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1.
Phys Rev Lett ; 132(22): 224001, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38877924

RESUMEN

A short, abrupt increase in energy injection rate into steady strongly driven rotating turbulent flow is used as a probe for energy transfer in the system. The injected excessive energy is localized in time and space and its spectra differ from those of the steady turbulent flow. This allows measuring energy transfer rates, in three different domains: In real space, the injected energy propagates within the turbulent field, as a wave packet of inertial waves. In the frequency domain, energy is transferred nonlocally to the low, quasigeostrophic modes. In wave number space, energy locally cascades toward small wave numbers, in a rate that is consistent with two-dimensional (2D) turbulence models. Surprisingly however, the inverse cascade of energy is mediated by inertial waves that propagate within the flow with small, but nonvanishing frequency. Our observations differ from measurements and theoretical predictions of weakly driven turbulence. Yet, they show that in strongly driven rotating turbulence, inertial waves play an important role in energy transfer, even in the vicinity of the 2D manifold.

2.
Brain Behav Immun ; 117: 529-540, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38346596

RESUMEN

Perioperative stress and inflammatory signaling can invigorate pro-metastatic molecular processes in patients' tumors, potentially worsening long-term survival. Yet, it is unknown whether pre-operative psychotherapeutic interventions can attenuate such effects. Herein, three weeks before surgery, forty women diagnosed with stage I-III invasive ductal/lobular breast carcinoma were randomized to a 6-week one-on-one psychological intervention (6 meetings with a medical psychologist and bi-weekly phone calls) versus standard nursing-staff-attention. The intervention protocol was individually tailored based on evaluation of patients' emotional, cognitive, physiological, and behavioral stress response-patterns, and also included psychoeducation regarding medical treatments and recruitment of social support. Resected primary tumors were subjected to whole-genome RNA sequencing and bioinformatic analyses, assessing a priori hypothesized cancer-relevant molecular signatures. Self-report questionnaires (BSI-18, Hope-18, MSPSS, and a stress-scale) were collected three (T1) and one (T2) week before surgery, a day before (T3) and after (T4) surgery, and three weeks (T5) and 3-months (T6) following surgery. The intervention reduced distress (GSI), depression, and somatization scores (BSI-18: p < 0.01, p < 0.05, p < 0.05; T5 vs. T1). Additionally, tumors from treated patients (vs. controls) showed: (i) decreased activity of transcription control pathways involved in adrenergic and glucocorticoid signaling (CREB, GR) (p < 0.001), pro-inflammatory signaling (NFkB) (p < 0.01), and pro-malignant signaling (ETS1, STAT and GATA families) (p < 0.001, p < 0.01, p < 0.005); (ii) increased M1 macrophage polarization (p < 0.05), and CD4+ T cell activity (p < 0.01); and an unexpected increase in epithelial-to-mesenchymal-transition (EMT) signature (p < 0.005). This is the first randomized controlled trial to show beneficial effects of a psychological perioperative intervention on tumor pro-metastatic molecular biomarkers.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/cirugía , Intervención Psicosocial , Biomarcadores , Adrenérgicos , Cognición
3.
Soft Matter ; 20(22): 4414-4421, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38767344

RESUMEN

Using a geometric formalism of elasticity theory we develop a systematic theoretical framework for shaping and manipulating the energy landscape of slender solids, and consequently their mechanical response to external perturbations. We formally express global mechanical properties associated with non-Euclidean thin sheets in terms of their local rest lengths and rest curvatures, and we interpret the expressions as both forward and inverse problems for designing the desired mechanical properties. We show that by wisely designing geometric frustration, anomalous mechanical properties can be encoded into a material using accessible experimental techniques. To test the methodology we derive a family of ribbon-springs with extreme mechanical behavior such as tunable, anharmonic, and even vanishing rigidities. The presented formalism can be discretized, offering a new methodology for designing mechanical properties and thus opens a new pathway for the design of both continuum and discrete solids and structures.

4.
Br J Clin Pharmacol ; 89(12): 3539-3550, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37463830

RESUMEN

AIMS: To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community-dwelling elderly subjects. METHODS: The cohort consisted of community-dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model. RESULTS: In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow-up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86-1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635-0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated. CONCLUSIONS: Chronic use of omeprazole was not associated with the occurrence of OF in elders.


