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1.
J Clin Rheumatol ; 28(5): 257-264, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35697042

RESUMEN

BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades del Tejido Conjuntivo , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Miositis , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Masculino , Miositis/complicaciones , Miositis/diagnóstico , Pronóstico
2.
Br J Surg ; 105(13): 1759-1767, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30132797

RESUMEN

BACKGROUND: Clinical guidelines recommend endovenous laser ablation (EVLA) over surgery based on short-term evidence, yet there are few studies reporting mid- to long-term outcomes. The aim of this study was to report the 5-year outcomes from an RCT of surgery versus EVLA for treatment of symptomatic great saphenous varicose veins. METHODS: Patients with symptomatic varicose veins due to great saphenous vein (GSV) incompetence were followed up 5 years after enrolment in a randomized trial of either surgery (saphenofemoral junction ligation, GSV strip to the knee and multiple avulsions of varicosities) or EVLA plus multiple avulsions. Outcomes included: clinical recurrence, defined as new varicose veins greater than 3 mm in diameter; Venous Clinical Severity Score (VCSS); quality of life measured by means of Short Form 36, EuroQol Five Dimensions (EQ-5D™) and Aberdeen Varicose Vein Questionnaire (AVVQ); patient satisfaction; and duplex ultrasound examination (DUS) findings. RESULTS: Some 218 of the 276 patients enrolled in the trial (79·0 per cent) were available for follow-up. Clinical recurrence was more frequent following surgery than EVLA at 5 years (34·3 versus 20·9 per cent; P = 0·010). Both groups demonstrated sustained significant improvements at 5 years over baseline in VCSS (surgery: median (i.q.r.) 1 (0-2) from 4 (3-5), P < 0·001; EVLA: 0 (0-1) from 4 (3-5), P < 0·001), AVVQ (surgery: 4·59 (0·56-9·78) from 13·69 (9·81-18·11), P < 0·001; EVLA: 3·35 (0·17 to 6·55) from 12·73 (9·41-17·32), P < 0·001) and EQ-5D™ (surgery: 1·000 (0·796-1·000) from 0·859 (0·796-1·000), P = 0·002; EVLA: 1·000 (0·796-1·000) from 0·808 (0·796-1·000), P = 0·002). VCSS was better for EVLA than surgery at 5 years (P = 0·031). Technical success assessed by DUS remained high at 5 years (85·4 per cent for surgery and 93·2 per cent for EVLA; P = 0·074). DUS-detected anatomical patterns of recurrence differed between the groups. CONCLUSION: EVLA was more effective than surgery in preventing clinical recurrence 5 years after treatment of great saphenous varicose veins. Patient-reported outcome measures were similar. Registration number: NCT00759434 (http://www.clinicaltrials.gov).


Asunto(s)
Terapia por Láser/métodos , Vena Safena/cirugía , Várices/cirugía , Procedimientos Endovasculares/estadística & datos numéricos , Humanos , Satisfacción del Paciente , Estudios Prospectivos , Recurrencia , Reoperación/estadística & datos numéricos , Vena Safena/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex , Várices/diagnóstico por imagen , Procedimientos Quirúrgicos Vasculares/estadística & datos numéricos
3.
J Wound Care ; 26(3): 107-114, 2017 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-28277989

RESUMEN

OBJECTIVE: Dialkylcarbomoyl chloride (DACC)-coated dressings (Leukomed Sorbact and Cutimed Sorbact) irreversibly bind bacteria at the wound surface that are then removed when the dressing is changed. They are a recent addition to the wound care professional's armamentarium and have been used in a variety of acute and chronic wounds. This systematic review aims to assess the evidence supporting the use of DACC-coated dressings in the clinical environment. METHOD: We included all reports of the clinical use of DACC-coated dressings in relation to wound infection. Medline, Embase, CENTRAL and CINAHL databases were searched to September 2016 for studies evaluating the role of DACC-coated dressings in preventing or managing wound infections. RESULTS: We identified 17 studies with a total of 3408 patients which were included in this review. The DACC-coating was suggested to reduce postoperative surgical site infection rates and result in chronic wounds that subjectively looked cleaner and had less bacterial load on microbiological assessments. CONCLUSION: Existing evidence for DACC-coated dressings in managing chronic wounds or as a surgical site infection (SSI) prophylaxis is limited but encouraging with evidence in support of DACC-coated dressings preventing and treating infection without adverse effects.


