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1.
Behav Res Ther ; 178: 104547, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38678755

RESUMO

Prior research suggests that repetitive negative thinking (RNT) negatively impacts mental health by intensifying and prolonging emotional reactivity to stress. This study investigated whether an intervention designed to reduce RNT alters emotional reactivity. Young adults with high trait RNT (N = 79) were randomly allocated to an RNT-focused intervention (smartphone app-based, 10 days) or a waiting list before exposure to a standardized stressor. The pre-registered analysis did not reveal a significant condition * time interaction for negative affect. However, exploratory analyses showed that whilst initial increases in negative affect in response to the stressor did not differ between conditions, participants in the intervention condition reported less negative affect throughout the following recovery phase. Additionally, participants in the intervention condition appraised their ability to cope with the stressor as higher and reported less RNT in the recovery phase. In contrast, the intervention did not affect biological stress responses. The findings indicate that RNT-focused interventions might have positive effects on mental health by breaking the self-reinforcing cycle of RNT, negative affect and maladaptive appraisals in response to stress. However, as findings are partly based on exploratory analyses, further research is needed to confirm whether reduced subjective stress reactivity mediates the effects of RNT-focused interventions on psychopathological symptoms.


Assuntos
Estresse Psicológico , Humanos , Masculino , Feminino , Estresse Psicológico/psicologia , Estresse Psicológico/terapia , Adulto Jovem , Adulto , Adaptação Psicológica , Adolescente , Aplicativos Móveis , Pessimismo/psicologia , Ruminação Cognitiva/fisiologia , Pensamento
2.
Curr Diab Rep ; 23(9): 231-243, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294513

RESUMO

PURPOSE OF REVIEW: Despite the crucial role that prediction models play in guiding early risk stratification and timely intervention to prevent type 2 diabetes after gestational diabetes mellitus (GDM), their use is not widespread in clinical practice. The purpose of this review is to examine the methodological characteristics and quality of existing prognostic models predicting postpartum glucose intolerance following GDM. RECENT FINDINGS: A systematic review was conducted on relevant risk prediction models, resulting in 15 eligible publications from research groups in various countries. Our review found that traditional statistical models were more common than machine learning models, and only two were assessed to have a low risk of bias. Seven were internally validated, but none were externally validated. Model discrimination and calibration were done in 13 and four studies, respectively. Various predictors were identified, including body mass index, fasting glucose concentration during pregnancy, maternal age, family history of diabetes, biochemical variables, oral glucose tolerance test, use of insulin in pregnancy, postnatal fasting glucose level, genetic risk factors, hemoglobin A1c, and weight. The existing prognostic models for glucose intolerance following GDM have various methodological shortcomings, with only a few models being assessed to have low risk of bias and validated internally. Future research should prioritize the development of robust, high-quality risk prediction models that follow appropriate guidelines, in order to advance this area and improve early risk stratification and intervention for glucose intolerance and type 2 diabetes among women who have had GDM.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Intolerância à Glucose , Gravidez , Feminino , Humanos , Diabetes Mellitus Tipo 2/complicações , Período Pós-Parto , Glucose , Glicemia
3.
Biol Psychol ; 178: 108528, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36868296

RESUMO

Previous research is inconclusive on when visual working memory (VWM) can be object-based or feature-based. Prior event-related potential (ERP) studies using change detection tasks have found that amplitudes of the N200-an ERP index of VWM comparison- are sensitive to changes in both relevant and irrelevant features, suggesting a bias toward object-based processing. To test whether VWM comparison processing can operate in a feature-based manner, we aimed to create circumstances that would support feature-based processing by: 1) using a strong task-relevance manipulation, and 2) repeating features within a display. Participants completed two blocks of a change detection task for four-item displays in which they were told to respond to color changes (task relevant) but not shape changes (task irrelevant). The first block contained only task-relevant changes to create a strong task-relevance manipulation. In the second block, both relevant and irrelevant changes were present. In both blocks, half of the arrays contained within-display feature repetitions (e.g. two items of the same color or shape). We found that during the second block, N200 amplitudes were sensitive to task-relevant but not irrelevant features regardless of repetition status, consistent with feature-based processing. However, analyses of behavioral data and N200 latencies suggested that object-based processing was occurring at some stages of VWM processing on task-irrelevant feature change trials. In particular, task-irrelevant changes may be processed after no task-relevant feature change is revealed. Overall, the results from the current study suggest that the VWM processing is flexible and can be either object- or feature-based.


