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1.
BMC Public Health ; 24(1): 1102, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649854

RESUMEN

BACKGROUND: To determine the prevalence, risk factors; and impact on patient health and economic outcomes across the laterality spectrum of multiple sensory impairment (MSI) in a multi-ethnic older Asian population. METHODS: In this population-based study of Singaporeans aged ≥ 60 years, MSI was defined as concomitant vision (visual acuity > 0.3 logMAR), hearing (pure-tone air conduction average > 25 dB), and olfactory (score < 12 on the Sniffin' Sticks test) impairments across the spectrum of laterality (any, unilateral, combination [of unilateral and bilateral], and bilateral). RESULTS: Among 2,057 participants (mean ± SD 72.2 ± 0.2 years; 53.1% female), the national census-adjusted prevalence rates of any, unilateral, combination, and bilateral MSI were 20.6%, 1.2%, 12.2%, and 7.2%, respectively. Older age, male gender, low socioeconomic status (SES), and smoking (all p < 0.05) were independently associated with higher likelihood of any MSI. Compared to those with no sensory loss, those with MSI had significantly decreased mobility (range 5.4%-9.2%), had poor functioning (OR range 3.25-3.45) and increased healthcare costs (range 4-6 folds) across the laterality spectrum. Additionally, bilateral MSI had a significant decrease in HRQoL (5.5%, p = 0.012). CONCLUSIONS: MSI is a highly prevalent medical condition, with 1 in 5; and almost 1 in 10 community-dwelling older Asians having any and bilateral MSI, respectively, with a higher likelihood in men, smokers, and those with low SES. Critically, MSI has a substantial negative impact on patient health and economic outcomes across the laterality spectrum. Sensory testing is critical to detect and refer individuals with MSI for management to improve their functional independence and QoL.


Asunto(s)
Trastornos de la Sensación , Humanos , Singapur/epidemiología , Femenino , Masculino , Anciano , Factores de Riesgo , Prevalencia , Persona de Mediana Edad , Trastornos de la Sensación/epidemiología , Anciano de 80 o más Años , Etnicidad/estadística & datos numéricos
2.
Org Biomol Chem ; 21(16): 3432-3446, 2023 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-37039282

RESUMEN

A convenient method for the synthesis of N3,N4-disubstituted 3,4-diaminopyrazolo[3,4-d]pyrimidines was developed using a three-component reaction of 3,5-diaminopyrazole-4-carbonitriles with primary amines and orthoesters. The preparation of 116 examples demonstrated the good scope of the reaction, which tolerated variations in the substrate structure and was particularly efficient under microwave irradiation. The short reaction time and chromatography-free product isolation add practicality to this method. The anti-leukemic activity was assessed in vitro using K562 and Jurkat T cells, and the selectivity of the most active compounds was evaluated using non-cancerous MRC5 cells. The most promising compound inhibited Jurkat T cells with a GI50 value of 0.5 µM and a selectivity index of 65.


Asunto(s)
Microondas , Pirimidinas , Pirimidinas/química
3.
Eur Arch Otorhinolaryngol ; 279(2): 639-644, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33590338

RESUMEN

PURPOSE: This study aims to evaluate the surgical outcomes with the use of a combination of the middle temporal artery (MTA) flap and the inferior musculoperiosteal (IMP) flap for mastoid obliteration after canal wall down mastoidectomy. METHODS: Seventy-five patients who have undergone canal wall down mastoidectomy and mastoid obliteration with the MTA and the IMP flaps at a single tertiary hospital were included. Surgical outcomes measured included the creation of a dry mastoid cavity as measured by a previously developed semi-quantitative scale, mastoid cavity epithelization time, rate of revision surgery needed, and rate of recurrent cholesteatoma. RESULTS: Patients were followed up for a median of 29 months. The median time to epithelization of the mastoid cavity was 2 months. At 1 and 3 months, 36.0% and 76.0% of patients had grade 0 and grade 1 cavities, respectively, with either a dry cavity or one or less episodes of mild otorrhea or sensation of wetness. Hundred percent of the patients achieved a grade 2 (more than one episode of otorrhea or the presence of granulation tissue that promptly resolved with simple treatment) or better cavity at 3 months. One patient re-presented with a grade 3 cavity with uncontrolled infection and daily otorrhea secondary to an attic perforation that manifested at 6 months, requiring revision surgery. There were no recurrent cholesteatomas during the follow-up period. CONCLUSIONS: The use of the MTA and the IMP flaps for mastoid obliteration may be considered as an adjunct to achieving a safe, dry ear after canal wall down mastoidectomy.