Asunto(s)
Antibacterianos/administración & dosificación , Antiinfecciosos/administración & dosificación , Hidrocarburos Clorados/administración & dosificación , Apósitos Oclusivos , Infección de la Herida Quirúrgica/prevención & control , Atención Ambulatoria/métodos , Vendajes , Humanos , Cicatrización de Heridas
4.
Planta ; 243(5): 1115-28, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26794967

RESUMEN

MAIN CONCLUSION: The latex from Thevetia peruviana is rich in plant defense proteins, including a 120 kDa cysteine peptidase with structural characteristics similar to germin-like proteins. More than 20,000 plant species produce latex, including Apocynaceae, Sapotaceae, Papaveraceae and Euphorbiaceae. To better understand the physiological role played by latex fluids, a proteomic analysis of Thevetia peruviana (Pers.) Schum latex was performed using two-dimensional gel electrophoresis and mass spectrometry. A total of 33 proteins (86 %) were identified, including storage proteins, a peptidase inhibitor, cysteine peptidases, peroxidases and osmotins. An unusual cysteine peptidase, termed peruvianin-I, was purified from the latex by a single chromatographic step involving gel filtration. The enzyme (glycoprotein) was inhibited by E-64 and iodoacetamide and exhibited high specific activity towards azocasein (K m 17.6 µM), with an optimal pH and temperature of 5.0-6.0 and 25-37 °C, respectively. Gel filtration chromatography, two-dimensional gel electrophoresis, and mass spectrometry revealed that peruvianin-I possesses 120 kDa, pI 4.0, and six subunits (20 kDa). A unique N-terminal amino acid sequence was obtained to oligomer and monomers of peruvianin-I (1ADPGPLQDFCLADLNSPLFINGYPCRNPALAISDDF36). High-resolution images from atomic force microscopy showed the homohexameric structure of peruvianin-I may be organized as a trimer of dimers that form a central channel similar to germin-like proteins. Peruvianin-I exhibited no oxalate oxidase and superoxide dismutase activity or antifungal effects. Peruvianin-I represents the first germin-like protein (GLP) with cysteine peptidase activity, an activity unknown in the GLP family so far.


Asunto(s)
Látex/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacología , Thevetia/química , Antifúngicos/farmacología , Caseínas/metabolismo , Proteasas de Cisteína/aislamiento & purificación , Proteasas de Cisteína/metabolismo , Proteasas de Cisteína/farmacología , Evaluación Preclínica de Medicamentos/métodos , Látex/metabolismo , Espectrometría de Masas/métodos , Proteínas de Plantas/aislamiento & purificación , Proteómica/métodos
5.
Osteoporos Int ; 27(4): 1281-1386, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26856587

RESUMEN

Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one's genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.


Asunto(s)
Densidad Ósea/fisiología , Desarrollo Óseo/fisiología , Estilo de Vida , Osteoporosis/prevención & control , Absorciometría de Fotón/métodos , Envejecimiento/fisiología , Composición Corporal/fisiología , Medicina Basada en la Evidencia/métodos , Ejercicio Físico/fisiología , Humanos , Fenómenos Fisiológicos de la Nutrición/fisiología , Fracturas Osteoporóticas/prevención & control , Tomografía Computarizada por Rayos X/métodos , Soporte de Peso/fisiología
6.
Osteoporos Int ; 27(1): 367-76, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26510847

RESUMEN

UNLABELLED: The aim was to meta-analyze randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention. Meta-analysis showed a significant 15 % reduced risk of total fractures (summary relative risk estimate [SRRE], 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). INTRODUCTION: Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults. METHODS: A PubMed literature search was conducted for the period from July 1, 2011 through July 31, 2015. RCTs reporting the effect of calcium plus vitamin D supplementation on fracture incidence were selected from English-language studies. Qualitative and quantitative information was extracted; random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for total and hip fractures. Statistical heterogeneity was assessed using Cochran's Q test and the I (2) statistic, and potential for publication bias was assessed. RESULTS: Of the citations retrieved, eight studies including 30,970 participants met criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures (SRRE, 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. A limitation is that this study utilized data from subgroup analysis of the Women's Health Initiative. CONCLUSIONS: This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Calcio/uso terapéutico , Suplementos Dietéticos , Fracturas Osteoporóticas/prevención & control , Vitamina D/uso terapéutico , Quimioterapia Combinada , Humanos , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/tratamiento farmacológico , Fracturas Osteoporóticas/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo/métodos
7.
Eur Radiol ; 26(8): 2730-9, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26560725

