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1.
Clin Infect Dis ; 78(1): 144-148, 2024 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-37606512

RESUMEN

Among 43 pregnant women receiving multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment with bedaquiline and/or delamanid, 98% had favorable treatment outcomes. Of 31 continued pregnancies, 81% had live births with no reported malformations, and 68% of neonates had normal birth weights. Effective MDR/RR-TB treatment during pregnancy can improve maternal outcomes without harming neonates.


Asunto(s)
Antituberculosos , Tuberculosis Resistente a Múltiples Medicamentos , Recién Nacido , Humanos , Femenino , Embarazo , Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Diarilquinolinas/uso terapéutico , Resultado del Tratamiento , Protocolos Clínicos , Nacimiento Vivo
2.
Radiology ; 311(2): e231386, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38713023

RESUMEN

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microesferas , Radioisótopos de Itrio , Humanos , Masculino , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Persona de Mediana Edad , Radioisótopos de Itrio/uso terapéutico , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos
3.
Cerebrovasc Dis ; 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38412839

RESUMEN

Introduction Stroke lesion volume on MRI or CT provides objective evidence of tissue injury as a consequence of ischemic stroke. Measurement of "final" lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome. The goals of this study were to quantify lesion growth during the first week after treatment, identify early predictors, and explore the association with clinical outcome. Methods This is a prospective study of stroke patients at two centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, and iii) had 3T MRI post-EVT at 24hr and 5-day. We defined "Early" and "Late" lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively. Complete reperfusion was defined as >90% reduction of the volume of tissue with perfusion delay (Tmax>6sec) between pre-EVT and 24hr post-EVT. Favorable clinical outcome was defined as modified Rankin scale (mRS) of 0-2 at 30 or 90 days. Results One hundred twelve patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 66% with M1 occlusion, and median baseline DWI volume 21.2mL. Successful recanalization was achieved in 87% and 68% had complete reperfusion, with an overall favorable clinical outcome rate of 53%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.3mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (64%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (87%: 46% mTICI 2b/ 41% mTICI 3). Late lesion growth patients had a 27.4mL change in Late lesion volume and 30.1mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome. Conclusion Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Most patients with no Early lesion growth had no Late lesion growth. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally, it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

4.
J Vasc Interv Radiol ; 35(1): 102-112.e5, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37696431

RESUMEN

PURPOSE: To study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002-2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items. RESULTS: Among 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment. CONCLUSIONS: HCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Anciano , Estados Unidos/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Medicare , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Personal de Salud , Análisis de Sistemas , Evaluación del Resultado de la Atención al Paciente , Satisfacción del Paciente , Encuestas de Atención de la Salud
5.
Mol Cell ; 63(2): 218-228, 2016 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-27397683

RESUMEN

Phosphorylation has been generally thought to activate the SR family of splicing factors for efficient splice-site recognition, but this idea is incompatible with an early observation that overexpression of an SR protein kinase, such as the CDC2-like kinase 1 (CLK1), weakens splice-site selection. Here, we report that CLK1 binds SR proteins but lacks the mechanism to release phosphorylated SR proteins, thus functionally inactivating the splicing factors. Interestingly, CLK1 overcomes this dilemma through a symbiotic relationship with the serine-arginine protein kinase 1 (SRPK1). We show that SRPK1 interacts with an RS-like domain in the N terminus of CLK1 to facilitate the release of phosphorylated SR proteins, which then promotes efficient splice-site recognition and subsequent spliceosome assembly. These findings reveal an unprecedented signaling mechanism by which two protein kinases fulfill separate catalytic features that are normally encoded in single kinases to institute phosphorylation control of pre-mRNA splicing in the nucleus.


Asunto(s)
Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Precursores del ARN/metabolismo , Empalme del ARN , ARN Mensajero/metabolismo , Empalmosomas/enzimología , Catálisis , Células HeLa , Humanos , Fosforilación , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Quinasas/genética , Interferencia de ARN , Precursores del ARN/genética , ARN Mensajero/genética , Ribonucleoproteína Nuclear Pequeña U1/metabolismo , Empalmosomas/genética , Factores de Tiempo , Transfección , Globinas beta/genética , Globinas beta/metabolismo
6.
Artículo en Inglés | MEDLINE | ID: mdl-38356017

