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2.
Adv Mater ; 33(44): e2103974, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510572

RESUMO

Continuous monitoring of vital signs is an essential aspect of operations in neonatal and pediatric intensive care units (NICUs and PICUs), of particular importance to extremely premature and/or critically ill patients. Current approaches require multiple sensors taped to the skin and connected via hard-wired interfaces to external data acquisition electronics. The adhesives can cause iatrogenic injuries to fragile, underdeveloped skin, and the wires can complicate even the most routine tasks in patient care. Here, materials strategies and design concepts are introduced that significantly improve these platforms through the use of optimized materials, open (i.e., "holey") layouts and precurved designs. These schemes 1) reduce the stresses at the skin interface, 2) facilitate release of interfacial moisture from transepidermal water loss, 3) allow visual inspection of the skin for rashes or other forms of irritation, 4) enable triggered reduction of adhesion to reduce the probability for injuries that can result from device removal. A combination of systematic benchtop testing and computational modeling identifies the essential mechanisms and key considerations. Demonstrations on adult volunteers and on a neonate in an operating NICUs illustrate a broad range of capabilities in continuous, clinical-grade monitoring of conventional vital signs, and unconventional indicators of health status.

3.
Adv Healthc Mater ; 10(17): e2100383, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33938638

RESUMO

Indwelling arterial lines, the clinical gold standard for continuous blood pressure (BP) monitoring in the pediatric intensive care unit (PICU), have significant drawbacks due to their invasive nature, ischemic risk, and impediment to natural body movement. A noninvasive, wireless, and accurate alternative would greatly improve the quality of patient care. Recently introduced classes of wireless, skin-interfaced devices offer capabilities in continuous, precise monitoring of physiologic waveforms and vital signs in pediatric and neonatal patients, but have not yet been employed for continuous tracking of systolic and diastolic BP-critical for guiding clinical decision-making in the PICU. The results presented here focus on materials and mechanics that optimize the system-level properties of these devices to enhance their reliable use in this context, achieving full compatibility with the range of body sizes, skin types, and sterilization schemes typically encountered in the PICU. Systematic analysis of the data from these devices on 23 pediatric patients, yields derived, noninvasive BP values that can be quantitatively validated against direct recordings from arterial lines. The results from this diverse cohort, including those under pharmacological protocols, suggest that wireless, skin-interfaced devices can, in certain circumstances of practical utility, accurately and continuously monitor BP in the PICU patient population.


Assuntos
Cuidados Críticos , Sinais Vitais , Pressão Sanguínea , Criança , Humanos , Recém-Nascido , Monitorização Fisiológica , Pele
4.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33972445

RESUMO

Vital signs monitoring is a fundamental component of ensuring the health and safety of women and newborns during pregnancy, labor, and childbirth. This monitoring is often the first step in early detection of pregnancy abnormalities, providing an opportunity for prompt, effective intervention to prevent maternal and neonatal morbidity and mortality. Contemporary pregnancy monitoring systems require numerous devices wired to large base units; at least five separate devices with distinct user interfaces are commonly used to detect uterine contractility, maternal blood oxygenation, temperature, heart rate, blood pressure, and fetal heart rate. Current monitoring technologies are expensive and complex with implementation challenges in low-resource settings where maternal morbidity and mortality is the greatest. We present an integrated monitoring platform leveraging advanced flexible electronics, wireless connectivity, and compatibility with a wide range of low-cost mobile devices. Three flexible, soft, and low-profile sensors offer comprehensive vital signs monitoring for both women and fetuses with time-synchronized operation, including advanced parameters such as continuous cuffless blood pressure, electrohysterography-derived uterine monitoring, and automated body position classification. Successful field trials of pregnant women between 25 and 41 wk of gestation in both high-resource settings (n = 91) and low-resource settings (n = 485) demonstrate the system's performance, usability, and safety.