RESUMEN

OBJECTIVES: To identify features of obstructive airway disease on sagittal reconstruction, compare the accuracy of findings to traditional imaging characteristics of COPD, and determine the fraction of additional cases identified using new characteristics. METHODS: The study was approved by the centre's Institutional Review Board and is HIPAA compliant. Two hundred sixteen patients with HRCT and spirometry within a 3-month window were included. Four radiologists evaluated each HRCT for traditional characteristics of COPD and new quantitative and qualitative features of obstruction on axial and sagittal reconstructions. Imaging characteristics were assessed for correlation with the spirometric diagnosis of obstructive airway disease. RESULTS: Quantitative and qualitative findings on sagittal reconstruction are highly specific for COPD (specificity >90 %). Features of hyperinflation on sagittal reconstruction are more accurate predictors of obstruction than traditional axial measures, with greater interobserver reliability (hyperinflation left hemidiaphragm: accuracy: 70.08 % ± 2.49 %; kappa: 0.511 versus traditional measures: accuracy: 62.00 % ± 5.38 %; kappa: 0.407). Sagittal reconstruction identified 27-70 % more patients with COPD than traditional axial findings (p < 0.05). CONCLUSIONS: Analysis of sagittal reconstruction enables greater accuracy and specificity in the diagnosis of obstructive airway disease compared to traditional measures on axial imaging. Use of sagittal reconstructions can help identify up to 70 % more patients with COPD than traditional imaging findings alone. KEY POINTS: • HRCT sagittal reconstruction is useful in the evaluation of obstructive lung disease. • Findings on sagittal reconstructions allow physicians to more accurately diagnose COPD. • Routine use of sagittal reconstructions increases the sensitivity for diagnosing COPD.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Espirometría , Adulto Joven
8.
NMR Biomed ; 28(3): 338-43, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25586623

RESUMEN

Lactate is a product of glucose metabolism. In tumour tissues, which exhibit enhanced glycolytic metabolism, lactate signals may be elevated, making lactate a potential useful tumour biomarker. Methods of lactate quantitation are complicated because of overlap between the lactate methyl doublet CH3 resonance and a lipid resonance at 1.3 ppm. This study presents the use of a selective homonuclear multiple quantum coherence transfer sequence (SelMQC-CSI), at 1.5 T, to better quantify lactate in the presence of lipids. Work performed on phantoms showed good lactate detection (49%) and lipid suppression (98%) efficiencies. To evaluate the method in the brain, the sequence was tested on a group of 23 patients with treated brain tumours, either glioma (N=20) or secondary metastases in the brain (N=3). Here it was proved to be of use in determining lactate concentrations in vivo. Lactate was clearly seen in SelMQC spectra of glioma, even in the presence of lipids, with high grade glioma (7.3 ± 1.9 mM, mean ± standard deviation) having higher concentrations than low grade glioma (1.9 ± 1.5 mM, p=0.048). Lactate was not seen in secondary metastases in the brain. SelMQC-CSI is shown to be a useful technique for measuring lactate in tumours whose signals are otherwise contaminated by lipid.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Ácido Láctico/análisis , Fantasmas de Imagen , Teoría Cuántica , Encéfalo/metabolismo , Encéfalo/patología , Humanos , Ácido Láctico/metabolismo , Lípidos/química , Imagen por Resonancia Magnética , Metaboloma
9.
Community Dent Health ; 32(2): 68-71, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26263597

RESUMEN

This paper describes a service evaluation of a dental treatment programme providing care to children not normally taken to the dentist. It explains the extension of the Back2School programme from the pilot phase and assesses if a mobile dental unit (MDU) can provide a high quality service. The public health competencies it illustrates include oral health improvement, developing and monitoring quality dental services, and collaborative working.


