RESUMEN
Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.
RESUMEN
OBJECTIVES: In observational studies, caffeine has been associated with a lower risk of obesity. However, whether the associations are causal and apply to coffee, which is a mixture of chemical compounds is unclear. DESIGN: Two sample Mendelian randomization study. SETTING AND PARTICIPANTS: Genetic instruments predicting caffeine were extracted from an existing GWAS of serum metabolites in 1960 individuals of European descent. For coffee consumption up to 91,462 individuals of European ancestry with top SNPs followed-up in ~30,062 coffee consumers and up to 375,833 individuals of European ancestry were taken from two separate studies. Genetic associations with obesity classes (n= 263,407), waist-to-hip ratio (WHR) (n=210,086), waist circumference (WC) (n= 231,355), and hip circumference (HC) (n=211,117) were obtained from summary statistics of individuals of European ancestry from the Genetic Investigation of Anthropocentric Traits (GIANT). METHODS: The inverse-variance weighted method (IVW) was used as the main analysis. We also employed the weighted median approach (WM) and MR-Egger regression as sensitivity analyses. To gauge evidence of directional pleiotropy, we used Cochrane's Q test, and MR-PRESSO global test, as measures of heterogeneity between ratio estimates of variants. RESULTS: There was little evidence to support an association between blood caffeine and any anthropometric measure of obesity in the primary and sensitivity analyses. However, genetically predicted coffee consumption was positively associated with higher class I obesity and WHR. Furthermore, this association was maintained after correction for multiple testing (P < 0.05/6 = 0.008). Results from the GWAS of coffee consumption were in tandem with results from the GWMA, but associations with class I obesity and waist to hip ratio (WHR) were not maintained after correction for multiple testing. CONCLUSION: We found little evidence that caffeine or coffee consumption protects against obesity, adding to growing literature suggesting that previous observational studies may have been confounded. This study demonstrates the dangers of ignoring genetic testing for targeted interventions and basing dietary policy recommendations solely on observational studies restricted to specific populations.
Asunto(s)
Cafeína , Café , Estudio de Asociación del Genoma Completo/métodos , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Obesidad/genética , Polimorfismo de Nucleótido SimpleRESUMEN
1. The aim of this trial was to determine the optimal supplementation level of a xylanase enzyme from Trichoderma citrinoviride on growth performance, apparent ileal and total tract nutrient retention, intestinal morphology, and intestinal concentration of volatile fatty acids in broiler chickens.2. A total of 600 broiler chickens (Ross 308) of mixed sex were randomly allotted to four treatments, on the basis of similar body weight. The dietary treatments were made from a corn-wheat-soy based diet supplemented with either 0, 3750, 7500, or 11 250 XU/kg xylanase and were fed to 32 d of age.3. A linear response to increasing dietary xylanase was demonstrated for overall weight gain (P < 0.05) and feed conversion ratio (P < 0.05). The apparent total tract digestibility of dry matter and gross energy, and the coefficient of apparent ileal digestibility (CIAD) of N and soluble non-starch polysaccharides were linearly improved when xylanase was added to the diet (P < 0.05). Moreover, a linear increase (P < 0.05) was observed in the CIAD of Arg, Lys, and Try with increasing dietary levels of xylanase.4. The viscosity of digesta in ileum was linearly decreased when dietary xylanase level increased (P < 0.05).5. An increase in villus height of the duodenum and jejunum were observed with increasing dietary levels of xylanase (linear, P < 0.05).6. Overall, the results showed that the effects of dietary xylanase supplementation on broiler performance was determined through effects on nutrient availability and intestinal morphology.