Assuntos
Memória de Curto Prazo , Percepção Visual , Humanos , Memória de Curto Prazo/fisiologia , Percepção Visual/fisiologia , Potenciais Evocados
5.
J Gen Intern Med ; 37(11): 2661-2668, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35233708

RESUMO

INTRODUCTION: COVID-19 disrupted access to critical healthcare and resources for many, especially affecting patients at safety-net hospitals who rely on regular care for multiple complex conditions. Students realized they could support patients from the sidelines by helping navigate abrupt healthcare changes and proactively addressing needs at home. AIM: To comprehensively identify and meet the clinical and social needs of Atlanta, Georgia's patients at highest risk, left without their usual access to healthcare, through proactive telephonic outreach. SETTING AND PATIENTS: Medical and Physician's Assistant students from Emory and Morehouse Schools of Medicine partnered with Grady Health System, Atlanta's safety-net hospital. Artificial intelligence prioritized over 15,000 patients by risk of morbidity and mortality from COVID-19. PROGRAM DESCRIPTION: In this novel program, students performed telephonic outreach to thousands of patients at highest risk of poor outcomes from COVID-19. Students used a custom REDCap form that served as both a call script and data collection tool. It provided step-by-step guidance to (1) screen for COVID-19 and educate on prevention; (2) help patients navigate health system changes to fill gaps in care; and (3) identify and address social needs. Based on patients' responses, the form prompted tailored reminders for next steps and connections to medical and social resources. PROGRAM EVALUATION: In the program's first 16 months, students made 7,988 calls, of which 3,354 were answered. Over half (53%) of patients had at least one need requiring action: 48% health and 16% social. DISCUSSION: This proactive, novel initiative identified substantial clinical and social need among patients at highest risk for poor outcomes and filled a pressing health system gap exacerbated by COVID-19. Simultaneously, interprofessional students gained applied exposure to health systems sciences. This program can serve as a model for rapid, cost-effective, high-yield outreach to promote patient health at home both during and beyond the pandemic.


Assuntos
COVID-19 , Inteligência Artificial , COVID-19/epidemiologia , Atenção à Saúde , Humanos , Pandemias/prevenção & controle , Estudantes
6.
Med Teach ; 44(3): 328-333, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34735302

RESUMO

INTRODUCTION: Health Systems Science (HSS) teaches students critical skills to navigate complex health systems, yet medical schools often find it difficult to integrate into their curriculum due to limited time and student disinterest. Co-developing content with students and teaching through appropriate experiential learning can improve student engagement in HSS coursework. METHODS: Medical students and faculty co-developed a patient outreach initiative during the early phases of the COVID-19 pandemic and integrated that experience into a new experiential HSS elective beginning May 2020. Students called patients identified as high-risk for adverse health outcomes and followed a script to connect patients to healthcare and social services. Subsequently, this initiative was integrated into the required third-year primary care clerkship. RESULTS: A total of 255 students participated in HSS experiential learning through the elective and clerkship from May 2020 through July 2021. Students reached 3,212 patients, encountering a breadth of medical, social, and health systems issues; navigated the EMR; engaged interdisciplinary professionals; and proposed opportunities for health systems improvement. DISCUSSION AND CONCLUSION: This educational intervention demonstrated the opportunity to partner with student-led initiatives, coproducing meaningful educational experiences for the learners within the confines of a busy medical curriculum.


