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BACKGROUND: Abnormal tau proteins are independent contributors to cognitive impairment. Nevertheless, not all individuals exposed to high-level tau pathology will develop cognitive dysfunction. We aimed to construct a model to predict cognitive trajectory for this high-risk population. METHOD: Longitudinal data of 181 non-demented adults (mean age= 73.1; female= 45%), who were determined to have high cerebral burden of abnormal tau by cerebrospinal fluid (CSF) measurements of phosphorylated tau (ptau181) or total tau, were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Cognitive decline was defined as Mini-Mental State Examination scores decline ≥ 3 over three years. A predictive nomogram was constructed using stepwise backward regression method. The discrimination, calibration, and clinical usefulness of the nomogram were evaluated. The model was validated in another 189 non-demented adults via a cross-sectional set (n=149, mean age = 73.9, female = 51%) and a longitudinal set (n= 40, mean age = 75, female = 48%). Finally, the relationships of the calculated risk scores with cognitive decline and risk of Alzheimer's disease were examined during an extended 8-year follow-up. RESULT: Lower volume of hippocampus (odds ratio [OR] = 0.37, p< 0.001), lower levels of CSF sTREM2 (OR = 0.76, p = 0.003), higher scores of Alzheimer's Disease Assessment Scale-Cognitive (OR = 1.15, p = 0.001) and Functional Activities Questionnaire (OR = 1.16, p = 0.016), and number of APOE ε4 (OR = 1.88, p = 0.039) were associated with higher risk of cognitive decline independent of the amyloid status and were included in the final model. The nomogram had an area of under curve (AUC) value of 0.91 for training set, 0.93 for cross-sectional validation set, and 0.91 for longitudinal validation set. Over the 8-year follow-up, the high-risk group exhibited faster cognitive decline (p< 0.001) and a higher risk of developing Alzheimer's dementia (HR= 6.21, 95% CI= 3.61-10.66, p< 0.001 ). CONCLUSION: APOE ε4 status, brain reserve capability, neuroinflammatory marker, and neuropsychological scores can help predict cognitive decline in non-demented adults with high burden of tau pathology, independent of the presence of amyloid pathology.
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Disfunção Cognitiva , Proteínas tau , Humanos , Feminino , Masculino , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Idoso , Proteínas tau/líquido cefalorraquidiano , Estudos Longitudinais , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Estudos Transversais , Biomarcadores/líquido cefalorraquidiano , Nomogramas , Testes de Estado Mental e Demência , Pessoa de Meia-IdadeRESUMO
A molecular diagnostic assay which could be stored at room temperature was developed to rapidly detect Mycobacterium tuberculosis (MTB) based on loop-mediated isothermal amplification (LAMP) technology and dry-reagent process. LAMP uses 4 or 6 primers and Bst DNA polymerase to amplify DNA at a constant temperature. The results showed that the LAMP assay could detect the amplification of IS6110 target gene within 20 min using real-time fluorescence signal detection. The sensitive of LAMP assay was similar to the PCR technology while the precision of PCR was better than LAMP (coefficient of variation, LAMP 18.9%, PCR 3.4%), meaning LAMP was more suitable for qualitative detection. The LAMP assay did not amplify DNA of other 10 types of pathogens, including Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Rubivirus, mumps virus, adenovirus (type 3), adenovirus (type 7), respiratory syncytial virus B and parainfluenza virus type 2, indicating a good specificity. Furthermore, a dry-reagent assay was developed using air-drying and freeze-drying process. The performance of dried reagents did not change after 10 days storage at 50 â, meaning the dried reagents could be stored at room temperature (25 â) for more than six months. The dry-reagent LAMP assay also successfully amplified MTB DNA from several clinical samples within 20 min. In conclusion, the developed LAMP assay together with isothermal amplifier could rapidly detection MTB.
