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1.
PLOS Glob Public Health ; 4(7): e0002875, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38990965

RESUMO

Despite high injury mortality rates, Cameroon currently lacks a formal prehospital care system. In other sub-Saharan African low and middle-income countries, Lay First Responder (LFR) programs have trained non-medical professionals with high work-related exposure to injury in principles of basic trauma care. To develop a context-appropriate LFR program in Cameroon, we used trauma registry data to understand current layperson bystander involvement in prehospital care and explore associations between current non-formally trained bystander-provided prehospital care and clinical outcomes. The Cameroon Trauma Registry (CTR) is a longitudinal, prospective, multisite trauma registry cohort capturing data on injured patients presenting to four hospitals in Cameroon. We assessed prevalence and patterns of prehospital scene care among all patients enrolled the CTR in 2020. Associations between scene care, clinical status at presentation, and outcomes were tested using univariate and multivariate logistic regression. Injury severity was measured using the abbreviated injury score. Data were analyzed using Stata17. Of 2212 injured patients, 455 (21%) received prehospital care (PC) and 1699 (77%) did not receive care (NPC). Over 90% (424) of prehospital care was provided by persons without formal medical training. PC patients were more severely injured (p<0.001), had markers of increased socioeconomic status (p = 0.01), and longer transport distances (p<0.001) compared to NPC patients. Despite increased severity of injury, patients who received PC were more likely to present with a palpable pulse (OR = 6.2, p = 0.02). Multivariate logistic regression adjusted for injury severity, socioeconomic status and travel distance found PC to be associated with reduced emergency department mortality (OR = 0.14, p<0.0001). Although prehospital injury care in Cameroon is rarely performed and is provided almost entirely by persons without formal medical training, prehospital intervention is associated with increased early survival after injury. Implementation of LFR training to strengthen the frequency and quality of prehospital care has considerable potential to improve trauma survival.

2.
J Child Health Care ; 27(4): 693-706, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35499965

RESUMO

Repression has been linked to greater illness, somatic symptoms, and poorer physical health, both in adult and pediatric populations. The current study examined psychological and pain profiles of children with chronic pain who may under-report levels of psychological distress at a first interdisciplinary chronic pain assessment. Children and their caregiver completed measures of psychopathology and pain intensity, while clinicians rated their levels of disability. Based on self-report measures, children were classified as "repressors" (low anxiety/high social desirability) or as "true low anxious" (low anxiety/low social desirability). Groups were then compared on psychological and pain characteristics. Compared to children with true low anxiety, repressors reported lower levels of depressive and somatic symptoms but provided higher ratings on pain intensity, pain-unpleasantness, and self-oriented perfectionism. Caregivers of repressors rated their children as having higher levels of adaptability compared to caregivers of children in the true low anxious group. Groups did not differ on clinician-rated level of disability. Children classified as repressors exhibited different profiles than children classified as having true low anxiety on both psychological outcomes and pain characteristics. Repression may be an important factor to consider for those assessing and treating children with chronic pain.


Assuntos
Dor Crônica , Sintomas Inexplicáveis , Adulto , Criança , Humanos , Autorrelato , Repressão Psicológica , Adaptação Psicológica , Ansiedade/psicologia
3.
Front Oncol ; 12: 1043538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439467

RESUMO

Integrin α6ß4 is highly expressed in triple negative breast cancer (TNBC) and drives its most aggressive traits; however, its impact on chemotherapeutic efficacy remains untested. We found that integrin α6ß4 signaling promoted sensitivity to cisplatin and carboplatin but not to other chemotherapies tested. Mechanistic investigations revealed that integrin α6ß4 stimulated the activation of ATM, p53, and 53BP1, which required the integrin ß4 signaling domain. Genetic manipulation of gene expression demonstrated that mutant p53 cooperated with integrin α6ß4 for cisplatin sensitivity and was necessary for downstream phosphorylation of 53BP1 and enhanced ATM activation. Additionally, we found that in response to cisplatin-induced DNA double strand break (DSB), integrin α6ß4 suppressed the homologous recombination (HR) activity and enhanced non-homologous end joining (NHEJ) repair activity. Finally, we discovered that integrin α6ß4 preferentially activated DNA-PK, facilitated DNA-PK-p53 and p53-53BP1 complex formation in response to cisplatin and required DNA-PK to enhance ATM, 53BP1 and p53 activation as well as cisplatin sensitivity. In summary, we discovered a novel function of integrin α6ß4 in promoting cisplatin sensitivity in TNBC through DNA damage response pathway.