Assuntos
COVID-19 , Estágio Clínico , Estudantes de Medicina , COVID-19/epidemiologia , Currículo , Docentes , Humanos , Pandemias , Aprendizagem Baseada em Problemas
7.
Infect Dis Clin Pract (Baltim Md) ; 29(6): e465-e467, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34803353

RESUMO

Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 may present with fever, elevated inflammatory markers, and multiorgan involvement. Although the gastrointestinal system is commonly affected in MIS-C patients, associated necrotizing pancreatitis is rare. We present an 11-year-old boy with B-cell acute lymphoblastic leukemia in remission undergoing maintenance chemotherapy presenting with acute necrotizing pancreatitis. He developed fevers, fluid and electrolyte imbalance, respiratory distress, cytopenias, and coagulopathy, and was found to have markedly elevated inflammatory markers and positive SARS-CoV-2 antibodies. The patient met criteria for MIS-C and was treated with intravenous immunoglobulin with significant clinical improvement. This is the first known reported case of a child with B-cell acute lymphoblastic leukemia who met criteria for MIS-C presenting as acute pancreatitis, and highlights the importance of considering a broader differential for pancreatitis in children given the current SARS-CoV-2 pandemic.

8.
BMC Pregnancy Childbirth ; 21(1): 569, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407775

RESUMO

BACKGROUND: Maternal obesity is associated with health risks for women and their babies and is exacerbated by excess gestational weight gain. The aim of this study was to describe women's experiences and perspectives in attending a Healthy Pregnancy Service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. METHODS: An explanatory sequential mixed methods study design utilised two questionnaires (completed in early and late pregnancy) to quantify feelings, motivation and satisfaction with the service, followed by semi-structured interviews that explored barriers and enablers of behaviour change. Data were analysed separately and then interpreted together. RESULTS: Overall, 49 women attending the service completed either questionnaire 1, 2 or both and were included in the analysis. Fourteen women were interviewed. Prior to pregnancy, many women had gained weight and attempted to lose weight independently, and reported they were highly motivated to achieve a healthy lifestyle. During pregnancy, diet changes were reported as easier to make and sustain than exercise changes. Satisfaction with the service was high. Key factors identified in qualitative analysis were: service support enabled change; motivation to change behaviour, social support, barriers to making change (intrinsic, extrinsic and clinic-related), post-partum lifestyle and needs. On integration of data, qualitative and quantitative findings aligned. CONCLUSIONS: The Healthy Pregnancy service was valued by women. Barriers and enablers to the delivery of an integrated model of maternity care that supported healthy lifestyle and recommended gestational weight gain were identified. These findings have informed and improved implementation and further scale up of this successful service model, integrating healthy lifestyle into routine antenatal care of women with obesity. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (no.12620000985987). Registration date 30/09/2020, retrospectively registered. http://www.anzctr.org.au/.


Assuntos
Ganho de Peso na Gestação , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Estilo de Vida Saudável , Obesidade/psicologia , Adulto , Austrália , Dieta/psicologia , Exercício Físico/psicologia , Feminino , Promoção da Saúde/métodos , Humanos , Estilo de Vida , Motivação , Gravidez , Inquéritos e Questionários , Adulto Jovem
9.
Blood ; 137(6): 788-800, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32785655

