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A novel Gram-stain-positive, aerobic, non-spore-forming, and rod-shaped bacterium designated as PW21was isolated from produced water sampled from an oil reservoir in Limbodara, Gujarat, India. Growth occurred at 30-45 °C (optimum 37 °C), at pH 6.5-9.5 (optimum pH 8.5) and in the presence of 0.5-5.0% (w/v) NaCl [optimum, 3% (w/v)]. Phylogenetic analysis based on the 16S rRNA gene sequences showed that PW21T belonged to the class Actinobacteria, order Actinomycetales, family Promicromonosporaceae, and genus Xylanimonas, with the highest sequence similarity to Isoptericola cucumis AP38 (97.95% with 98.8% completeness), followed by Xylanimonas pachnodae NBRC 107,786T (97.82%) and Xylanimonas allomyrinae 2JSPR-7T(97.75%) with 100% completeness for the mentioned strains of Xylanimonas. The genome size of PW21T was 3.4 Mbp with a G+C content of 73.0 mol% (draft genome sequence). The average nucleotide identity (ANI) value of the draft genomes between PW21T and related species were found in between 76.99 and 78.93%. Major cellular fatty acids (> 10% of total fatty acids) of PW21Twere iso-C15:0, anteiso-C15:0, and C16:0. Phylogenetic, physiological, and biochemical characterisation identified strain PW21T (= KCTC 49,338T = JCM 33,795T = MCC 3936T) as a novel species of the genus Xylanimonas, and hence, name Xylanimonas oleitrophica sp. nov. PW21T is proposed.
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Actinomycetales , Petróleo , Actinobacteria , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Ácidos Grasos , Hidrocarburos , Yacimiento de Petróleo y Gas , Fosfolípidos , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
Adult aging is associated with differences in structure, function, and connectivity of brain areas. Age-based brain comparisons have typically rested on the assumption that brain areas exhibit a similar spatial organization across age; we evaluate this hypothesis directly. Area parcellation methods that identify locations where resting-state functional correlations (RSFC) exhibit abrupt transitions (boundary-mapping) are used to define cortical areas in cohorts of individuals sampled across a large range of the human adult lifespan (20-93 years). Most of the strongest areal boundaries are spatially consistent across age. Differences in parcellation boundaries are largely explained by differences in cortical thickness and anatomical alignment in older relative to younger adults. Despite the parcellation similarities, age-specific parcellations exhibit better internal validity relative to a young-adult parcellation applied to older adults' data, and age-specific parcels are better able to capture variability in task-evoked functional activity. Incorporating age-specific parcels as nodes in RSFC network analysis reveals that the spatial topography of the brain's large-scale system organization is comparable throughout aging, but confirms that the segregation of systems declines with increasing age. These observations demonstrate that many features of areal organization are consistent across adulthood, and reveal sources of age-related brain variation that contribute to the differences.
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Envejecimiento/fisiología , Corteza Cerebral/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Adulto JovenRESUMEN
OBJECTIVE: To investigate which attributes of reproductive endocrinology and infertility (REI) fellowship applicants are most valued by fellowship program directors during the match process. STUDY DESIGN: An electronic survey was administered to determine characteristics most favored by program directors in the selection of REI fellows. A 5-point Likert scale was utilized to rank characteristics, with 1 being "most important" and 5 being" least important." The main outcome measures were factors desired by REI fellowship directors. RESULTS: The overall response rate was 61%. Objective factors that ranked highly were training at a competitive obstetrics and gynecology (OB/GYN) residency program, and clinical or basic science research experience. First authorship research ranked favorably regardless of whether it was in the form of a peer-reviewed paper, oral presentation, or poster abstract. Personal interview and perceived ability to work well with others were subjective factors considered favorably by REI fellowship directors. CONCLUSION: When selecting REI fellows for interviews, fellowship directors value candidates who have trained at competitive OB/GYN residency programs, who have clinical or basic science research experience, and who have contributed to scientific literature as first author. When subsequently ranking fellowship applicants, however, the most important factors are those found in the interview process, such as identification as a "team player".