Asunto(s)
Fracturas de Cadera , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Anciano , Masculino , Humanos , Anciano de 80 o más Años , Femenino , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Omeprazol/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología
5.
J Drugs Dermatol ; 22(11): 1099-1102, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37943274

RESUMEN

BACKGROUND: Pincer nail deformity (PND) is a common toenail disorder characterized by transverse over-curvature of the nail plate. It can cause severe pain, chronic inflammation, and recurrent infections. Both conservative and surgical treatment options carry different disadvantages of limited efficacy, high recurrence rate, and poor cosmetic outcome. The study aimed to evaluate the safety and effectiveness of carbon dioxide (CO2) laser matricectomy for the treatment of PND. METHODS: The database of the laser unit of a tertiary medical center was retrospectively searched for all patients who were diagnosed with PND in 2016-2022 and treated with lateral and/or medial matricectomy using CO2 laser. Clinical and follow-up data were collected from the medical files.  Results: The cohort included 19 patients (5 male, 14 female) who underwent 25 partial matricectomies during the study period (some patients had more than one diseased nail). All procedures were successful, with no intraoperative or postoperative complications. There was one documented recurrence at 7 months after treatment. CONCLUSION: Partial CO2 laser matricectomy is safe and effective for the treatment of PND. J Drugs Dermatol. 2023;22(11):1099-1102     doi:10.36849/JDD.7574.


Asunto(s)
Láseres de Gas , Humanos , Femenino , Masculino , Láseres de Gas/efectos adversos , Estudios Retrospectivos , Dióxido de Carbono , Bases de Datos Factuales , Inflamación
6.
Lasers Med Sci ; 38(1): 156, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37402025

RESUMEN

Hair removal with lasers and intense pulsed light (IPL) is considered safe. However, data on the efficacy and safety of these procedures specifically in the pediatric population remain sparse. To determine the efficacy and safety of lasers and IPL for hair reduction in children and adolescents, a systematic review was conducted of original studies evaluating hair removal with lasers or IPL in patients aged less than 18 years. Primary outcome measures were efficacy and safety of treatment. The literature review yielded 2 retrospective cohort studies and 11 case reports/case series including a total of 71 patients aged 9 months to 17 years. Diagnoses ranged from localized lumbosacral to generalized hypertrichosis. Six treatment modalities were evaluated: alexandrite, Nd:YAG, Q-switched Nd:YAG, ruby, and diode lasers and IPL. Only one of the cohort studies (n = 28), using the ruby laser, provided efficacy data. The results showed a 63% hair loss in 89% of patients after completion of treatment, although partial regrowth was evident during 6 to 32 weeks of follow-up. Most of the case reports and case series (10/11) reported significant hair reduction following laser and IPL treatments. None of the patients experienced scarring or dyspigmentation. Some kind of pain management was necessary in 65% of patients; 25% required general anesthesia. On the basis of the limited available data which consisted primary of case reports and case series, lasers and IPL might be effective for pediatric hair reduction. Recurrence following treatment may be higher in children than adults, and pain control may be a limiting factor.


Asunto(s)
Remoción del Cabello , Terapia por Láser , Láseres de Estado Sólido , Adulto , Adolescente , Humanos , Niño , Remoción del Cabello/métodos , Estudios Retrospectivos , Fototerapia/métodos , Cabello , Láseres de Estado Sólido/uso terapéutico , Resultado del Tratamiento
7.
Breast Cancer Res Treat ; 193(2): 507-514, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35391652

RESUMEN

PURPOSE: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. METHODS: The study group consisted of 330 women with pathogenic variants (PVs) in BRCA1/2 attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients aged 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended by international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. RESULTS: The total biopsy rate per 1000 follow-up years was 61.7 in the study group and 22.7 in the control group (p < 0.001). The corresponding positive biopsy rates per 1000 follow-up years were 26.4 and 2.0 (p < 0.001), and the positive biopsy percentages, 42.9% and 8.7% (p < 0.0001). CONCLUSION: Women aged 50 + years with PVs in BRCA1/2 attending a dedicated clinic have a 2.7 times higher biopsy rate per 1000 follow-up years, a 13.2 times higher positive biopsy rate per 1000 follow-up years, and a 4.9 times higher positive biopsy percentage than same-aged women in the general population.