5.
Dev Psychobiol ; 63(5): 1521-1533, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33521969

RESUMO

Robust literature supports the positive effects of kangaroo mother care (KMC) on infant physiologic stability and parent-infant bonding in the Neonatal Intensive Care Unit (NICU). Comparatively little is known about kangaroo father care (KFC) in the NICU, and KFC implementation has been limited. Our pilot feasibility study objective was to examine KFC effects on premature infants and fathers as compared to KMC. Parents of preterm NICU infants independently completed a 90-min Kangaroo Care (KC) session on consecutive days. Infant heart rate variability (HRV) and apnea/periodicity measures were compared (pre-KC to KC; KFC to KMC). Additionally, we assessed the feasibility of administering three psychosocial questionnaires to fathers and mothers in the NICU and after discharge. Ten preterm infants completed 20 KC sessions (334/7 -374/7  weeks post-menstrual age). Results demonstrated similar infant physiologic responses between KMC and KFC, including significant differences in measures of HRV (p < .05) between KC and non-KC periods. Eighty-eight percentage of questionnaires administered were completed, supporting the utilization of these instruments in future research of this population. If confirmed, these preliminary results identify an opportunity to objectively assess KFC effects, supporting the development of empirically based KFC programs benefitting NICU families.

7.
Cleft Palate Craniofac J ; 58(8): 990-998, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302728

RESUMO

BACKGROUND: The role of perioperative antibiotics in cleft palate remains a topic of debate. Advocates stress their importance in preventing local and systemic infections and decreasing the incidence of oronasal fistula formation. However, few studies to date have directly evaluated the role of antibiotics and other antimicrobial measures in cleft palate surgery. OBJECTIVE: The aim of this review is to evaluate the evidence surrounding the use of perioperative antibiotics and other antimicrobial interventions in cleft palate surgery. Additionally, we review the literature on the oral flora unique to the cleft palate patient population. METHODS: This was accomplished utilizing PubMed, Medline, and the Cochrane Library with MeSH and generic terms. Articles were selected based on predefined inclusion and exclusion criteria. RESULTS: This review highlights the lack of higher level evidence on perioperative antibiotic use and other antimicrobial interventions in cleft palatoplasty and calls for further research on the matter. CONCLUSIONS: The literature appears to support the use of preoperative antibiotics for cleft palatoplasty, but the benefits of prolonged postoperative antibiotic use remain questionable.


Assuntos
Fenda Labial , Fissura Palatina , Doenças Nasais , Antibacterianos , Fissura Palatina/cirurgia , Humanos , Lactente , Fístula Bucal , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
8.
Sci Transl Med ; 12(574)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33328330

RESUMO

Precise form-fitting of prosthetic sockets is important for the comfort and well-being of persons with limb amputations. Capabilities for continuous monitoring of pressure and temperature at the skin-prosthesis interface can be valuable in the fitting process and in monitoring for the development of dangerous regions of increased pressure and temperature as limb volume changes during daily activities. Conventional pressure transducers and temperature sensors cannot provide comfortable, irritation-free measurements because of their relatively rigid construction and requirements for wired interfaces to external data acquisition hardware. Here, we introduce a millimeter-scale pressure sensor that adopts a soft, three-dimensional design that integrates into a thin, flexible battery-free, wireless platform with a built-in temperature sensor to allow operation in a noninvasive, imperceptible fashion directly at the skin-prosthesis interface. The sensor system mounts on the surface of the skin of the residual limb, in single or multiple locations of interest. A wireless reader module attached to the outside of the prosthetic socket wirelessly provides power to the sensor and wirelessly receives data from it, for continuous long-range transmission to a standard consumer electronic device such as a smartphone or tablet computer. Characterization of both the sensor and the system, together with theoretical analysis of the key responses, illustrates linear, accurate responses and the ability to address the entire range of relevant pressures and to capture skin temperature accurately, both in a continuous mode. Clinical application in two prosthesis users demonstrates the functionality and feasibility of this soft, wireless system.


