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1.
J Assist Reprod Genet ; 37(11): 2767-2775, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32995971

RESUMEN

As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other's limitations.


Asunto(s)
Investigación Biomédica/tendencias , Infertilidad/genética , Técnicas Reproductivas Asistidas/tendencias , Adulto , Femenino , Humanos , Infertilidad/terapia , Reino Unido/epidemiología , Estados Unidos/epidemiología
2.
Oncology ; 94(4): 200-206, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29393227

RESUMEN

PURPOSE: The aim of this study was to evaluate the prevalence of menopausal symptoms in young cancer survivors immediately following the completion of chemotherapy. METHODS: This prospective cohort study followed 124 young females with a new diagnosis of cancer requiring chemotherapy to assess symptoms of menopause before treatment and immediately following chemotherapy. Symptoms were compared before and after treatment using the McNemar test and between cancer patients and 133 similar-aged healthy controls using Pearson χ2 and Fisher's exact tests. RESULTS: Participants undergoing cancer therapy reported more menopausal symptoms compared to controls prior to the initiation of any treatment (hot flashes or night sweats 33 vs. 7%, p < 0.01, trouble sleeping 57 vs. 31%, p < 0.01, headaches 50 vs. 35%, p = 0.02, and decreased libido 36 vs. 16%, p < 0.01) and also reported a greater prevalence of symptoms immediately after cancer therapy compared to pretreatment prevalence (vasomotor symptoms, p < 0.01, vaginal dryness, p < 0.01, decreased concentration, p < 0.01, and body aches, p = 0.01). Cancer patients with lower anti-Müllerian hormone (AMH) levels after treatment (<0.10 ng/mL) had an increased risk of vasomotor symptoms (OR 2.2, p = 0.04), mood swings (OR 2.4, p = 0.03), feeling sad (OR 2.2, p = 0.04), trouble sleeping (OR 2.7, p = 0.02), and decreased libido (OR 3.0, p = 0.03) when controlled for age and cancer type, and the incidence of these symptoms was not affected by the use of systemic hormones or psychiatric medications. Treatment length, use of alkylating agents, pelvic radiation, and marital status were also not associated with the prevalence of menopausal symptoms. CONCLUSIONS: Premenopausal women with a new cancer diagnosis have more menopausal symptoms than females of similar age before and after cancer treatment, the effects of which are not mitigated by systemic hormone use. Decreased AMH levels were associated with an increased likelihood of reporting physiologic symptoms after therapy. IMPLICATIONS FOR CANCER SURVIVORS: This information is imperative for counseling; ultimately, improved symptom management during and after cancer therapies will improve quality of life in young cancer survivors.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sofocos/epidemiología , Neoplasias/tratamiento farmacológico , Trastornos del Sueño-Vigilia/epidemiología , Sudoración , Adolescente , Adulto , Hormona Antimülleriana/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Casos y Controles , Femenino , Cefalea/epidemiología , Humanos , Libido/efectos de los fármacos , Trastornos del Humor/epidemiología , Neoplasias/sangre , Premenopausia/sangre , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Sudoración/efectos de los fármacos , Adulto Joven
3.
Blood ; 122(24): 3960-3, 2013 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-24100449

RESUMEN

Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in vitro survival of CD5(+)B220(dull) leukemic cells derived from the murine Eµ-TCL1-Tg (TCL1-Tg [transgenic]) model for CLL. APRIL-TCL1 double-Tg mice showed a significantly earlier onset of leukemia and disruption of splenic architecture, and survival was significantly reduced. Interestingly, clonal evolution of CD5(+)B220(dull) cells (judged by BCR clonality) did not seem to be accelerated by APRIL; both mouse strains were oligoclonal at 4 months. Although APRIL binds different receptors, APRIL-mediated leukemic cell survival depended on tumor necrosis factor receptor superfamily member 13B (TACI) ligation. These findings indicate that APRIL has an important role in CLL and that the APRIL-TACI interaction might be a selective novel therapeutic target for human CLL.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteína Activadora Transmembrana y Interactiva del CAML/metabolismo , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación , Unión Proteica , Proteínas Proto-Oncogénicas/genética , Factores de Tiempo , Proteína Activadora Transmembrana y Interactiva del CAML/genética , Células Tumorales Cultivadas , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética
4.
medRxiv ; 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38496589

