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1.
Eur J Neurosci ; 60(3): 4346-4361, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38858126

RESUMEN

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Estenosis Carotídea , Circulación Cerebrovascular , Animales , Femenino , Masculino , Lesiones Traumáticas del Encéfalo/fisiopatología , Ratones , Circulación Cerebrovascular/fisiología , Estenosis Carotídea/fisiopatología , Ratones Endogámicos C57BL , Caracteres Sexuales , Factores Sexuales , Memoria Espacial/fisiología , Modelos Animales de Enfermedad , Aprendizaje Espacial/fisiología
2.
Matern Child Health J ; 28(7): 1258-1263, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38461475

RESUMEN

OBJECTIVE: To elucidate the association between GBS infection and maternal risk for obstetric hemorrhage (OBH) and OBH-related morbidities (OBH-M). METHODS: This was a retrospective cohort study of all deliveries with a documented GBS status at a single large academic medical center from 2018 to 2019. GBS status was determined by either urine culture or rectovaginal culture collected during the antepartum period. The primary outcomes were quantitative blood loss (QBL), OBH, and a composite of OBH-M. Secondary outcomes were individual components of the OBH-M composite and frequency of hemorrhage-related interventions utilized intrapartum and postpartum. A stratified analysis was conducted examining only patients who were diagnosed intrapartum with an intrapartum intraamniotic infection (III). RESULTS: Of 4679 pregnant individuals who delivered a live infant between January 1, 2018 and January 1,2019 with a documented GBS status, 1,487 were identified as GBS positive (+) and 3192 were identified as GBS negative (-). The GBS + group did not have significantly higher QBL (p = 0.29) or rate of OBH (p = 0.35). There were no significant differences by GBS status in OBH morbidity (p = 0.79) or its individual components or frequency of individual pharmacologic or non-pharmacologic OBHrelated interventions. There were also no significant differences by GBS status among patients with an III. CONCLUSIONS FOR PRACTICE: GBS infection at the time of delivery was not associated with increased risk for OBH or OBH-M. Further research is needed to further explore the relationship between peripartum infections and OBH risk.


Asunto(s)
Hemorragia Posparto , Infecciones Estreptocócicas , Streptococcus agalactiae , Humanos , Femenino , Embarazo , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/complicaciones , Estudios Retrospectivos , Adulto , Streptococcus agalactiae/aislamiento & purificación , Hemorragia Posparto/epidemiología , Hemorragia Posparto/etiología , Complicaciones Infecciosas del Embarazo/epidemiología , Factores de Riesgo , Estudios de Cohortes
3.
Arch Gynecol Obstet ; 309(2): 491-501, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-36781431

RESUMEN

PURPOSE: Prolonged duration of intrapartum oxytocin exposure is included as a risk factor within widely adopted obstetric hemorrhage risk stratification tools. However, the duration of exposure that confers increased risk is poorly understood. This study aimed to assess the association between duration of intrapartum oxytocin exposure and obstetric blood loss, as measured by quantitative blood loss, and hemorrhage-related maternal morbidity. METHODS: This was a retrospective cohort study of all deliveries from 2018 to 2019 at a single medical center. We included patients who had received any intrapartum oxytocin, and we categorized them into 1 of 5 groups: > 0-2, ≥ 2-4, ≥ 4-6, ≥ 6-12, and ≥ 12 h of intrapartum oxytocin exposure. The primary outcomes were mean quantitative blood loss, proportion with obstetric hemorrhage (defined as quantitative blood loss ≥ 1000 mL), and proportion with obstetric hemorrhage-related morbidity, a composite of hemorrhage-related morbidity outcomes. Secondary outcomes were hemorrhage-related pharmacologic and procedural interventions. A stratified analysis was also conducted to examine primary and secondary outcomes by delivery mode. RESULTS: Of 5332 deliveries between January 1, 2018 and December 31, 2019 at our institution, 2232 (41.9%) utilized oxytocin for induction or augmentation. 326 (14.6%) had exposure of > 0-2 h, 295 (13.2%) ≥ 2-4 h, 298 (13.4%) ≥ 4-6 h, 562 (25.2%) ≥ 6-12 h, and 751 (33.6%) ≥ 12 h. Across all deliveries, there was higher mean quantitative blood loss (p < 0.01) as well as increased odds of obstetric hemorrhage (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.21-1.91) for those with ≥ 12 h of oxytocin compared to all groups between > 0-12 h of exposure. In our stratified analysis, ≥ 12 h of oxytocin exposure was associated with higher mean quantitative blood loss (p = 0.04) and odds of obstetric hemorrhage in vaginal deliveries (aOR 1.47, 95% CI: 1.03-2.11), though not in cesarean deliveries (aOR 1.16, 95% CI 0.82-1.62). There were no differences in proportion with obstetric hemorrhage-related morbidity across all deliveries (p = 0.40) or in the stratified analysis. CONCLUSION: Intrapartum oxytocin exposure of ≥ 12 h was associated with increased quantitative blood loss and odds of obstetric hemorrhage in vaginal, but not cesarean, deliveries.