4.
J Anxiety Disord ; 92: 102637, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36179438

RESUMO

Adolescents' use of online resources to self-manage anxiety is growing. The objective of the current trial was to assess the effectiveness of an online, primarily self-led cognitive behavioral therapy (CBT) program in reducing anxiety symptoms compared to an active comparator, access to anxiety resources on a static website. A total of 563 adolescents (13-19 years) with self-identified anxiety concerns were enrolled. Self-reported anxiety symptoms were assessed pre- and post-intervention (6 weeks). Adolescents were further assessed 3 months post-intervention. Other outcomes assessed at the three time-points were quality of life (QOL) and healthcare utilization. Both interventions reduced anxiety symptoms after use. Group differences in symptom change were not significant post-intervention (p = 0.16), but were at 3 months (favouring online CBT; p = 0.04) with male participants reporting more symptom change (p = 0.03). Across time-points, as anxiety symptoms decreased, QOL increased (p < 0.001). Among participants that provided healthcare utilization before and after intervention use, the greatest changes in use were among online CBT users particularly for mental health provider visits (psychiatrist, -41.0 % vs. +18.5 %; social worker, -42.5 % vs. -22.1 %), hospital-based care (emergency department visits, -80.0 % vs. +79.4 %; hospital admissions, -76.1 % vs. +42.9 %), and use of self-help or alternative treatments (-60.0 % vs. +6.6 %). Results suggest that, over time, use of online CBT by adolescents can result in improved anxiety symptoms and fewer use of other healthcare resources compared to traditional online information seeking.


Assuntos
Terapia Cognitivo-Comportamental , Qualidade de Vida , Adolescente , Masculino , Humanos , Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Internet , Cognição , Resultado do Tratamento
5.
Ann Glob Health ; 88(1): 76, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118273

RESUMO

Background: Surgical site infection (SSI) is a prevalent but preventable complication in low-and-middle income countries (LMIC), with reported incidence varying from 8-30%. In 2018, the MEDIPINAS surgical mission to the Philippines observed a 28.8% rate of SSI despite adherence to WHO intraoperative protocols.The objective of this study was to introduce an educational program for wound care and early identification of wound infection. This program included provision of wound care materials and systematic protocol to ensure adequate and effective follow-up. Barriers to SSI prophylaxis in the Philippines include limited resources in regional hospitals and isolation of patients living in rural areas. The MEDIPINAS mission utilized mobile health software to connect with regional providers and to reinforce the wound care educational program introduced at discharge. Methods: The 2019 MEDIPINAS mission returned to the Philippines and operated on 187 patients in San Antonio de Padua Diocesan Hospital and Santa Maria Josefa Hospital. Before discharge, patients were individually consulted about maintaining the cleanliness of their surgical wound. Each patient was discharged with a wound care infographic and a kit to change dressings. In collaboration with regional care providers, we utilized a secure mobile health software to monitor wound healing 7 and 30 days following the operation. Results: Between the 2018 and 2019 surgical missions, we observed a decrease in SSI from 28.8% to 9.7%. Fourteen patients (7.5%) were lost to follow-up. Postoperative infection was diagnosed using photos provided by hospital-based nurses. Individuals with infections were treated with antibiotics and all but two SSI resolved after 30 days. Conclusions: Patient education, discharge with basic sanitary resources, and development of a mobile health-based follow-up infrastructure may contribute to significant reductions in SSI in LMICs. A limitation to implementation of such a program was integration of the mobile health software into the practice of local healthcare providers.