RESUMEN

Phytase is crucial in enhancing the bioavailability and release of phosphorus and other nutrients bound to phytic acid, making them more bioavailable for animal absorption. This study was carried out to inspect the effect of supplementing low phosphorus (P) diet with di-calcium phosphate (DCP) and liquid phytase enzyme (LP), which contains 1500 FTU/kg, on growth performance, intestinal morphometry, proximate body chemical composition, blood profile, immunity status, liver mitochondrial enzyme activities, the expression response and economic returns of Nile tilapia (Oreochromis niloticus). Three triplicate groups of fish (initial weight 5.405 ± 0.045 g, N = 90) were fed on three different diets for 90 days. The first was a control diet with zero DCP; the second was a control diet supplemented with 0.71% DCP; the third was a control diet supplemented with 0.03% LP. The groups were designated as CG, DCP and LP, respectively. Results showed that LP induced considerable improvements (p < 0.05) in FBW, body weight gain, weight gain rate, specific growth rate, HIS, viscero-somatic index, spleen-somatic index, feed conversion ratio, blood parameters and the histomorphometry assessment of intestinal villi absorptive capacity, compared with the other groups. Also, whole-body protein and lipid contents pointedly (p < 0.05) increased by LP, compared with the DCP group. A positive response (p < 0.05) to the phytase enzyme was noted in complexes I, III and IV of the mitochondrial liver complex enzyme activity. Likewise, the relative gene expression levels of (GHr-1, IGF-1, FAS and LPL) were notably (p < 0.05) upregulated by phytase enzyme, associated with DCP and control groups. Further, phytase recorded the highest total return and profit percentage. It can be concluded that Nile tilapia benefits from using phytase enzyme 1500 FTU/kg at 0.03% without adding DCP in terms of good performance and profits.

7.
Funct Integr Genomics ; 23(3): 212, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37368046

RESUMEN

In recent years, significant progress has been made in understanding the biosynthetic pathway and regulation of flavonoids through forward genetic approaches. However, there remains a notable gap in knowledge regarding the functional characterization and underlying processes of the transport framework responsible for flavonoid transport. This aspect requires further investigation and clarification to achieve a comprehensive understanding. Presently, there are a total of four proposed transport models associated with flavonoids, namely glutathione S-transferase (GST), multidrug and toxic compound extrusion (MATE), multidrug resistance-associated protein (MRPs), and bilitranslocase-homolog (BTL). Extensive research has been conducted on the proteins and genes related to these transport models. However, despite these efforts, numerous challenges still exist, leaving much to be explored in the future. Gaining a deeper understanding of the mechanisms underlying these transport models holds immense potential for various fields such as metabolic engineering, biotechnological approaches, plant protection, and human health. Therefore, this review aims to provide a comprehensive overview of recent advancements in the understanding of flavonoid transport mechanisms. By doing so, we aim to paint a clear and coherent picture of the dynamic trafficking of flavonoids.


Asunto(s)
Flavonoides , Plantas , Humanos , Transporte Biológico , Plantas/genética , Glutatión Transferasa/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
8.
Microb Ecol ; 85(4): 1276-1287, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35366684

RESUMEN

Here we describe the antimicrobial potential of secondary metabolites, fulvic acid (F.A.) and anhydrofulvic acid (AFA), produced by RDE147, an endophyte of Rosa damascena Mill. The endophyte was identified as Cercospora piaropi by ITS and ß-tubulin-based phylogenetic analyses, while chemoprofiling of the endophyte by column chromatography and spectroscopy yielded two pure compounds, F.A. and AFA. The compounds demonstrated different antimicrobial profiles, with AFA suppressing the growth of C. albicans at 7.3 µg ml-1 IC50. Further studies revealed that AFA strongly restricted the biofilm production and hyphae formation in C. albicans by down-regulating several biofilm and morphogenesis-related genes. The time-kill assays confirmed the fungicidal activity of AFA against C. albicans, killing 83.6% of the pathogen cells in 24 h at the MIC concentration, and the post-antibiotic effect (PAE) experiments established the suppression of C. albicans growth for extended time periods. The compound acted synergistically with amphotericin B and nystatin and reduced ergosterol biosynthesis by the pathogen, confirmed by ergosterol estimation and comparative expression profiling of selected genes and molecular docking of AFA with C. albicans squalene epoxidase. AFA also suppressed the expression of several other virulence genes of the fungal pathogen. The study determines the anti-C. albicans potential of AFA and its impact on the biology of the pathogen. It also indicates that Cercospora species may yield potential bioactive molecules, especially fulvic acid derivatives. However, it is imperative to conduct in vivo studies to explore this molecule's therapeutic potential further.


