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OBJECTIVE: To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). METHODS: The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. RESULTS: The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P < 0.05), demonstrating POI-like changes. Compared with the control mice, oocyte-specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL- 2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P < 0.05). CONCLUSION: FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis.
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Insuficiencia Ovárica Primaria , Animales , Femenino , Humanos , Ratones , Apoptosis , Células de la Granulosa , Ratones Noqueados , Ratones Transgénicos , Insuficiencia Ovárica Primaria/genética , Proteínas Proto-Oncogénicas c-bcl-2 , Transducción de Señal , Serina-Treonina Quinasas TORRESUMEN
Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (â ¢ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (â ¢ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.
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Inflamación , Nomogramas , Neoplasias del Recto , Biomarcadores de Tumor , Antígeno Carcinoembrionario , Humanos , Inflamación/clasificación , Linfocitos , Neutrófilos , Periodo Preoperatorio , Pronóstico , Neoplasias del Recto/cirugía , Estudios RetrospectivosRESUMEN
Objective: To evaluate the feasibility, safety and efficacy of robotic-assisted lateral lymph node dissection for mid-low advanced rectal cancer. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) age between 18 and 80 years old; (2) rectal adenocarcinoma diagnosed by pathology; (3) without distant metastasis by preoperative CT or MRI; (4) patients underwent robotic-assisted total mesorectal resection (TME). Exclusion criteria: (1) conversion to open surgery; (2) multiple primary tumors; (3) patients underwent combined multiple organ resection. According to the above criteria, 137 patients undergoing robotic-assisted mid-low rectal cancer resection in the First Affiliated Hospital of Xi'an Jiaotong University from December 2016 to April 2019 were enrolled. Ninety-seven cases underwent robotic-assisted total mesorectal excision (TME group) and 40 underwent robotic-assisted total mesorectal resection with lateral lymph node dissection (LLND) (TME+LLND group, pelvic LLND was performed with neurovascular guidance to retain pelvic autonomic nerves in the order of the left side the first and then the right side). The propensity score matching of 1:1 was performed with R software, based on age, sex, BMI, ASA classification, distance from tumor to the anal verge, preoperative chemoradiotherapy history, preoperative abdominal surgery history, the size of tumors and TNM stage. The operative indicators, postoperative recovery, pathology and postoperative complications within 30 days were compared between the two groups. Results: A total of 72 cases were successfully matched (36 in each group), and there were no statistically significant differences in baseline data between the two groups (all P>0.05). The operation time of TME+LLND group was significantly longer than that of TME group [275.0 (180-405) minutes vs. 220.0 (140-320) minutes, Z=-3.680, P<0.001], while there were no statistically significant differences in blood loss during operation, time to postoperative first flatus, postoperative hospital stay, total hospital cost, tumor differentiation, and distal resection length of margin (all P>0.05). Circumferential resection margin was all negative in both groups. The number of harvested lymph modes in the TME+LLND groups was higher than that in the TME group [26 (18-37) vs. 14 (9-36), Z=-6.407, P<0.001]. In addition, there were no statistically significant differences in postoperative morbidity and Clavien-Dindo classification of complication within 30 days between the two groups (both P>0.05). Conclusions: Although robotic lateral lymph node dissection requires longer operation time, it is a feasible, safe and effective procedure.
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Proctectomía/métodos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados , Humanos , Laparoscopía , Escisión del Ganglio Linfático , Mesenterio/cirugía , Puntaje de Propensión , Neoplasias del Recto/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC). PATIENTS AND METHODS: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm. RESULTS: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29). CONCLUSION: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC.
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Algoritmos , Cistadenocarcinoma Papilar/tratamiento farmacológico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Aprendizaje Automático , Neoplasias Uterinas/tratamiento farmacológico , Anciano , Cistadenocarcinoma Papilar/patología , Cistadenocarcinoma Papilar/cirugía , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Femenino , Humanos , Estadificación de Neoplasias , Nomogramas , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugíaRESUMEN
BACKGROUND: Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential. AIM: To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications. METHODS: Colitis was induced in male Sprague-Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days. RESULTS: TNBS induced significant (p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited (p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited (p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated (p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited (p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated (p < 0.05) TNBS-induced colonic aberrations. CONCLUSION: Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-α and IL's), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).