Asunto(s)
Atención Dental para Niños , Accesibilidad a los Servicios de Salud , Unidades Móviles de Salud , Poblaciones Vulnerables , Citas y Horarios , Niño , Preescolar , Análisis Costo-Beneficio , Atención Dental para Niños/economía , Atención Dental para Niños/normas , Atención Dental para Niños/estadística & datos numéricos , Restauración Dental Permanente/estadística & datos numéricos , Retroalimentación , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Londres , Evaluación de Necesidades , Calidad de la Atención de Salud , Seguridad , Clase Social , Odontología Estatal , Extracción Dental/estadística & datos numéricos , Poblaciones Vulnerables/estadística & datos numéricos
10.
West Indian Med J ; 65(1): 67-77, 2015 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-26645593

RESUMEN

BACKGROUND: African-Caribbean men, particularly Jamaican men, have one of the highest incidences of prostate cancer in the world. This cross-sectional study was conducted to investigate knowledge, attitudes, practices and factors associated with prostate cancer screening among men in western Jamaica. METHODS: A questionnaire was administered to men 40-93 years old during May to August 2007. The outcome variable of interest was previous prostate cancer screening. RESULTS: Approximately 35% of men were previously screened for prostate cancer. Men > 70 years were 93% less likely to be screened compared to men 40-49 years (95% CI: 0.01, 0.56). Men living in the parish of Trelawny were 10.5 times more likely not to be screened compared to men in St James (95% CI: 2.33, 47.17) and manual labourers were 5.5 times less likely to have been screened than non-manual labourers (95% CI: 0.97, 31.68). Men who had not been advised to have prostate cancer screening were 92% less likely to be screened than those advised (95% CI: 0.02, 0.29), and men who were not sure of how frequently screening should be conducted were 6.1 times more likely not to be screened compared to those who knew that screening should be conducted annually (95% CI: 1.10, 33.35). Men who visit healthcare providers only when they feel sick were 6.4 times more likely not to be screened compared to men who visit annually (95% CI: 1.63, 25.41). CONCLUSION: A substantial proportion of Jamaican men ≥ 40 years had never been screened for prostate cancer. Interventions should be instituted to make prostate cancer screening readily available and to promote active participation of men in these programmes especially men ≥ 70 years, men with less economic resources, and men who do not routinely visit a physician or health facility.

11.
Br J Surg ; 101(9): 1093-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24916467

RESUMEN

BACKGROUND: Endovenous laser ablation (EVLA) is a popular treatment for superficial venous insufficiency. Debate continues regarding the optimal management of symptomatic varicose tributaries following ablation of the main saphenous trunk. This randomized trial compared the 5-year outcomes of endovenous laser therapy with ambulatory phlebectomy (EVLTAP) with concomitant ambulatory phlebectomy, and EVLA alone with sequential treatment if required following a delay of at least 6 weeks. METHODS: Patients undergoing EVLA for great saphenous vein insufficiency were randomized to receive EVLTAP or EVLA alone with sequential phlebectomy, if required. Outcomes included disease-specific quality of life (QoL) (Aberdeen Varicose Vein Questionnaire; AVVQ), requirement for secondary procedures, clinical severity (Venous Clinical Severity Score; VCSS), residual and recurrent varicose tributaries, and generic QoL. Patients were followed up for 5 years. RESULTS: Fifty patients were randomized equally into two parallel groups. The EVLTAP group had lower VCSS scores at 12 weeks (median 0 (i.q.r. 0-1) versus 2 (0-2); P <0·001), and lower AVVQ scores at 6 weeks (median 7·9 (i.q.r. 4·1-10·7) versus 13·5 (10·9-18·1); P < 0·001) and 12 weeks (2·0 (0·4-7·7) versus 9·6 (2·2-13·8); P = 0·015). VCSS and AVVQ scores were equivalent by 1 year, but only after 16 of 24 patients in the EVLA group, compared with one of 25 in the EVLTAP group (P < 0·001), had received a secondary intervention. From 1 to 5 years both groups had equivalent outcomes. CONCLUSION: EVLA with either concomitant or sequential management of tributaries is acceptable treatment for symptomatic varicose veins, with both treatments achieving excellent results at 5 years. Concomitant treatment of varicosities is associated with optimal improvement in both clinical disease severity and QoL.