Asunto(s)
Pollos , Trichoderma , Alimentación Animal/análisis , Animales , Digestión , PolisacáridosRESUMEN
BACKGROUND: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. PATIENTS AND METHODS: In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. RESULTS: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). CONCLUSION: XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number NCT01470443).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Biliar/patología , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Supervivencia sin Progresión , Tasa de Supervivencia , GemcitabinaRESUMEN
STUDY DESIGN: Retrospective study. OBJECTIVES: The objective of this study was to find out whether ossification of posterior longitudinal ligament (OPLL) characteristics, including size, shape and subtype, can be used to diagnose myelopathy using somatosensory evoked potential (SEP) in cervical OPLL patients. SETTING: Yonsei University College of Medicine, Seoul, Korea. METHODS: We retrospectively reviewed the medical records of 153 cervical OPLL patients who underwent SEP study. OPLL anterior-posterior (AP) diameter, area and involved longitudinal vertebral level were measured. OPLL was classified into subtypes according to longitudinal continuity and shape. Correlation analysis and receiver operating curve were used. RESULTS: Tibial SEP latency was significantly correlated with OPLL AP diameter (P=0.001), diameter occupying ratio (P=0.019), area (P=0.007), area occupying ratio (P=0.008), involved longitudinal vertebral level (P=0.028) and space available for the spinal cord (P=0.019). The cutoff values that were diagnostic for SEP prolongation suggesting myelopathy were 4.91 mm for OPLL AP diameter, 6.02 mm for space available for the spinal cord, 44.5% for diameter occupying ratio, 63.4 mm2 for area, 36.1% for area occupying ratio and level 2 for the involved longitudinal vertebral level. CONCLUSIONS: Our results revealed that tibial SEP latency was significantly correlated with OPLL size and suggested cutoff values of OPLL diameter (4.91 mm, 44.5%) and area (63.4 mm2, 36.1%) for early diagnosis of myelopathy. These results can help to establish treatment plans.
Asunto(s)
Potenciales Evocados Somatosensoriales , Osificación del Ligamento Longitudinal Posterior/diagnóstico por imagen , Osificación del Ligamento Longitudinal Posterior/fisiopatología , Enfermedades de la Médula Espinal/diagnóstico , Enfermedades de la Médula Espinal/fisiopatología , Diagnóstico Precoz , Femenino , Humanos , Masculino , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Osificación del Ligamento Longitudinal Posterior/complicaciones , Estudios Retrospectivos , Sensibilidad y Especificidad , Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/complicaciones , Nervio Tibial/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics.
Asunto(s)
Microglía/fisiología , Plasticidad Neuronal/fisiología , Animales , Trastorno del Espectro Autista/fisiopatología , Autofagia/fisiología , Encéfalo/metabolismo , Dendritas , Espinas Dendríticas/genética , Espinas Dendríticas/fisiología , Modelos Animales de Enfermedad , Ratones , Microglía/metabolismo , Neuronas/fisiología , Conducta Social , Sinapsis/fisiologíaRESUMEN
Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
Asunto(s)
Neoplasias de la Mama/genética , Mutación de Línea Germinal , Adulto , Proteína BRCA1/química , Proteína BRCA1/genética , Proteína BRCA2/química , Proteína BRCA2/genética , Estudios de Cohortes , Estudios Transversales , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Malasia , Linaje , Proteínas Supresoras de Tumor/química , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia-induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia-induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site. METHODS: We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naïve rats. RESULTS: Sig-1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0-3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3-6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naïve rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of αßmeATP. CONCLUSION: Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain.