RESUMEN

Capsule: In this study the presence of uterine fibroids was significantly associated with an increased risk of development of hypertensive disorders of pregnancy even when accounting for age and BMI in meta-regression. This finding has potential implications for risk stratification and monitoring for hypertension during pregnancy in this population. Objective: To examine the association between uterine fibroids and the development of hypertensive disorders in pregnancy. Data sources: Cochrane, Embase, PubMed, MEDLINE, Scopus, and Web of Science databases were searched from inception through April 2023. Study Selection and Synthesis: Cohort, case-control, or case series studies including uterine fibroid status and hypertensive disorders of pregnancy status were included. The comparison group was pregnant women without uterine fibroids. Inverse-variance weighted random effects models were used to pool RR and OR estimates separately. Age and BMI were explored as potential sources of heterogeneity using inverse-variance weighted meta-regression. Main Outcomes: Hypertensive disorders of pregnancy (HDP) defined as gestational hypertension, pre-eclampsia, eclampsia, superimposed preeclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Results: A total of 17 studies were included (Total N=1,374,395 participants, N=64,968 with uterine fibroids). Thirteen studies were retrospective cohorts and four were case-control studies. Women with uterine fibroids had a significantly higher risk of hypertensive disorders in pregnancy compared to women without uterine fibroids with RR 1.74 (95% CI 1.33-2.27, p<0.01), and OR 2.87 (95% CI 1.38-5.97, p<0.01), in cohort studies and case-control studies, respectively. In meta-regression analyses, age did not significantly change the positive association between uterine fibroids and hypertensive disorders in pregnancy. Conclusion: Uterine fibroids were associated with an increased risk of hypertensive disorders of pregnancy when all available literature was synthesized, including when shared risk factors are examined in meta-regression analyses. Relevance: If confirmed in future studies, investigations into the mechanisms of this association are needed as this finding potentially has implications for risk stratification and monitoring for hypertensive disorders of pregnancy in this population. Trial Registration: PROSPERO, ID # 331528.

5.
Diabetes Technol Ther ; 26(S3): 24-31, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38377317

RESUMEN

Background: The MiniMed™ 780G system (MM780G) with Guardian™ 4 sensor includes a 100 mg/dL glucose target (GT) and automated insulin corrections up to every 5 min and was recently approved for use in the United States. In the present study, early real-world MM780G performance and the use of recommended system settings (100 mg/dL GT with an active insulin time of 2 h), by individuals with type 1 diabetes, were evaluated. Methods: CareLink™ personal data uploaded between the launch of the MM780G to August 22, 2023 were aggregated and underwent retrospective analysis (based on user consent) and if users had ≥10 days of continuous glucose monitoring (CGM) data. The 24-h day CGM metrics, including mean glucose, percentage of time spent in (%TIR), above (%TAR), and below (%TBR) target range (70-180 mg/dL), in addition to delivered insulin and closed-loop (CL) exits, were compared between an overall group (n = 7499) and individuals who used recommended settings (each, for >95% of the time). An analysis of the same metrics for MiniMed™ 770G system (MM770G) users (n = 3851) who upgraded to the MM780G was also conducted (paired t-test or Wilcoxon signed-rank test, P < 0.05 considered statistically significant). Results: For MM780G users, CGM use, and time in CL were >90% and all MM780G CGM metrics exceeded consensus-recommended goals. With recommended settings (22% of all users), mean %TIR and %TITR (70-140 mg/dL) were 81.4% and 56.4%, respectively. For individuals who upgraded from the MM770G, %TIR and %TITR increased from 73.2% to 78.3% and 45.8% to 52.6%, respectively, while %TAR reduced from 25.1% to 20.2% (P < 0.001, for all three). CL exits/week averaged <1, for all MM780G users. Conclusions: Early real-world MM780G use in the United States demonstrated a high percentage of time in range with low time above and below range. These outcomes are similar to those observed for real-world MM780G use in other countries.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 1 , Estados Unidos , Humanos , Automonitorización de la Glucosa Sanguínea , Estudios Retrospectivos , Insulina/uso terapéutico , Insulina Regular Humana , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucosa , Hipoglucemiantes/uso terapéutico , Sistemas de Infusión de Insulina
6.
J Biol Chem ; 287(44): 37434-46, 2012 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-22961987