Asunto(s)
Oxitocina , Hemorragia Posparto , Embarazo , Femenino , Humanos , Oxitocina/efectos adversos , Estudios Retrospectivos , Hemorragia Posparto/inducido químicamente , Hemorragia Posparto/epidemiología , Parto , Parto Obstétrico/efectos adversos
4.
Am J Perinatol ; 2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36351443

RESUMEN

OBJECTIVE: The aim of this study was to assess whether inclusion of intrapartum risk factors improves our obstetric hemorrhage risk stratification tool in predicting obstetric hemorrhage, transfusion, and related severe morbidity. STUDY DESIGN: This is a retrospective cohort study using all live deliveries at a single institution over a 2-year period (n = 5,332). Obstetric hemorrhage risk factors, hemorrhage burden, and severe maternal morbidity index outcomes were assessed through chart abstraction. Hemorrhage risk was assessed at (1) "time of admission" through chart abstraction and (2) "predelivery" by calculation after inclusion of all abstracted intrapartum risk factors. Admission high risk was compared with predelivery high risk for sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio in predicting obstetric hemorrhage, obstetric hemorrhage requiring transfusion, and obstetric hemorrhage-related severe morbidity. Significance levels were calculated using descriptive statistical methods including chi-squared tests and McNemar's tests. RESULTS: The sensitivities of the risk assessment tool using admission risk classification for high-risk patients is 25% for obstetric hemorrhage, 37% for obstetric hemorrhage requiring transfusion, and 22% for obstetric hemorrhage-related severe morbidity. After intrapartum factor inclusion, the sensitivities increase to 55% for obstetric hemorrhage, 59% for obstetric hemorrhage requiring transfusion, and 47% for obstetric hemorrhage-related severe morbidity. This "predelivery" risk assessment is significantly more sensitive across all three end points (p < 0.001 for all three outcomes). While the positive likelihood ratios for obstetric hemorrhage are equal on admission and predelivery (2.10 on admission and predelivery), they increase after intrapartum factor inclusion for obstetric hemorrhage requiring transfusion and obstetric hemorrhage-related severe morbidity (on admission, 2.74 and 1.6, respectively, and predelivery: 4.57 and 3.58, respectively). CONCLUSION: Inclusion of intrapartum risk factors increases the accuracy of this obstetric hemorrhage risk stratification tool in predicting patients requiring hemorrhage management with transfusion and obstetric hemorrhage-related severe morbidity. KEY POINTS: · There are little data to validate intrapartum hemorrhage risk reassessment.. · Including intrapartum factors improves risk stratification for transfusion and related morbidity.. · Future research should clinically validate risk reassessment in the intrapartum period..