Asunto(s)
Candida albicans , Rosa , Candida albicans/metabolismo , Factores de Virulencia/metabolismo , Rosa/metabolismo , Cercospora/metabolismo , Simulación del Acoplamiento Molecular , Filogenia , Biopelículas , Ergosterol/metabolismo , Proliferación Celular , Antifúngicos/farmacología , Antifúngicos/metabolismo , Pruebas de Sensibilidad Microbiana
9.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36902433

RESUMEN

Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of -9.7, and -9.4 kcal/mol, respectively, while the positive control had a BE of -9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.


Asunto(s)
Gastroenteritis , Norovirus , Humanos , Simulación de Dinámica Molecular , Unión Proteica , ARN Polimerasa Dependiente del ARN/metabolismo , Antivirales/farmacología , Simulación del Acoplamiento Molecular
10.
Curr Opin Pulm Med ; 28(2): 115-120, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34652296

RESUMEN

PURPOSE OF REVIEW: In this review, we will discuss the current status and recent developments in precision medicine in chronic obstructive pulmonary disease (COPD) through the lens of treatable traits. RECENT FINDINGS: Although the term 'treatable traits' in the treatment of COPD is relatively recent, this concept has been used for many years if one considers interventions such as long-term oxygen therapy or alpha-1 antitrypsin replacement therapy. Recent advances have included expanding the definition of COPD to include a broader population of people with lower respiratory disease but not meeting the strict criteria for obstruction, advances in imaging to aid in the diagnosis and treatment of COPD, advances in understanding symptoms and exacerbations to define severity, using biomarkers to guide therapy and better understanding and addressing polymorbidity and frailty. In addition, there is a concerted effort to use these concepts to identify COPD patients earlier in the disease process wherein disease modification may be possible. SUMMARY: Focusing on subsets of patients with COPD with certain characteristics should lead to better outcomes and fewer adverse effects from treatment. VIDEO ABSTRACT: http://links.lww.com/COPM/A30.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Deficiencia de alfa 1-Antitripsina , Biomarcadores , Progresión de la Enfermedad , Humanos , Terapia por Inhalación de Oxígeno , Medicina de Precisión , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/terapia
11.
Bioorg Chem ; 126: 105869, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35598571

RESUMEN

The quest for new antifungal and antitubercular drugs is a need of the hour because of morbid co-pathogenesis and an increase in immunocompromised patients. One of the ways forward is to explore and repurpose the established pharmacophores for the desired application. Oxazolidinones are well-known antibacterial agents, with few investigations reported to exploit their antifungal properties. Herein, we report the design and synthesis of a series of linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents. Studies revealed that two of the novel oxazolidinones 2 and 3a exhibited excellent anticandidiasis activity against different Candida fungus strains, superior to standard drugs. Mechanistic and docking studies revealed that oxazolidinones were better inhibitors of the ergosterol biosynthesis pathway than the controls used. In addition, the oxazolidinones 2 and 3a also exhibited prominent inhibitory activity against M. tuberculosis H37Rv with MIC values of 1 and 2 µg/ml, respectively. Computational studies demonstrated the binding of the compounds to the transcriptional regulatory repressor protein, which was reinforced by the molecular dynamics simulations. The pharmacophore modeling experiments validated the molecular docking results in both the target proteins.


Asunto(s)
Mycobacterium tuberculosis , Oxazolidinonas , Antibacterianos/farmacología , Antifúngicos/farmacología , Antituberculosos/farmacología , Humanos , Linezolid/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Oxazolidinonas/química , Oxazolidinonas/farmacología
12.
Ecotoxicol Environ Saf ; 231: 113187, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35030526