RESUMEN

A proliferation-inducing ligand (APRIL), a member of the TNF ligand superfamily with an important role in humoral immunity, is also implicated in several cancers as a prosurvival factor. APRIL binds two different TNF receptors, B cell maturation antigen (BCMA) and transmembrane activator and cylclophilin ligand interactor (TACI), and also interacts independently with heparan sulfate proteoglycans. Because APRIL shares binding of the TNF receptors with B cell activation factor, separating the precise signaling pathways activated by either ligand in a given context has proven quite difficult. In this study, we have used the protein design algorithm FoldX to successfully generate a BCMA-specific variant of APRIL, APRIL-R206E, and two TACI-selective variants, D132F and D132Y. These APRIL variants show selective activity toward their receptors in several in vitro assays. Moreover, we have used these ligands to show that BCMA and TACI have a distinct role in APRIL-induced B cell stimulation. We conclude that these ligands are useful tools for studying APRIL biology in the context of individual receptor activation.


Asunto(s)
Proteínas Mutantes/química , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/química , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Antígeno de Maduración de Linfocitos B , Linfocitos B/metabolismo , Linfocitos B/fisiología , Supervivencia Celular , Cristalografía por Rayos X , Células HEK293 , Humanos , Enlace de Hidrógeno , Inmunoglobulina A/biosíntesis , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Unión Proteica , Estructura Terciaria de Proteína , Transporte de Proteínas , Proteína Activadora Transmembrana y Interactiva del CAML
7.
Blood ; 117(25): 6856-65, 2011 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-21543761

RESUMEN

APRIL (A proliferation-inducing ligand) is a TNF family member that binds two TNF receptor family members, TACI and BCMA. It shares these receptors with the closely related TNF family member, B-cell activating factor (BAFF). Contrary to BAFF, APRIL binds heparan sulfate proteoglycans (HSPGs), which regulates cross-linking of APRIL and efficient signaling. APRIL was originally identified as a growth promoter of solid tumors, and more recent evidence defines APRIL also as an important survival factor in several human B-cell malignancies, such as chronic lymphocytic leukemia (CLL). To target APRIL therapeutically, we developed two anti-human APRIL antibodies (hAPRIL.01A and hAPRIL.03A) that block APRIL binding to BCMA and TACI. Their antagonistic properties are unique when compared with a series of commercially available monoclonal anti-human APRIL antibodies as they prevent in vitro proliferation and IgA production of APRIL-reactive B cells. In addition, they effectively impair the CLL-like phenotype of aging APRIL transgenic mice and, more importantly, block APRIL binding to human B-cell lymphomas and prevent the survival effect induced by APRIL. We therefore conclude that these antibodies have potential for further development as therapeutics to target APRIL-dependent survival in B-cell malignancies.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígeno de Maduración de Linfocitos B/inmunología , Linfocitos B/inmunología , Linfoma de Células B/inmunología , Proteína Activadora Transmembrana y Interactiva del CAML/inmunología , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Linfocitos B/citología , Línea Celular Tumoral , Células Cultivadas , Femenino , Humanos , Inmunoglobulina A/inmunología , Linfoma de Células B/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL
8.
Simul Healthc ; 17(2): 78-87, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34387245