Asunto(s)
Terapia por Láser/métodos , Vena Safena/cirugía , Várices/cirugía , Insuficiencia Venosa/cirugía , Terapia Combinada , Estudios de Seguimiento , Humanos , Satisfacción del Paciente , Calidad de Vida , Resultado del Tratamiento
12.
Br J Surg ; 106(6): 800-801, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30973991
13.
Mol Psychiatry ; 18(5): 543-56, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22641180

RESUMEN

Schizophrenia is a chronic, severe and highly complex mental illness. Current treatments manage the positive symptoms, yet have minimal effects on the negative and cognitive symptoms, two prominent features of the disease with critical impact on the long-term morbidity. In addition, antipsychotic treatments trigger serious side effects that precipitate treatment discontinuation. Here, we show that activation of the trace amine-associated receptor 1 (TAAR1), a modulator of monoaminergic neurotransmission, represents a novel therapeutic option. In rodents, activation of TAAR1 by two novel and pharmacologically distinct compounds, the full agonist RO5256390 and the partial agonist RO5263397, blocks psychostimulant-induced hyperactivity and produces a brain activation pattern reminiscent of the antipsychotic drug olanzapine, suggesting antipsychotic-like properties. TAAR1 agonists do not induce catalepsy or weight gain; RO5263397 even reduced haloperidol-induced catalepsy and prevented olanzapine from increasing body weight and fat accumulation. Finally, TAAR1 activation promotes vigilance in rats and shows pro-cognitive and antidepressant-like properties in rodent and primate models. These data suggest that TAAR1 agonists may provide a novel and differentiated treatment of schizophrenia as compared with current medication standards: TAAR1 agonists may improve not only the positive symptoms but also the negative symptoms and cognitive deficits, without causing adverse effects such as motor impairments or weight gain.


Asunto(s)
Antipsicóticos/uso terapéutico , Peso Corporal/efectos de los fármacos , Depresión/tratamiento farmacológico , Receptores Acoplados a Proteínas G/agonistas , Esquizofrenia/complicaciones , Esquizofrenia/tratamiento farmacológico , Análisis de Varianza , Animales , Antipsicóticos/farmacología , Atención/efectos de los fármacos , Atención/fisiología , Benzodiazepinas/uso terapéutico , Cocaína/administración & dosificación , Condicionamiento Operante/efectos de los fármacos , Depresión/etiología , Modelos Animales de Enfermedad , Inhibidores de Captación de Dopamina/administración & dosificación , Electroencefalografía , Alucinógenos/toxicidad , Haloperidol/efectos adversos , Humanos , Macaca fascicularis , Imagen por Resonancia Magnética , Masculino , Recuerdo Mental/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microinyecciones , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Mutación , Olanzapina , Oocitos , Oxazoles/farmacocinética , Fenciclidina/toxicidad , Fenetilaminas/farmacocinética , Unión Proteica/efectos de los fármacos , Unión Proteica/genética , Pirrolidinonas/administración & dosificación , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G/genética , Refuerzo en Psicología , Esquizofrenia/etiología , Esquizofrenia/genética , Natación/psicología , Telemetría , Tritio/farmacocinética , Xenopus
14.
bioRxiv ; 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38352467

RESUMEN

Genome editing technologies have the potential to transform our understanding of how genetic variation gives rise to complex traits through the systematic engineering and phenotypic characterization of genetic variants. However, there has yet to be a system with sufficient efficiency, fidelity, and throughput to comprehensively identify causal variants at the genome scale. Here we explored the ability of templated CRISPR editing systems to install natural variants genome-wide in budding yeast. We optimized several approaches to enhance homology-directed repair (HDR) with donor DNA templates, including donor recruitment to target sites, single-stranded donor production by bacterial retrons, and in vivo plasmid assembly. We uncovered unique advantages of each system that we integrated into a single superior system named MAGESTIC 3.0. We used MAGESTIC 3.0 to dissect causal variants residing in 112 quantitative trait loci across 32 environmental conditions, revealing an enrichment for missense variants and loci with multiple causal variants. MAGESTIC 3.0 will facilitate the functional analysis of the genome at single-nucleotide resolution and provides a roadmap for improving template-based genome editing systems in other organisms.