Asunto(s)
Canales Iónicos Sensibles al Ácido/fisiología , Hiperalgesia/metabolismo , Isquemia/complicaciones , Dolor/metabolismo , Receptores Purinérgicos P2X/fisiología , Receptores sigma/fisiología , Adenosina Trifosfato/análogos & derivados , Animales , Etilenodiaminas , Miembro Posterior/irrigación sanguínea , Hiperalgesia/etiología , Isquemia/metabolismo , Masculino , Morfolinas , Dolor/etiología , Ratas , Ratas Sprague-Dawley , Receptor Sigma-1RESUMEN
A simple chemical method was established for inducing bioactivity of Ti metal. In the present study, two kinds of mixed acid solutions were used to treat Ti specimens to induce Ca-P formation. Following a strong mixed acid activation process, Ca-P coatings successfully formed on the Ti surfaces in the simulated body fluid. Strong mixed acid etching was used to increase the roughness of the metal surface, because the porous and rough surfaces allow better adhesion between Ca-P coatings and substrate. Nano-scale modification of titanium surfaces can alter cellular and tissue responses, which may benefit osseointegration and dental implant therapy. Some specimens were treated with a 5 M NaOH aqueous solution, and then heat treated at 600 °C in order to form an amorphous sodium titanate layer on their surface. This treated titanium metal is believed to form a dense and uniform bone-like apatite layer on its surface in a simulated body fluid (SBF). This study proved that mixed acid treatment is not only important for surface passivation but is also another bioactive treatment for titanium surfaces, an alternative to alkali treatment. In addition, mixed acid treatment uses a lower temperature and shorter time period than alkali treatment.
Asunto(s)
Ácidos/química , Materiales Biomiméticos/química , Durapatita/química , Titanio/química , Materiales Biomiméticos/metabolismo , Líquidos Corporales/metabolismo , Durapatita/metabolismo , Propiedades de SuperficieAsunto(s)
Bacteriemia/microbiología , Fusobacterium necrophorum/fisiología , Síndrome de Lemierre/microbiología , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Diagnóstico Diferencial , Fusobacterium necrophorum/efectos de los fármacos , Fusobacterium necrophorum/aislamiento & purificación , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Síndrome de Lemierre/diagnóstico , Síndrome de Lemierre/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Spinal astrocytes have emerged as important mechanistic contributors to the genesis of mechanical allodynia (MA) in neuropathic pain. We recently demonstrated that the spinal sigma non-opioid intracellular receptor 1 (σ1 receptor) modulates p38 MAPK phosphorylation (p-p38), which plays a critical role in the induction of MA in neuropathic rats. However, the histological and physiological relationships among σ1, p-p38 and astrocyte activation is unclear. EXPERIMENTAL APPROACH: We investigated: (i) the precise location of σ1 receptors and p-p38 in spinal dorsal horn; (ii) whether the inhibition of σ1 receptors or p38 modulates chronic constriction injury (CCI)-induced astrocyte activation; and (iii) whether this modulation of astrocyte activity is associated with MA development in CCI mice. KEY RESULTS: The expression of σ1 receptors was significantly increased in astrocytes on day 3 following CCI surgery. Sustained intrathecal treatment with the σ1 antagonist, BD-1047, attenuated CCI-induced increase in GFAP-immunoreactive astrocytes, and the treatment combined with fluorocitrate, an astrocyte metabolic inhibitor, synergistically reduced the development of MA, but not thermal hyperalgesia. The number of p-p38-ir astrocytes and neurons, but not microglia was significantly increased. Interestingly, intrathecal BD-1047 attenuated the expression of p-p38 selectively in astrocytes but not in neurons. Moreover, intrathecal treatment with a p38 inhibitor attenuated the GFAP expression, and this treatment combined with fluorocitrate synergistically blocked the induction of MA. CONCLUSIONS AND IMPLICATIONS: Spinal σ1 receptors are localized in astrocytes and blockade of σ1 receptors inhibits the pathological activation of astrocytes via modulation of p-p38, which ultimately prevents the development of MA in neuropathic mice.
Asunto(s)
Astrocitos/metabolismo , Hiperalgesia/metabolismo , Neuralgia/metabolismo , Receptores sigma/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Modelos Animales de Enfermedad , Ratones , Fosforilación , Nervio Ciático/lesiones , Receptor Sigma-1RESUMEN
The effect of thermo-cycling treatment on the bond strength and flexural strength of porcelain veneered zirconia was evaluated. After thermo-cycling treatment between 5 degrees C to 55 degrees C, porcelain-zirconia bond strength and zirconia flexural strength was not significantly affected. In the phase analyses using XRD after thermo-cycling treatment, both the experimental group and the control group showed only tetragonal phases. That is, the porcelain-zirconia bond strength and zirconia flexural strength were not affected by low temperature degradation. So low temperature aging treatment did not reduce the flexural strength and the effect of temperature applied to the aging treatment could beignorable.