RESUMEN

INTRODUCTION: Current training for robotic surgery crisis management, specifically emergency robotic undocking protocol (ERUP), remains limited to anecdotal experience. A curriculum to impart the skills and knowledge necessary to recognize and complete a successful ERUP was developed using an education approach then evaluated. METHODS: Baseline knowledge and confidence regarding ERUP were established for 5 robotic teams before completing 2 full-immersion simulations separated by an online self-paced learning module. In each simulation, teams operated on a perfused hydrogel model and were tasked to dissect a retroperitoneal tumor abutting a major vessel. During vascular pedicle ligation, a major vascular bleed and nonrecoverable robotic fault were remotely induced, necessitating ERUP with open conversion. After the simulation, participants completed surgery task load index (cognitive load assessment) and realism surveys. Weighted checklists scored participants' actions during each simulation. Surgical metrics including estimated blood loss, time to control bleeding, and undocking time were recorded. Curriculum retention was assessed by repeating the exercise at 6 months. RESULTS: Participants experienced high levels of cognitive demand and agreed that the simulation's realism and stress mimicked live surgery. Longitudinal analysis showed significant knowledge (+37.5 points, p = 0.004) and confidence (+15.3 points, p < 0.001) improvements from baseline to completion. Between simulations, checklist errors, undocking time, and estimated blood loss decreased (38⇾17, -40 seconds, and -500 mL, respectively), whereas action scores increased significantly (+27 points, p = 0.008). At 6 months, insignificant changes from curriculum completion were seen in knowledge (-4.8 points, p = 0.36) and confidence (+3.7 points, p = 0.1). CONCLUSIONS: This simulation-based curriculum successfully improves operative team's confidence, knowledge, and skills required to manage robotic crisis events.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Competencia Clínica , Simulación por Computador , Curriculum , Humanos , Procedimientos Quirúrgicos Robotizados/educación , Procedimientos Quirúrgicos Robotizados/métodos
9.
Radiographics ; 31(2): 569-83, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21415197

RESUMEN

Ovarian cancer is the fifth leading cause of cancer death among women in the United States and has a high likelihood of recurrence despite aggressive treatment strategies. Detection and exact localization of recurrent lesions are critical for guiding management and determining the proper therapeutic approach, which may prolong survival. Because of its high sensitivity and specificity compared with those of conventional techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, fluorine 18 fluorodeoxyglucose positron emission tomography (PET) combined with CT is useful for detection of recurrent or residual ovarian cancer and for monitoring response to therapy. However, PET/CT may yield false-negative results in patients with small, necrotic, mucinous, cystic, or low-grade tumors. In addition, in the posttherapy setting, inflammatory and infectious processes may lead to false-positive PET/CT results. Despite these drawbacks, PET/CT is superior to CT and MR imaging for depiction of recurrent disease.


Asunto(s)
Fluorodesoxiglucosa F18 , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Ováricas/diagnóstico , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Radiofármacos , Técnica de Sustracción , Adulto Joven
10.
Abdom Imaging ; 36(4): 463-71, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21465110

RESUMEN

Although the current literature is limited, available data suggest that (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) imaging improves the evaluation of patients with recurrent pancreatic carcinoma and cholangiocarcinoma. There is evidence that PET/CT is particularly useful in the setting of elevated tumor markers and negative or equivocal CT findings. This article reviews the nature of these carcinomas in the post-therapy setting and describes the strengths and limitations of PET/CT when used for monitoring recurrence.