Asunto(s)
Colesteatoma del Oído Medio , Apófisis Mastoides , Colesteatoma del Oído Medio/cirugía , Conducto Auditivo Externo , Humanos , Apófisis Mastoides/cirugía , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Arterias Temporales , Resultado del Tratamiento
4.
Genes Dev ; 26(20): 2286-98, 2012 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-23019124

RESUMEN

Embryonic stem cell (ESC) pluripotency depends on a well-characterized gene regulatory network centered on Oct4, Sox2, and Nanog. In contrast, little is known about the identity of the key coregulators and the mechanisms by which they may potentiate transcription in ESCs. Alongside core transcription factors, the orphan nuclear receptor Esrrb (estrogen-related receptor ß) is vital for the maintenance of ESC identity and furthermore is uniquely associated with the basal transcription machinery. Here, we show that Ncoa3, an essential coactivator, is required to mediate Esrrb function in ESCs. Ncoa3 interacts with Esrrb via its ligand-binding domain and bridges Esrrb to RNA polymerase II complexes. Functionally, Ncoa3 is critical for both the induction and maintenance of pluripotency. Through chromatin immunoprecipitation (ChIP) sequencing and microarray experiments, we further demonstrate that Ncoa3 shares overlapping gene regulatory functions with Esrrb and cooperates genome-wide with the Oct4-Sox2-Nanog circuitry at active enhancers to up-regulate genes involved in self-renewal and pluripotency. We propose an integrated model of transcriptional and coactivator control, mediated by Ncoa3, for the maintenance of ESC self-renewal and somatic cell reprogramming.


Asunto(s)
Reprogramación Celular/genética , Células Madre Embrionarias/citología , Coactivador 3 de Receptor Nuclear/metabolismo , Receptores de Estrógenos/metabolismo , Animales , Células COS , Proliferación Celular , Chlorocebus aethiops , Femenino , Regulación del Desarrollo de la Expresión Génica , Genoma/genética , Células HEK293 , Humanos , Masculino , Ratones , Receptores de Estrógenos/genética
5.
Rheumatol Int ; 37(4): 633-639, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28013358

RESUMEN

The prevalence of neuropathic low back pain differs in different ethnic populations. The aims of the study are to determine its frequency and associations in a multi-ethnic cohort of Asian low back pain patients. This was a cross-sectional study of low back patients seen at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia. Neuropathic low back pain patients were identified using the painDETECT questionnaire and compared with non-neuropathic (unclear or nociceptive) low back pain patients, in terms of socio-demographic and clinical factors, pain severity (numerical pain rating scale, NPRS), disability (Roland Morris Disability Questionnaire, RMDQ), as well as anxiety and depression (Hospital Anxiety and Depression Scale, HADS). Of 210 patients, 26 (12.4%) have neuropathic low back pain. Neuropathic pain is associated with non-Chinese ethnicity, higher body mass index and pain radiation below the knee. Patients with neuropathic pain have significantly higher NPRS and RMDQ scores, and there are more subjects with anxiety on HADS. However, there are no differences between the groups in age, gender, pain duration or underlying diagnosis of low back pain. The prevalence of neuropathic low back pain in a multi-ethnic Malaysian cohort is lower than previously reported in other populations with possible differences between ethnic groups. It is associated with greater pain severity, disability and anxiety.


Asunto(s)
Dolor de la Región Lumbar/epidemiología , Neuralgia/epidemiología , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Dolor de la Región Lumbar/psicología , Masculino , Persona de Mediana Edad , Neuralgia/psicología , Prevalencia , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
6.
Ann Vasc Surg ; 29(7): 1454.e21-5, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26133995