RESUMEN
Mismatch specific endonuclease (MSE) method was used to detect natural polymorphisms in Pvs25 and Pv38 genes of Plasmodium vivax. Eighty seven patients with P. vivax were recruited in the Republic of Korea (ROK). Pvs25 and Pv38 genes were amplified by polymerase chain reaction (PCR), and the PCR amplicons were mixed with reference DNA sequences. Following the denaturation and gradual annealing, the product mixtures were cleaved by the MSE. Heteroduplex types were readily detected by gel electrophoresis, where extra bands with shorter sizes would appear from the cleavage. After MSE cleavage of 657- bp product from Pvs25 mixtures, three genotypes were detected, while Pv38 mixtures with 1220-bp products presented two genotypes in ROK isolates. After the MSE cleavage, the mismatched samples of Pvs25 and Pv38 were completely sequenced, and the results were in complete agreement with the MSE analyses. In conclusion, genotyping of Pvs25 and Pv38 with MSE cleavage could be a potential method for the high-throughput screening of the large field samples.
Asunto(s)
Endonucleasas , Técnicas de Genotipaje/métodos , Plasmodium vivax/clasificación , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Genotipo , Humanos , Malaria Vivax/parasitología , Plasmodium vivax/aislamiento & purificación , Polimorfismo Genético , República de Corea , Factores de TiempoRESUMEN
INTRODUCTION: Various techniques have been described deceased donor liver transplantation (DDLT) procurement. One is a technique whereby almost total dissection is done in the porta hepatis and perihepatic detachment is carried out before cross-clamping the donor aorta. In another approach, after the donor aorta is cross-clamped, rapid and minimal en bloc dissection is performed with minimal manipulation. We evaluated early posttransplant graft function among liver procurement techniques. METHOD: Between January 2008 and August 2012, we performed 45 consecutive adult DDLTs. One patient was excluded from this analysis due to early death from sepsis after transplantation. The 44 included patients were divided into two cohorts according to the procurement technique: A warm dissection (n = 23; 52%) and a cold dissection group (n = 21; 48%). We compared early posttransplant graft function using the aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-bil), and prothrombin time (PT) values of the two groups from the first to seventh postoperative day. RESULT: The AST values in the warm group were significantly greater than those in the cold group on postoperative days 3 and 5. In addition, the ALT values in the warm group were greater than those in the cold group on postoperative days 4, 5, and 6. Moreover, the T-bil values in the warm group were greater than those in the cold group on postoperative days 2, 3, 4, 5, 6, and 7. However, there were no differences in PT values. CONCLUSION: During liver procurement for DDLT, rapid en bloc procurement with minimal manipulation after clamping the donor aorta achieved better early graft function posttransplantation.
Asunto(s)
Trasplante de Hígado , Donantes de Tejidos , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de ProtrombinaRESUMEN
PURPOSE: The aim of the present study was to examine the clinical course of nonvascular hepatic ischemia following adult living donor liver transplantation (LDLT). METHODS: This retrospective study reviewed the medical records of 1782 patients who underwent LDLT from January 2003 to September 2010. Nine subjects (0.5%) suffered idiopathic hepatic parenchymal infarcts (IHPI) classified according to the morphology and extent of the infarcted area as peripheral or central. RESULTS: Increased levels of liver enzymes were observed in all IHPI patients. Liver cell damage closely correlated with the extent of the infarcted area. Most patients with peripheral-type IHPI showed favoarable spontaneous recovery, occasionally requiring liver support with plasmapheresis or a prolonged period. By contrast, 2 patients with central-type IHPI died due to progressive expansion of the infarcted area with subsequent graft failure. CONCLUSIONS: In the present study the incidence of IHPI following LDLT was 0.5%. The severity of the infarct depended upon its location and size; central-type IHPI showed a worse prognosis. Thus, special attention should be paid to patients showing a central-type infarction.