Asunto(s)
Neoplasias de la Mama , Proteína BRCA1/genética , Proteína BRCA2/genética , Biopsia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Femenino , Humanos , Persona de Mediana Edad , Mutación , Derivación y Consulta , Estudios Retrospectivos
8.
Gerontology ; 68(12): 1375-1383, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35316810

RESUMEN

INTRODUCTION: The association of anemia with dementia in elders is controversial. We examined the potential association of anemia with dementia in a large population of elders. METHODS: Historical-prospective registry-based study. Included 36,951 community-dwelling elders (65-113 years) that were followed during 2002-2012. Anemia of all kinds was defined according to Clalit Health Services (CHS) definitions: hemoglobin (HGB) <14 g/dL men, <12 g/dL women; and World Health Organization (WHO): HGB <13 g/dL men, <12 g/dL women. Anemia was categorized as mild (HGB 11-13 g/dL men, 11-12 g/dL women) or moderate-severe (HGB <8-10.9 g/dL men and women). Background data, laboratory values, and diagnosis of dementia and cognitive decline (DCD) were reviewed. RESULTS: During the 10-year follow-up period, DCD was newly diagnosed in 7,180 subjects (19.4%). Subjects with DCD had a higher rate of anemia than those without DCD. Time to development of DCD was 1.5 years shorter in those with than without anemia. On multivariate Cox regression analysis adjusted for age and sex, the hazard ratio (HR) for DCD was 1.45 (95% CI: 1.37-1.54) by CHS and 1.51 (95% CI: 1.41-1.61) WHO anemia criteria. The more severe the anemia, the greater the risk of DCD development (HGB 13-14 g/dL [men only], HR = 1.20 [95% CI: 1.09-1.32]; mild anemia, HR = 1.38 [95% CI: 1.28-1.49]; moderate-severe anemia, HR = 1.64 [CI: 1.41-1.90]). Every decrease in 1 standard deviation of HGB (1.4 g/dL) increased the DCD risk by 15%. A competing risk model has weakened the association of anemia with DCD risk. CONCLUSIONS AND IMPLICATIONS: Anemia in community-dwelling elders appears to be associated with an increased DCD risk in a dose-response manner. Application of the WHO anemia criteria in men may miss patients with mild anemia that places them at DCD risk. Further research should look at anemia as a cause of reversible dementia.


Asunto(s)
Anemia , Disfunción Cognitiva , Demencia , Masculino , Humanos , Femenino , Anciano , Vida Independiente , Anemia/complicaciones , Anemia/epidemiología , Hemoglobinas , Disfunción Cognitiva/complicaciones , Demencia/complicaciones
9.
Harefuah ; 161(2): 121-124, 2022 Feb.
Artículo en Hebreo | MEDLINE | ID: mdl-35195975

RESUMEN

INTRODUCTION: Mammography as a screening tool can reduce mortality from breast cancer. Nevertheless, it has disadvantages such as false positive results, false negative, impaired sensitivity in women with dense breast over-diagnosis and radiation. Due to the different weight given to the advantages versus the disadvantages of mammography, different approaches to screening have developed. These range from annual screening starting at the age of 40 years, to biannual screening starting at the age of 50. The official screening program in Israel is biannual screening between the ages of 50 and 74.


Asunto(s)
Neoplasias de la Mama , Mamografía , Adulto , Anciano , Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad
10.
Phys Rev Lett ; 127(10): 105501, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34533349

RESUMEN

We present a unifying approach that describes both surface bending and fracture in the same geometrical framework. An immediate outcome of this view is a prediction for a new mechanical transition: the buckling-fracture transition. Using responsive gel strips that are subjected to nonuniform osmotic stress, we show the existence of the transition: Thin plates do not fracture. Instead, they release energy via buckling, even at strains that can be orders of magnitude larger than the Griffith fracture criterion. The analysis of the system reveals the dependence of the transition on system's parameters and agrees well with experimental results. Finally, we suggest a new description of a mode I crack as a line distribution of Gaussian curvature. It is thus exchangeable with extrinsic generation of curvature via buckling. The work opens the way for the study of mechanical problems within a single nonlinear framework. It suggests that fracture driven by internal stresses can be completely avoided by a proper geometrical design.

11.
Carcinogenesis ; 41(10): 1395-1401, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32458980

RESUMEN

Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol found in cruciferous vegetables, can potentially prevent carcinogenesis and tumor development. The primary aim of this prospective single-arm study was to investigate the effect of DIM supplementation on breast density, a recognized predictive factor of breast cancer risk. Participants were 23 healthy female BRCA carriers (median age 47 years; 78% postmenopausal) who were treated with oral DIM 100 mg × 1/day for 1 year. The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI) performed before and after the intervention was scored by two independent expert radiologists using the Breast Imaging and Reporting Data System. The results showed a decrease in the average score for FGT amount from 2.8 ± 0.8 at the onset to 2.65 ± 0.84 after 1 year (P = 0.031), with no significant change in BPE (P = 0.429). A group of DIM-untreated age- and menopausal-status-matched women from the BRCA clinic did not show a significant change in FGT amount (P = 0.33) or BPE (P = 0.814) in a parallel year. Mean estradiol level decreased from 159 to 102 pmol/l (P = 0.01), and mean testosterone level decreased from 0.42 to 0.31 pmol/l (P = 0.007). Side effects were grade 1. In conclusion, 1 year's supplementation with DIM 100 mg × 1/day in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings.