RESUMO

MALT1 inhibitors are promising therapeutic agents for B-cell lymphomas that are dependent on constitutive or aberrant signaling pathways. However, a potential limitation for signal transduction-targeted therapies is the occurrence of feedback mechanisms that enable escape from the full impact of such drugs. Here, we used a functional genomics screen in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) cells treated with a small molecule irreversible inhibitor of MALT1 to identify genes that might confer resistance or enhance the activity of MALT1 inhibition (MALT1i). We find that loss of B-cell receptor (BCR)- and phosphatidylinositol 3-kinase (PI3K)-activating proteins enhanced sensitivity, whereas loss of negative regulators of these pathways (eg, TRAF2, TNFAIP3) promoted resistance. These findings were validated by knockdown of individual genes and a combinatorial drug screen focused on BCR and PI3K pathway-targeting drugs. Among these, the most potent combinatorial effect was observed with PI3Kδ inhibitors against ABC-DLBCLs in vitro and in vivo, but that led to an adaptive increase in phosphorylated S6 and eventual disease progression. Along these lines, MALT1i promoted increased MTORC1 activity and phosphorylation of S6K1-T389 and S6-S235/6, an effect that was only partially blocked by PI3Kδ inhibition in vitro and in vivo. In contrast, simultaneous inhibition of MALT1 and MTORC1 prevented S6 phosphorylation, yielded potent activity against DLBCL cell lines and primary patient specimens, and resulted in more profound tumor regression and significantly improved survival of ABC-DLBCLs in vivo compared with PI3K inhibitors. These findings provide a basis for maximal therapeutic impact of MALT1 inhibitors in the clinic, by disrupting feedback mechanisms that might otherwise limit their efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Retroalimentação Fisiológica/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Receptores de Antígenos de Linfócitos B/imunologia , Receptores Toll-Like/imunologia , Animais , Antineoplásicos/farmacologia , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/fisiologia , Proteínas de Neoplasias/fisiologia , Organoides/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , RNA Interferente Pequeno/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Hum Fertil (Camb) ; 24(5): 367-375, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31597488

RESUMO

Poor endometrial development during in vitro fertilization remains challenging. Indeed, no broadly accepted definition of poor endometrial development exists, and no treatment has shown any improvement in the condition. The aim of this study was to analyze whether treatment with a combination of pentoxifylline and tocopherol increases endometrial volume. This monocentric and retrospective study includes patients with previous miscarriages, in vitro fertilization failure, or poor endometrial development. The patients had an ultrasonography during the mid-luteal phase to assess both endometrial thickness and endometrial volume (EV). If the volume was less than 2 mL, they were given pentoxifylline (PTX) and tocopherol for at least 2 months before a second ultrasound assessment. One hundred and forty-four patients were analyzed. The mean duration of treatment was 132 days. The combination of tocopherol and PTX significantly increased the EV by 0.47 mL (p < 0.0001; 95% CI 0.38-0.57). The mean ± SD EV was 1.34 ± 0.38 mL and 1.82 ± 0.63 mL before and after the treatment respectively. No data concerning pregnancy rates were interpretable. We showed an improvement of poor endometrial proliferation with a treatment including PTX and tocopherol. These promising results should be followed up by a prospective study.


Assuntos
Pentoxifilina , Endométrio/diagnóstico por imagem , Feminino , Fertilização in vitro , Humanos , Pentoxifilina/uso terapêutico , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Tocoferóis
11.
J Clin Med ; 9(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348671

RESUMO

Maternal obesity is associated with health risks for women and their babies, exacerbated by excess gestational weight gain. We describe health professionals' perspectives in the provision of a Healthy Pregnancy service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. Semi-structured interviews were conducted with health professionals. Questions were based on the Theoretical Domains Framework (TDF) and deductive thematic analysis was performed. A total of 14 multidisciplinary staff were interviewed. Six themes were identified: 1. health professionals view themselves as part of a team; 2. health professionals reported having necessary skills; 3. experience generated confidence in discussing gestational weight gain; 4. gestational weight gain is considered of variable importance; 5. health professionals want women to be comfortable; 6. the environmental context and resources presented some barriers. Staff were supportive of the Healthy Pregnancy service and valued developing teamwork with staff and rapport with women. Most felt relatively comfortable discussing weight gain with women. Barriers included ability to navigate sensitive topics with women, limited awareness of the intervention among new staff, communication between teams, and waiting time for women. Barriers and enablers to the delivery of an integrated model of maternity care were identified. These findings should inform and improve implementation of service models integrating healthy lifestyle in the antenatal care of women with obesity.