5.
J Eval Clin Pract ; 30(1): 37-41, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37035996

RESUMEN

AIMS AND OBJECTIVES: Our goal is to describe the association between total quantitative blood loss (QBL) and risk of obstetric haemorrhage-related morbidity (OBH-M) to assess the utility of the current definition of obstetric haemorrhage (OBH). METHODS: This was a retrospective cohort study completed of all patients who had a live delivery at the only urban safety-net hospital over a 2-year period from 2018 to 2019. We categorized deliveries into 10 equally sized deciles based on QBL and compared the proportion with OBH-M in each. Among the two deciles with the highest proportions of OBH-M, we stratified deliveries into seven groups of ascending intervals of 250cc QBL. Finally, we compared the positive predictive value (PPV) of the standard definition of OBH (QBL ≥ 1000cc) to a definition extrapolated from our stratified analysis. The primary outcome was proportion of deliveries within each QBL decile affected by OBH-M. The secondary outcome was PPV. RESULTS: We found a significant increase in OBH-M from decile 9 (895-1201cc QBL) to decile 10 (1205-8325cc QBL) (p < 0.001). In our stratified analysis, we found QBL of 1500cc to be an inflection point for an increased proportion of OBH-M. Our secondary analysis showed an increased PPV for OBH-M using QBL of 1500cc (20.5%) compared with that of QBL 1000cc (9.8%). CONCLUSIONS: Our findings suggest that a higher QBL threshold than the currently accepted definition of OBH is more predictive of OBH-M.


Asunto(s)
Parto Obstétrico , Hemorragia , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Hemorragia/diagnóstico , Hemorragia/epidemiología , Hemorragia/etiología , Morbilidad , Parto Obstétrico/efectos adversos
7.
Am J Lifestyle Med ; 16(5): 577-588, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36072687

RESUMEN

In an era of ever-increasing healthcare expenditures, yet simultaneously worsening outcomes, many of our patients choose between traditional medical care or often unproven alternative therapies. While the recognition of lifestyle change in addressing cardiovascular and metabolic disease grows, there is less understanding of the impact of lifestyle change on issues facing women every day. Millions of women around the globe struggle with infertility, cancer, sexual dysfunction, and dermatologic needs. Yet, research on the benefits of lifestyle change on these conditions is scarce, and gaps exist both in our understanding of evidence-based approaches to address these issues, as well as adequate provider education when evidence exists. The Women's Health Member Interest Group convened medical experts in these areas that affect women's lives to provide insights and meaningful education applicable not only for our patients, but also in our own lives.

8.
J Matern Fetal Neonatal Med ; 35(25): 10036-10043, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35704050

RESUMEN

BACKGROUND: The gold standard intrapartum treatment for preeclampsia with severe features is magnesium sulfate in order to provide prophylaxis against eclampsia. However, though magnesium sulfate is known to have a relaxant effect on uterine muscle, there have been variable reports in the literature in regard to the association between magnesium and obstetric hemorrhage (OBH). OBJECTIVE: We aim to compare OBH incidence in patients with hypertensive disease of pregnancy (HDP) with or without exposure to intrapartum magnesium sulfate. METHODS: We performed a retrospective cohort study of all deliveries at our institution associated with a diagnosis of hypertensive disease of pregnancy (HDP) (e.g. chronic and gestational hypertension, preeclampsia with or without severe features, eclampsia, or HELLP) from January 1, 2018 to December 31, 2019. The category of HDP diagnosis was determined by a detailed chart review by trained chart abstractors. The primary outcome was total quantitative blood loss (QBL) and the rate of obstetric hemorrhage. Secondary outcomes included a composite of obstetric hemorrhage-related maternal morbidity outcomes (OBH-M), the individual composite components and the incidence of additional hemorrhage-related interventions (e.g. uterotonics and surgical interventions). We also examined the same primary and secondary outcomes in a stratified analysis based on delivery mode (i.e. vaginal deliveries only and cesarean deliveries only). RESULTS: Of 791 patients with a diagnosis of HDP, 411 patients received magnesium sulfate for eclampsia prophylaxis and 380 patients did not receive magnesium sulfate. For all delivery modes, there was a significantly higher QBL (p < .01), increased rate of OBH (p = .04) and increased OBH-M (p < .01) in deliveries associated with intrapartum exposure to magnesium compared to those without. However, our stratified analysis by delivery mode demonstrated that magnesium-related hemorrhage risk only persisted for vaginal deliveries (QBL p < .01; OBH aOR 1.47, 95% CI: 0.75-2.85; OBH-M aOR 1.47, 95% CI 1.00-7.55) with no significant hemorrhage-related differences among cesareans with or without magnesium exposure (QBL p = .51; OBH aOR 1.45, 95% CI: 0.85-2.47; OBH-M 1.50 95% CI: 0.70-3.23). CONCLUSION: Intrapartum exposure to magnesium sulfate use was associated with an increase in QBL and risk of OBH-M in vaginal deliveries, but not associated with any hemorrhage-related outcome differences in cesarean deliveries. More research is needed to explore the effects of hypertensive disease, magnesium exposure, and delivery mode on obstetric hemorrhage risk.