Asunto(s)
Anticarcinógenos/administración & dosificación , Proteína BRCA1/genética , Proteína BRCA2/genética , Densidad de la Mama/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Carcinogénesis/efectos de los fármacos , Indoles/administración & dosificación , Adulto , Anciano , Anticarcinógenos/farmacología , Femenino , Heterocigoto , Humanos , Indoles/farmacología , Persona de Mediana Edad
12.
Phys Rev Lett ; 125(17): 178001, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33156660

RESUMEN

While living organisms have mastered the dynamic control of residual stresses within sheets to induce shape transformation and locomotion, man-made implementations are rudimentary. We present the first autonomously shape-shifting sheets made of a gel that shrinks and swells in response to the phase of an oscillatory chemical (Belousov-Zhabotinsky) reaction. Propagating reaction-diffusion fronts induce localized deformation of the gel. We show that these localized deformations prescribe a spatiotemporal pattern of Gaussian curvature, leading to time-periodic global shape changes. We present the computational tools and experimental protocols needed to control this system, principally the relationship between the Gaussian curvature and the reaction phase, and optical imprinting of the wave pattern. Together, our results demonstrate a route for developing fully autonomous soft machines mimicking some of the locomotive capabilities of living organisms.


Asunto(s)
Materiales Biomiméticos/química , Membranas/química , Modelos Biológicos , Modelos Químicos , Elasticidad , Geles/química , Estrés Mecánico
13.
Dermatology ; 236(6): 493-499, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32289785

RESUMEN

INTRODUCTION: Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD); however, nonsurgical approaches have gained popularity in recent years. OBJECTIVES: To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. METHODS: A systematic review and meta-analysis of nonsurgical EMPD treatments was performed. The primary outcome was complete response (CR); secondary outcomes were clinical regression by ≥50%, adverse events, and recurrence rate. RESULTS: The systematic review included 43 observational studies (341 patients; 7 prospective cohort studies, 19 retrospective cohort studies, and 17 cases series) evaluating 5 treatment modalities. Imiquimod (13 studies, 110 patients) administered at variable doses ranging from daily to twice weekly for 2-56 weeks demonstrated CR of 54% (95% CI, 40-67%; I2 = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22-53%; I2 = 52%) of patients achieved CR. Radiotherapy (12 studies, 67 patients) showed CR of 97%, but was associated with local and systemic side effects. Ablative lasers and topical fluorouracil and calcipotriene lacked adequate evidence of efficacy. CONCLUSIONS: Imiquimod and radiotherapy are the most appropriate nonsurgical modalities for EMPD treatment given their good efficacy and safety profile. PDT has limited efficacy but may be appropriate in selected clinical settings.


Asunto(s)
Enfermedad de Paget Extramamaria/terapia , Humanos
14.
Breast J ; 26(5): 946-951, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31876341

RESUMEN

There is growing evidence that intraoperative radiation therapy (IORT) may be a viable option in selected patients with early breast cancer. This study reports our 4-year experience with IORT. The perioperative outcome and imaging data of all patients who underwent IORT for early breast cancer at a tertiary medical center in 2014-2018 were retrospectively retrieved. The cohort included 158 patients aged 52-84 years (mean 68) with stage I (n = 137) or II (n = 21) breast cancer. Mean applicator size was 4.13 cm; IORT added a mean of 29 minutes to the operative time. Minor wound infections (n = 18, 11.4%) requiring antibiotics and drainage were the only postoperative complication. In 25 patients (15%), postoperative mammography demonstrated a seroma (n = 22) or fat necrosis (n = 3). The risk of wound infection or a new postoperative imaging finding was unrelated to patient age, operative time, tumor size, or comorbid diabetes or obesity. After a mean of 30 months' follow-up, none of the patients who met the institutional criteria for IORT had local recurrence, regardless of age, histology, tumor grade, KI67 proliferation index, pathologic stage, Recurrence Score, or additional whole-breast irradiation or adjuvant treatment. Patients for whom a Recurrence Score was determined (n = 55, 35%) had a significantly higher tumor grade, pathologic stage, and whole-breast irradiation/adjuvant chemotherapy rate than the remaining patients. IORT may be a safe alternative to traditional external beam radiation in well-selected patients with early breast cancer, with few minor complications and good 30-month outcome.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Cuidados Intraoperatorios , Mastectomía Segmentaria , Recurrencia Local de Neoplasia/cirugía , Radioterapia Adyuvante , Estudios Retrospectivos
15.
Isr Med Assoc J ; 21(9): 612-614, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31542907