RESUMEN

Mesentericoportal venous thrombosis (MVT) is a rare condition, accounting for 5-15% of acute mesenteric ischemia. Primary MVT is even rarer, with some reports quoting an incidence rate of 10-30% of reported cases. It presents a diagnostic challenge and is associated with a significant mortality rate, ranging from 13% to 50%. As it is an uncommon condition, the evidence in current literature regarding the treatment of MVT is limited. We discuss our surgical experience with a case of acute primary MVT that was managed with good clinical outcome and discuss the current evidence for the treatment of acute MVT. A 50-year-old Chinese lady with no significant past medical history presented with a 2-day history of abdominal pain and epigastric tenderness on examination. Computed tomography of her abdomen and pelvis showed evidence of extensive acute thrombi present in portal confluence extending into the superior mesenteric vein, associated with submucosal edema in some central jejunal loops. Despite systemic anticoagulation therapy with intravenous heparin, the patient deteriorated clinically, and decision was made for an exploratory laparotomy, small bowel resection, and open thrombectomy. Postoperative recovery was uneventful. She was discharged on postoperative day 13 with lifelong oral anticoagulation. In conclusion, we describe the successful management of a patient with extensive acute primary MVT where open thrombectomy was performed together with small bowel resection.


Asunto(s)
Isquemia Mesentérica/cirugía , Oclusión Vascular Mesentérica/cirugía , Venas Mesentéricas/cirugía , Vena Porta/cirugía , Trombectomía , Enfermedad Aguda , Administración Oral , Anticoagulantes/administración & dosificación , Procedimientos Quirúrgicos del Sistema Digestivo , Femenino , Humanos , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/fisiopatología , Oclusión Vascular Mesentérica/diagnóstico , Oclusión Vascular Mesentérica/fisiopatología , Venas Mesentéricas/diagnóstico por imagen , Venas Mesentéricas/fisiopatología , Persona de Mediana Edad , Flebografía/métodos , Vena Porta/diagnóstico por imagen , Vena Porta/fisiopatología , Circulación Esplácnica , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ultrasonografía
7.
Eur Arch Otorhinolaryngol ; 272(10): 2777-82, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25217083

RESUMEN

Sudden sensorineural hearing loss is typically treated with systemic steroids. The aim of this meta-analysis was to evaluate the efficacy of salvage intratympanic steroid treatment in patients who have initial treatment failure with systemic steroids. A MEDLINE literature search was performed, supported by searches of Web of Science, Biosis, and Science Direct. Articles of all languages were included. Selection of relevant publications was conducted independently by three authors. Only randomized controlled trials were considered. In one arm of the studies, the patients received salvage intratympanic steroids. In the other arm, patients did not receive further treatment. The standard difference in mean (SDM) amount of improvement in hearing threshold between patients who did and did not receive salvage intratympanic steroids was calculated. From an initial 184 studies found via the search strategy, 5 studies met inclusion criteria and were included. There was a statistically significant greater reduction in hearing threshold on pure-tone audiometry in patients who received salvage intratympanic steroids than in those who did not (SDM = -0.401, p = 0.005). Subgroup analysis showed that administration by intratympanic injection (SDM = -0.375, p = 0.013) rather than a round window catheter (SDM = -0.629, p = 0.160) yielded significant improvement in outcome. The usage of dexamethasone yielded better outcomes (SDM = -0.379, p = 0.039) than the use of methylprednisolone (SDM = -0.459, p = 0.187). No serious side effect of treatment was reported. In patients who have failed initial treatment with systemic steroids, additional treatment with salvage intratympanic dexamethasone injections demonstrate a statistically significant reduction in the hearing thresholds as compared to controls.


Asunto(s)
Glucocorticoides/administración & dosificación , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Súbita/tratamiento farmacológico , Terapia Recuperativa/métodos , Pérdida Auditiva Sensorineural/fisiopatología , Pérdida Auditiva Súbita/fisiopatología , Humanos , Inyección Intratimpánica , Resultado del Tratamiento
8.
Am J Otolaryngol ; 35(4): 508-13, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24818630

RESUMEN

OBJECTIVE: CT temporal bone scans are often performed to aid in surgical planning and management of cholesteatomas. With improvements in the resolution of CT scans today, it is now possible to obtain more information from these scans than before. The aim of this study is to compare findings on high resolution CT (HRCT) temporal bone scans to intra-operative findings, so as to determine how well various middle ear structures are assessed by HRCT scanning. STUDY DESIGN: Retrospective study. SETTING: Otology clinic of a tertiary otolaryngology centre. SUBJECTS AND METHODS: 32 mastoidectomies performed by a single otologist for clinically confirmed cholesteatoma were included. Correlation of CT and intra-operative findings on the status of structures including the ossicles, semicircular canals, facial canal and tegmen was analysed using kappa and AC1 statistics. RESULTS: In all patients, a soft tissue mass with bony erosion in keeping with a cholesteatoma was seen on CT. Radiosurgical agreement was excellent for the presence of semicircular canal erosion (k=0.89, AC1=0.96), facial canal dehiscence (k=0.74, AC1=0.76), tegmen erosion (k=0.76, AC1=0.92) and malleus erosion (k=0.76, AC1=0.85). It was good for incus erosion (k=0.71, AC1=0.92) and stapes erosion (k=0.63, AC1=0.73). CONCLUSION: There was good to excellent radiosurgical agreement in the assessment of the status of various middle ear structures. Improvement in radiosurgical agreement from existing studies in the literature was noted. This was especially true for features such as facial canal dehiscence. With technological advancements, CT temporal bone scans appear even more valuable for evaluation of patients prior to cholesteatoma surgery.