15.
Mol Psychiatry ; 17(3): 242-66, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21894153

RESUMEN

Second-generation antipsychotics (SGAs), such as risperidone, clozapine and olanzapine, are the most common drug treatments for schizophrenia. SGAs presented an advantage over first-generation antipsychotics (FGAs), particularly regarding avoidance of extrapyramidal symptoms. However, most SGAs, and to a lesser degree FGAs, are linked to substantial weight gain. This substantial weight gain is a leading factor in patient non-compliance and poses significant risk of diabetes, lipid abnormalities (that is, metabolic syndrome) and cardiovascular events including sudden death. The purpose of this article is to review the advances made in the field of pharmacogenetics of antipsychotic-induced weight gain (AIWG). We included all published association studies in AIWG from December 2006 to date using the Medline and ISI web of knowledge databases. There has been considerable progress reaffirming previous findings and discovery of novel genetic factors. The HTR2C and leptin genes are among the most promising, and new evidence suggests that the DRD2, TNF, SNAP-25 and MC4R genes are also prominent risk factors. Further promising findings have been reported in novel susceptibility genes, such as CNR1, MDR1, ADRA1A and INSIG2. More research is required before genetically informed, personalized medicine can be applied to antipsychotic treatment; nevertheless, inroads have been made towards assessing genetic liability and plausible clinical application.


Asunto(s)
Antipsicóticos/efectos adversos , Aumento de Peso/efectos de los fármacos , Antipsicóticos/clasificación , Antipsicóticos/farmacocinética , Apetito/genética , Monoaminas Biogénicas/metabolismo , Transporte Biológico/genética , Biotransformación/genética , Enfermedades Cardiovasculares/etiología , Epigénesis Genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Metabolismo de los Lípidos/genética , Metaanálisis como Asunto , Síndrome Metabólico/etiología , Neurotransmisores/metabolismo , Obesidad/inducido químicamente , Obesidad/complicaciones , Obesidad/genética , Cooperación del Paciente , Medicina de Precisión , Receptores de Neurotransmisores/genética , Receptores de Neurotransmisores/metabolismo , Aumento de Peso/genética
16.
Eur Radiol ; 23(2): 428-34, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23052642

RESUMEN

OBJECTIVE: To determine the measurement reproducibility of perfusion fraction f, pseudodiffusion coefficient D and diffusion coefficient D in colorectal liver metastases and normal liver. METHODS: Fourteen patients with known colorectal liver metastases were examined twice using respiratory-triggered echo-planar DW-MRI with eight b values (0 to 900 s/mm(2)) 1 h apart. Regions of interests were drawn around target metastasis and normal liver in each patient to derive ADC (all b values), ADC(high) (b values ≥ 100 s/mm(2)) and intravoxel incoherent motion (IVIM) parameters f, D and D by least squares data fitting. Short-term measurement reproducibility of median ADC, ADC(high), f, D and D values were derived from Bland-Altman analysis. RESULTS: The measurement reproducibility for ADC, ADC(high) and D was worst in colorectal liver metastases (-21 % to +25 %) compared with liver parenchyma (-6 % to +8 %). Poor measurement reproducibility was observed for the perfusion-sensitive parameters of f (-75 % to +241 %) and D (-89 % to +2,120 %) in metastases, and to a lesser extent the f (-24 % to +25 %) and D (-31 % to +59 %) of liver. CONCLUSIONS: Estimates of f and D derived from the widely used least squares IVIM fitting showed poor measurement reproducibility. Efforts should be made to improve the measurement reproducibility of perfusion-sensitive IVIM parameters.


Asunto(s)
Neoplasias Colorrectales/patología , Imagen de Difusión por Resonancia Magnética/métodos , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Adulto , Anciano , Algoritmos , Estudios de Casos y Controles , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Perfusión , Estudios Prospectivos , Estándares de Referencia , Reproducibilidad de los Resultados
17.
AJR Am J Roentgenol ; 201(3): 550-4, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23971445