RESUMEN

BACKGROUND: Young women concerned about a breast cancer diagnosis will visit breast care centers and request breast cancer screening, including imaging studies, on their initial visit. OBJECTIVES: To explore the role of breast examination and breast ultrasound in self-referred asymptomatic women under the age of 40 years. METHODS: We identified 3524 women under the age of 40 at our medical clinic from 1 January 2010 until 1 June 2014. Of this group, 164 women with above average breast cancer risk were excluded and 233 were excluded because of breast complaints. Of 3127 women, 220 underwent breast ultrasound following the initial visit to the clinic and formed the study group. RESULTS: Of 220 women evaluated with ultrasound, 68 had prior positive clinical findings. Of this group 8 women had no sonographic findings, and in the remaining 60, a total of 30 simple cysts, 15 fibroadenomas, and 15 suspicious solid masses were identified. One infiltrating ductal carcinoma and one ductal carcinoma in situ were found in a biopsy. The remaining 152 of the 220 total women who underwent breast ultrasound without showing prior physical findings did not require follow-up. CONCLUSIONS: In the absence of clinical findings during physical breast examination, the addition of breast ultrasonography does not provide additional information to supplement the physical examination in self-referred women under age 40 who do not have any major risk factors for developing breast cancer.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Mamografía/estadística & datos numéricos , Ultrasonografía Mamaria/estadística & datos numéricos , Adulto , Mama/diagnóstico por imagen , Femenino , Humanos , Israel/epidemiología , Examen Físico/estadística & datos numéricos , Riesgo , Adulto Joven
16.
Brain Behav Immun ; 73: 294-309, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29800703

RESUMEN

Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n = 38), we tested the combined perioperative use of the ß-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4). Drugs were well tolerated. Results based on a-priori hypotheses indicated that already before surgery (T2), serum levels of pro-inflammatory IL-6, CRP, and IFNγ, and anti-inflammatory, cortisol and IL-10, increased. At T2 and/or T3, drug treatment reduced serum levels of the above pro-inflammatory cytokines and of TRAIL, as well as activity of multiple inflammation-related transcription factors (including NFκB, STAT3, ISRE), but not serum levels of cortisol, IL-10, IL-18, IL-8, VEGF and TNFα. In the excised tumor, treatment reduced the expression of the proliferation marker Ki-67, and positively affected its transcription factors SP1 and AhR. Exploratory analyses of transcriptome modulation in PBMCs revealed treatment-induced improvement at T2/T3 in several transcription factors that in primary tumors indicate poor prognosis (CUX1, THRa, EVI1, RORa, PBX1, and T3R), angiogenesis (YY1), EMT (GATA1 and deltaEF1/ZEB1), proliferation (GATA2), and glucocorticoids response (GRE), while increasing the activity of the oncogenes c-MYB and N-MYC. Overall, the drug treatment may benefit breast cancer patients through reducing systemic inflammation and pro-metastatic/pro-growth biomarkers in the excised tumor and PBMCs.


Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Neoplasias de la Mama/sangre , Neoplasias de la Mama/terapia , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Citocinas/sangre , Etodolaco/administración & dosificación , Propranolol/administración & dosificación , Adulto , Anciano , Biomarcadores/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Femenino , Humanos , Antígeno Ki-67/efectos de los fármacos , Antígeno Ki-67/genética , Células Asesinas Naturales/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Persona de Mediana Edad , Periodo Perioperatorio/métodos , Receptores Adrenérgicos beta/metabolismo , Transducción de Señal , Transcriptoma/efectos de los fármacos
17.
Soft Matter ; 15(1): 116-126, 2018 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-30534682