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Becas , Ginecología/educación , Internado y Residencia , Obstetricia/educación , Criterios de Admisión Escolar , Humanos , Infertilidad , Masculino , Encuestas y CuestionariosRESUMEN
AIM: The aim of this study was to compare canal transportation and centering ability of Twisted files (TF) and ProTaper (PT) files with conventional stainless steel (SS) K files. MATERIALS AND METHODS: Thirty mandibular premolar teeth with root curvature of 25 to 35° were selected. The samples were randomly divided into three groups of 10 each according to the type of files used for instrumentation. Group I was instrumented using TF, group II with PT files according to the manufacturer's recommendations, and group III with samples prepared with pre-curved SS K files using a step-back technique. After preparation, the samples were assessed using spiral computed tomography. Three sections were recorded at coronal, middle, and apical levels. Amount of transportation was assessed comparing with preinstrumentation images. Centering ability was calculated using Gambill's formula. The three groups were statistically compared using Student's t-test. RESULTS: Twisted files showed the least canal transportation and the best centering ability followed by PT file system. Stainless steel K files showed the highest transportation and least centering ability. CONCLUSION: Twisted files showed the least amount of transportation and better centering compared with the other file systems. CLINICAL SIGNIFICANCE: The study gives information of TF, a recently introduced rotary system (2008) with regard to its efficacy in preparing curved root canals. This study has shown that the centering ratio of rotary nickel titanium was better than that of SS files.
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Instrumentos Dentales , Cavidad Pulpar/diagnóstico por imagen , Preparación del Conducto Radicular/instrumentación , Aleaciones Dentales , Diseño de Equipo , Humanos , Técnicas In Vitro , Acero Inoxidable , Tomografía Computarizada EspiralRESUMEN
Hydantoinase-mediated enzymatic synthesis of optically pure carbamoyl amino acids was investigated as an environmentally friendly, energy-efficient alternative to the otherwise energy-intensive, polluting chemical synthesis. Hydantoinase-producing bacterial strain was identified as Pseudomonas aeruginosa by 16S rRNA gene sequencing and biochemical profiling using the BIOLOG Microbial Identification System. Hydantoinase activity was assessed using hydantoin analogs and 5-monosubstituted hydantoins as substrates in a colorimetric assay. The hydantoinase gene was PCR amplified using gene-specific primers and sequenced on an automated gene analyzer. Hydantoinase gene sequence of P. aeruginosa MCM B-887 revealed maximum homology of only 87 % with proven hydantoinase gene sequences in GenBank. MCM B-887 resting cells converted >99 % of substrate into N-carbamoyl amino acids under optimized condition at 42 °C, pH 8.0, and 100 mM substrate concentration in <120 min. Hydantoin hydrolyzing activity was D-selective and included broad substrate profile of 5-methyl hydantoin, 5-phenyl hydantoin, 5-hydroxyphenyl hydantoin, o-chlorophenyl hydantoin, as well as hydantoin analogs such as allantoin, dihydrouracil, etc. MCM B-887 resting cells may thus be suitable for bio-transformations leading to the synthesis of optically pure, unnatural carbamoyl amino acids of industrial importance.
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Amidohidrolasas/metabolismo , Aminoácidos/metabolismo , Carbamatos/metabolismo , Hidantoínas/metabolismo , Pseudomonas aeruginosa/enzimología , Amidohidrolasas/genética , Aminoácidos/aislamiento & purificación , Biotransformación , ADN Bacteriano/genética , Concentración de Iones de Hidrógeno , Reacción en Cadena de la Polimerasa , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crecimiento & desarrollo , Especificidad por Sustrato , TemperaturaRESUMEN
OBJECTIVE: To determine if current recommendations for weight gain in twin pregnancies according to maternal prepregnancy body mass index (PPBMI) influence perinatal outcomes. METHODS: We identified women with twins enrolled in a maternity risk screening and education program with initial screening and prenatal care initiated at <20 weeks and delivery at >23.9 weeks. Women with normal, overweight, or obese PPBMI were included (n = 5129). Pregnancy outcomes were compared between those women with weight gain meeting or exceeding 2009 Institute of Medicine recommendations and patients who did not meet weight gain guidelines. RESULTS: Rates of spontaneous preterm delivery at <35 weeks were higher in all PPBMI groups for those with weight gain below guidelines. In all PPBMI groups, numbers of pregnancies with both infants weighing >2500 g or >1500 g were significantly higher for women gaining weight at or above guidelines. Logistic regression analysis was utilized to assess multivariate impact on outcome of spontaneous preterm delivery at <35 weeks showing that regardless of PPBMI level, women who gain below recommended guidelines are 50% more likely to deliver spontaneously at <35 weeks. CONCLUSION: In twin pregnancies, weight gain below recommended guidelines determined by maternal PPBMI is associated with higher rates of spontaneous preterm delivery at <35 weeks.