Asunto(s)
Colesteatoma del Oído Medio/cirugía , Procedimientos Quirúrgicos Otológicos , Cuidados Preoperatorios/métodos , Hueso Temporal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Colesteatoma del Oído Medio/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Hueso Temporal/cirugía
9.
Otol Neurotol ; 45(5): 564-571, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728560

RESUMEN

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease. STUDY DESIGN: Prospective, unblinded, cohort study. SETTING: Tertiary care neurotology clinic. PATIENTS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria. INTERVENTIONS: A single injection of a long-acting gel formulation under direct visualization into the round window niche. MAIN OUTCOME MEASURES: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer. RESULTS: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment. CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.


Asunto(s)
Dexametasona , Enfermedad de Meniere , Ventana Redonda , Humanos , Enfermedad de Meniere/tratamiento farmacológico , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Persona de Mediana Edad , Masculino , Femenino , Anciano , Adulto , Resultado del Tratamiento , Estudios Prospectivos , Anciano de 80 o más Años , Preparaciones de Acción Retardada , Estudios de Cohortes , Vértigo/tratamiento farmacológico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Geles , Adulto Joven
10.
Innov Aging ; 7(8): igad101, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37886627

RESUMEN

Background and Objectives: To determine the impact of hearing impairment (HI) on health indicators in a multiethnic Singaporean population of older adults. Research Design and Methods: In this cross-sectional, population-based study, pure-tone averages of air-conduction thresholds at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz were calculated for each ear. Eight categories of HI were defined ranging from: 1: No HI to 8: Bilateral severe HI. Health indicators included hearing-related quality of life (H-QoL), depressive symptoms, frailty, gait speed, instrumental activities of daily living, sarcopenia, and cognitive impairment. Multivariable regression models determined the independent associations between HI and outcomes. Results: A total of 2,503 older adults (mean age ± SD 73.4 ± 8.4; 55.2% female participants) were enrolled. Of these, 289 (11.6%), 259 (10.4%), 798 (31.9%), 303 (12.1%), 515 (20.6%), 52 (2.1%), 155 (6.2%), and 115 (4.6%) had hearing levels in Cats 1 to 8, respectively; and 20 (0.8%) used a hearing aid. Compared to those with no HI, participants with unilateral mild HI (Cat 2) had a 107% reduction in H-QoL (ß: 0.63; CI: 0.18, 1.09, p = .006), increasing to a 2,816% reduction (ß: 16.78; CI: 13.25, 20.31, p < .001) in those with bilateral severe HI-Cat 8 (p-trend < .001). Those with Cat 8 also had lower gait speed and we observed a nonsignificant increase in odds of frailty as HI worsened. Discussion and Implications: H-QoL is affected across the spectrum of severity and laterality of HI. Interventions to alleviate the effects of HI and provision of QoL support are warranted. Other health indicators were only affected in late stages, suggesting that slowing disease progression is crucial in clinical management.