RESUMEN

Symmetry considerations preclude the possibility of twist or continuous helical symmetry in bulk crystalline structures. However, as has been shown nearly a century ago, twisted molecular crystals are ubiquitous and can be formed by about 1/4 of organic substances. Despite its ubiquity, this phenomenon has so far not been satisfactorily explained. In this work we study twisted molecular crystals as geometrically frustrated assemblies. We model the molecular constituents as uniaxially twisted cubes and examine their crystalline assembly. We exploit a renormalization group (RG) approach to follow the growth of the rod-like twisted crystals these constituents produce, inquiring in every step into the evolution of their morphology, response functions and residual energy. The gradual untwisting of the rod-like frustrated crystals predicted by the RG approach is verified experimentally using silicone rubber models of similar geometry. Our theory provides a mechanism for the conveyance of twist across length-scales observed experimentally and reconciles the apparent paradox of a twisted single crystal as a finite size effect.

18.
Proc Natl Acad Sci U S A ; 112(35): 10873-8, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26261331

RESUMEN

We study the geometry of defects in amorphous materials and their elastic interactions. Defects are defined and characterized by deviations of the material's intrinsic metric from a Euclidian metric. This characterization makes possible the identification of localized defects in amorphous materials, the formulation of a corresponding elastic problem, and its solution in various cases of physical interest. We present a multipole expansion that covers a large family of localized 2D defects. The dipole term, which represents a dislocation, is studied analytically and experimentally. Quadrupoles and higher multipoles correspond to fundamental strain-carrying entities. The interactions between those entities, as well as their interaction with external stress fields, are fundamental to the inelastic behavior of solids. We develop analytical tools to study those interactions. The model, methods, and results presented in this work are all relevant to the study of systems that involve a distribution of localized sources of strain. Examples are plasticity in amorphous materials and mechanical interactions between cells on a flexible substrate.

19.
PLoS Comput Biol ; 12(4): e1004819, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27074136

RESUMEN

Differentiation into well-defined patterns and tissue growth are recognized as key processes in organismal development. However, it is unclear whether patterns are passively, homogeneously dilated by growth or whether they remodel during tissue expansion. Leaf vascular networks are well-fitted to investigate this issue, since leaves are approximately two-dimensional and grow manyfold in size. Here we study experimentally and computationally how vein patterns affect growth. We first model the growing vasculature as a network of viscoelastic rods and consider its response to external mechanical stress. We use the so-called texture tensor to quantify the local network geometry and reveal that growth is heterogeneous, resembling non-affine deformations in composite materials. We then apply mechanical forces to growing leaves after veins have differentiated, which respond by anisotropic growth and reorientation of the network in the direction of external stress. External mechanical stress appears to make growth more homogeneous, in contrast with the model with viscoelastic rods. However, we reconcile the model with experimental data by incorporating randomness in rod thickness and a threshold in the rod growth law, making the rods viscoelastoplastic. Altogether, we show that the higher stiffness of veins leads to their reorientation along external forces, along with a reduction in growth heterogeneity. This process may lead to the reinforcement of leaves against mechanical stress. More generally, our work contributes to a framework whereby growth and patterns are coordinated through the differences in mechanical properties between cell types.


Asunto(s)
Modelos Biológicos , Hojas de la Planta/crecimiento & desarrollo , Haz Vascular de Plantas/crecimiento & desarrollo , Anisotropía , Arabidopsis/crecimiento & desarrollo , Fenómenos Biomecánicos , Tipificación del Cuerpo , Biología Computacional , Simulación por Computador , Estrés Mecánico
20.
J Exp Bot ; 67(18): 5509-5515, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27651350

RESUMEN

We study in situ the mechanics and growth of a leaf. Young Nicotiana tabacum leaves respond to applied mechanical stress by altering both their mechanical properties and the characteristics of their growth. We observed two opposite behaviours, each with its own typical magnitude and timescale. On timescales of the order of minutes, the leaf deforms in response to applied tensile stress. During this phase we found a high correlation between the applied stress field and the local strain field throughout the leaf surface. For times over 12 hours the mechanical properties of the leaf become anisotropic, making it more resilient to deformation and restoring a nearly isotropic growth field despite the highly anisotropic load. These observations suggest that remodelling of the tissue allows the leaf to respond to mechanical perturbations by changing its properties. We discuss the relevance of the observed behaviour to the growth regulation that leads to proper leaf shape during growth.


Asunto(s)
Hojas de la Planta/crecimiento & desarrollo , Fenómenos Biomecánicos , Hojas de la Planta/fisiología , Reología , Estrés Mecánico , Resistencia a la Tracción , Nicotiana/crecimiento & desarrollo , Nicotiana/fisiología
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