Asunto(s)
Colangiocarcinoma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Imagen Multimodal/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Carcinoma/diagnóstico por imagen , Humanos , Recurrencia Local de Neoplasia/diagnóstico por imagen
11.
Glob Implement Res Appl ; 1(1): 17-29, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36032522

RESUMEN

Background: It is now widely understood that successful implementation of evidence-based treatments is facilitated by several favorable conditions (e.g., community buy-in, invested agency leadership). However, strategies for supporting agencies in promoting these conditions have been examined to a lesser extent. In this exploratory study, the implementation support procedures of Parenting with Love and Limits (PLL), an evidence-informed family treatment for child/adolescent behavior problems in which the training team follows structured procedures to help coordinate implementation support activities, are illustrated, and their preliminary effectiveness examined. Methods: PLL documents and communication records between PLL and n = 23 sites across the U.S. that initiated PLL pre-implementation activities were reviewed. In addition, implementation activities completed for each agency were entered into the Stages of Implementation Completion (SIC) dashboard. Results: The prescriptive nature of the PLL implementation support protocol was illustrated through descriptions of procedural documents and case examples. Quantitative analyses revealed that, among the 23 sites that began pre-implementation, 9 discontinued, with a trend toward sites in metropolitan areas being more likely to discontinue than those in less populous areas. In addition, the 14 sites that launched PLL demonstrated a high amount of consistency in activities, with sites in the sustainability phase completing an average of 86% of implementation behaviors. Conclusions: Training team-coordination of implementation activities may be one promising approach for supporting agencies in completing tasks to facilitate successful uptake of evidence-supported interventions. In turn, sustained implementation of evidence-supported treatments could allow communities to benefit from practice innovations to a greater extent.

12.
Fertil Steril ; 115(2): 431-437, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33455812

RESUMEN

OBJECTIVE: To develop and internally validate a clinical predictive tool to assess the likelihood that a young cancer patient will experience diminished ovarian reserve (DOR) after chemotherapy. DESIGN: Prospective cohort study. SETTING: University hospitals. PATIENT(S): Postpubertal adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Diminished ovarian reserve after completion of and recovery from chemotherapy, defined as serum antimüllerian hormone (AMH) <1 ng/mL at 8-24 months after completion of chemotherapy. RESULT(S): A multivariable logistic regression model which includes age, cancer type, exposure to an alkylating agent, and baseline AMH value accurately predicts the diagnosis of DOR after chemotherapy with an area under the receiver operating characteristic curve of 0.89. CONCLUSION(S): Pretreatment information on age, cancer type, use of an alkylating agent, and baseline AMH levels make up a clinically useful predictive tool to identify which women are most at risk for DOR caused by chemotherapy.


Asunto(s)
Antineoplásicos/efectos adversos , Modelos Biológicos , Neoplasias/tratamiento farmacológico , Reserva Ovárica/efectos de los fármacos , Reproducción/efectos de los fármacos , Adolescente , Adulto , Estudios de Cohortes , Femenino , Predicción , Humanos , Estudios Longitudinales , Neoplasias/fisiopatología , Reserva Ovárica/fisiología , Estudios Prospectivos , Reproducción/fisiología , Adulto Joven
13.
J Endourol ; 35(3): 376-382, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32967467