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Composición Corporal/fisiología , Índice de Masa Corporal , Peso Corporal/fisiología , Adhesión a Directriz/estadística & datos numéricos , Embarazo Gemelar/fisiología , Nacimiento Prematuro/etiología , Aumento de Peso/fisiología , Adulto , Femenino , Guías como Asunto , Humanos , Recién Nacido , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Estados UnidosRESUMEN
Aims and objectives: This study aimed to describe the application of low-cost inter-professional simulation over 4 phases in identifying structural and design issues, latent safety threats as well as test systems, processes, including facilitated team training during the design of a new pediatric intensive care unit (PICU). Materials and methods: The four-phase inter-professional simulation sessions involving clinical and non-clinical teams were conducted over a 3-month period in a corporate hospital during the designing of a new PICU. Low-cost resources, such as floor tapes, low-tech manikins, reused sterilized consumables, and actual patient beds and equipment, were used for the in situ simulation sessions. A plus-delta method of debriefing was done, and changes agreed on consensus were implemented after each simulated session. Results: There were 10 simulation sessions conducted over 4 phases during the 3-month period of designing the PICU. The participants included 10 doctors from PICU and adult critical care, 25 critical care nurses, 12 members from the project team, and 2 hospital administrators in various combinations. The first phase led to the re-design of workspace and clinical areas for better space utilization. The second phase required further revision to facilitate better mobility and facilities. In the third phase, the number of beds was reduced to 6 beds following the simulated drills involving the actual placement of patient cots and equipment. The fourth phase had thematic 5 simulated exercises involving the newly recruited clinical teams that enabled the identification of systems and process issues. Cognitive aids and video orientation of the setup, team training, and human factors training were addressed, and the unit was open for patient care in a week. Conclusion: A phased inter-professional simulation exercise with low-cost resources can enable the identification of structural challenges, design issues, latent safety threats, test systems, processes, patient flow, and facilitated team training during the design of a new PICU. Further studies are needed to understand the generalization of the study findings into designing PICU.
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A woman presented with virilization symptoms and elevated testosterone; however, a neoplastic source of excess androgen was not found on imaging. Eventually, the patient revealed she was exposed to transdermal testosterone used by her partner. This case highlights the importance of considering exogenous androgens in the differential diagnosis of virilization.
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Andrógenos/efectos adversos , Testosterona/efectos adversos , Virilismo/inducido químicamente , Femenino , Humanos , Adulto JovenRESUMEN
We sought to determine if outcomes of nulliparous twin pregnancies differ based on maternal age. Nulliparous women with current twin pregnancies were identified from a database of women enrolled for outpatient nursing surveillance. Data were stratified into four groups by maternal age: less than 20, 20 to 34, 35 to 39, and greater than or equal to 40 years. Maternal and neonatal outcomes for women less than 20, 35 to 39, and 40 or more were compared with 20- to 34-year-old controls using Kruskal-Wallis, Mann-Whitney, and Pearson chi-square analyses. We analyzed 2144 nulliparous twin pregnancies. Patients ≥35 years (34 to 39, 78.5% or ≥40, 85.9%) were more likely to have cesarean deliveries compared with controls 20 to 34 years old (71.2%). Women aged 35 to 39 were less likely to deliver at <37 weeks, and women in the ≥40 group were less likely to deliver at <35 weeks due to spontaneous preterm labor compared with the controls. Neonates born to women aged 35 to 39 had a greater gestational age at delivery and larger average birth weight than controls. Maternal and neonatal outcomes were not adversely influenced by advanced maternal age in nulliparous women carrying twin gestations.