RESUMEN

Ammonia exposure can be considered more stressful for aquatic animals when it coincides with high temperature. This study was conducted to detect the effects of ammonia exposure and heat stress and their interactions on the histological features of gills and liver tissues and the expression responses of immune and antioxidative related genes in Nile tilapia. Thus, 180 fish were divided into four groups (triplicates), where the first and third groups were kept in clean water without total ammonium nitrogen (TAN) exposure. At the same time, the second and fourth groups were exposed to 5 mg TAN/L. After seven days, the water temperature was raised in the third (without ammonia toxicity) and fourth (exposed with 5 mg TAN/L) groups up to 32 °C and kept under these conditions for 24 h. While the first (without ammonia toxicity) and second (exposed with 5 mg TAN/L) groups were kept under optimum water temperature (27.28 °C) then gills and liver tissues were dissected. Marked upregulation of keap1 was seen in the gills of fish exposed to ammonia/heat stress. The expression of mRNA levels for nrf2, nqo-1, cat, and gpx genes were downregulated in all stressed groups, with the lowest was recorded in the ammonia/heat stress group. The transcription of ho-1 was upregulated in the ammonia and heat stress groups while downregulated in the ammonia/heat stress group. The transcription of the complement C3 gene was downregulated in the livers of heat stress and ammonia/heat stress groups, while the lysozyme gene was downregulated in the ammonia/heat stress group. The mRNA expression levels of nf-κB, il-1ß, and tnf-α genes were higher in the ammonia group than in the heat stress group. The highest transcription level of nf-κB, il-1ß, tnf-α, il-8, and hsp70 genes and the lowest C3 and lysozyme genes were observed in fish exposed to ammonia/heat stress. The co-exposure to ammonia with heat stress triggered degeneration of primary and secondary gill filaments with telangiectasia and vascular congestion of secondary epithelium while, the liver showed hepatic vascular congestion and visible necrotic changes with nuclear pyknosis. In conclusion, the combined exposure of ammonia and heat stress induced oxidative stress, immunosuppression, and inflammation in Nile tilapia.


Asunto(s)
Cíclidos , Contaminantes Químicos del Agua , Amoníaco/metabolismo , Amoníaco/toxicidad , Animales , Antioxidantes/metabolismo , Cíclidos/genética , Cíclidos/metabolismo , Branquias/metabolismo , Respuesta al Choque Térmico/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Hígado/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad
13.
J Community Psychol ; 50(2): 983-991, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34416030

RESUMEN

Pain is a complex, multidimensional phenomenon and integral component of illness but little is known about its religious construction and interpretation. This article discusses an important yet neglected component of terminal illness which is the religious construction of pain. Eleven hepatitis C Muslim patients admitted to the liver center were recruited for this study. In-depth interviews helped the identification of dominant themes. The study found that terminal patients construct pain in a religious context and interpret it into religious realms. For them, pain helps to realize their debility and helplessness. They think pain has a transformatory potential and can help them turn to be very strong and brave. The participants also reported having a belief that pain in this world could be compensated in the life hereafter and they will be rewarded with good deeds and bestowed with the Jannah (paradise). The terminal patients strongly influenced by religion and spirituality believed to be experiencing pain as a punishment of their misdeeds. Thus, pain was helping them to normalize their end-of-life experiences and ease the terminal stage of their illness.


Asunto(s)
Hepatitis C , Islamismo , Humanos , Dolor , Espiritualidad , Enfermo Terminal
14.
Phys Rev Lett ; 126(11): 117403, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33798368

RESUMEN

Ultrafast changes of charge density distribution in diamond after irradiation with an intense x-ray pulse (photon energy, 7.8 keV; pulse duration, 6 fs; intensity, 3×10^{19} W/cm^{2}) have been visualized with the x-ray pump-x-ray probe technique. The measurement reveals that covalent bonds in diamond are broken and the electron distribution around each atom becomes almost isotropic within ∼5 fs after the intensity maximum of the x-ray pump pulse. The 15 fs time delay observed between the bond breaking and atomic disordering indicates nonisothermality of electron and lattice subsystems on this timescale. From these observations and simulation results, we interpret that the x-ray-induced change of the interatomic potential drives the ultrafast atomic disordering underway to the following nonthermal melting.

15.
Cerebrovasc Dis ; 50(6): 738-745, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34284378

RESUMEN

INTRODUCTION: The absence of an ischemic lesion on MRI fluid-attenuated inversion recovery (FLAIR) is helpful in predicting stroke onset within 4.5 h. However, some ischemic strokes become visible on FLAIR within 4.5 h. We hypothesized that the early lesion visibility on FLAIR may predict stroke outcome 90 days after intravenous (IV) thrombolysis, independent of time. MATERIALS AND METHODS: We analyzed data from acute ischemic stroke patients presenting over the last 10 years who were screened with MRI and treated with IV thrombolysis within 4.5 h from onset. Three independent readers assessed whether ischemic lesions seen on diffusion-weighted imaging were also FLAIR positive based on visual inspection. Multivariable regression analyses were used to obtain an adjusted odds ratio of favorable clinical and radiological outcomes based on FLAIR positivity. RESULTS: Of 297 ischemic stroke patients, 25% had lesion visibility on initial FLAIR. The interrater agreement for the FLAIR positivity assessment was 84% (κ = 0.604, 95% CI: 0.557-0.652). Patients with FLAIR-positive lesions had more right hemispheric strokes (57 vs. 41%, p = 0.045), were imaged later (129 vs. 104 min, p = 0.036), and had less frequent favorable 90-day functional outcome (49 vs. 63%, p = 0.028), less frequent early neurologic improvement (30 vs. 58%, p = 0.001), and more frequent contrast extravasation to the cerebrospinal fluid space (44 vs. 26%, p = 0.008). CONCLUSIONS: Early development of stroke lesion on FLAIR within 4.5 h of onset is associated with reduced likelihood of favorable 90-day outcome after IV thrombolysis.