RESUMEN

Introduction: The da Vinci Skills Simulator (DVSS) is an effective platform for robotic skills training. Novel training methods using expert gaze patterns to guide trainees have demonstrated superiority to traditional instruction. Portable head-mounted eye-trackers (HMET) offer the opportunity for eye tracking technology to enhance surgical robotic simulation training. Objective: To evaluate if training guided by expert gaze patterns can improve trainee performance over standard movement training techniques during robotic simulation. Methods: Medical students were recruited and randomized into gaze training (GT, n = 9) and movement training (MT, n = 8) groups. First, the participants reviewed an instructional video, with the GT group emulating expert gaze patterns and the MT group (n = 8) standard movement-based instruction. Training consisted of 10 repetitions of "Suture Sponge 3" on the DVSS while wearing HMET; the first three repetitions were followed by group-appropriate video coaching (gaze vs movement feedback), while the remaining repetitions were without feedback. Finally, two multitasking repetitions with a secondary bell-counting task were completed. Primary outcomes included DVSS scores during training and multitasking. Secondary outcomes included metrics collected from the HMET (gaze patterns and gaze entropy). Results: Total score, efficiency, and penalties improved significantly over the training in both groups; the GT group achieved higher scores on every attempt. Total scores in the GT group were higher than the MT group postvideo review (20.3 ± 21.8 vs 3.0 ± 6.2, p = 0.047), after coaching repetitions (61.8 ± 18.8 vs 30.1 ± 26.2, p = 0.01), and at the last training attempt (73.0 ± 16.5 vs 63.1 ± 17.4, p = 0.247). During multitasking, the GT group maintained higher total scores (75 ± 10.1 vs 63.3 ± 15.3, p = 0.01), efficiency (86.3 ± 7.4 vs 77.4 ± 11.2, p = 0.009), and superior secondary task performance (error: 6.3% ± 0.06 vs 10.7% ± 0.11, p = 0.20). Gaze entropy (cognitive-load indicator) and gaze pattern analysis showed similar trends. Conclusion: Gaze-augmented training leads to more efficient movements through adoption of expert gaze patterns that withstand additional stressors.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Entrenamiento Simulado , Realidad Virtual , Competencia Clínica , Simulación por Computador , Humanos , Suturas
14.
FASEB J ; 23(5): 1584-95, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19141538

RESUMEN

A proliferation-inducing ligand (APRIL) (also known as TALL-2 and TRDL-1) is a member of the tumor necrosis factor (TNF) superfamily that has tumorigenic properties but is also important for the induction of humoral immune responses. APRIL binds two TNF receptors: transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA) as well as heparan sulfate proteoglycans (HSPGs). The aim of this study was to clarify the role of the HSPG interaction in canonical APRIL signaling, because it has been proposed to act as a docking site and also to play a role in direct signaling. In this study, we generated point mutants of soluble APRIL that lack either the capacity to bind HSPGs or TACI and BCMA and then tested the function of these mutants in mouse B-cell assays. In contrast to previous reports, we found that APRIL alone is sufficient to costimulate B-cell proliferation and drive IgA production and does not require artificial antibody cross-linking. We found no evidence that APRIL requires signaling through HSPGs but, notably, were able to show that binding of APRIL to HSPGs is crucial for mediating natural APRIL cross-linking to allow for optimal activation of murine B cells.


Asunto(s)
Linfocitos B/citología , Proteoglicanos de Heparán Sulfato/metabolismo , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Animales , Antígeno de Maduración de Linfocitos B/metabolismo , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Células Cultivadas , Reactivos de Enlaces Cruzados/metabolismo , Humanos , Inmunoglobulina A/biosíntesis , Leucosialina/inmunología , Ligandos , Ratones , Modelos Moleculares , Estructura Terciaria de Proteína , Transducción de Señal , Proteína Activadora Transmembrana y Interactiva del CAML/fisiología , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo
15.
J Cancer Surviv ; 14(5): 607-613, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32323140

RESUMEN

PURPOSE: This study sought to evaluate the prevalence of menopausal symptoms in a population of reproductive-aged women remote from cancer therapy compared with a group of healthy similar-aged controls and with a cohort of late reproductive-aged (LR) controls. METHODS: Participants were assessed for symptoms of menopause, early follicular phase hormones, and ultrasound examinations. Menopausal symptoms were analyzed in exposed participants and controls using χ2 analyses, Wilcoxon-Mann Whitney tests, and multivariable logistic regression models. RESULTS: One hundred seventy cancer survivors, 135 similar-aged controls, and 71 LR controls were followed prospectively for an average of 38 months. Compared with similar-aged controls, a greater proportion of survivors reported vasomotor symptoms at some point over the study period (35% vs 19%, p < 0.01), and this proportion was similar to LR controls (44%, p = 0.22). Survivors were more likely to be bothered by vaginal dryness (27%) than similar-aged controls (16%, p = 0.02) or LR controls (14%, p = 0.02). FSH levels were 38.4% higher in those with vasomotor symptoms compared with those without symptoms (p = 0.021). CONCLUSIONS: Reproductive-aged cancer survivors have a higher prevalence of vasomotor symptoms and vaginal dryness than their similar-aged peers. IMPLICATIONS FOR CANCER SURVIVORS: Providers should be attuned to the high prevalence of menopausal symptoms in cancer survivors.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Menopausia/fisiología , Neoplasias/fisiopatología , Reserva Ovárica/fisiología , Reproducción , Adolescente , Adulto , Hormona Antimülleriana/sangre , Estudios de Casos y Controles , Quimioradioterapia , Femenino , Humanos , Menopausia/efectos de los fármacos , Menopausia/efectos de la radiación , Persona de Mediana Edad , Neoplasias/terapia , Reserva Ovárica/efectos de los fármacos , Reserva Ovárica/efectos de la radiación , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Ultrasonografía , Adulto Joven
16.
J Clin Endocrinol Metab ; 104(5): 1813-1822, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30566616