Assuntos
Infecção da Ferida Cirúrgica , Telemedicina , Antibacterianos , Humanos , Alta do Paciente , Filipinas/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle
6.
Gut Microbes ; 14(1): 2083417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35658830

RESUMO

Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.


Assuntos
Microbioma Gastrointestinal , Amidoidrolases/metabolismo , Animais , Ácidos e Sais Biliares , Fibras na Dieta , Microbioma Gastrointestinal/fisiologia , Humanos , Camundongos
8.
Psychol Rep ; 125(3): 1556-1572, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33726575

RESUMO

In two studies, using a mix of samples, we examined the influence of weight bias on behaviors in competitive, potentially high stakes situations. As predicted, weight bias directed focal actors' treatment of counterparts in a negotiation. Negotiators made lower value offers to overweight counterparts relative to average-weight counterparts. In addition, overweight counterparts also received more negative messages over the course of their negotiation and were evaluated less favorably after the negotiation than average-weight counterparts.


Assuntos
Negociação , Preconceito de Peso , Humanos , Sobrepeso
9.
J Cell Sci ; 135(2)2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34897465

RESUMO

Integrin α6ß4 binds plectin to associate with vimentin; however, the biological function remains unclear. Here, we utilized various integrin ß4 mutants and CRISPR-Cas9 editing to investigate this association. Upon laminin binding, integrin α6ß4 distinctly distributed peripherally as well as centrally, proximal to the nucleus. Upon fibronectin addition, integrin α6ß4 was centrally recruited to large focal adhesions (FAs) and enhanced Fak (also known as PTK2) phosphorylation. Integrin ß4 plectin-binding mutants or genetic deletion of plectin inhibited ß4 recruitment to FAs and integrin α6ß4-enhanced cell spreading, migration and three-dimensional invasive growth. Loss of the ß4 signaling domain (but retaining plectin binding) blocked migration and invasiveness but not cell spreading, recruitment to FAs or colony growth. Immunostaining revealed that integrin α6ß4 redistributed vimentin perinuclearly, where it colocalized with plectin and FAs. Depletion of vimentin completely blocked integrin ß4-enhanced invasive growth, Fak phosphorylation and proliferation in three dimensions but not two dimensions. In summary, we demonstrate the essential roles of plectin and vimentin in promoting an invasive phenotype downstream of integrin α6ß4. This article has an associated First Person interview with the first author of the paper.


Assuntos
Integrina alfa6beta4 , Plectina , Adesão Celular , Humanos , Integrina alfa6beta4/genética , Integrina beta4/genética , Filamentos Intermediários , Plectina/genética , Vimentina/genética
10.
Microbiology (Reading) ; 168(12)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36748632

RESUMO

Pseudomonas aeruginosa uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. It has previously been shown that lasR QS mutations frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether other QS system mutations arise during infection or in other environments. To test this, we utilized 852 publicly available sequenced P. aeruginosa genomes from the Pseudomonas International Consortium Database (IPCD) to study P. aeruginosa QS mutational signatures. To study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. We also worked with a small collection of isolates in vitro to determine the impact of lasR and pqs mutations on isolate phenotypes. We found that lasR mutations are common across all environments and are not specific to infection nor a particular infection type. We also found that the pqs system proteins PqsA, PqsH, PqsL and MexT, a protein of increasing importance to the QS field, are highly variable. Conversely, RsaL, a negative transcriptional regulator of the las system, was found to be highly conserved, suggesting selective pressure to repress las system activity. Overall, our findings suggest that QS mutations in P. aeruginosa are common and not limited to the las system; however, LasR is unique in the frequency of putative loss-of-function mutations.