Asunto(s)
Eclampsia , Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Humanos , Sulfato de Magnesio/efectos adversos , Eclampsia/epidemiología , Preeclampsia/epidemiología , Preeclampsia/tratamiento farmacológico , Estudios Retrospectivos , Magnesio , Hipertensión Inducida en el Embarazo/tratamiento farmacológico , Parto Obstétrico/efectos adversos
9.
Psychol Rep ; 124(3): 1335-1352, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32460674

RESUMEN

To date, no research has examined need for power as a reason why narcissists engage in antisocial behavior. The purpose of the current research is to examine need for power as a potential mediating factor between narcissism and antisocial behavior. The current research was conducted in two studies. Participants (n = 408) of study one consisted of undergraduate students who completed an online survey focusing on narcissism, need for power, and aggression. The results of Study 1 found that Need for Power fully mediated the association between narcissism and aggression. Participants (n = 323) of study two consisted of adults who completed an online survey through Mechanical Turk. Study 2 focused on seven types of narcissism, four types of need for power, need for influence, and lifetime criminal behavior. The results of Study 2 found that most forms of narcissism positively associated with criminal behavior but only the desire to resist subordination mediated the link between narcissism and criminal behavior.


Asunto(s)
Agresión/psicología , Narcisismo , Poder Psicológico , Criminales/psicología , Femenino , Humanos , Internet , Masculino , Estudiantes/psicología , Encuestas y Cuestionarios , Adulto Joven
10.
Am J Lifestyle Med ; 15(5): 514-525, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34646100

RESUMEN

A gaping void of adequate lifestyle medicine (LM) training exists across the medical education continuum. The American College of Lifestyle Medicine's (ACLM's) undergraduate medical education (UME) Task Force champions the need for widespread integration of LM curriculum in UME by sharing ideas for catalyzing success, lessons learned, and publishing standards and competencies to facilitate curriculum reform. When it comes to graduate medical education and fellowship, the ACLM and American Board of Lifestyle Medicine have made great strides in filling the void, developing both Educational and Experiential Pathways through which physicians may become certified LM Physicians or LM Specialists (LMSs). The Lifestyle Medicine Residency Curriculum meets the Educational Pathway requirements and prepares resident graduates for the LM Physician board certification. LMS is the second tier of LM certification that demonstrates expertise in disease reversal. The LMS Fellowship is an Educational Pathway intent on American Board of Medical Specialties recognition of LM as a new subspecialty in the near future. Finally, continuing medical education and maintenance of certification equip physicians with LM training to support knowledge, application, and certification in LM.

11.
Am J Lifestyle Med ; 15(4): 414-424, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34366740

RESUMEN

Over the course of the reproductive life span, it is common for women to experience one or more of the most common gynecologic conditions, including sexual dysfunction, polycystic ovary syndrome, fibroids, endometriosis, and infertility. Although current management guidelines often turn to the established pharmaceutical approaches for each of these diagnoses, the scientific literature also supports an evidence-based approach rooted in the paradigm of food as medicine. Achieving healthy dietary patterns is a core goal of lifestyle medicine, and a plant-forward approach akin to the Mediterranean diet holds great promise for improving many chronic gynecologic diseases. Furthermore, creating an optimal preconception environment from a nutritional standpoint may facilitate epigenetic signaling, thus improving the health of future generations. This state-of-the-art review explores the literature connecting diet with sexual and reproductive health in premenopausal women.

12.
Am J Lifestyle Med ; 15(5): 526-530, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34646101

RESUMEN

Lifestyle medicine (LM) is an emerging specialty that is gaining momentum and support from around the world. The American Medical Association passed a resolution to support incorporating LM curricula in medical schools in 2017. Since then, the American College of Lifestyle Medicine Undergraduate Medical Education Task Force has created a framework for incorporating LM into medical school curricula. This article provides competencies for medical school LM curriculum implementation and illustrates how they relate to the Association of American Medical College's Core Entrustable Professional Activities and the LM Certification Competencies from the American Board of Lifestyle Medicine. Finally, standards are presented for how medical schools may receive certification for integrating LM into their curriculum and how medical students can work toward becoming board certified in LM through an educational pathway.