RESUMEN

OBJECTIVE: We retrospectively reviewed the CT findings of lower respiratory tract infection (LRTI) due to parainfluenza virus (PIV) to determine the imaging features of PIV infection and to identify any differences compared with the CT appearances of LRTIs due to respiratory syncytial virus (RSV), adenovirus, and influenza virus. MATERIALS AND METHODS: The imaging features of LRTI from PIV over a 51-month period were retrospectively reviewed. The specific CT findings and overall pattern of infection in patients with LRTI due to PIV were recorded and were then compared with the CT appearances of RSV, adenovirus, and influenza LRTIs using data from a previous study. RESULTS: Twenty-four chest CT examinations of 24 patients with PIV infection were analyzed. Tree-in-bud opacities were the most common finding (13/24, 54%), and the airway-centric pattern of disease--characterized by combinations of bronchial wall thickening, tree-in-bud opacities, and peribronchiolar consolidation (bronchitis, bronchiolitis, and bronchopneumonia)--was the most common pattern (16/24, 67%). In comparison with previous data on RSV, adenovirus, and influenza virus, PIV showed tree-in-bud opacities and airway-centric patterns significantly more often than adenovirus or influenza virus. PIV and RSV showed similar CT findings and patterns of disease. CONCLUSION: Despite varying CT appearances of PIV LRTI, it most often shows airway-centric disease and is similar to the appearance of RSV infection, both of which are members of the Paramyxoviridae family of viruses.


Asunto(s)
Infecciones por Paramyxoviridae/diagnóstico por imagen , Infecciones del Sistema Respiratorio/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Yohexol , Yopamidol , Masculino , Persona de Mediana Edad , Infecciones por Paramyxoviridae/virología , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estados Unidos
18.
Diabetes Res Clin Pract ; 196: 110230, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36563881

RESUMEN

AIM: To gain a better understanding of how the FreeStyle Libre (FSL) flash glucose monitor influences the eating habits and relationship with food of adults with type 1 diabetes (T1D). METHODS: Reflexive thematic analysis was conducted on fifteen semi-structured interviews conducted with adults with T1D, exploring their experiences of at least one year of FSL use. RESULTS: Four themes were constructed from the qualitative data: (1) Personal Food Story (what food represented before and after diabetes diagnosis), (2) New Opportunities (the FSL offered novel discoveries and increased self-confidence regarding food choices), (3) Body as a Machine (participants viewed their bodies as a collection of complex processes requiring continuous maintenance), and (4) re-evaluating Diabetes (participants expressed a shift in their expectations of themselves and their diabetes management). Although the FSL offered participants more freedom and flexibility with their eating, this was constrained by feeling forever under scrutiny from the data. CONCLUSIONS: Findings suggest the FSL influences users' eating habits, including when, why, what and how much they eat. Participants described both the positive and negative impact of these changes on their emotional wellbeing and relationship with diabetes, arguing for a need to address patients' relationship with food in routine clinic care.


Asunto(s)
Diabetes Mellitus Tipo 1 , Humanos , Adulto , Glucemia , Automonitorización de la Glucosa Sanguínea , Conducta Alimentaria
19.
MethodsX ; 10: 102088, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36926266

RESUMEN

Soil organic matter (SOM) constitutes roughly 60% organic carbon (OC) and therefore plays a crucial role in regulating global climate. However, our understanding of the long-term dynamics of the soil carbon pool remains constrained by limitations in analytical approaches capable of providing high resolution molecular-level information from arguably the most complex biomaterial on the planet. In this contribution, we combine hydrofluoric acid (HF) treatment with a spectroscopic approach as a strategy to provide refined molecular-level information on the interactions between soil minerals and SOM. Critically, we have not seen the use of this combined approach anywhere in the literature and strongly believe that it could allow us to improve our overall understanding to the mechanisms and pathways that regulate SOM transformation. Results clearly illustrates which organic structures are preferentially adsorbed to soil minerals and are likely to be protected from degradation, as well as spatial co-variations of SOM with specific mineral components such as Al3+, Si4+ and dibasic cations such as Mg2+as a function of their importance in the interaction process.•Soil samples were collected from different land-use types in rural farming communities of the Upper Rio Grande Valley.•Samples were oven dried, disaggregated, sieved, treated with 10% HF, rinsed and oven dried.•Oven dried samples were subjected to Mid-infrared (4000-400 cm-1), XRD and ED-XRF analyses.

20.
Front Immunol ; 14: 1301991, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38173720

RESUMEN

Rationale: Sarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis. Methods: In this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability. Results: We identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases. Conclusion: Tregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity.


Asunto(s)
Linfadenopatía , Sarcoidosis , Humanos , Linfocitos T Reguladores , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Estudios Prospectivos , Antígeno Ki-67/metabolismo , Sarcoidosis/metabolismo , Pronóstico , Factores de Transcripción Forkhead/metabolismo
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