Assuntos
Proteínas de Bactérias , Pseudomonas aeruginosa , Percepção de Quorum , Humanos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fibrose Cística , Regulação Bacteriana da Expressão Gênica , Mutação , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas , Percepção de Quorum/genética , Transativadores/genética , Transativadores/metabolismo
11.
Aging Clin Exp Res ; 33(12): 3303-3311, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34050916

RESUMO

BACKGROUND: Cognitive screening is important for the oldest-old (age 90 +). This age group is the fastest growing and has the highest risk of dementia. However, norms and score equivalence for screening tests are lacking for this group. AIMS: To provide norms and score equivalence for commonly used cognitive screening tests for the oldest-old. METHODS: Data on 157 participants of the Center for Healthy Aging Longevity Study aged 90 + were analyzed. First, we derived norms for (1) subtests and cognitive domains of the in-person Montreal Cognitive Assessment having a maximum score of 30 (MoCA-30) and (2) the total MoCA-22 score, obtained from the in-person MoCA-30 by summing the subtests that do not require visual input to a maximum score of 22. These norms were derived from 124 participants with a Mini-Mental State Examination (MMSE) ≥ 27. Second, we derived score equivalences for MMSE to MoCA-30 and MoCA-22, and MoCA-30 to MoCA-22 using equipercentile equating method with log-linear smoothing, based on all 157 participants. RESULTS: MoCA-22 total score norms are: mean = 18.3(standard deviation = 2.2). An MMSE score of 27 is equivalent to a MoCA-30 score of 22 and a MoCA-22 score of 16. DISCUSSION AND CONCLUSIONS: Subtest, domain and MoCA-22 norms will aid in evaluation of the oldest-old who cannot complete the MoCA-30 or are tested over the phone. The equivalences of the three cognitive tests (MMSE, MoCA-30, MoCA-22) in the oldest-old will facilitate continuity of cognitive tracking of individuals tested with different tests over time and comparison of the studies that use different cognitive tests.


Assuntos
Disfunção Cognitiva , Idoso de 80 Anos ou mais , Humanos , Programas de Rastreamento , Testes de Estado Mental e Demência , Testes Neuropsicológicos
12.
Surg Obes Relat Dis ; 17(6): 1218-1225, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33814315

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is one of the most common causes of postoperative mortality following bariatric surgery. The majority of VTE events occur after discharge from the hospital. Little consensus exists regarding who should receive extended enoxaparin thromboprophylaxis or how they should be dosed, namely whether to use weight-based or BMI-stratified dosing strategies. OBJECTIVES: Provide an overview of the risk factors associated with VTE in procedures among bariatric patients including the use of predictive tools to stratify risk and the various approaches to enoxaparin chemoprophylaxis in obesity. SETTING: Multiple centers. METHODS: A review of the literature identified studies evaluating risk factors for VTE including demographic characteristics, co-morbidities, and operative factors. The use of calculators to stratify patients by risk and approaches to extended thromboprophylaxis in obesity were evaluated as well. RESULTS: VTE was associated with increased age, weight, male sex, and prior history of VTE, all frequently included in risk calculators. Outside of those major risk factors, there is little consensus about the importance of patient diagnoses. Weight-based dosing was often superior to standardized dosing in studies across disciplines in generating target anti-Xa levels however there is no consistent association of reduced risk of VTE with therapeutic anti-Xa levels. CONCLUSIONS: Risk calculators may be a valuable tool for identifying patients at high-risk for VTE, but their efficacy depends on the rating algorithm and inclusion of various risk factors and is methodologically limited by prophylactic interventions. Future work should consider if biochemical factors should be included in patient stratification approaches in particular when defining the ideal chemoprophylaxis approach. Transparency and consistency in data collection and reporting is needed to better assess and inform the ideal dosing strategy to prevent VTE following bariatric surgery.