Assuntos
Membros Artificiais , Fontes de Energia Elétrica , Desenho de Prótese , Pele , Temperatura
9.
Plast Reconstr Surg ; 146(5): 599e-606e, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33136957

RESUMO

BACKGROUND: One of the arguments against early intervention for micrognathia in Pierre Robin sequence is the concept that the growth of the mandible will eventually "catch up." Long-term growth of the mandible and occlusal relationships of conservatively managed Pierre Robin sequence patients remain unknown. In this study, the authors evaluated the orthognathic surgery requirements for Pierre Robin sequence patients at skeletal maturity. METHODS: Orthognathic surgical requirements of conservatively managed Pierre Robin sequence and isolated cleft patients (aged ≥13 years) at two institutions were reviewed and analyzed using t test, chi-square test, and Fisher's exact test. Values of p < 0.05 were considered statistically significant. RESULTS: Of the Pierre Robin sequence patients (n = 64; mean age ± SD, 17.9 ± 2.9 years), 65.6 percent were syndromic (primarily Stickler and velocardiofacial syndrome), 96.9 percent had a cleft palate, and 39.1 percent required orthognathic surgery at skeletal maturity. Nonsyndromic and syndromic Pierre Robin sequence patients demonstrated no differences in occlusal relationships or mandibular surgery frequency. The majority of Pierre Robin sequence patients requiring mandibular advancement had a class II occlusion. Comparison of Pierre Robin sequence patients to isolated cleft palate patients (n = 17) revealed a comparable frequency of orthognathic surgery between the two; however, Pierre Robin sequence patients did require mandibular advancement surgery at a greater frequency than cleft palate patients (p = 0.006). CONCLUSIONS: The present study found that 39.1 percent of conservatively managed Pierre Robin sequence patients required orthognathic surgery at skeletal maturity, of which the vast majority required mandibular advancement for class II malocclusion. These data suggest that mandibular micrognathia in conservatively managed Pierre Robin sequence patients may not resolve over time and may require surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Fissura Palatina/cirurgia , Tratamento Conservador/efeitos adversos , Má Oclusão Classe II de Angle/epidemiologia , Procedimentos Cirúrgicos Ortognáticos/estatística & dados numéricos , Síndrome de Pierre Robin/terapia , Adolescente , Cefalometria/estatística & dados numéricos , Fissura Palatina/complicações , Tratamento Conservador/métodos , Feminino , Seguimentos , Humanos , Masculino , Má Oclusão Classe II de Angle/diagnóstico , Má Oclusão Classe II de Angle/prevenção & controle , Má Oclusão Classe II de Angle/cirurgia , Mandíbula/anatomia & histologia , Mandíbula/crescimento & desenvolvimento , Mandíbula/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Síndrome de Pierre Robin/complicações , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Nat Commun ; 11(1): 5990, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239608

RESUMO

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.


Assuntos
Implantes Absorvíveis , Terapia por Estimulação Elétrica/instrumentação , Traumatismos dos Nervos Periféricos/terapia , Poliuretanos/química , Tecnologia sem Fio/instrumentação , Animais , Modelos Animais de Doenças , Terapia por Estimulação Elétrica/métodos , Feminino , Humanos , Teste de Materiais , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Ratos , Regeneração , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia
11.
Lab Chip ; 20(23): 4391-4403, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33089837

RESUMO

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important. This paper introduces a low-profile skin-interfaced system that couples disposable microfluidic sampling devices with reusable 'stick-on' electrodes and wireless readout electronics that remain isolated from the sweat. An ultra-thin capping layer on the microfluidic platform permits high-sensitivity, contactless capacitive measurements of both sweat loss and sweat conductivity. This architecture avoids the potential for corrosion of the sensing components and eliminates the need for cleaning/sterilizing the electronics, thereby resulting in a cost-effective platform that is simple to use. Optimized electrode designs follow from a combination of extensive benchtop testing, analytical calculations and FEA simulations for two sensing configurations: (1) sweat rate and loss, and (2) sweat conductivity, which contains information about electrolyte content. Both configurations couple to a flexible, wireless electronics platform that digitizes and transmits information to Bluetooth-enabled devices. On-body field testing during physical exercise validates the performance of the system in scenarios of practical relevance to human health and performance.