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Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Indicadores e Reagentes , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , DNARESUMO
Objective: To investigate frailty progress status and related factors in the elderly living in communities. Methods: A cohort of elderly people aged 65 and over in Pingyi community of Dujiangyan, Sichuan province, was established. Face-to-face questionnaire survey was conducted by trained interviewers. The frailty status, cognitive function, nutrition status and other functions of the subjects surveyed were evaluated at baseline survey and during follow-up. The socio-demographic and clinical characteristics of the subjects surveyed were assessed at baseline survey. Binary logistic regressions were used to identify factors associated with frailty progress. Results: A total of 653 elderly people were surveyed in January 2014, and 507 elderly people were followed up while 146 elderly people terminated further follow-up in January 2017. The prevalence rates of frailty and pre-frailty at baseline survey were 11.2% (n=57) and 26.2% (n=133), respectively. After 3 years, 205 subjects (40.4%) surveyed experienced frailty progress, 276 (54.5%) remained to be in frailty state at baseline survey, and 26 (5.1%) had improvement. Disability (OR=8.27, 95%CI: 1.62-42.26), visual problem (OR=2.02, 95%CI: 1.27-3.22), cognitive impairment (OR=1.94, 95%CI: 1.08-3.48), poor self-rated health (OR=1.89, 95%CI: 1.07-3.31), chronic pain (OR=1.57, 95%CI: 1.03-2.40) and older age (OR=1.12, 95%CI: 1.08-1.17) were independently associated with the progress of frailty. In contract, overweight was a protective factor (OR=0.54, 95%CI: 0.34-0.85). Conclusions: Frailty is a dynamic syndrome affected by several socio-demographic factors and geriatric factors. The results of the study can be used in the prevention of frailty progress in the elderly in communities.
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Idoso Fragilizado/estatística & dados numéricos , Fragilidade , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Idoso Fragilizado/psicologia , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Estudos Prospectivos , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
Objective: To explore the relationship between frailty syndrome and falls in the elderly diabetics, in the communities. Methods: A three-year cohort study involving 653 community-dwelling adults who were over 65 years of age and participated in the Survey of Disease, Psychological and Social Needs in Dujiangyan Pingyi Community. Diabetic patients would include those who self-reported as having histories of diabetes or on anti-hyperglycemic therapies. Frailty, functional and other geriatric status were assessed respectively. Falls was defined as having had multiple falls or at least one event but with injury. Results: The highest prevalence of falls was found in the group of frail diabetic group (62.5%). Data showed that baseline frailty was associated with falls in both diabetic and non-diabetic groups but the odds ratio in the diabetic group was higher than that of the non-diabetic group (OR=3.87, 95%CI: 1.45-10.28 vs. OR=6.68, 95%CI: 1.14-38.99). Conclusion: Frailty could be used as a strong clinical predictor to prevent falls, for the elderly diabetic Chinese living in the communities.
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Acidentes por Quedas/estatística & dados numéricos , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Vida Independente , Idoso , Estudos de Coortes , Avaliação Geriátrica/métodos , Humanos , Razão de Chances , Prevalência , Estudos Prospectivos , Medição de Risco/métodos , Inquéritos e Questionários , SíndromeRESUMO
The prevalence of pathogen inhibitors bacteria has motivate the study for antimicrobial compounds. Bioactive fungicide have always received considerable attention. A bacterial isolated strain HAB-5 showed antifungal activity against plant fungi. Based on morphological, physiological, biochemical and 16SrDNA sequence analysis, the strain was identified to be a Bacillus atrophaeus. This strain possessed a broad spectrum antifungal activity against various plant pathogenic fungi. Extraction of antifungal substance was performed and the crude extract had potent antifungal ability and showed great potential for swelling and inhibiting spore germination. This antifungal displayed heat stability and active in a wide pH range 5.0-10.0. Moreover no reduction was found in its activity after enzyme treatment. The toxicity test was evaluated in Danio rerio. The acute toxicity test indicated that the 24, 48, 72, 96h LC50 values of UMTLS to the zebrafish were 14.4, 13.8, 13.4, and 12.9%, respectively. Based on the results obtained in this study, antifungal substance was not toxic to zebra. Analyses of disease suppression showed that HAB-5 was effective to reduce the incidence of anthracnose symptoms on mango fruits, also prevent disease infection and protect tobacco seedling from Phytophtora nicotianae. The bioactive substance from Bacillus atrophaeus HAB-5 could be a candidate in the generation of new antifungal agents in crop.