Assuntos
Cirurgia Bariátrica , Tromboembolia Venosa , Assistência ao Convalescente , Anticoagulantes/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Enoxaparina/uso terapêutico , Humanos , Masculino , Alta do Paciente , Fatores de Risco , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
13.
Psychol Rep ; 124(3): 1298-1315, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32437255

RESUMO

In two studies, we examine how objective complexity-in terms of numbers of negotiable issues-affects negotiators' aspirations, perceptions, actions, and ultimately, the quality of agreements they reach. We hypothesized and found that when negotiators had a greater number of issues to resolve, they were less ambitious for their own outcomes and developed less accurate insights into their partners' interests.


Assuntos
Objetivos , Julgamento , Negociação , Feminino , Humanos , Masculino , Negociação/psicologia , Resolução de Problemas , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-32664373

RESUMO

Background: Low fertility persists but remains unexplained in Japan. We examined whether the probability of pregnancy was influenced by coital frequency, age, reproductive age (assessed by antimüllerian hormone, AMH), and BMI. Methods: We established a two-year prospective study with a sample of hormonally monitored Japanese women aged 23-34 years wanting to conceive their first child. For a maximum of 24 weeks participants recorded menstrual bleeding, sexual intercourse, ovulation, and pregnancy. Additional information on pregnancy and infertility treatment was collected one and two years after intake. Results: The natural conception rate and coital frequency were both low in this sample. Among 80 participants, 44% (35) naturally conceived in 24 weeks. After two years, 74% (59) of women had delivered or were currently pregnant, 50% (40) due to natural and 24% (19) due to assisted conception, and 5% (4) were lost to follow-up. By two years, 56% (45) of women had sought fertility treatment. In 18% (58/319) of the observed ovarian cycles across 24 weeks there was no intercourse in a fertile period. Higher coital frequency at intake was associated with increased probability of conception by 24 weeks of follow-up (OR 1.23, 95%CI 1.02, 1.47). Chronological age, reproductive age, and BMI were not associated with the probability of pregnancy at 24 weeks. Conclusions: Our results suggest that first, natural conception rates could potentially increase with more frequent and well timed intercourse, and second that further work is needed to understand why even in a motivated sample of women monitoring their fertile periods, both the conception and coitus rates were low.


Assuntos
Coito , Fertilidade , Resultado da Gravidez , Adulto , Fatores Etários , Feminino , Humanos , Lactente , Japão/epidemiologia , Gravidez , Probabilidade , Estudos Prospectivos , Adulto Jovem
15.
JMIR Ment Health ; 7(7): e13356, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32706720

RESUMO

BACKGROUND: Internet-based cognitive behavioral therapy (ICBT) is a treatment approach recently developed and studied to provide frontline treatment to adolescents with anxiety disorders. OBJECTIVE: This study aimed to pilot procedures and obtain data on methodological processes and intervention satisfaction to determine the feasibility of a definitive randomized controlled trial (RCT) to test the effectiveness of a self-managed ICBT program, Breathe (Being Real, Easing Anxiety: Tools Helping Electronically), for adolescents with anxiety concerns. METHODS: This study employed a two-arm, multisite, pilot RCT. Adolescents aged 13 to 17 years with a self-identified anxiety concern were recruited online from health care settings and school-based mental health care services across Canada between April 2014 and May 2016. We compared 8 weeks of ICBT with ad hoc telephone and email support (Breathe experimental group) to access to a static webpage listing anxiety resources (control group). The primary outcome was the change in self-reported anxiety from baseline to 8 weeks (posttreatment), which was used to determine the sample size for a definitive RCT. Secondary outcomes were recruitment and retention rates, a minimal clinically important difference (MCID) for the primary outcome, intervention acceptability and satisfaction, use of cointerventions, and health care resource use, including a cost-consequence analysis. RESULTS: Of the 588 adolescents screened, 94 were eligible and enrolled in the study (49 adolescents were allocated to Breathe and 45 were allocated to the control group). Analysis was based on 74% (70/94) of adolescents who completed baseline measures and progressed through the study. Enrolled adolescents were, on average, 15.3 years old (SD 1.2) and female (63/70, 90%). Retention rates at 8 weeks were 28% (13/46; Breathe group) and 58% (24/43; control group). Overall, 39% (14/36) of adolescents provided feedback on completion of the Breathe program. Adolescents' scores on a satisfaction survey indicated a moderate level of satisfaction. All but one adolescent indicated that Breathe was easy to use and they understood all the material presented. The most frequent barrier identified for program completion was difficulty in completing exposure activities. The power analysis indicated that 177 adolescents per group would be needed to detect a medium effect size (d=0.3) between groups in a definitive trial. Data for calculating an MCID or conducting a cost-consequence analysis were insufficient due to a low response rate at 8 weeks. CONCLUSIONS: Adolescents were moderately satisfied with Breathe. However, program adjustments will be needed to address attrition and reduce perceived barriers to completing key aspects of the program. A definitive RCT to evaluate the effectiveness of the program is feasible if protocol adjustments are made to improve recruitment and retention to ensure timely study completion and increase the completeness of the data at each outcome measurement time point. TRIAL REGISTRATION: ClinicalTrials.gov NCT02059226; http://clinicaltrials.gov/ct2/show/NCT02059226.