13.
Inflamm Bowel Dis ; 27(3): 371-378, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-32448906

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a reduced quality of life. Minority patients with IBD specifically report more impairing symptoms compared with nonminority patients. Sleep quality, a key component of quality of life, is significantly compromised in minority patients compared with nonminority patients. Nevertheless, subjective and objective sleep assessments in minority patients with IBD have not explicitly been assessed. The purpose of this prospective cohort study is to assess and compare objective sleep parameters utilizing wrist actigraphy between minority and nonminority IBD patients. METHODS: In this institutional review board approved study, 74 patients with IBD were recruited and stratified into 2 cohorts by self-identification: white nonminority patients and minority patients. Patients in the minority cohort included black and Hispanic individuals (black and nonblack). Exclusion criteria included significant comorbidity, a history of an underlying sleep disorder, or patients who did not self-identify into categorized cohorts. Sleep was measured not only through wrist-based actigraphy but also with sleep surveys. Sleep parameters were compared between minority and nonminority cohorts. Regression analyses were performed to assess for factors independently associated with parameters of poor sleep quality. RESULTS: Sixty-four patients (86.4%) were included in the final analysis. Thirty-one individuals (48.4%) were categorized into the nonminority cohort, and 33 (51.6%) patients were in the minority cohort. A significantly higher number of minority patients had poorer sleep efficiency and fragmented sleep compared with nonminority patients (90.9% vs 67.7%; P = 0.03 and 87.8% vs 61.3%; P = 0.02). In the adjusted analysis, minority status was independently associated with poor sleep efficiency (odds ratio = 6.41; 95% confidence interval, 1.48-28.17; P = 0.0139) and fragmented sleep (odds ratio = 4.98; 95% confidence interval, 1.09-22.89; P = 0.0389). CONCLUSIONS: Minority patients with IBD were shown to have poorer objective measures of sleep as assessed through wrist actigraphy compared to nonminority patients. Cultural competency in the care of minority patients with IBD, specifically focusing on the management of psychosocial issues, is needed to address these disparities in sleep. The inclusion of minority patients with IBD in studies investigating sleep and other psychosocial issues are warranted not only to assess potential disparities in disease course but also to determine the etiologies of poor sleep in minority patients with IBD.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Grupos Minoritarios , Calidad del Sueño , Actigrafía , Enfermedad Crónica , Humanos , Enfermedades Inflamatorias del Intestino/etnología , Estudios Prospectivos , Calidad de Vida , Muñeca
14.
Nat Nanotechnol ; 13(6): 489-495, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29610528

RESUMEN

Solar vapour generation is an efficient way of harvesting solar energy for the purification of polluted or saline water. However, water evaporation suffers from either inefficient utilization of solar energy or relies on complex and expensive light-concentration accessories. Here, we demonstrate a hierarchically nanostructured gel (HNG) based on polyvinyl alcohol (PVA) and polypyrrole (PPy) that serves as an independent solar vapour generator. The converted energy can be utilized in situ to power the vaporization of water contained in the molecular meshes of the PVA network, where water evaporation is facilitated by the skeleton of the hydrogel. A floating HNG sample evaporated water with a record high rate of 3.2 kg m-2 h-1 via 94% solar energy from 1 sun irradiation, and 18-23 litres of water per square metre of HNG was delivered daily when purifying brine water. These values were achievable due to the reduced latent heat of water evaporation in the molecular mesh under natural sunlight.