11.
Otol Neurotol ; 43(9): e1020-e1023, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36047684

RESUMEN

OBJECTIVE: We report a novel postmastoidectomy hyperacusis syndrome (PMHS) in patients who have had cortical mastoidectomies and experience hyperacusis to stimuli involving touch of the pinna and periauricular area. This report aims to describe the clinical characteristics of patients predisposed to this disabling complication after mastoid surgery and describes surgical treatment with mastoid cortex resurfacing with hydroxyapatite bone cement. PATIENTS: Three patients who have undergone intact canal wall mastoidectomies for nonchronic middle ear-related pathologies all reported a similar constellation of postoperative symptoms. None of the patients had any ossicular chain or middle ear abnormalities, and none had preoperative conductive hearing loss. All patients reported disabling hyperacusis related to light touch stimuli in the periauricular area. On examination, all three patients demonstrated synchronous movement of the tympanic membrane when the postauricular area was palpated. INTERVENTIONS: After a period of observation, none of the patients noted any improvement to their symptoms. Resurfacing of the mastoid cortex with hydroxyapatite bone cement was performed in all patients. MAIN OUTCOME MEASURES: Presence of touch-induced hyperacusis and audiometry was assessed postoperatively. Patients were also examined for synchronous movement of the tympanic membrane with palpation of the postauricular area. RESULTS: All patients experienced complete resolution of touch-induced hyperacusis postoperatively. Pure-tone audiometric hearing thresholds remained unchanged after mastoid cortex resurfacing, and there was no longer tympanic membrane movement with palpation of the postauricular area. CONCLUSIONS: PMHS can occur in patients after cortical mastoidectomy when there is no history of ossicular chain or history of chronic middle ear disease or middle ear abnormalities. PMHS can cause significant distress to patients and remain underrecognized unless synchronous tympanic membrane movement is specifically examined for. Treatment via mastoid cortex surfacing with hydroxyapatite bone cement is safe and effective.


Asunto(s)
Colesteatoma del Oído Medio , Hiperacusia , Audiometría de Tonos Puros , Cementos para Huesos , Cadáver , Colesteatoma del Oído Medio/cirugía , Humanos , Hidroxiapatitas , Hiperacusia/etiología , Hiperacusia/cirugía , Apófisis Mastoides/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
12.
RSC Adv ; 12(14): 8323-8332, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35424837

RESUMEN

A practical three-component method for the synthesis of pyrazolo[3,4-d]pyrimidin-4-ones was developed. The reaction was performed in a one-pot manner under controlled microwave irradiation using easily accessible methyl 5-aminopyrazole-4-carboxylates, trimethyl orthoformate, and primary amines. Under the optimized conditions, challenging substrates, such as N-1 unsubstituted 5-aminopyrazole-4-carboxylates with another substituted amino group in position 3, reacted selectively affording 5-substituted 3-arylamino-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones. The reaction tolerated a range of primary amines, including anilines. The advantages of the developed protocol include short reaction time, pot- and step-economy, and convenient chromatography-free product isolation. The structural features of representative products were explored by X-ray crystallography.

13.
Acta Haematol ; 125(3): 107-14, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21109731

RESUMEN

BACKGROUND: Febrile neutropenia (FN) is a dose-limiting complication of chemotherapy. Judicious usage of prophylactic granulocyte-colony-stimulating factors, such as pegfilgrastim, can prevent the occurrence of FN. Although studies have been conducted to evaluate the effectiveness of pegfilgrastim to prevent FN in lymphoma patients receiving myelosuppressive chemotherapy, limited data is available to identify patients who are at risk of developing FN despite primary prophylaxis with pegfilgrastim (breakthrough FN). OBJECTIVES: The aim of this study is to: (1) identify clinical characteristics of patients who develop breakthrough FN, and (2) provide descriptive data on the incidence of breakthrough FN among lymphoma patients. METHODS: This is a single-centre, retrospective cohort study. Non-Hodgkin's lymphoma patients who received CHOP-based chemotherapy with pegfilgrastim between January 2007 and May 2009 were identified through the Singapore Lymphoma Registry. Patient demographics, past and present medical history, cancer treatment history and laboratory parameters were collected from electronic databases and medical records. In this study, patients did not receive oral antibiotic prophylaxis along with chemotherapy. RESULTS: A total of 132 patients were included in the final analysis. Median age of patients was 55 years. The incidence of breakthrough FN among patients in cycle 1 and across all cycles was 4.5% and 13.6%, respectively (n = 132). 3.3% (n = 60) of the patients receiving dose-dense chemotherapy had breakthrough FN, and this was 22.2% (n = 72) in patients receiving standard dose chemotherapy. Administration of chemotherapy every 21 days (adjusted OR = 12.1, p = 0.009) and patients with positive blood cultures (adjusted OR = 18.1, p = 0.001) were strongly associated with the occurrence of breakthrough FN. CONCLUSION: Despite routine administration of pegfilgrastim with CHOP chemotherapy, a high proportion of patients experienced FN after chemotherapy. Identifying patients at risk for breakthrough FN events may allow the optimization of myeloid growth factor usage among lymphoma patients receiving chemotherapy.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Linfoma no Hodgkin/complicaciones , Neutropenia/tratamiento farmacológico , Premedicación/métodos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Cohortes , Femenino , Fiebre , Filgrastim , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neutropenia/prevención & control , Polietilenglicoles , Proteínas Recombinantes , Estudios Retrospectivos , Factores de Riesgo
14.
OTO Open ; 5(2): 2473974X211010408, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33948529