16.
Bio Protoc ; 10(7): e3579, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33659549

RESUMO

Metastasis accounts for the majority of cancer related deaths. The genetically engineered mouse (GEM) models and cell line-based subcutaneous and orthotopic mouse xenografts have been developed to study the metastatic process. By using lung cancer cell line A549 as an example, we present a modified protocol to establish the cell line-based xenograft. Our protocol ensures sufficient establishment of the mouse xenografts and allows us to monitor tumor growth and spontaneous metastasis. This protocol could be adapted to other types of established cancer cell lines or primary cancer cells to study the mechanism of metastatic process as well as to test the effect of the potential anti-cancer agents on tumor growth and metastatic capacity.

17.
J Cancer Educ ; 35(1): 205-209, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30887313

RESUMO

In 2017, the National Cancer Institute (NCI) announced new guidelines for the Cancer Center Support Grant (CCSG) application that requires reporting on education and career development activities in a section entitled, "Cancer Research Career Enhancement and Related Activities" (CRCERA). While these cancer education and training programs previously have been a required part of the CCSG application, the new guidelines require greater rigor in conducting and reporting these endeavors. In this commentary, I give my perspective of how I have built a cancer education program, first as a program director and then as an associate director of cancer education and mentoring, the critical role leadership plays in the process, and how I have recruited contributors to this educational "stone soup."


Assuntos
Liderança , Oncologia/educação , Tutoria/métodos , Mentores/educação , Neoplasias/terapia , Pesquisadores/educação , Humanos , Neoplasias/diagnóstico
18.
PLoS One ; 14(11): e0224836, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714906

RESUMO

The opportunistic pathogen Escherichia coli, a common member of the human gut microbiota belonging to the Enterobacteriaceae family, is the causative agent of the majority of urinary tract infections (UTIs). The gut microbiota serves as a reservoir for uropathogenic E. coli where they are shed in feces, colonize the periurethral area, and infect the urinary tract. Currently, front line treatment for UTIs consists of oral antibiotics, but the rise of antibiotic resistance is leading to higher rates of recurrence, and antibiotics cause collateral damage to other members of the gut microbiota. It is commonly believed that incorporation of the American cranberry, Vaccinium macrocarpon, into the diet is useful for reducing recurrence of UTIs. We hypothesized such a benefit might be explained by a prebiotic or antimicrobial effect on the gut microbiota. As such, we tested cranberry extracts and whole cranberry powder on a human gut microbiome-derived community in a gut simulator and found that cranberry components broadly modulate the microbiota by reducing the abundance of Enterobacteriaceae and increasing the abundance of Bacteroidaceae. To identify the specific compounds responsible for this, we tested a panel of compounds isolated from cranberries for activity against E. coli, and found that salicylate exhibited antimicrobial activity against both laboratory E. coli and human UTI E. coli isolates. In a gut simulator, salicylate reduced levels of Enterobacteriaceae and elevated Bacteroidaceae in a dose dependent manner.