Assuntos
Técnicas Biossensoriais , Suor , Eletrônica , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica , Pele
12.
Ann Surg Oncol ; 27(12): 4622-4627, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32710273

RESUMO

BACKGROUND: Guidelines recommend surgical excision of atypical ductal hyperplasia (ADH) due to the concern of undersampling a potential malignancy on core needle biopsy (CNB). The purpose of this study was to determine clinical, radiological and pathological variables associated with ADH upstaging to cancer and to develop a predictive risk calculator capable of identifying women who have a low oncological risk of upstaging. METHODS: A prospectively collected database from a tertiary breast referral center was analyzed for women diagnosed with ADH on CNB between January 2013 to December 2017 who underwent surgical excision. CNB and surgical pathology reports were examined to determine rate of upstaging. The association between clinical, radiological and pathological variables were evaluated using regression analysis to determine predictors of ADH upstaging to cancer. Significant variables (p ≤ 0.05) identified on univariate analysis were assigned a score of "1" and were included in the ADH upstaging risk calculator. RESULTS: A total of 1986 patients underwent surgery for a high-risk lesion. We identified 318 (16.0%) patients who had ADH identified on their CNB who underwent surgery-of which 290 were included in our study. The upstage rate was 24.8%. Five variables were associated with upstaging and included in our calculator: (1) lesion > 5 mm on ultrasound; (2) lesion > 5 mm on mammogram; (3) one or more "high-risk" lesion(s) on CNB; (4) pathological suspicion for cancer and; (5) incomplete removal of calcifications on CNB. Patients with a score of 0 had a 2% risk of being upstaged to cancer and were deemed low risk with 17.2% of patients falling within this category. CONCLUSIONS: Patients with ADH on CNB can be stratified into a low oncological cohort who have a 2% risk of being upstaged to carcinoma. In the future, these select patients may be counselled and potentially offered observation as an alternative to surgery.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Biópsia com Agulha de Grande Calibre , Mama/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Estudos Prospectivos
13.
Nat Med ; 26(3): 418-429, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32161411

RESUMO

Standard clinical care in neonatal and pediatric intensive-care units (NICUs and PICUs, respectively) involves continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, can involve catheter-based pressure sensors inserted into the arteries. These systems entail risks of causing iatrogenic skin injuries, complicating clinical care and impeding skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to existing clinical standards for heart rate, respiration rate, temperature and blood oxygenation, but also provides a range of important additional features, as supported by data from pilot clinical studies in both the NICU and PICU. These new modalities include tracking movements and body orientation, quantifying the physiological benefits of skin-to-skin care, capturing acoustic signatures of cardiac activity, recording vocal biomarkers associated with tonality and temporal characteristics of crying and monitoring a reliable surrogate for systolic blood pressure. These platforms have the potential to substantially enhance the quality of neonatal and pediatric critical care.


Assuntos
Técnicas Biossensoriais , Unidades de Terapia Intensiva Neonatal , Unidades de Terapia Intensiva Pediátrica , Monitorização Fisiológica , Pele/anatomia & histologia , Tecnologia sem Fio , Monitorização Ambulatorial da Pressão Arterial , Criança , Pré-Escolar , Eletrocardiografia , Desenho de Equipamento , Humanos , Recém-Nascido , Fotopletismografia , Fatores de Tempo
14.
Am J Surg ; 219(5): 780-784, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145920