RESUMEN

OBJECTIVES: There is a lack of evidence-based guidelines with regard to eye protection for aerosol-generating procedures in otolaryngology practice. In addition, some recommended personal protective equipment (PPE) is not compatible with commonly used ENT equipment. This study aims to investigate the degree of eye protection that commonly used PPE gives. STUDY DESIGN: Simulation model. SETTING: Simulation laboratory. METHODS: A custom-built setup was utilized to simulate the clinical scenario of a patient cough in proximity of a health care worker. A system that sprays a xanthan-fluorescein mixture was set up and calibrated to simulate a human cough. A mannequin with cellulose paper placed on its forehead, eyes, and mouth was fitted with various PPE combinations and exposed to the simulated cough. The degree of contamination on the cellulose papers was quantified with a fluorescent microscope able to detect aerosols ≥10 µm. RESULTS: When no eye protection was worn, 278 droplets/aerosols reached the eye area. The use of the surgical mask with an attached upward-facing shield alone resulted in only 2 droplets/aerosols reaching the eye area. In this experiment, safety glasses and goggles performed equally, as the addition of either brought the number of droplets/aerosols reaching the eye down to 0. CONCLUSION: When used with an upward-facing face shield, there was no difference in the eye protection rendered by safety goggles or glasses in this study. Safety glasses may be considered a viable alternative to safety goggles in aerosol-generating procedures.

15.
Chem Biol Drug Des ; 97(5): 1048-1058, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33455074

RESUMEN

Cholinesterase inhibitors remain the mainstay of Alzheimer's disease treatment, and the search for new inhibitors with better efficacy and side effect profiles is ongoing. Virtual screening (VS) is a powerful technique for searching large compound databases for potential hits. This study used a sequential VS workflow combining ligand-based VS, molecular docking and physicochemical filtering to screen for central nervous system (CNS) drug-like acetylcholinesterase inhibitors (AChEIs) amongst the 6.9 million compounds of the CoCoCo database. Eleven in silico hits were initially selected, resulting in the discovery of an AChEI with a Ki of 3.2 µM. In vitro kinetics and in silico molecular dynamics experiments informed the selection of an additional seven analogues. This led to the discovery of two further AChEIs, with Ki values of 2.9 µM and 0.65 µM. All three compounds exhibited reversible, mixed inhibition of acetylcholinesterase. Importantly, the in silico physicochemical filter facilitated the discovery of CNS drug-like compounds, such that all three inhibitors displayed high in vitro blood-brain barrier model permeability.


Asunto(s)
Acetilcolinesterasa/química , Butirilcolinesterasa/química , Inhibidores de la Colinesterasa/química , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Animales , Sitios de Unión , Butirilcolinesterasa/metabolismo , Dominio Catalítico , Inhibidores de la Colinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Bases de Datos de Compuestos Químicos , Donepezilo/química , Donepezilo/metabolismo , Donepezilo/uso terapéutico , Electrophorus/metabolismo , Caballos/metabolismo , Cinética , Simulación de Dinámica Molecular , Permeabilidad/efectos de los fármacos
17.
Mutat Res ; 647(1-2): 52-8, 2008 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-18778721

RESUMEN

Embryonic stem cells (ESCs) are characterized by their broad developmental potential and the capacity to self-renew. The advent of high-throughput technologies has facilitated genome-wide studies of transcriptional network, resulting in an ever-increasing repertoire of transcription factors implicated in the maintenance of the embryonic stem cell state. While the transcriptional circuitry continues to expand, epigenetic regulation has also gained attention as an important process in stem cell function. Herein, we discuss the recent advancements made in understanding the transcriptional and epigenetic regulations of embryonic stem cells.