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Antifúngicos/farmacologia , Bacillus/química , Colletotrichum/efeitos dos fármacos , Peixe-Zebra , Animais , Antifúngicos/toxicidade , Colletotrichum/fisiologia , Produtos Agrícolas/microbiologia , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Mangifera/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Esporos Fúngicos/efeitos dos fármacos , Testes de Toxicidade AgudaRESUMO
OBJECTIVE: This study was designed to investigate the clinical effects of adopting perforator pedicled propeller flap in the proper digital artery for treatment and sensory reconstruction of finger pulp defects in children. PATIENTS AND METHODS: Perforator pedicled propeller flap of proper digital arteries in thirty-one fingers from twenty-three children patients were selected for repairing the pulp defects on the 2nd to the 5th fingers. All cases were treated from September 2012 to December 2013. To properly reconstruct the pulps' feeling we needed the dorsal branch of the proper digital nerve in the flap to be consistent with the broken end of proper digital nerve in pulps' wound. A free skin graft was carried out with full-thickness skin taken from the medial thigh for flap donor area. We scheduled two post-operation return visits, one in six months and the second visit in twelve months following the operation. Parents' satisfaction with the postoperative appearance of their children's fingers was assessed based on Michigan Hand Outcome Questionnaire. RESULTS: All operations were performed successfully and all wounds healed in the first period and all flaps survived. During the final follow-up, the shape recovery of flaps and their donor areas were examined and satisfactory results were obtained. All pulps were full and round without any obvious pigmentation or scar contracture. The sensory recovery of pulps was achieved S3+, and the two-point discrimination was 4.5 to 6.0 mm (with 5.1 mm being the average value). Parents' satisfaction with the postoperative results was very promising with twenty-one cases of very satisfied and two cases of satisfied parents. CONCLUSIONS: The operation method used in this study demonstrated to be a safe and reliable procedure producing a very good flap blood supply as well as excellent sensory recovery and satisfactory postoperative appearance.
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Traumatismos dos Dedos/cirurgia , Retalho Perfurante/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Artérias , Criança , Pré-Escolar , Cicatriz/cirurgia , Feminino , Dedos/irrigação sanguínea , Mãos/cirurgia , Humanos , Masculino , Período Pós-Operatório , Pele , CicatrizaçãoRESUMO
Growing high-quality and uniform dielectric on black phosphorus is challenging since it is easy to react with O2 or H2O in ambient. In this work, we have directly grown Al2O3 on BP using plasma-enhanced atomic layer deposition (PEALD). The surface roughness of BP with covered Al2O3 film can reduce significantly, which is due to the removal of oxidized bubble in BP surface by oxygen plasma. It was also found there is an interfacial layer of PO x in between amorphous Al2O3 film and crystallized BP, which is verified by both X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) measurements. By increasing temperature, the PO x can be converted into fully oxidized P2O5.
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Objective: To summarize experiences of rescuing arterial hemorrhage and pseudoaneurysm caused by infection in donation after cardiac death (DCD) kidney transplantation. Methods: A total of 198 consecutive DCD kidney transplantations between 1 June 2013 and 30 July 2016 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The means of rescuing infective arterial hemorrhage and pseudoaneurysm after operation and their therapeutic effects were summarized. Results: A total of 5 infective arterial hemorrhage, 2 infective pseudoaneurysm with hemorrhage, and 1 infective pseudoaneurysm developed in 198 DCD kidney transplantation recipients with total morbidity of 4.0%, and the morbidity of fungal infection accounted for 2.5%. One case received open surgical therapy. Two cases were treated with endovascular interventional therapy. Five cases received combined treatments of open surgery and endovascular intervention. Selective antibiotics were used based on drug sensitivity test postoperation. The wound was drained, and the drainage was repeatedly cultured to monitor the pathogen till the results turned to negative. Five patients received graft nephrectomy and were restored to hemodialysis. Two patients were successfully rescued with stable graft function. One case died. The mortality of patient was 1/8. Graft loss rate was 5/8. Both patients with stable graft function were mainly treated by intervention. Conclusions: Infective arterial hemorrhage and pseudoaneurysm were primary risk factors causing patient/graft death postoperation in DCD kidney transplantation. Endovascular therapy can be used as an effective rescuing method under the circumstance of infection. The measure allows opportunity of successfully rescuing kidney graft and deserves recommendation.