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Peso al Nacer , Edad Materna , Resultado del Embarazo , Embarazo Múltiple , Adulto , Cesárea , Distribución de Chi-Cuadrado , Femenino , Edad Gestacional , Humanos , Trabajo de Parto Prematuro , Paridad , Embarazo , Estadísticas no Paramétricas , Gemelos , Adulto JovenRESUMEN
PURPOSE: Poor nutritional status has been associated with increased postoperative morbidity and mortality in surgical patients. The purpose of this study is to evaluate if decreased nutritional parameters correlate with increased postoperative complications regardless of other risk factors in the gynecologic cancer patient. METHODS: A retrospective chart review was performed among women who underwent surgical management for gynecologic malignancies from October 2006 to June 2008. Variables included age, race, medical comorbidities, cancer type/stage, preoperative albumin, absolute lymphocyte count (ALC), and body mass index (BMI), estimated blood loss (EBL), intraoperative blood transfusion (BT), intraoperative or postoperative complications, intensive care unit (ICU) admissions, hospital readmissions, reoperations, and cancer recurrence. RESULTS: Three hundred gynecologic oncology patients with preoperative nutritional parameters were included in the study. Decreased albumin was significantly associated with more postoperative complications (p < 0.001), hospital readmissions (p = 0.01), reoperations (p = 0.03), ICU admissions (p < 0.001), and cancer recurrence (p < 0.001). Decreased ALC and BMI preoperatively was also significantly associated with higher incidence of cancer recurrence (p = 0.01, p = 0.01). Surgical cases involving increased EBL (p = 0.01, p < 0.001) and more BT (p < 0.001, p < 0.001) had significantly more postoperative complications and more ICU admissions. Multivariable logistic regression found preoperative albumin to be an independent predictor of increased postoperative complications. CONCLUSIONS: Decreased albumin is significantly associated with more postoperative complications, hospital readmissions, reoperations, ICU admissions, and cancer recurrence. This nutritional parameter is an important predictor of postoperative morbidity and mortality. Thus, it is important to assess nutritional status preoperatively and offer nutritional support or alternate treatment options if necessary.
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Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/cirugía , Desnutrición/complicaciones , Estado Nutricional , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Transfusión Sanguínea , Índice de Masa Corporal , Enfermedades del Colon/etiología , Enfermedades del Colon/cirugía , Cuidados Críticos , Femenino , Humanos , Incidencia , Complicaciones Intraoperatorias , Modelos Logísticos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Readmisión del Paciente , Pronóstico , Reoperación , Estudios Retrospectivos , Albúmina Sérica/metabolismoRESUMEN
OBJECTIVE: To compare blood loss and need for blood transfusions in women who underwent abdominal myomectomies after receiving vasopressin or combined vasopressin and tourniquet. METHODS: A retrospective chart review was performed reviewing abdominal myomectomies that took place at our institution. Subjects were divided into three groups: no intervention, vasopressin, or combined vasopressin and tourniquet. Blood loss, need for blood transfusion, and drop in hemoglobin and hematocrit were compared across all groups. RESULTS: One-hundred and thirty-two subjects were included in the study. No statistically significant difference was found between groups in blood loss, drop in hemoglobin or hematocrit, or blood transfusions. CONCLUSION: Combined vasopressin and tourniquets was not associated with a statistically significant decrease in blood loss or need for blood transfusion.
