battery, Katz Index of Independence in Activities of Daily Living, and single-night PSG. Subjects were divided into two groups (n = 7 each) according to their results in Neuropsi memory and attention subtests: cognitively unimpaired (CU), with normal results; and CIND, with -2.5 standard deviations in memory and/or attention subtests. AIs per hour of sleep during N1, N2, N3, and REM stages were obtained and correlated with Neuropsi total score (NTS). RESULTS: AI (REM)  was significantly higher in CU group than in CIND group. For the total sample, a positive correlation between AI (REM)  and NTS was found (r = 0.68, p = 0.006), which remained significant when controlling for the effect of age and education. In CIND group, the AI (N2)  was significantly higher than the AI (REM) . CONCLUSION: In CIND older adults, this attenuation of normal arousal mechanisms in REM sleep are dissociated from the relative excess of arousals observed in stage N2. We propose as probable etiology an early hypoactivity at the locus coeruleus noradrenergic system, associated to its early pathological damage, present in the AD continuum.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Projetos Piloto , Atividades Cotidianas , Sono , Disfunção Cognitiva/psicologia , Nível de Alerta
20.
Front Endocrinol (Lausanne) ; 14: 1206336, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484969

RESUMO

Background: The purpose of the present study was to investigate the role of oxidative stress, platelet activation, and endocan levels in renal dysfunction in normal glucose tolerance (NGT) patients with 1-h plasma glucose values ≥155 mg/dl (NGT ≥ 155), compared to NGT < 155, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) newly diagnosed subjects. We enlisted 233 patients subjected to an oral glucose tolerance test (OGTT). Materials and methods: The serum levels of platelet activation (glycoprotein VI and sP-selectin), oxidative stress biomarkers (8-isoprostane and Nox-2), and endocan were evaluated using an ELISA test. Results: Among NGT < 155 patients and the T2DM group, there was a statistically significant increase in 8-isoprostane (p < 0.0001), Nox-2 (p < 0.0001), glycoprotein VI (p < 0.0001), and sP-selectin (p < 0.0001) serum levels. Higher serum endocan levels were found with the worsening of metabolic profile (p < 0.0001); specifically, NGT ≥ 155 patients presented higher serum endocan values when compared to NGT < 155 patients (p < 0.0001). From the multivariate linear regression analysis, 1-h glucose resulted in the major predictor of estimated glomerular filtration rate (e-GFR) justifying 23.6% of its variation (p < 0.0001); 8-isoprostane and Nox-2 added respectively another 6.0% (p < 0.0001) and 3.2% (p = 0.001). Conclusion: Our study confirmed the link between 1-h post-load glucose ≥155 mg/dl during OGTT and the possible increased risk for chronic kidney disease (CKD) in newly diagnosed patients. The novelty is that we demonstrated a progressive increase in oxidative stress, platelet activation, and serum endocan levels with the worsening of metabolic profile, which becomes evident early during the progression of CKD.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Glicemia/metabolismo , Teste de Tolerância a Glucose , Biomarcadores , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/complicações
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