12.
Blood Adv ; 4(17): 4180-4194, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32886754

RESUMO

Multiple myeloma (MM) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (PCs) in the bone marrow (BM). Patient outcome may be improved with BiTE (bispecific T-cell engager) molecules, which redirect T cells to lyse tumor cells. B-cell maturation antigen (BCMA) supports PC survival and is highly expressed on MM cells. A half-life extended anti-BCMA BiTE molecule (AMG 701) induced selective cytotoxicity against BCMA-expressing MM cells (average half-maximal effective concentration, 18.8 ± 14.8 pM), T-cell activation, and cytokine release in vitro. In a subcutaneous mouse xenograft model, at all doses tested, AMG 701 completely inhibited tumor formation (P < .001), as well as inhibited growth of established tumors (P ≤ .001) and extended survival in an orthotopic MM model (P ≤ .01). To evaluate AMG 701 bioactivity in cynomolgus monkeys, a PC surface phenotype and specific genes were defined to enable a quantitative digital droplet polymerase chain reaction assay (sensitivity, 0.1%). Dose-dependent pharmacokinetic and pharmacodynamic behavior was observed, with depletion of PC-specific genes reaching 93% in blood and 85% in BM. Combination with a programmed cell death protein 1 (PD-1)-blocking antibody significantly increased AMG 701 potency in vitro. A model of AMG 701 binding to BCMA and CD3 indicates that the distance between the T-cell and target cell membranes (ie, the immunological synapse) is similar to that of the major histocompatibility complex class I molecule binding to a T-cell receptor and suggests that the synapse would not be disrupted by the half-life extending Fc domain. These data support the clinical development of AMG 701.


Assuntos
Anticorpos Biespecíficos , Mieloma Múltiplo , Animais , Complexo CD3 , Macaca fascicularis , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Plasmócitos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Mol Cancer Ther ; 19(9): 1875-1888, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518207

RESUMO

Despite advances in the treatment of acute myeloid leukemia (AML), novel therapies are needed to induce deeper and more durable clinical response. Bispecific T-cell Engager (BiTE) molecules, which redirect patient T cells to lyse tumor cells, are a clinically validated modality for hematologic malignancies. Due to broad AML expression and limited normal tissue expression, fms-related tyrosine kinase 3 (FLT3) is proposed to be an optimal BiTE molecule target. Expression profiling of FLT3 was performed in primary AML patient samples and normal hematopoietic cells and nonhematopoietic tissues. Two novel FLT3 BiTE molecules, one with a half-life extending (HLE) Fc moiety and one without, were assessed for T-cell-dependent cellular cytotoxicity (TDCC) of FLT3-positive cell lines in vitro, in vivo, and ex vivo FLT3 protein was detected on the surface of most primary AML bulk and leukemic stem cells but only a fraction of normal hematopoietic stem and progenitor cells. FLT3 protein detected in nonhematopoietic cells was cytoplasmic. FLT3 BiTE molecules induced TDCC of FLT3-positive cells in vitro, reduced tumor growth and increased survival in AML mouse models in vivo Both molecules exhibited reproducible pharmacokinetic and pharmacodynamic profiles in cynomolgus monkeys in vivo, including elimination of FLT3-positive cells in blood and bone marrow. In ex vivo cultures of primary AML samples, patient T cells induced TDCC of FLT3-positive target cells. Combination with PD-1 blockade increased BiTE activity. These data support the clinical development of an FLT3 targeting BiTE molecule for the treatment of AML.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Inibidores de Checkpoint Imunológico/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Tirosina Quinase 3 Semelhante a fms/metabolismo , Animais , Anticorpos Biespecíficos/farmacologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Citotoxicidade Imunológica , Sinergismo Farmacológico , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Células K562 , Leucemia Mieloide Aguda/metabolismo , Macaca fascicularis , Camundongos , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores
15.
Toxicol Sci ; 177(1): 94-107, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589753