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Alcaloides/farmacología , Benzodioxoles/farmacología , Colitis/prevención & control , Inhibidor NF-kappaB alfa/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Proteínas de Uniones Estrechas/metabolismo , Animales , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Citocinas/genética , Modelos Animales de Enfermedad , Alimentos Funcionales , Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Ácido Trinitrobencenosulfónico/toxicidadRESUMEN
SummaryRenal clear cell carcinoma is prone to distant metastasis, especially in the head and neck, but it is rare to transfer to infratemporal fossa and pterygopalatine fossa. We reported a 62-year-old male patient with complains of numbness and burning sensation on the left side of the face for more than 3 months. Left kidney removal was performed 8 years ago due to renal cancer. Preoperative enhancement CT showed a large blood-rich occupation in the left nasopharyngeal and pterygopalatine with adjacent paranasal sinus and skull base bone destruction. Under the general anesthesia, the anterior lacrimal recess approach was used for tumor resection. Preoperative interventional embolization of the feeding artery, intraoperative pathology, frozen section showed metastasis of renal cell carcinoma, and postoperative immunohistochemical examination, confirmed metastatic renal clear cell carcinomaï¼infratemporal fossa and pterygopalatine fossaï¼. The patients were transferred to the oncology department for further radiotherapy and chemotherapy.
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Carcinoma de Células Renales , Fosa Pterigopalatina , Neoplasias de la Base del Cráneo , Humanos , Neoplasias Renales , Masculino , Persona de Mediana Edad , Base del CráneoAsunto(s)
Asma/inmunología , Tos/fisiopatología , Leucotrienos/inmunología , Antiasmáticos , Asma/metabolismo , Tos/metabolismo , HumanosRESUMEN
The cancer stem cell (CSC) theory depicts a special population within the cancer mass that self-renew and sustain the cancer, even if the other cells were eliminated by therapies. How CSCs acquire these unique traits is still unclear. Crumbs homolog 3 (CRB3), a member of the CRB polarity complex, has been reported to act as a tumor suppressor. Here, we detected significantly lower or negative CRB3 expression in human breast cancer tissues. Knockdown of CRB3 generated non-tumorigenic, immortalized breast epithelial cell line MCF 10A with CSC properties. Simultaneously, we found that CRB3 downregulation induced the epithelial-mesenchymal transition and activated TAZ (transcriptional co-activator with PDZ-binding motif) and ß-catenin. Significantly, the activation of TAZ and ß-catenin sufficed in conferring MCF 10A cells with CSC properties. This study demonstrates that cell polarity proteins may serve as a switch of the differentiated vs multipotent states in breast cancers.
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Disruption of the endothelial barrier in response to Gram positive (G+) bacterial toxins is a major complication of acute lung injury (ALI) and can be further aggravated by antibiotics which stimulate toxin release. The integrity of the pulmonary endothelial barrier is mediated by the balance of disruptive forces such as the small GTPase RhoA, and protective forces including endothelium-derived nitric oxide (NO). How NO protects against the barrier dysfunction is incompletely understood and our goal was to determine whether NO and S-nitrosylation can modulate RhoA activity and whether this mechanism is important for G+ toxin-induced microvascular permeability. We found that the G+ toxin listeriolysin-O (LLO) increased RhoA activity and that NO and S-NO donors inhibit RhoA activity. RhoA was robustly S-nitrosylated as determined by biotin-switch and mercury column analysis. MS revealed that three primary cysteine residues are S-nitrosylated including cys16, cys20 and cys159. Mutation of these residues to serine diminished S-nitrosylation to endogenous NO and mutant RhoA was less sensitive to inhibition by S-NO. G+-toxins stimulated the denitrosylation of RhoA which was not mediated by S-nitrosoglutathione reductase (GSNOR), thioredoxin (TRX) or thiol-dependent enzyme activity but was instead stimulated directly by elevated calcium levels. Calcium-promoted the direct denitrosylation of WT but not mutant RhoA and mutant RhoA adenovirus was more effective than WT in disrupting the barrier integrity of human lung microvascular endothelial cells. In conclusion, we reveal a novel mechanism by which NO and S-nitrosylation reduces RhoA activity which may be of significance in the management of pulmonary endothelial permeability induced by G+-toxins.
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Toxinas Bacterianas/farmacología , Endotelio Vascular/metabolismo , Proteínas de Choque Térmico/farmacología , Proteínas Hemolisinas/farmacología , Compuestos Nitrosos/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Animales , Células COS , Calcio/metabolismo , Chlorocebus aethiops , Células Endoteliales/metabolismo , Células HEK293 , Humanos , Pulmón/irrigación sanguínea , Microvasos/metabolismo , Mutación , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/farmacología , Permeabilidad , Proteína de Unión al GTP rhoA/genéticaRESUMEN
OBJECTIVES: Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes. METHODS: Repeated measures of weight and height were collected from 5969 children 2-4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index (BMI) of 25 and 30 kg m(-)(2) at age 18. RESULTS: The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HL A, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (P for trend=0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age 4 (odds ratio, 2.41; 95% confidence interval, 1.21-4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes. CONCLUSIONS: The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children with genetic risk for type 1 diabetes.