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Pérdida de Sangre Quirúrgica , Hemostasis Quirúrgica/métodos , Leiomioma/cirugía , Torniquetes , Neoplasias Uterinas/cirugía , Vasopresinas/uso terapéutico , Adulto , Transfusión Sanguínea , Volumen Sanguíneo , Femenino , Hematócrito , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The burden of diabetes is higher in urban areas and among racial and ethnic minorities. The purpose of this research was to evaluate the effectiveness of extending a diabetes intervention program (DIP) by engaging a team, including a community health worker (CHW), to provide care for patients to meet glycemic control, specifically in a predominantly urban, minority patient population. The DIP enrolled diabetic patients from an internal medicine clinic. A CHW facilitated the collection of glucose meter readings. The CHW coached patients on glycemic control while the CHW's registered nurse partner titrated the patient's recommended insulin dose. Subsequent HbA1c values for participants were compared to those seen at the same clinic who were not enrolled. The DIP was deployed for nine months. One hundred forty-four patients were enrolled in the DIP and 348 patients constituted the comparator group. Ninety-three DIP participants had pre- and post-intervention HbA1c values and were compared to 348 non-DIP participants. Propensity score weighted adjusted analyses suggest that participants were more likely to reduce their HbA1c values by at least 1.0% and have HbA1c values of less than 8.0% (64 mmol/mol) than non-participants (adjusted odds ratio = aOR = 1.47, 95% CI 1.26-1.71, and aOR = 1.23, 95% CI 1.06-1.43, respectively). CHW coaches as part of a team in a clinical setting improved glycemic control in a predominantly urban, minority patient population.
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Overexpression of a novel hydantoinase (hyuH) from P. aeruginosa (MCM B-887) in E. coli yielded optically pure carbamoyl amino acids. The use of optically pure carbamoyl amino acids as substrates facilitates the synthesis of non-proteinogenic amino acids. The enzyme hyuH shared a maximum of 92 % homology with proven hydantoinase protein sequences from the GenBank database, highlighting its novelty. Expression of hydantoinase gene was improved by >150 % by overexpressing it as a fusion protein in specialized E. coli CODONâ¯+â¯host cells, providing adequate machinery for effective translation of the GC-rich gene. The presence of distinct residues in the substrate binding and active site of MCM B-887 hydantoinase enzyme explained its unique and broad substrate profile desirable for industrial applications. The purified enzyme, with a specific activity of 53U/mg of protein, was optimally active at 42⯰C and pH 9.0 with a requirement of 2â¯mM Mn2+ ions. Supplementation of 500â¯mM of Na-glutamate enhanced the thermostability of the enzyme by more than 200 %.
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Amidohidrolasas/metabolismo , Aminoácidos/biosíntesis , Proteínas Bacterianas/metabolismo , Pseudomonas aeruginosa/enzimología , Amidohidrolasas/química , Amidohidrolasas/genética , Amidohidrolasas/aislamiento & purificación , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Dominio Catalítico , Escherichia coli/genética , Escherichia coli/metabolismo , Concentración de Iones de Hidrógeno , Manganeso , Modelos Moleculares , Filogenia , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Estereoisomerismo , Especificidad por Sustrato , TemperaturaRESUMEN
BACKGROUND: Metabolic and bariatric surgery is an effective strategy to curb the natural history of obesity progression and improve psychosocial status in the short term for adolescents with severe obesity. The medium- and long-term psychosocial impact of bariatric surgery in this population is not established. METHODS: We searched MEDLINE (Ovid), EMBASE, Web of Science, PsycInfo, and the Cochrane Libraries through October 2017 for reports of weight loss surgery (roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric banding) on adolescents with severe obesity (age ≤ 21 years) having ≥ 6 months of follow-up. The primary outcome for inclusion in systematic review was use of a validated quality of life (QoL) or other psychosocial instrument at baseline and postoperatively. We used standardized mean difference (SMD) and random-effects modeling to provide summary estimates across different instruments. RESULTS: We reviewed 5155 studies, of which 20 studies met inclusion criteria for qualitative synthesis. There were 14 studies and 9 unique cohorts encompassing 573 patients which were eligible for meta-analysis regarding postoperative change in QoL. Across surgical procedures, there was significant improvement in QoL of 1.40 SMD (95% confidence interval 0.95 to 1.86; I2 = 89%; p < 0.001) at last follow-up (range 9-94 months). Trends in QoL improvement demonstrated the greatest improvement at 12 months; however, significant improvement was sustained at longest follow-up of 60+ months. CONCLUSIONS: Weight loss surgery is associated with sustained improvement in QoL for adolescents with severe obesity across surgical procedures. Long-term data for psychosocial outcomes reflecting other mental health domains is lacking.