Asunto(s)
Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Administración Intravenosa , Imagen de Difusión por Resonancia Magnética , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Resultado del Tratamiento
16.
Eur Spine J ; 30(4): 865-869, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33179129

RESUMEN

PURPOSE: No clinical CT-based classification system is currently in use for lumbar foraminal stenosis. MRI scanners are not easily available, are expensive and may be contraindicated in an increasing number of patients. This study aimed to propose and evaluate the reproducibility of a novel CT-based classification for lumbar foraminal stenosis. MATERIALS AND METHODS: The grading was developed as four grades: normal foramen-Grade 0, anteroposterior (AP)/superoinferior (SI) (single plane) fat compression-Grade 1, both AP/SI compression (two planes) without distortion of nerve root-Grade 2 and Grade 2 with distortion of nerve root-Grade 3. A total of 800 lumbar foramen of a cohort of 100 random patients over the age of 60 who had undergone both CT and MRI scans were reviewed by two radiologists independently to assess agreement of the novel CT classification against the MRI-based grading system of Lee et al. Interobserver(n = 400) and intraobserver agreement(n = 160) was also evaluated. Agreement analysis was performed using the weighted kappa statistic. RESULTS: A total of 100 patients (M:F = 45:55) with a mean age of 68.5 years (range 60-83 years were included in the study. The duration between CT and MRI scans was 98 days (range 0-540, SD-108). There was good correlation between CT and MRI with kappa scores (k = 0.81) and intraobserver kappa of 0.89 and 0.98 for the two readers. CONCLUSION: The novel CT-based classification correlates well with the MRI grading system and can safely and accurately replace it where required.


Asunto(s)
Estenosis Espinal , Anciano , Anciano de 80 o más Años , Constricción Patológica , Humanos , Vértebras Lumbares , Región Lumbosacra , Imagen por Resonancia Magnética , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X
17.
Med Teach ; 43(9): 1005-1009, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563060

RESUMEN

The intensive care unit (ICU) provides unique educational opportunities for both undergraduate and postgraduate learners, including procedural training, ventilator management guidance, complex communication scenarios, and didactic lectures on dynamic topics like multi-system organ failure. However, certain challenges are inherent in this setting that can make teaching difficult. Different trainee educational backgrounds, variability in disease states, time limitations and urgent patient care considerations highlight some challenges that limit teaching opportunities. The following twelve tips address these unique aspects of the ICU environment and provide strategies to optimize teaching. These tips focus on three main goals: creating an optimal learning environment, increasing learner engagement, and critically challenging learners.


Asunto(s)
Unidades de Cuidados Intensivos , Aprendizaje , Comunicación , Humanos , Enseñanza
18.
Orbit ; 40(4): 306-315, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32543976

RESUMEN

PURPOSE: Orbital exenteration is a radical oncological surgery that is usually indicated for advanced primary orbital tumors or invasion from local malignancy. We report a 5-year series from a tertiary head and neck center with particular focus on our ablative and reconstructive approach. METHODS: We performed a clinicopathological review of patients referred to Guy's and St Thomas' NHS Foundation Trust Head and Neck multidisciplinary team for management input of an orbital malignancy during the period of 2013 to 2018. Cases involving local invasion from sinonasal malignancy were excluded. The reconstructive approach, perioperative complications, disease-free and overall survival were analyzed. RESULTS: 27 patients were identified and of those treated surgically, a radical extended orbital exenteration was required in almost half (44.4%), with squamous cell carcinoma being the most common pathology (55.6%). A concurrent neck dissection and parotidectomy were commonly performed with confirmed or suspected regional disease, or in the presence of high-risk pathological features. This approach resulted in favourable 2-year overall survival in these advanced stage cases of 84.6% and disease-free survival of 73.2%, with 92% achieving a negative surgical margin. The majority of treated patients required a free flap reconstruction, especially when an extended exenteration defect or adjuvant treatment was anticipated. The anterolateral thigh flap was the most commonly used donor site, and we present our algorithm for reconstruction of these defects. CONCLUSIONS: A multidisciplinary approach to advanced orbital malignancy with a comprehensive approach to surgical resection and reconstruction results in favorable oncological outcomes and addresses functional and cosmetic patient rehabilitation.