Assuntos
Bacteroidaceae/crescimento & desenvolvimento , Enterobacteriaceae/crescimento & desenvolvimento , Microbioma Gastrointestinal , Modelos Biológicos , Extratos Vegetais/farmacologia , Vaccinium macrocarpon/química , Bacteroidaceae/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hidroxibenzoatos/farmacologia , Testes de Sensibilidade Microbiana , Pós , Ácido Salicílico/farmacologia , Infecções Urinárias/microbiologia
19.
Am J Clin Nutr ; 110(3): 722-732, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380559

RESUMO

BACKGROUND: Plant-based diets may help improve measures of body fat, blood cholesterol, glucose metabolism, and inflammation. However, limited evidence suggests that the health effects of reducing animal products may depend on the quality of plant-based foods consumed as caloric replacements. OBJECTIVE: This study examined how temporarily restricting consumption of meat, dairy, and egg (MDE) products for religious purposes influences cardiometabolic health biomarkers and whether any effects of MDE restriction on biomarkers are modified by concurrent shifts in calories, fish, and distinct plant-based foods. DESIGN: This study followed a sample of 99 individuals in the United States with varying degrees of adherence to Orthodox Christian (OC) guidance to abstain from MDE products during Lent, the 48-d period prior to Easter. Dietary composition was estimated from FFQs and 7-d food records; measures of body fat, blood lipids, glucose metabolism, and inflammation were collected prior to and at the end of Lent. RESULTS: Each serving decrease in MDE products was associated with an average -3.7% (95% CI: -5.5%, -2.0%; P < 0.0001) and -3.6% (95% CI: -5.8%, -1.3%; P = 0.003) change in fasting total and LDL blood cholesterol, respectively, which were partly explained by minor weight loss. However, the total/HDL cholesterol ratio did not significantly decrease due to an average -3.2% (95% CI: -5.8%, -0.6%; P = 0.02) change in HDL cholesterol. No associations between MDE restrictions and shifts in measures of body fat, glucose, insulin, or C-reactive protein were observed. The data could not provide evidence that changes in cardiometabolic health biomarkers in relation to MDE restriction were modified by concurrent shifts in calories, fish, or plant-based foods. CONCLUSION: Temporary MDE restrictions practiced by this sample of OCs in the United States during Lent had minimal effects on cardiometabolic disease risk factors. Further research among larger samples of OCs is needed to understand how nutritionally distinct and complex combinations of plant-based foods may modify the health effects of religious fasting from MDE products.


Assuntos
Doenças Cardiovasculares/sangue , Ortodoxia Oriental , Ovos , Jejum , Carne , Doenças Metabólicas/sangue , Tecido Adiposo , Adulto , Idoso , Animais , Biomarcadores/sangue , Laticínios , Dieta , Ingestão de Energia , Feminino , Glucose/metabolismo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
20.
Nat Commun ; 10(1): 3708, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420553

RESUMO

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and ß1-integrin receptors, resulting in Met/ß1-integrin co-internalization and co-accumulation on endosomes. This provides persistent signals to activate the FAK/p130Cas pathway, thereby promoting CRC cell migration, invasion and metastasis. Blocking endocytosis or endosomal Met/ß1-integrin/FAK signaling profoundly inhibits the oncogenic effects of both NRP1 variants. These findings reveal an important role for these NRP1 splice variants in the regulation of endocytic trafficking for cancer cell dissemination.


Assuntos
Neoplasias Colorretais/genética , Endossomos/metabolismo , Neuropilina-1/genética , Processamento Alternativo/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Proteína Substrato Associada a Crk/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Glicosilação , Células HCT116 , Células HT29 , Humanos , Integrina beta1/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Neuropilina-1/metabolismo , Transporte Proteico , Proteínas Proto-Oncogênicas c-met/metabolismo , Transdução de Sinais
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