RESUMO

Feline McDonough Sarcoma-like tyrosine kinase 3 (FLT3), a tyrosine-protein kinase involved in hematopoiesis, is detectable on the cell surface of approximately 80% of leukemia isolates from adult patients with acute myeloid leukemia (AML). AMG 553 is an investigational chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of AML. FLT3 expression analysis and in vitro and in vivo studies were leveraged to evaluate the nonclinical safety of AMG 553. Cynomolgus monkeys administered autologous anti-FLT3 CAR T cells demonstrated no evidence of CAR T-cell-mediated toxicity, expansion, or persistence, likely due to restricted cell surface FLT3 protein expression in healthy animals. This highlights the limited value of such in vivo studies for safety assessment of the CAR T-cell modality when directed against a target with restricted expression. To complement these studies and directly evaluate the potential toxicities of eliciting T-cell-mediated cytotoxicity against cells with surface expression of FLT3 protein in vivo, data from cynomolgus monkey toxicology studies with 2 bispecific T-cell engager molecules targeting FLT3 were leveraged; findings were consistent with the targeted killing of bone marrow cells expressing cell surface FLT3. Potential AMG 553-induced cytotoxicity was assessed against a wide range of normal human primary cells and cell lines; cytotoxicity was observed against FLT3-positive AML cell lines and a percentage of primary bone marrow CD34+ cells. In conclusion, the nonclinical safety data suggest that AMG 553 can target FLT3 protein on AML cells, whereas only affecting a percentage of normal hematopoietic stem and progenitor cells, supporting clinical development.


Assuntos
Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Adulto , Animais , Gatos , Linhagem Celular Tumoral , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Macaca fascicularis
16.
BMC Med ; 16(1): 153, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30165842

RESUMO

BACKGROUND: The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions. METHODS: Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes. RESULTS: Overall, 5874 studies were identified and 23 were included (n = 1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes. CONCLUSIONS: Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.


Assuntos
Peso Fetal/etnologia , Resultado da Gravidez/etnologia , Aumento de Peso/etnologia , Aumento de Peso/fisiologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez
17.
Chem Rev ; 118(18): 8435-8473, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30148347

RESUMO

Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes from Gram-positive bacteria are secreted virulence factors that aid in downregulating host immunity. These PI-PLCs are minimalist peripheral membrane enzymes with a distorted (ßα)8 TIM barrel fold offering a conserved and stable scaffold for the conserved catalytic amino acids while membrane recognition is achieved mostly through variable loops. Decades of experimental and computational research on these enzymes have revealed the subtle interplay between molecular mechanisms of catalysis and membrane binding, leading to a semiquantitative model for how they find, bind, and cleave their respective substrates on host cell membranes. Variations in sequence and structure of their membrane binding sites may correlate with how enzymes from different Gram-positive bacteria search for their particular targets on the membrane. Detailed molecular characterization of protein-lipid interactions have been aided by cutting-edge methods ranging from 31P field-cycling NMR relaxometry to monitor protein-induced changes in phospholipid dynamics to molecular dynamics simulations to elucidate the roles of electrostatic and cation-π interactions in lipid binding to single molecule fluorescence measurements of dynamic interactions between PI-PLCs and vesicles. This toolkit is readily applicable to other peripheral membrane proteins including orthologues in Gram-negative bacteria and more recently discovered eukaryotic minimalist PI-PLCs.


Assuntos
Bactérias/enzimologia , Fosfatidilinositol Diacilglicerol-Liase/química , Fosfatidilinositol Diacilglicerol-Liase/metabolismo , Fosfatidilinositóis/metabolismo , Regulação Alostérica/fisiologia , Biocatálise , Domínio Catalítico , Membrana Celular/metabolismo , Cinética , Ligação Proteica , Conformação Proteica , Especificidade por Substrato
18.
Cell Rep ; 23(2): 499-511, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29642007