RESUMO

INTRODUCTION: A breast cancer synoptic operative report was developed using a modified Delphi process METHODS: Data from the British Columbia Cancer Breast Cancer Outcomes Unit (BCOU) was used to analyze the association between the completion of a synoptic operative report and reporting of operative details and The American Society of Breast Surgeons quality indicators. RESULTS: 3662 patients had surgery for breast cancer by 185 surgeons. 2281 reports were narrative and 1007 synoptic. Requested surgical details were more commonly reported with synoptic reports for both posterior (96 vs 58%, p < 0.0001) and anterior margins (96 vs 5%, p < 0.0001). This was true for high and low volume surgeons. Quality Indicators were higher in those cases with an associated synoptic report for high and low volume surgeons. CONCLUSION: Communication of operative details is improved with synoptic reporting. Investment in platforms to facilitate synoptic reporting could improve patient care through improved multidisciplinary communication.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Registros Médicos/normas , Indicadores de Qualidade em Assistência à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica , Técnica Delfos , Feminino , Humanos , Margens de Excisão , Pessoa de Meia-Idade , Complicações Pós-Operatórias
15.
Eur J Surg Oncol ; 46(2): 235-239, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31685259

RESUMO

BACKGROUND: Routine excision of flat epithelial atypia (FEA) of the breast found on core needle biopsy (CNB) is being questioned and a policy of selective excision of FEA was adopted in our area. The purpose of this study was to evaluate the upstage rate to malignancy across multiple diagnostic centers in our area following the policy of selective excision and to identify factors predictive of malignancy. METHODS: Patients having excision of CNB FEA at our regional Hospital between 2013 and 2017 were identified. The primary endpoint was upstage to malignancy after excision. We also assessed for clinical, radiological, and pathological features associated with malignancy. RESULTS: We identified 187 patients. Eighty-nine had pure FEA, 71 had concurrent ADH, and 18 had other pathological lesions. Following surgical excision, 9 patients were upstaged to malignancy (4. 8%) with 8 having concurrent ADH (2 invasive ductal carcinoma, 6 DCIS) and 1 with concurrent Complex Sclerosing Lesion (DCIS). None of the pure FEA cases upstaged. The presence of ADH or CSL in the CNB were the only factors found to be predictive of upstaging (p = 0.001, p = 0.0001 respectively). CONCLUSIONS: The upstage rate to malignancy after excision of pure FEA at out center is 0%. Therefore, we recommend that pure FEA with radiology and pathology concordance does not require surgical excision and can instead be followed with serial imaging. However, patients with FEA in association with other high-risk lesions should be managed as per indicated for the other high-risk lesion and FEA with ADH should be excised.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade
16.
Nat Biomed Eng ; 4(2): 148-158, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31768002

RESUMO

Skin-mounted soft electronics that incorporate high-bandwidth triaxial accelerometers can capture broad classes of physiologically relevant information, including mechano-acoustic signatures of underlying body processes (such as those measured by a stethoscope) and precision kinematics of core-body motions. Here, we describe a wireless device designed to be conformally placed on the suprasternal notch for the continuous measurement of mechano-acoustic signals, from subtle vibrations of the skin at accelerations of around 10-3 m s-2 to large motions of the entire body at about 10 m s-2, and at frequencies up to around 800 Hz. Because the measurements are a complex superposition of signals that arise from locomotion, body orientation, swallowing, respiration, cardiac activity, vocal-fold vibrations and other sources, we exploited frequency-domain analysis and machine learning to obtain-from human subjects during natural daily activities and exercise-real-time recordings of heart rate, respiration rate, energy intensity and other essential vital signs, as well as talking time and cadence, swallow counts and patterns, and other unconventional biomarkers. We also used the device in sleep laboratories and validated the measurements using polysomnography.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Fenômenos Fisiológicos , Tecnologia sem Fio/instrumentação , Clavícula , Desenho de Equipamento , Exercício Físico/fisiologia , Humanos , Processamento de Sinais Assistido por Computador , Fenômenos Fisiológicos da Pele , Sono/fisiologia , Vibração
17.
Nat Commun ; 10(1): 5513, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797921