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Transplante de Rim , Falso Aneurisma , Artérias , Morte , Sobrevivência de Enxerto , Hemorragia , Humanos , Rim , Micoses , Nefrectomia , Estudos Retrospectivos , Fatores de Risco , Doadores de TecidosRESUMO
ANK3, encoding the adaptor protein Ankyrin-G (AnkG), has been implicated in bipolar disorder by genome-wide association studies. ANK3 has multiple alternative first exons, and a bipolar disorder-associated ANK3 variant has been shown to reduce the expression of exon 1b. Here we identify mechanisms through which reduced ANK3 exon 1b isoform expression disrupts neuronal excitation-inhibition balance. We find that parvalbumin (PV) interneurons and principal cells differentially express ANK3 first exon subtypes. PV interneurons express only isoforms containing exon 1b, whereas excitatory principal cells express exon 1e alone or both 1e and 1b. In transgenic mice deficient for exon 1b, PV interneurons lack voltage-gated sodium channels at their axonal initial segments and have increased firing thresholds and diminished action potential dynamic range. These mice exhibit an Ank3 gene dosage-dependent phenotype including behavior changes modeling bipolar disorder, epilepsy and sudden death. Thus ANK3's important association with human bipolar susceptibility may arise from imbalance between AnkG function in interneurons and principal cells and resultant excessive circuit sensitivity and output. AnkG isoform imbalance is a novel molecular endophenotype and potential therapeutic target.
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Anquirinas/genética , Anquirinas/metabolismo , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Epilepsia/genética , Epilepsia/metabolismo , Adolescente , Processamento Alternativo , Animais , Transtorno Bipolar/patologia , Criança , Epilepsia/patologia , Éxons , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Interneurônios/metabolismo , Interneurônios/patologia , Camundongos , Camundongos Transgênicos , Parvalbuminas/metabolismo , Polimorfismo de Nucleotídeo Único , Isoformas de ProteínasRESUMO
OBJECTIVE: To explore the surgical method of using the modified chevron osteotomy combined distal soft tissue reconstruction to treat high-grade bunionette deformity. METHODS: From June 2013 to June 2015, the modified chevron osteotomy combined distal soft tissue reconstruction was used for surgical treatment of high-grade bunionette deformity in the Department of Hand and Foot Microsurgery in Xuzhou Central Hospital.Twenty-six patients with 28 feet high-grade bunionette deformity were hospitalized for treatment, with 3 male (3 feet) and 23 female (25 feet) cases, aged 22-73 (mean 47.1) years old.The average fourth-fifth intermetatarsal angle, lateral deviation of the fifth metatarsal angle and metatarsophalangeal-fifth angle were measured on the pre-and post- operative anterior to posterior weight-beating X rays of treated feet.The American Orthopaedic Foot and Ankle Society (AOFAS) Lesser Toe Metatarsophalangeal-Interphalangeal Scale was used to evaluate the post-operative outcomes. RESULTS: All of 26 patients were followed, with a mean 15.7 months (range 8-25 months). Primarily healing of the wound was achieved in all cases.No postoperative infection and nonunion on the osteotomy site was found during the follow-up time.The fracture healing time was 6-15 (mean 12.2) weeks.All the patients had satisfactory appearance and sensory function without callosum and metastatic metatarsalgia at the final follow-up.The post-operative fourth-fifth intermetatarsal angle, lateral deviation of the fifth metatarsal angle and metatarsophalangeal-fifth angle were significantly lesser than the pre-operative at the 6th week after operation, respectively [(5.5±1.7)°, (2.1±0.8)°, (5.7±2.6)°vs (16.4±4.2)°, (6.0±2.2)°, (10.5±7.4)°; all P<0.01]. The post-operative AOFAS score was significantly greater than the pre-operative [(87.1±6.7) vs (62.3±9.8) points, P<0.001]. CONCLUSION: The modified chevron osteotomy combined distal soft tissue reconstruction is a safe and easy treatment option for the high-grade bunionette deformity and provides patient satisfaction results.