Asunto(s)
Trasplante de Hígado , Hígado/patología , Donadores Vivos , Humanos , Hígado/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: National Health Insurance (NHI) claim records could provide valuable data for epidemiological studies of asthma in Korea. The aim of this study is to estimate the prevalence of adult asthma and to investigate asthma-related healthcare use and prescription patterns in Korea over 5 years. METHODS: National Health Insurance claim records from January 1, 2006 to December 31, 2010 were analyzed in a retrospective, population-based study. Outcome measures included asthma prevalence, healthcare use, and prescription patterns over time, by type of hospital, and by medical specialty. Additionally, we assessed differences in healthcare use between newly diagnosed and previously diagnosed patients in 2009. RESULTS: Over 5 years, the prevalence of asthma among Korean adults increased from 4944 to 5707 cases per 100,000 population (from 3760 to 4445 in men and from 6108 to 6951 in women). Asthma-related outpatient visits decreased from 4.82 ± 8.02 to 3.44 ± 5.50. Approximately 3% of all patients were hospitalized and 2.4% received asthma-related emergency treatment each year. Pulmonary function tests were performed in 10-11% of patients an average of 1.3 times per year. Newly diagnosed patients experienced fewer asthma-related hospitalizations (1.78% vs 4.35%) and emergency department visits (0.80% vs 2.11%) than the previously diagnosed group. Prescriptions of inhaled corticosteroids-based inhalers were maintained with about 20% of average of all types of hospitals. CONCLUSIONS: The prevalence of asthma in Korea has increased over a recent 5-year period, and asthma is still suboptimally controlled. Public health strategies are needed to improve the management of asthma in adults.
Asunto(s)
Asma/economía , Asma/terapia , Bases de Datos Factuales , Revisión de Utilización de Seguros/economía , Programas Nacionales de Salud/estadística & datos numéricos , Honorarios por Prescripción de Medicamentos , Adulto , Asma/epidemiología , Femenino , Humanos , Revisión de Utilización de Seguros/tendencias , Cobertura del Seguro/tendencias , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/economía , Programas Nacionales de Salud/tendencias , Prevalencia , República de Corea , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. METHODS: We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. RESULTS: We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. CONCLUSION: Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455).
Asunto(s)
Cefalosporinas/efectos adversos , Cefalosporinas/farmacología , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad Inmediata/inducido químicamente , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Hipersensibilidad Inmediata/diagnóstico , Hipersensibilidad Inmediata/epidemiología , Incidencia , Pruebas Intradérmicas , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Distribución por Sexo , Adulto JovenRESUMEN
AIMS: Although hyperphagia is a common manifestation of diabetes mellitus, data on food craving in patients with diabetes are limited. This study compared food craving in patients with Type 2 diabetes mellitus and a control group without diabetes. METHODS: A total of 210 subjects (105 with Type 2 diabetes and 105 age-, sex- and BMI-matched control subjects) participated in two food craving surveys. The surveys were as follows: the General Food Cravings Questionnaire--Trait, which assesses the general trait of food craving; and the Food Cravings Questionnaire--State, which assesses the state of food craving or current desire for high-carbohydrate or high-fat foods in response to pictures of food. Follow-up Food Cravings Questionnaire--State surveys were administered approximately 3 months later to the subjects with diabetes. Survey results were analysed to assess relationships between food craving and glycaemic control. RESULTS: The General Food Cravings Questionnaire--Trait scores in the group with Type 2 diabetes and the control group were not significantly different. The group with Type 2 diabetes had higher carbohydrate craving scores, but lower fat craving scores, than the control group. Carbohydrate craving scores in subjects with diabetes were positively correlated with HbA(1c). In follow-up surveys, carbohydrate craving scores declined in patients with improved glycaemic control. CONCLUSIONS: The surveys showed that patients with Type 2 diabetes had higher carbohydrate cravings and lower fat cravings than the age-, sex- and BMI-matched control group. Carbohydrate craving in patients with diabetes was associated with poor glycaemic control.