RESUMO

Recently introduced classes of thin, soft, skin-mounted microfluidic systems offer powerful capabilities for continuous, real-time monitoring of total sweat loss, sweat rate and sweat biomarkers. Although these technologies operate without the cost, complexity, size, and weight associated with active components or power sources, rehydration events can render previous measurements irrelevant and detection of anomalous physiological events, such as high sweat loss, requires user engagement to observe colorimetric responses. Here we address these limitations through monolithic systems of pinch valves and suction pumps for purging of sweat as a reset mechanism to coincide with hydration events, microstructural optics for reversible readout of sweat loss, and effervescent pumps and chemesthetic agents for automated delivery of sensory warnings of excessive sweat loss. Human subject trials demonstrate the ability of these systems to alert users to the potential for dehydration via skin sensations initiated by sweat-triggered ejection of menthol and capsaicin.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pele/metabolismo , Suor/metabolismo , Biomarcadores/metabolismo , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Retroalimentação Fisiológica , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Estado de Hidratação do Organismo , Reprodutibilidade dos Testes , Pele/química , Suor/química
18.
Breast Cancer Res Treat ; 178(1): 87-94, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31332665

RESUMO

PURPOSE: In recent years, routine excision of papillary neoplasms (PN) of the breast has been questioned and controversy exists over when excision is necessary. The aim of this study was to evaluate the upstage rate to malignancy of core needle biopsy (CNB) diagnosed PNs from multiple diagnostic centers in our area and to identify factors predictive of malignancy. METHODS: Patients presenting to our surgical center between 2013 and 2017 for excision of CNB PN were evaluated. The primary endpoint was upstage to malignancy. The association of age, diagnostic center where CNB performed, type of CNB, palpability, discharge, clinical exam size, imaging size, family history of breast cancer, and presence of atypia, as risk factors for upstaging to cancer were also evaluated. RESULTS: Of the 317 PN cases, 83 upstaged to malignancy following surgical excision. 77% of patients with CNB of Atypical PN upstaged, 39% of PN with concurrent atypical ductal hyperplasia, and 0% of PN with concurrent atypical lobular hyperplasia/flat epithelial atypia. Of the 206 non-atypical PNs on CNB, 3.4% upstaged to malignancy, but further review demonstrated a 1% upstage rate when atypia excluded. Factors found to be associated with malignancy included: older patient age, larger size, and presence of atypia. CONCLUSION: We recommend excision of PN with atypia, concurrent cancerous lesion, or radiologic-pathologic non-concordance, and serial imaging follow up may be considered for image detected PN, less than 1 cm, with no atypia.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Papilar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/cirurgia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição de Risco , Adulto Jovem
19.
J Vis Exp ; (148)2019 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-31282896

RESUMO

The fabrication of devices containing thin film composite membranes necessitates the transfer of these films onto the surfaces of arbitrary support substrates. Accomplishing this transfer in a highly controlled, mechanized, and reproducible manner can eliminate the creation of macroscale defect structures (e.g., tears, cracks, and wrinkles) within the thin film that compromise device performance and the usable area per sample. Here, we describe a general protocol for the highly controlled and mechanized transfer of a polymeric thin film onto an arbitrary porous support substrate for eventual use as a water filtration membrane device. Specifically, we fabricate a block copolymer (BCP) thin film on top of a sacrificial, water-soluble poly(acrylic acid) (PAA) layer and silicon wafer substrate. We then utilize a custom-designed, 3D-printed transfer tool and drain chamber system to deposit, lift-off, and transfer the BCP thin film onto the center of a porous anodized aluminum oxide (AAO) support disc. The transferred BCP thin film is shown to be consistently placed onto the center of the support surface due to the guidance of the meniscus formed between the water and the 3D-printed plastic drain chamber. We also compare our mechanized transfer-processed thin films to those that have been transferred by hand with the use of tweezers. Optical inspection and image analysis of the transferred thin films from the mechanized process confirm that little-to-no macroscale inhomogeneities or plastic deformations are produced, as compared to the multitude of tears and wrinkles produced from manual transfer by hand. Our results suggest that the proposed strategy for thin film transfer can reduce defects when compared to other methods across many systems and applications.