Assuntos
Joanete do Alfaiate/cirurgia , Hallux Valgus/cirurgia , Ossos do Metatarso/cirurgia , Osteotomia/métodos , Feminino , Consolidação da Fratura , Hallux Valgus/diagnóstico por imagem , Humanos , Extremidade Inferior , Masculino , Ossos do Metatarso/diagnóstico por imagem , Satisfação do Paciente , Complicações Pós-Operatórias , Período Pós-Operatório , Radiografia , Resultado do TratamentoRESUMO
OBJECTIVE: To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac-death (DCD) kidney transplantation. METHODS: A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized. RESULTS: Ninety-one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group. CONCLUSIONS: Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation.
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Transplante de Rim , Micoses/prevenção & controle , Nefrectomia , Complicações Pós-Operatórias/virologia , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Cardiopatias/mortalidade , Hemorragia/virologia , Humanos , Rim , Lipopeptídeos/uso terapêutico , Micafungina , Artéria Renal , Estudos Retrospectivos , Doadores de Tecidos , Resultado do TratamentoRESUMO
Sirolimus (SRL)-based immunosuppressive regimens have been used for preventing rejection after kidney transplantation. This review analyzes their merits and demerits compared with other conventional regimes from the aspects of acute rejection rate, graft function, as well as patient/graft survival rates. In general, SRL is mostly recommended to be used as conversion therapy from calcineurin inhibitor (CNI) after kidney transplantation in most studies. Minimization or withdrawal of cyclosporine A (CsA) could also be considered when it was combined with SRL. SRL can replace mycophenolate mofetil (MMF), and the CNI dose should be reduced appropriately in this setting. Quadruple maintenance regimens containing SRL need future study to clarify their superiority. De novo use of low-dose CNI combined with SRL has no apparent merits and thus is not recommended. De novo use of standard-dose CNI combined with SRL followed by maintenance, de novo use of CNI-free regimens, as well as SRL use in delayed graft function (DGF) patients who spare antibody induction and postpone CNI administration should also be avoided. SRL supports steroids withdrawal after kidney transplantation, and SRL combined with tacrolimus is recommended in this setting. Loading dose is recommended when initiating SRL treatment and its trough blood level should be routinely monitored.
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Rejeição de Enxerto , Imunossupressores , Transplante de Rim , Sirolimo , Adulto , Feminino , Humanos , Masculino , Inibidores de Calcineurina/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Período Pós-Operatório , Sirolimo/uso terapêutico , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
The remarkable properties of graphene and transition metal dichalcogenides (TMDCs) have attracted increasing attention on two-dimensional materials, but the gate oxide, one of the key components of two-dimensional electronic devices, has rarely reported. We found the single-layer oxide can be used as the two dimensional gate oxide in 2D electronic structure, such as TiO2. However, the electrical performance is seriously influenced by the defects existing in the single-layer oxide. In this paper, a nondestructive and noncontact solution based on spectroscopic ellipsometry has been used to detect the defect states and energy level of single-layer TiO2 films. By fitting the Lorentz oscillator model, the results indicate the exact position of defect energy levels depends on the estimated band gap and the charge state of the point defects of TiO2.