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Autoanticuerpos/genética , Autoinmunidad/genética , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-DQ/genética , Obesidad Infantil/genética , Edad de Inicio , Peso al Nacer , Estatura , Índice de Masa Corporal , Peso Corporal , Preescolar , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/inmunología , Femenino , Finlandia/epidemiología , Predisposición Genética a la Enfermedad , Genotipo , Alemania/epidemiología , Humanos , Islotes Pancreáticos , Masculino , Tamizaje Masivo , Madres , Obesidad Infantil/epidemiología , Obesidad Infantil/inmunología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Suecia/epidemiología , Estados Unidos/epidemiologíaRESUMEN
AIMS/HYPOTHESIS: Viruses are candidate causative agents in the pathogenesis of autoimmune (type 1) diabetes. We hypothesised that children with a rapid onset of type 1 diabetes may have been exposed to such agents shortly before the initiation of islet autoimmunity, possibly at high dose, and thus study of these children could help identify viruses involved in the development of autoimmune diabetes. METHODS: We used next-generation sequencing to search for viruses in plasma samples and examined the history of infection and fever in children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study who progressed to type 1 diabetes within 6 months from the appearance of islet autoimmunity, and in matched islet-autoantibody-negative controls. RESULTS: Viruses were not detected more frequently in plasma from rapid-onset patients than in controls during the period surrounding seroconversion. In addition, infection histories were found to be similar between children with rapid-onset diabetes and control children, although episodes of fever were reported less frequently in children with rapid-onset diabetes. CONCLUSIONS/INTERPRETATION: These findings do not support the presence of viraemia around the time of seroconversion in young children with rapid-onset type 1 diabetes.
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Diabetes Mellitus Tipo 1/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Virus/genética , Autoinmunidad/genética , Autoinmunidad/inmunología , Preescolar , Diabetes Mellitus Tipo 1/virología , Femenino , Humanos , Lactante , Recién Nacido , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/metabolismo , Masculino , Virosis/genéticaRESUMEN
Precisely-controlled fabrication of single ZnO nanoemitter arrays and their possible application in low energy parallel electron beam exposure are reported. A well defined polymethyl methacrylate (PMMA) nanohole template was employed for local solution-phase growth of single ZnO nanoemitter arrays. Chlorine plasma etching for surface smoothing and pulsed-laser illumination in nitrogen for nitrogen doping were performed, which can significantly enhance the electron emission and improve the emitter-to-emitter uniformity in performance. Mechanisms responsible for the field emission enhancing effect are proposed. Low voltage (368 V) e-beam exposure was performed by using a ZnO nanoemitter array and a periodical hole pattern (0.72-1.26 µm in diameter) was produced on a thin (25 nm) PMMA. The work demonstrates the feasibility of utilizing single ZnO nano-field emitter arrays for low voltage parallel electron beam lithography.
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Cristalización/métodos , Nanoestructuras/química , Nanoestructuras/ultraestructura , Óxido de Zinc/química , Electrones , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
AIMS/HYPOTHESIS: Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study. METHODS: We genotyped the most disease-predicting single-nucleotide polymorphisms at the 18 susceptibility loci in 3,108 families and used existing genotype data for 2,319 families from the original study, providing 7,013 parent-child trios for analysis. We tested for association using the transmission disequilibrium test. RESULTS: Seventeen of the 18 susceptibility loci reached nominal levels of significance (p < 0.05) in the expanded family collection, with 14q24.1 just falling short (p = 0.055). When we allowed for multiple testing, ten of the 17 nominally significant loci reached the required level of significance (p < 2.8 × 10(-3)). All susceptibility loci had consistent direction of effects with the original study. CONCLUSIONS/INTERPRETATION: The results for the novel GWA study-identified loci are genuine and not due to population stratification. The next step, namely correlation of the most disease-associated genotypes with phenotypes, such as RNA and protein expression analyses for the candidate genes within or near each of the susceptibility regions, can now proceed.