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Cirugía Bariátrica , Obesidad Mórbida , Calidad de Vida/psicología , Pérdida de Peso , Adolescente , Humanos , Obesidad Mórbida/psicología , Obesidad Mórbida/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Dental erosion is a multifactorial condition, which is mostly influenced by environmental factors. The aim of this study was to determine the prevalence of dental erosion, its associated risk factors, and their correlation with severity of the condition. MATERIALS AND METHODS: A total of 430 patients who attended the outpatient section of Government Dental College, Thiruvananthapuram, Kerala, India, were selected by systematic sampling method. Erosion was diagnosed by clinical examination and graded using Basic Erosive Wear Examination (BEWE) index. A pretested structured questionnaire on age, gender, medical history, medication history, and food habits was used. RESULTS AND CONCLUSION: Among the study population, 44% (95% confidence interval, 39.3%-48.7%) had dental erosion. Age above 45 years (79.7%, P = 0.000), male population (50%, P = 0.032), residents of rural area (49.1%, P = 0.000), patients with asthma (84.2%, P = 0.000), diabetes (90.9%, P = 0.000), gastroesophageal reflux disorder (91.7%, P = 0.001), and frequent consumption of orange (68.9%, P = 0.000) were identified as factors associated with erosion. The prevalence of dental erosion in the community was high. Results of the study established that better awareness of the condition, better facilities for its early diagnosis in the community, and development of proper preventive strategies are required to reduce the severity of dental erosion.
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OBJECTIVE: To determine whether fresh embryo transfers are at a higher risk of abnormal implantation compared with frozen embryo transfers while accounting for the embryo stage at transfer. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): We used data from the Society for Assisted Reproductive Technologies to identify all fresh and frozen autologous IVF cycles from 2004-2013 resulting in a positive pregnancy test. The cycles were parameterized into a four-level predictor of [1] fresh blastocyst transfer, [2] fresh non-blastocyst transfer, [3] frozen blastocyst transfer, and [4] frozen non-blastocyst transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We examined a composite outcome of abnormal implantation, defined as biochemical pregnancy, ectopic/heterotopic pregnancy, and first-trimester pregnancy loss. Regression modeling was performed with repeated measures multivariable logistic regression, adjusted for age, parity, number of embryos transferred, infertility diagnosis, and calendar year of treatment. RESULT(S): Of 509,938 cycles analyzed, 31.8% resulted in abnormal implantation. Compared with a fresh blastocyst transfer, a fresh non-blastocyst transfer had a 22% increase risk of abnormal implantation, a frozen blastocyst transfer had a 36% increase risk, and a frozen non-blastocyst transfer had a 57% increase risk. When individual outcomes were analyzed, fresh embryo transfers had a lower risk of biochemical pregnancy and pregnancy loss but a higher risk for ectopic/heterotopic pregnancy. CONCLUSION(S): Fresh blastocyst transfers had the lowest overall risk of abnormal implantation but a higher risk of ectopic/heterotopic pregnancy. Although embryo cryopreservation is indicated in certain treatment cycles, elective embryo cryopreservation may not be the optimal strategy to adopt for all cycles.
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Criopreservación/estadística & datos numéricos , Pérdida del Embrión/mortalidad , Transferencia de Embrión/mortalidad , Infertilidad/mortalidad , Infertilidad/terapia , Resultado del Embarazo/epidemiología , Embarazo Ectópico/mortalidad , Adolescente , Adulto , Distribución por Edad , Estudios de Cohortes , Criopreservación/métodos , Transferencia de Embrión/estadística & datos numéricos , Femenino , Fertilización In Vitro , Humanos , Incidencia , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galß1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vitro and suppresses tumour growth in mice when introduced intratumourally. The present study assessed the effect of SRL on tumour growth when introduced intraperitoneally in BALB/c nude mice and investigated the pharmacokinetics and biodistribution of SRL in Swiss albino mice. When 9 doses of SRL (30 mg/kg body weight/mice) was administered to BALB/c nude mice bearing human colon cancer HT-29 xenografts, a substantial reduction in tumour size was observed. A 35.8% reduction in tumour size was noted in the treated animals after 17 days. SRL treatment also inhibited angiogenesis, and the tumours from the treated animals were observed to carry fewer blood vessels and express less angiogenesis marker protein CD31, than that from the control animals. Pharmacokinetics and biodistribution analysis revealed that SRL was detected in the serum after 1 h and its level peaked after 24 h. SRL was not detected in any of the organs apart from the kidney where a trace amount was detected after 24 h of SRL injection. No significant changes were observed in any of the biochemical parameters tested including SGOT, SGPT, LDH, CREAT and BUN in the SRL-treated mice compared to these levels in the controls. This suggests that SRL has good potential to be developed as a therapeutic agent for cancer treatment and warrant further investigations in vivo and subsequent clinical trials.