RESUMO

The role of microenvironment-mediated biophysical forces in human lymphomas remains elusive. Diffuse large B cell lymphomas (DLBCLs) are heterogeneous tumors, which originate from highly proliferative germinal center B cells. These tumors, their associated neo-vessels, and lymphatics presumably expose cells to particular fluid flow and survival signals. Here, we show that fluid flow enhances proliferation and modulates response of DLBCLs to specific therapeutic agents. Fluid flow upregulates surface expression of B cell receptors (BCRs) and integrin receptors in subsets of ABC-DLBCLs with either CD79A/B mutations or WT BCRs, similar to what is observed with xenografted human tumors in mice. Fluid flow differentially upregulates signaling targets, such as SYK and p70S6K, in ABC-DLBCLs. By selective knockdown of CD79B and inhibition of signaling targets, we provide mechanistic insights into how fluid flow mechanomodulates BCRs and integrins in ABC-DLBCLs. These findings redefine microenvironment factors that regulate lymphoma-drug interactions and will be critical for testing targeted therapies.


Assuntos
Linfoma Difuso de Grandes Células B/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Animais , Apoptose/efeitos dos fármacos , Antígenos CD79/antagonistas & inibidores , Antígenos CD79/genética , Antígenos CD79/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Doxorrubicina/farmacologia , Humanos , Integrinas/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Camundongos Endogâmicos NOD , Microfluídica/instrumentação , Microfluídica/métodos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Antígenos de Linfócitos B/genética , Resistência ao Cisalhamento , Transdução de Sinais , Microambiente Tumoral , Regulação para Cima , Quinases da Família src/metabolismo
19.
J Exp Psychol Hum Percept Perform ; 44(7): 1086-1102, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29620379

RESUMO

Attentional templates can be represented in visual working memory (VWM) when the target varies from trial-to-trial and can be represented in long-term memory (LTM) when the target is consistent during trial runs. Given that attentional templates can be represented in either VWM or LTM, are there any differences in how these representations impact visual search when targets are consistent compared with varying? The current study tested the consistent template hypothesis, which predicts faster performance with a consistent target compared with a varying target. Experiment 1 examined whether consistent targets could lead to consistent templates that would improve template establishment, guidance, and/or comparison of the template to search items. Search response time was faster for consistent targets, and consistent targets produced faster comparison processes, but not more efficient guidance. Experiment 2 examined the consistent template restoration hypothesis, which predicts faster template establishment and comparison processes for a previously encountered consistent target. Experiment 2 replicated the consistent template hypothesis and supported the consistent template restoration hypothesis. These studies demonstrate that although attentional guidance is similar with varying and consistent attentional templates, consistent templates improve search performance by speeding template establishment and comparison processes. (PsycINFO Database Record


Assuntos
Atenção/fisiologia , Percepção de Cores/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Adulto Jovem
20.
J Exp Psychol Learn Mem Cogn ; 44(3): 387-398, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28661177

RESUMO

Attention allocation determines the information that is encoded into memory. Can participants learn to optimally allocate attention based on what types of information are most likely to change? The current study examined whether participants could incidentally learn that changes to either high spatial frequency (HSF) or low spatial frequency (LSF) Gabor patches were more probable and to use this incidentally learned probability information to bias attention during encoding. Participants detected changes in orientation in arrays of 6 Gabor patches: 3 HSF and 3 LSF. For half of the participants, an HSF patch changed orientation on 75% of the trials, and for the other half, an LSF patch changed orientation on 75% of the trials. Experiment 1 demonstrated a change probability effect and an attention allocation effect. Specifically, change detection performance was highest for the probable-change type, and participants learned to use a global spread of attention (fixating between Gabor patches) when LSF patches were most likely to change and to use a local allocation of attention (fixating directly on Gabor patches) when HSF patches were most likely to change. Experiments 2 and 3 replicated these effects and demonstrated that an internal monitoring system is sufficient for these effects. That is, the effects do not require explicit feedback or point rewards. This study demonstrates that incidental learning of probability information can affect the allocation of attention during encoding and can therefore affect what information is stored in visual working memory. (PsycINFO Database Record


Assuntos
Atenção/fisiologia , Fixação Ocular/fisiologia , Memória de Curto Prazo/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Aprendizagem por Probabilidade , Adulto , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Adulto Jovem
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