16.
Am J Infect Control ; 45(12): 1378-1381, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29195582

RESUMEN

BACKGROUND: Newborns are suctioned with a blue bulb manual suction device to remove naso-oropharyngeal secretions and promote airway clearance. This study identifies and discusses the microbial profile and characterization of the bulb used in newborns on intrapartum and postpartum units. METHODS: This was a descriptive study with convenience sampling of a total of 50 bulbs used in cesarean births, vaginal births, and on the postpartum unit. The bulbs were tested for microbial growth, and the percentages of contaminated bulbs were calculated. The χ2 test was used to compare the proportion of bulbs with microbial growth by route of birth among bulbs sampled from the intrapartum unit. RESULTS: Microbial profile and characterization identified a total of 57 different gram-positive cocci and rods and gram-negative rods. Among 50 bulbs cultured, bacterial growth was present in 42% of the bulbs, and Escherichia coli was identified in 55% of the gram-negative rod isolates. The χ2 test comparing vaginal and cesarean bulbs showed a statistically significant difference in the percentages of contaminated bulbs for any growth (P = .023) and for any Staphylococcus spp (P = .050). CONCLUSIONS: New empirical evidence confirms the bulb is a potential bacterial reservoir and poses a potential health risk for nosocomial infections for newborns. Further studies are needed to identify bacterial transmission, newborn outcomes, bactericidal bulb cleaning methods, and quality and safe suction practices.


Asunto(s)
Obstrucción de las Vías Aéreas/terapia , Bacterias/aislamiento & purificación , Infección Hospitalaria/microbiología , Succión/instrumentación , Humanos , Recién Nacido , Periodo Posparto
17.
Biophys Rev ; 6(1): 89-95, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25309634

RESUMEN

PI3Kα, a heterodimeric lipid kinase, catalyzes the conversion of phosphoinositide-4,5-bisphosphate (PIP2) to phosphoinositide-3,4,5-trisphosphate (PIP3), a lipid that recruits to the plasma membrane proteins that regulate signaling cascades that control key cellular processes such as cell proliferation, carbohydrate metabolism, cell motility, and apoptosis. PI3Kα is composed of two subunits, p110α and p85, that are activated by binding to phosphorylated receptor tyrosine kinases (RTKs) or their substrates. The gene coding for p110α, PIK3CA, has been found to be mutated in a large number of tumors; these mutations result in increased PI3Kα kinase activity. The structure of the complex of p110α with a fragment of p85 containing the nSH2 and the iSH2 domains has provided valuable information about the mechanisms underlying the physiological activation of PI3Kα and its pathological activation by oncogenic mutations. This review discusses information derived from x-ray diffraction and theoretical calculations regarding the structural and dynamic effects of mutations in four highly mutated regions of PI3K p110α, as well as the proposed mechanisms by which these mutations increase kinase activity. During the physiological activation of PI3Kα, the phosphorylated tyrosine of RTKs binds to the nSH2 domain of p85, dislodging an inhibitory interaction between the p85 nSH2 and a loop of the helical domain of p110α. Several of the oncogenic mutations in p110α activate the enzyme by weakening this autoinhibitory interaction. These effects involve structural changes as well as changes in the dynamics of the enzyme. One of the most common p110α mutations, H1047R, activates PI3Kα by a different mechanism: it increases the interaction of the enzyme with the membrane, maximizing the access of the PI3Kα to its substrate PIP2, a membrane lipid.

18.
Ann Biomed Eng ; 38(8): 2553-62, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20369296

RESUMEN

Unilateral vocal fold paralysis (UVP) results from damage to the recurrent laryngeal nerve (RLN). The most common causes of UVP are associated with compromised RLN tissue. The purpose of this research was to investigate the biomechanical properties of piglet RLN and identify differences in these properties along its length and in between the left and right side. Quasi-static uniaxial tensile testing and isotropic constitutive modeling was performed on seven piglet RLNs. Stiffness and other biomechanical parameters were derived from these tests and compared from conducting two different statistical analysis for the between and within nerve comparisons. Results showed higher stiffness values in the left RLN segment than for the right. Descriptive data demonstrated a higher stiffness in RLN segments surrounding the aortic arch, indicating a more protective role of the extracellular matrix in these nerves. This research offers insight regarding the protective function of the RLN connective tissues and structural compromise due to its environment.


Asunto(s)
Nervio Laríngeo Recurrente/fisiología , Parálisis de los Pliegues Vocales/fisiopatología , Parálisis de los Pliegues Vocales/cirugía , Animales , Fenómenos Biomecánicos , Femenino , Masculino , Nervio Laríngeo Recurrente/fisiopatología , Nervio Laríngeo Recurrente/cirugía , Porcinos , Resultado del Tratamiento , Parálisis de los Pliegues Vocales/etiología
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