Asunto(s)
Evisceración Orbitaria , Procedimientos de Cirugía Plástica , Humanos , Estudios Retrospectivos , Colgajos Quirúrgicos , Reino Unido
19.
Bratisl Lek Listy ; 122(12): 871-875, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34904849

RESUMEN

OBJECTIVES: This study evaluated the role of ultrasound in postoperative care after major lung resection. BACKGROUND: High accuracy of lung ultrasound imaging was proved in various medical fields. The experience with ultrasound after thoracic surgery is limited. METHODS: Patients scheduled for major lung resection were consecutively included in a prospective study comparing two modalities of imaging examinations, namely those employing ultrasound and X-ray in the diagnoses of pneumothorax and pleural effusion. Two examinations were performed. One after recovery from anaesthesia, the second before chest tube removal. RESULTS: Forty-eight patients underwent 87 examinations. X-ray and ultrasound examinations showed substantial and fair agreements for pneumothorax (Cohen's kappa coefficients 0.775 and 0.397) and slight and substantial agreements for pleural effusion (Cohen's kappa coefficients 0.036 and 0.611). The sensitivity bounds for pneumothorax were 45.5-58.5 % at the first and 29.7-59.4 % at the second examination. Sensitivity bounds for pleural effusion were 0-86.2 % at the first and 32.6-36.9 % at the second examination. Except for two cases of pneumothorax being missed by X-ray imaging, the rest of mismatches were clinically irrelevant conditions with no impact on clinical decision and patient's outcome. CONCLUSION: The use of ultrasound can reduce the number of X-ray examinations and thus lower the radiation exposure after major lung resections (Tab. 4, Ref. 30).


Asunto(s)
Pulmón , Humanos , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Estudios Prospectivos , Radiografía , Ultrasonografía , Rayos X
20.
Crit Care ; 24(1): 566, 2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32958059

RESUMEN

BACKGROUND: Reduced body weight at the time of intensive care unit (ICU) admission is associated with worse survival, and a paradoxical benefit of obesity has been suggested in critical illness. However, no research has addressed the survival effects of disaggregated body constituents of dry weight such as skeletal muscle, fat, and bone density. METHODS: Single-center, prospective observational cohort study of medical ICU (MICU) patients from an academic institution in the USA. Five hundred and seven patients requiring CT scanning of chest or abdomen within the first 24 h of ICU admission were evaluated with erector spinae muscle (ESM) and subcutaneous adipose tissue (SAT) areas and with bone density determinations at the time of ICU admission, which were correlated with clinical outcomes accounting for potential confounders. RESULTS: Larger admission ESM area was associated with decreased odds of 6-month mortality (OR per cm2, 0.96; 95% CI, 0.94-0.97; p < 0.001) and disability at discharge (OR per cm2, 0.98; 95% CI, 0.96-0.99; p = 0.012). Higher bone density was similarly associated with lower odds of mortality (OR per 100 HU, 0.69; 95% CI, 0.49-0.96; p = 0.027) and disability at discharge (OR per 100 HU, 0.52; 95% CI, 0.37-0.74; p < 0.001). SAT area was not significantly associated with these outcomes' measures. Multivariable modeling indicated that ESM area remained significantly associated with 6-month mortality and survival after adjusting for other covariates including preadmission comorbidities, albumin, functional independence before admission, severity scores, age, and exercise capacity. CONCLUSION: In our cohort, ICU admission skeletal muscle mass measured with ESM area and bone density were associated with survival and disability at discharge, although muscle area was the only component that remained significantly associated with survival after multivariable adjustments. SAT had no association with the analyzed outcome measures.


Asunto(s)
Tejido Adiposo/fisiopatología , Composición Corporal , Huesos/fisiopatología , Músculo Esquelético/fisiopatología , Anciano , Estudios de Cohortes , Femenino , Humanos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Estudios Prospectivos , Estudios Retrospectivos
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