Asunto(s)
Células Madre Embrionarias/fisiología , Epigénesis Genética , Transcripción Genética , Metilación de ADN , Regulación de la Expresión Génica , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina , Proteínas del Grupo Polycomb , Proteína Metiltransferasas/metabolismo , Proteínas Represoras/metabolismo
18.
Otolaryngol Head Neck Surg ; 159(4): 743-749, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29807479

RESUMEN

Objective The degree of pneumatization of the temporal bone has implications in the pathophysiology and surgical considerations of many temporal bone disorders. This study aims to identify common pneumatization patterns in the petrous apex, mastoid, and infralabyrinthine compartments of the temporal bone. Variables associated with temporal bone pneumatization were also identified. Study Design Case series with chart review. Setting Single tertiary hospital. Subjects and Methods In total, 299 high-resolution computed tomography scans of the temporal bone performed on patients between 2013 and 2016 were reviewed. Only normal temporal bone scans in patients aged 13 years and older were included. Previously published grading systems were used to classify pneumatization patterns in the petrous apex, mastoid, and infralabyrinthine region. Results The most common pneumatization pattern in the petrous apex was group 2 (less than half of the petrous apex medial to the labyrinth is pneumatized), that in the mastoid was group 4 (hyperpneumatization), and that in the infralabyrinthine region was type B (limited pneumatization), at 54.8%, 55.4%, and 76.0% of patients, respectively. Patients with increased pneumatization of 1 temporal bone compartment tended to have increased pneumatization of the same compartment on the contralateral side and the other compartments on the ipsilateral side ( P < .05). Younger age ( P < .001) and male sex ( P = .001) were associated with increased pneumatization in the petrous apex and infralabyrinthine compartments. Conclusion The degree of temporal bone pneumatization varies among the different compartments. Age and sex have a significant association with the degree of pneumatization of the petrous apex and infralabyrinthine compartment.


Asunto(s)
Enfermedades Óseas/diagnóstico por imagen , Enfermedades Óseas/patología , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/patología , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Resorción Ósea/clasificación , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Centros de Atención Terciaria , Adulto Joven
19.
J Biotechnol ; 131(4): 466-72, 2007 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-17825935

RESUMEN

A key challenge in molecular breeding of orchids is the creation of efficient and reproducible gene transformation systems. In this study, we report a new transformation method utilizing L-methionine sulfoximine (MSO) as a novel agent for selection of transgenic Dendrobium hybrids D. Madame Thong-In and D. Chao Praya Smile with the bialaphos resistance (bar) gene as a selectable marker. Gene transformation was performed by biolistic bombardment with a 4-day recovery period on MSO-free medium and two selection stages on media with increasing amounts of selection agent, using concentrations of 5 and 10 microM MSO for D. Madame Thong-In, and 0.5 and 2 microM MSO for D. Chao Praya Smile. Independent transgenic orchid lines were obtained and the presence of the transgene was confirmed by PCR and Southern blot analysis. Because of substantial time and economic savings, the new transformation system using MSO as a selection agent will facilitate functional studies on orchid genes and genetic engineering of orchids with commercially valuable traits.


Asunto(s)
Dendrobium/efectos de los fármacos , Dendrobium/genética , Metionina Sulfoximina/farmacología , Transformación Genética/efectos de los fármacos , Plantas Modificadas Genéticamente , Reacción en Cadena de la Polimerasa
20.
Head Neck ; 39(2): 297-304, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27696557

RESUMEN

BACKGROUND: There are reports about the changing epidemiology of tongue squamous cell carcinoma (SCC), with recent reports indicating an increasing incidence in young women. METHODS: Data on incident cases of tongue SCC were collected from cancer registries worldwide. RESULTS: Data from a total of 22 cancer registries and 89,212 incident cases of tongue SCC worldwide were included. Most areas experienced an incidence increase ranging from 0.4% to 3.3% per year. There was a significant difference in the incidence increase between sexes in 11 of the 22 registries. In 14 of the 22 registries studied, the increase in incidence of tongue SCC was higher in the group of subjects <45 years old than those ≥45 years old. CONCLUSION: This study suggests a general but not universal increase in the incidence of tongue SCC worldwide. In some regions of the world, we observed a shifting trend toward women and/or younger patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 297-304, 2017.


Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Salud Global , Neoplasias de Cabeza y Cuello/epidemiología , Sistema de Registros , Neoplasias de la Lengua/epidemiología , Adulto , Distribución por Edad , Carcinoma de Células Escamosas/diagnóstico , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/epidemiología , Prevalencia , Pronóstico , Medición de Riesgo , Programa de VERF , Distribución por Sexo , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Lengua/diagnóstico , Adulto Joven
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