Asunto(s)
Conducta Adictiva , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos , Carbohidratos de la Dieta/efectos adversos , Hiperglucemia/prevención & control , Cooperación del Paciente , Adulto , Anciano , Índice de Masa Corporal , Señales (Psicología) , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Grasas de la Dieta/efectos adversos , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Sobrepeso/complicaciones , República de Corea , Caracteres SexualesRESUMEN
The aim of the present study was to evaluate the anxiolytic effects of the ethanol extract of Cirsium japonicum (CJ) in mice. The extract was orally administered at dosages of 50, 100, 200, or 400 mg/kg of body weight. The CJ-induced behavioral changes were assessed using the open-field and elevated-plus maze test. The ethanol extract of CJ did not affect overall locomotor activity of mice in the open-field test, however, it showed increase exploration in the unprotected center zone, which is thought to reflect anxiolyticlike effects. Furthermore, the CJ extract (100 and 200 mg/kg) significantly increased the percentage of time spent in the open arms of the elevated plus-maze, indicating the anxiolytic effects of the substance. This anxiolytic effects of the extract were comparable to that of the benzodiazepine, diazepam. To further characterize the anxiolytic activities of CJ, its action on human neuroblastoma cells were assessed. The CJ extract dose-dependently increased chloride ion (Cl(â)) influx, which was blocked by coadministration of the GABA(A) receptor competitive antagonist, bicuculline, suggesting a GABA(A) receptor - Cl(â)) channel mechanism of action. Taken altogether, the present study demonstrates that the ethanol extract of CJ has anxiolytic effects, probably mediated through GABAergic neurotransmission.
Asunto(s)
Ansiolíticos/farmacología , Cloruros/metabolismo , Cirsium/química , Extractos Vegetales/farmacología , Receptores de GABA-A/metabolismo , Animales , Ansiolíticos/aislamiento & purificación , Ansiolíticos/uso terapéutico , Línea Celular Tumoral , Canales de Cloruro/metabolismo , Relación Dosis-Respuesta a Droga , Etanol/química , Humanos , Transporte Iónico , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Componentes Aéreos de las Plantas , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéuticoRESUMEN
AIMS: Dystrophic neurites are associated with ß-amyloid (Aß) plaques in the brains of Alzheimer's disease (AD) patients and are also found in some specific areas of normal, aged brains. This study assessed the molecular characteristics of dystrophic neurites in normal ageing and its difference from AD. METHODS: We compared the dystrophic neurites in normal aged human brains (age 20-70 years) and AD brains (Braak stage 4-6) by immunostaining against ChAT, synaptophysin, γ-tubulin, cathepsin-D, Aß1-16, Aß17-24, amyloid precursor protein (APP)-CT695 and APP-NT. We then tested the reproducibility in C57BL/6 mice neurone cultures. RESULTS: In normal, aged mice and humans, we found an increase in clustered dystrophic neurites of cholinergic neurones in CA1 regions of the hippocampus and layer II and III regions of the entorhinal cortex, which are the major and earliest affected areas in AD. These dystrophic neurites showed accumulation of sAPPα peptides cleaved from the amyloid precursor protein by α-secretase rather than Aß or C-terminal fragments. In contrast, Aß and APP-CTFs accumulated in the dystrophic neurites in and around Aß plaques of AD patients. Several experiments suggested that the accumulation of sAPPα resulted from ageing-related proteasomal dysfunction. CONCLUSIONS: Ageing-associated impairment of the proteasomal system and accumulation of sAPPα at cholinergic neurites in specific areas of brain regions associated with memory could be associated with the normal decline of memory in aged individuals. In addition, these age-related changes might be the most vulnerable targets of pathological insults that result in pathological accumulation of Aß and/or APP-CTFs and lead to neurodegenerative conditions such as AD.