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We sequenced the complete mitochondrial genome of Phalera flavescens. The mitogenome is 15,659 bp in length, including 13 protein-coding genes (atp6, atp8, cox1-3, nad1-6, nad4L, cob), two ribosomal RNAs (rrnS and rrnL), 22 transfer RNAs and an AT-rich region, a putative control region (D-loop). Gene order and orientation were found to be identical to those of other completely sequenced lepidopteran mitogenomes. All 13 protein-coding genes start with the common codon ATN, except for the cox1 gene, which uses CGA as the initial codon. Nine of the 13 protein-coding genes stop with codon TAA, while the cox1, cox2, nad5, and nad4 genes stop with the single nucleotide T. All tRNA genes can be folded into canonical cloverleaf secondary structure, except for trnS1, which loses the ''DHU'' arm. Six overlapping sequences totaling 20 bp (1-8 bp for each sequence) and 16 intergenic spacer sequences, totaling 276 bp (1-58 bp for each sequence) are scattered throughout the genome; the largest intergenic spacer is located between the trnQ and nad2 genes. A microsatellite-like structure (AT)(6)ACC(AT)(6) and 16-bp poly-T elements preceded by the ATTTA motif are present in the D-loop region. Additionally, unexpectedly, an extra 190-bp insertion, with unknown function, was found in the small subunit rRNA gene (rrnS); this gene is the longest known (1020 bp) among all of the Lepidoptera.
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Genoma Mitocondrial , Mariposas/genética , Sequência Rica em At , Animais , Sequência de Bases , Códon , Genes de Insetos , Sequências Repetidas Invertidas , Anotação de Sequência Molecular , Dados de Sequência Molecular , Fases de Leitura Aberta , RNA de Transferência/genética , Ribossomos/genética , Análise de Sequência de DNARESUMO
In adult cortices, the ratio of excitatory and inhibitory conductances (E/I ratio) is presumably balanced across a wide range of stimulus conditions. However, it is unknown how the E/I ratio is postnatally regulated, when the strength of synapses are rapidly changing. Yet, understanding of such a process is critically important, because there are numerous neuropsychological disorders, such as autism, epilepsy and schizophrenia, associated with disturbed E/I balances. Here we directly measured the E/I ratio underlying locally induced synaptic conductances in principal neurons from postnatal day 8 (P8) through 60. We found that (1) within each developmental period, the E/I ratio across four major cortical layers was maintained at a similar value under wide range of stimulation intensities; and (2) there was a rapid developmental decrease in the E/I ratio, which occurred within a sensitive period between P8 to P18 with exception of layer II/III. By comparing the excitatory and inhibitory conductances, as well as key synaptic protein expressions, we found a net increase in the number and strength of inhibitory, but not excitatory synapses, is responsible for the developmental decrease in the E/I ratio in the barrel cortex. The inhibitory markers were intrinsically co-regulated, gave rise to a sharp increase in the inhibitory conductance from P8 to P18. These results suggest that the tightly regulated E/I ratios in adults cortex is a result of drastic changes in relative weight of inhibitory but not excitatory synapses during critical period, and the local inhibitory structural changes are the underpinning of altered E/I ratio across postnatal development.
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Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Potenciais Pós-Sinápticos Excitadores , Potenciais Pós-Sinápticos Inibidores , Neurônios/fisiologia , Animais , Córtex Cerebral/efeitos dos fármacos , Técnicas In Vitro , Camundongos , Camundongos Transgênicos , N-Metilaspartato/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Fatores de Tempo , Valina/análogos & derivados , Valina/farmacologiaRESUMO
OBJECTIVE: Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months. METHODS: Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy. RESULTS: There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group. CONCLUSION: CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.