Assuntos
Resinas Acrílicas/química , Membranas Artificiais , Silício/química , Óxido de Alumínio/química , Porosidade , Impressão Tridimensional
20.
Autophagy ; 15(9): 1523-1538, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30821592

RESUMO

PHLPP1 (PH domain and leucine rich repeat protein phosphatase 1) is a newly identified family of Ser/Thr phosphatases that catalyzes the dephosphorylation of a conserved regulatory motif of the AGC kinases resulting in a tumor suppressive function, while CDKN1B/p27 also acts as a tumor suppressor by regulating cell cycle, senescence, apoptosis, and cell motility. Our most recent studies reveal that CDKN1B is required for PHLPP1 abundance, which contributes to the inhibition of carcinogenic arsenite-induced cell malignant transformation through inhibition of RPS6-mediated Hif1a translation. However, nothing is known about the mechanisms underlying the crosstalk between these 2 key tumor suppressors in intact cells. Here, for the first time to the best of our knowledge, we show that CDKN1B is able to promote PHLPP1 protein translation by attenuating the abundance of Mir6981, which binds directly to the 5'untranslated region (UTR) of Phlpp1 mRNA. Further studies indicate that the attenuation of Mir6981 expression is due to macroautophagy/autophagy-mediated degradation of Mir6981 in an SQSTM1/p62-dependent fashion. Moreover, we have determined that Sqstm1 is upregulated by CDKN1B at the level of transcription via enhancing SP1 protein stability in an HSP90-depdendent manner. Collectively, our studies prove that: 1) SQSTM1 is a CDKN1B downstream effector responsible for CDKN1B-mediated autophagy; 2) by promoting the autophagy-mediated degradation of Mir6981, CDKN1B exerts a positive regulatory effect on PHLPP1 translation; 3) Mir6981 suppresses PHLPP1 translation by binding directly to its mRNA 5'-UTR, rather than classical binding to the 3'-UTR. These findings provide significant insight into understanding the crosstalk between CDKN1B and PHLPP1. Abbreviations: ATG: autophagy related; ACTB: actin beta; BAF: bafilomycin; BECN1: beclin 1; Cdkn1b/p27: cyclin-dependent kinase inhibitor 1B; CHX: cycloheximide; DMEM: dulbecco's modified eagle medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde -3-phosphate dehydrogenase; Hif1a: hypoxia inducible factor 1, alpha subunit; Hsp90: heat shock protein 90; JUN: Jun proto-oncogene, AP1 transcription factor subunit; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MG132: proteasome inhibitor; Mtor: mechanistic target of rapamycin kinase; Phlpp1: PH domain and leucine rich repeat protein phosphatase 1; Phlpp2: PH domain and leucine rich repeat protein phosphatase 2; Pp2c: protein phosphatase 2 C; RPS6: ribosomal protein S6; Sp1: trans-acting transcription factor 1; Sqstm1/p62: sequestosome 1; TUBA: alpha tubulin; 3'-UTR; 3'-untranslated region; 5'-UTR: 5'-untranslated region.


Assuntos
Autofagia/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , MicroRNAs/metabolismo , Fosfoproteínas Fosfatases/genética , Biossíntese de Proteínas/genética , Estabilidade de RNA , Células 3T3 , Regiões 5' não Traduzidas/genética , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Movimento Celular/genética , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p27/genética , Regulação para Baixo/genética , Proteínas de Choque Térmico HSP90/metabolismo , Camundongos , MicroRNAs/genética , Fosfoproteínas Fosfatases/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/genética , Fator de Transcrição Sp1/metabolismo , Regulação para Cima
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