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Antineoplásicos/administración & dosificación , Basidiomycota/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Lectinas/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Neoplasias del Colon/irrigación sanguínea , Neoplasias del Colon/metabolismo , Proteínas Fúngicas/administración & dosificación , Proteínas Fúngicas/farmacocinética , Células HT29 , Humanos , Lectinas/farmacocinética , Ratones , Ratones Desnudos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We have previously reported that a fungal lectin, Rhizoctonia bataticola lectin (RBL), stimulates proliferation and secretion of Th1/Th2 cytokines in human peripheral blood mononuclear cells (PBMC). In the present study, we evaluated the ability of RBL to differentiate human monocytes to macrophages. RBL induced morphological changes indicative of differentiation in primary monocytes and THP-1 cells. Stimulation with RBL resulted in significant up-regulation of differentiation markers - CD54, HLA-DR, CD11b and CD11c and secretion of proinflammatory cytokines - IL-1ß, TNF-α and IL-6. Functionally, RBL profoundly increased phagocytic activity in monocytes. In THP-1 cells, RBL-induced phagocytosis was higher compared to the effect induced by combination of phorbol-12-myristate-13-acetate (PMA) and lipopolysaccharide (LPS). RBL induced a significant increase in matrix metalloproteinase-9 (MMP-9) activity in comparison with a combined treatment of PMA+LPS. Mechanistic studies revealed the involvement of the NF-κB pathway in RBL-induced differentiation of monocytes. The data suggest that RBL mimics the combined action of PMA and LPS to induce morphological and functional differentiation in human monocytes and monocytic cell line - THP-1 to macrophages. Human monocytes differentiated to macrophages with RBL have the potential as an in vitro model to study macrophage biology.
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Lectinas/farmacología , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Rhizoctonia/química , Unión Competitiva , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Células Cultivadas , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Lectinas/metabolismo , Lipopolisacáridos/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Microscopía Confocal , Monocitos/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Nitrilos/farmacología , Fagocitosis/efectos de los fármacos , Sulfonas/farmacología , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
The neuropeptide kisspeptin is essential for sexual maturation and reproductive function. In particular, kisspeptin-expressing neurons in the anterior rostral periventricular area of the third ventricle are generally recognized as mediators of estrogen positive feedback for the surge release of LH, which stimulates ovulation. Estradiol induces kisspeptin expression in the neurons of the rostral periventricular area of the third ventricle but suppresses kisspeptin expression in neurons of the arcuate nucleus that regulate estrogen-negative feedback. To focus on the intracellular signaling and response to estradiol underlying positive feedback, we used mHypoA51 cells, an immortalized line of kisspeptin neurons derived from adult female mouse hypothalamus. mHypoA51 neurons express estrogen receptor (ER)-α, classical progesterone receptor (PR), and kisspeptin, all key elements of estrogen-positive feedback. As with kisspeptin neurons in vivo, 17ß-estradiol (E2) induced kisspeptin and PR in mHypoA51s. The ERα agonist, 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, produced similar increases in expression, indicating that these events were mediated by ERα. However, E2-induced PR up-regulation required an intracellular ER, whereas kisspeptin expression was stimulated through a membrane ER activated by E2 coupled to BSA. These data suggest that anterior hypothalamic kisspeptin neurons integrate both membrane-initiated and classical nuclear estrogen signaling to up-regulate kisspeptin and PR, which are essential for the LH surge.