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Diabetes Mellitus Tipo 1/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Población Blanca/genética , Genotipo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
The feasibility to detect lactobacilli in mail-in infant stools collected monthly from 3-18 months old children was investigated. The aim was to determine total lactobacilli and Lactobacillus plantarum (L. plantarum) content (ng/g feces) in 50 infants each from Colorado (648 samples), Finland (624 samples) and Sweden (685 samples) who participated in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. Total lactobacilli content varied markedly between 5 and 16,800 ng/g feces in the three clinical sites within and between individuals especially in infants. L.plantarum also varied markedly intra- and inter-individually from <0.5 - 736 ng/g feces. A higher variability of total lactobacilli was found before 10 months of age than after in the three different clinical sites. Sweden had the lowest total lactobacilli content compared to Colorado and Finland while the L.plantarum content was higher in Sweden. Mail-in stool samples from infants should prove useful in analyzing probiotics in childhood.
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OBJECTIVE: To examine the relationship between high-risk human leukocyte antigen (HLA) genotypes for type 1 diabetes and birth size in combination with prenatal ch aracteristics in different countries. STUDY DESIGN: Four high-risk HLA genotypes were enrolled in the Environmental determinants of Diabetes in the Young study newborn babies from the general population in Finland, Germany, Sweden and the United States. Stepwise regression analyses were used to adjust for country, parental physical characteristics and environmental factors during pregnancy. RESULT: Regression analyses did not reveal differences in birth size between the four type 1 diabetes high-risk HLA genotypes. Compared with DQ 4/8 in each country, (1) DQ 2/2 children were heavier in the United States (P=0.028) mostly explained however, by parental weight; (2) DQ 2/8 (P=0.023) and DQ 8/8 (P=0.046) children were longer in Sweden independent of parents height and as well as (3) in the United States for DQ 2/8 (P=0.023), but again dependent on parental height. CONCLUSION: Children born with type 1 diabetes high-risk HLA genotypes have comparable birth size. Longitudinal follow-up of these children should reveal whether birth size differences between countries contribute to the risk for islet autoimmunity and type 1 diabetes.
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Peso al Nacer , Estatura , Diabetes Mellitus Tipo 1/genética , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-DQ/genética , Padres , Peso Corporal , Femenino , Finlandia , Alemania , Humanos , Recién Nacido , Masculino , Embarazo , Factores de Riesgo , Suecia , Estados UnidosRESUMEN
We use the dynamical cluster approximation to understand the proximity of the superconducting dome to the quantum critical point in the two-dimensional Hubbard model. In a BCS formalism, T(c) may be enhanced through an increase in the d-wave pairing interaction (V(d)) or the bare pairing susceptibility (χ(0d)). At optimal doping, where V(d) is revealed to be featureless, we find a power-law behavior of χ(0d)(ω=0), replacing the BCS log, and strongly enhanced T(c). We suggest experiments to verify our predictions.
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The present study was conducted to assess genetic associations for type 1 diabetes (T1D) reported in previous genome-wide association studies (GWAS). A total of 21 previously reported single-nucleotide polymorphisms (SNPs) were genotyped by TaqMan assays in 1434 Caucasian T1D patients and 1864 normal controls from Georgia. Analysis of the samples identified 18 SNPs (PTPN22, INS, IFIH1, SH2B3, ERBB3, CTLA4, C14orf181, CTSH, CLEC16A, CD69, ITPR3, C6orf173, SKAP2, PRKCQ, RNLS, IL27, SIRPG and CTRB2) with putative association.
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Diabetes Mellitus Tipo 1/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple/genética , Adolescente , Edad de Inicio , Alelos , Niño , Mapeo Cromosómico , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Georgia/epidemiología , Humanos , Masculino , Población Blanca/genética , Adulto JovenRESUMEN
Hypoxia and exertion are considered as the two main factors in the development of high-altitude pulmonary oedema (HAPE), however its pathophysiology remains unclear. Therefore, we established a model in which 32 Sprague-Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise. An altitude of 4,700 m was simulated using hypobaric hypoxia, while exercise consisted 48 h walk with 15-20 min breaks every 4 h. Arterial blood gas, bronchoalveolar lavage (BAL), lung wet-to-dry weight (W/D) ratio and histological measurements were conducted on each animal. In rats exercising in hypoxia, BAL protein and lung W/D ratio were significantly increased but no changes in BAL leukotriene B(4) and immunoglobulin M were observed. In the same group, lung histology showed typical haemorrhagic lung oedema and disruption of both alveolar epithelium and capillary endothelium while hypoxia or exertion alone only induced slight endothelium and epithelium swelling/disruption. Our study established a direct link between histological and physiological evidence of HAPE-like symptoms and we demonstrated that hypoxia and exertion can synergistically induce HAPE-like symptoms in Sprague-Dawley rats without inducing lung inflammation. We therefore propose that alveolar epithelium and capillary endothelium stress failure play a major role in the development of HAPE.