RESUMEN

CONTEXT: Recent studies have examined level and rate of change of anti-Müllerian hormone (AMH) for predicting time to menopause. Limited prospective, longitudinal data exists evaluating measures of ovarian reserve (MOR) in cancer survivors. PURPOSE: Determine the rate of change of MOR in survivors (15 to 39 years) compared with similar-aged controls and compared with late reproductive-aged controls (40 to 50 years). DESIGN: Prospective cohort. SETTING: Quaternary university hospital. PARTICIPANTS: Survivors at least 1 year from therapy completion, similar-aged controls, and late reproductive-aged controls. INTERVENTIONS: Annual visits with early follicular-phase hormone analysis and ultrasound. MAIN OUTCOME MEASURE: Changes in AMH and antral follicle count (AFC) were modeled using random effects linear regression. RESULTS: Cancer survivors (170) and 135 similar-aged controls had annual visits for an average of 38 months; 71 late reproductive-aged controls were followed for an average of 24 months. In models adjusted for body mass index, time since cancer therapy (for survivors), and exogenous hormone use, the geometric mean AMH and AFC levels were lower in the survivors than similar-aged controls at all ages. After age 24.5 AMH and AFC declined in both groups at rates that were similar (P = 0.78 for AMH, P = 0.37 for AFC). Late reproductive-aged controls declined at a much more precipitous rate of 30% per year for AMH and 16% per year for AFC (P < 0.01 compared with survivors). CONCLUSIONS: Although survivors had lower levels of AMH and AFC at the time of enrollment, the rate of change of AMH and AFC is not significantly different than similar-aged controls.


Asunto(s)
Hormona Antimülleriana/sangre , Supervivientes de Cáncer/estadística & datos numéricos , Longevidad , Neoplasias/rehabilitación , Reserva Ovárica/fisiología , Ovario/fisiología , Reproducción , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Ovario/citología , Pronóstico , Estudios Prospectivos , Adulto Joven
17.
IEEE Trans Neural Netw ; 19(5): 899-913, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18467217

RESUMEN

This paper investigates whether spike-timing-dependent plasticity (STDP) can minimize the effect of mismatch within the context of a depth-from-motion algorithm. To improve noise rejection, this algorithm contains a spike prediction element, whose performance is degraded by analog very large scale integration (VLSI) mismatch. The error between the actual spike arrival time and the prediction is used as the input to an STDP circuit, to improve future predictions. Before STDP adaptation, the error reflects the degree of mismatch within the prediction circuitry. After STDP adaptation, the error indicates to what extent the adaptive circuitry can minimize the effect of transistor mismatch. The circuitry is tested with static and varying prediction times and chip results are presented. The effect of noisy spikes is also investigated. Under all conditions the STDP adaptation is shown to improve performance.