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Citocromo P-450 CYP3A/genética , Transplante de Rim/imunologia , Polimorfismo Genético , Tacrolimo/uso terapêutico , Adolescente , Adulto , Cadáver , Criança , Creatinina/sangue , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/patologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Tacrolimo/sangue , Doadores de Tecidos , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: Our aim was to evaluate the prognostic effect of peripheral blood lymphocyte subgroup CD4+ and CD8+ cells on renal transplant patients with cytomegalovirus (CMV) viremia. MATERIALS AND METHODS: Using 41 renal transplant patients with CMV-PCR(+) in peripheral blood and stable values of serum creatinine (SCr), we evaluated the changes in lymphocyte subgroup CD4+ and CD8+ cells with onset of antiviral therapy with gancyclovir for treatment of pneumonia. We compared patients with or without pneumonia. RESULTS: The lower the peripheral blood lymphocyte subgroup CD4+ and CD8+ cell numbers, the higher the incidence of CMV pneumonia. The numbers of CD4+ and CD8+ cells at 1 month posttransplantation and at the time of CMV-PCR(+) detection were significantly lower than those before transplantation in the CMV pneumonia group (P < .01) and also in the nonpneumonia group. CONCLUSIONS: The decrease in peripheral blood lymphocyte subgroup CD4+ and CD8+ cells after renal transplantation in patients with CMV viremia showed prognostic value for pneumonia. Increased CD4+ and CD8+ cells in peripheral blood combined with preemptive therapy may reduce the incidence of pneumonia among patients with CMV viremia.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/etiologia , Transplante de Rim/imunologia , Adulto , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Quimioterapia Combinada , Feminino , Ganciclovir/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Reação em Cadeia da Polimerase , PrognósticoRESUMO
This study prospectively compared immunoprophylaxis with a single dose of daclizumab versus no induction in kidney transplant recipients treated with a cyclosporine, mycophenolate mofetil, and prednisone-based immunosuppression regimen seeking to observe the impact of a single-dose regimen for prevention of acute rejection among Chinese renal allograft recipients. A total of 118 renal transplant recipients were randomized into a daclizumab induction therapy group (daclizumab group, n = 58) and a no induction group (control group, n = 60). The daclizumab group received a single-dose (1 mg/kg of ideal body weight by intravenous infusion) 2 hours before the operation. There was no induction therapy in the control group. There was no significant difference in the baseline parameters at randomization between the two groups. The mean time to the first episode of acute rejection was 41.2 +/- 3.2 days for the daclizumab group versus 11.2 +/- 4.6 days for the control group. The number of first biopsy-confirmed acute rejection episodes during the 6-months after transplantation was significantly different in the daclizumab (7,12.1%) versus the control group (14,23.3%; P < .001). At the end of 12 months, patient and graft survivals were 100% in the groups with or without daclizumab. We noted that the incidence of infection, including serious infection was similar, in the daclizumab group to that in the control group, 17.2% and 20.0%, respectively. This study showed that a single-dose of daclizumab effectively prevented acute rejection in Chinese renal allograft recipients.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Sobrevivência de Enxerto/fisiologia , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , China , Daclizumabe , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/efeitos adversos , Imunossupressores/efeitos adversos , Sobreviventes , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Transplante HomólogoRESUMO
We are the first to report the use of thymosin alpha1 to treat cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation. The patients were divided into the thymosin alpha1 group (Zadaxin group, n = 32) and the control group (n = 14). All patients received the same rescue therapy protocol. Suitable antiviral (ganciclovir, 5 mg/kg every 12 hours, intravenously), antibacterial, or antifungal treatment was given if needed. In addition, patients in the Zadaxin group received thymosin alpha1, (1.6 mg) subcutaneously every other day or every day. The rescue success rate was significantly higher in the Zadaxin than in the control group (78.1% vs 50.0%) while the death rate was greatly reduced (21.9% vs 50%). In the Zadaxin group, the CD4(+) lymphocyte level was significantly increased on day 14; so was the ratio of CD4(+) and CD8(+) T-lymphocyte subsets. In the survival group, CD4(+) and CD8(+) lymphocyte cell counts were significantly increased on days 7, 14, and 21 compared with admission. This study suggested that thymosin alpha1 significantly promoted CD4(+) and CD8(+) lymphocytes, repairing cellular immunity and successfully reinforcing resistance to cytomegalovirus disease.