Asunto(s)
Redes Neurales de la Computación , Algoritmos , Electrónica , Plasticidad Neuronal , Neuronas/fisiología , Transistores Electrónicos
18.
Artículo en Inglés | MEDLINE | ID: mdl-29786564

RESUMEN

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell-matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/fisiología , Matriz Extracelular/fisiología , Laminina/fisiología , Células Madre/fisiología , Matriz Extracelular/clasificación , Humanos
19.
Fertil Steril ; 107(5): 1214-1222.e3, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28476182

RESUMEN

OBJECTIVE: To assess reproductive choices of reproductive-age women in the United States and factors that influence consideration of elective egg freezing (EF). DESIGN: Cross-sectional internet-based survey. SETTING: Not applicable. PATIENTS: One thousand women aged 21-45 years. INTERVENTION(S): An anonymous 63-item self-administered questionnaire was distributed to a representative cross-section of women aged 21-45 years, stratified by age <35 years. One-half of the sample had at least one child, and the other one-half did not. All of the participants were interested in having children. MAIN OUTCOME MEASURE(S): Ordinal logistic regression was performed to characterize the association of population characteristics and reproductive knowledge with likelihood to consider EF. Willingness to pay was assessed with the use of a linear prediction model that calculated dollar amounts at varying success rates. RESULT(S): Overall, 87.2% of the sample reported awareness of EF for fertility preservation and 25% would consider this option, yet only 29.8% knew what the EF process entails. Once informed of the process, 30% of women changed their level of consideration. In a multivariable model, Asian race, single status, and infertility increased the likelihood of considering EF. Women likely to consider egg freezing would be willing to pay $3,811.55 (95% confidence interval $2,862.66-$4,760.44). If the total cost were $10,000, 91% of the cohort would accept at minimum a 50% chance of successful delivery. CONCLUSION(S): This study is one of the largest cohorts of reproductive-age women in the United States addressing reproductive choices and factors associated with the importance of having a biologically related child and the likelihood of considering EF to preserve fertility. This study provides important insight into the willingness to pay for this elective endeavor.


Asunto(s)
Criopreservación/economía , Costos de la Atención en Salud/estadística & datos numéricos , Infertilidad Femenina/economía , Recuperación del Oocito/economía , Prioridad del Paciente/economía , Técnicas Reproductivas Asistidas/economía , Adulto , Estudios Transversales , Criopreservación/métodos , Criopreservación/estadística & datos numéricos , Femenino , Encuestas de Atención de la Salud , Alfabetización en Salud/economía , Alfabetización en Salud/estadística & datos numéricos , Humanos , Infertilidad Femenina/terapia , Persona de Mediana Edad , Recuperación del Oocito/estadística & datos numéricos , Oocitos/citología , Oocitos/trasplante , Prioridad del Paciente/estadística & datos numéricos , Embarazo , Prevalencia , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Estados Unidos/epidemiología , Salud de la Mujer/economía , Adulto Joven
20.
IEEE Trans Neural Netw ; 17(2): 482-95, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16566474

RESUMEN

We propose a simplified depth-from-motion vision model based on leaky integrate-and-fire (LIF) neurons for edge detection and two-dimensional depth recovery. In the model, every LIF neuron is able to detect the irradiance edges passing through its receptive field in an optical flow field, and respond to the detection by firing a spike when the neuron's firing criterion is satisfied. If a neuron fires a spike, the time-of-travel of the spike-associated edge is transferred as the prediction information to the next synapse-linked neuron to determine its state. Correlations between input spikes and their timing thus encode depth in the visual field. The adaptation of synapses mediated by spike-timing-dependent plasticity is used to improve the algorithm's robustness against inaccuracy caused by spurious edge propagation. The algorithm is characterized on both artificial and real image sequences. The implementation of the algorithm in analog very large scale integrated (aVLSI) circuitry is also discussed.


Asunto(s)
Biomimética/métodos , Percepción de Profundidad/fisiología , Modelos Neurológicos , Percepción de Movimiento/fisiología , Red Nerviosa/fisiología , Redes Neurales de la Computación , Vías Visuales/fisiología , Animales , Simulación por Computador , Humanos , Reconocimiento de Normas Patrones Automatizadas/métodos
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