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SummaryObjectiveLocal field potentials (LFPs) arise from synchronous activation of millions of neurons, producing seemingly consistent waveform shapes and relative synchrony across electrodes. Interictal spikes (IISs) are LFPs associated with epilepsy that are commonly used to guide surgical resection. Recently, changes in neuronal firing patterns observed in the minutes preceding seizure onset were found to be reactivated during postseizure sleep, a process called seizure‐related consolidation (SRC), due to similarities with learning‐related consolidation. Because IISs arise from summed neural activity, we hypothesized that changes in IIS shape and relative synchrony would be observed in the minutes preceding seizure onset and would be reactivated preferentially during postseizure slow‐wave sleep (SWS).MethodsScalp and intracranial recordings were obtained continuously across multiple days from clinical macroelectrodes implanted in patients undergoing treatment for intractable epilepsy. Data from scalp electrodes were used to stage sleep. Data from intracranial electrodes were used to detect IISs using a previously established algorithm. Partial correlations were computed for sleep and wake periods before and after seizures as a function of correlations observed in the minutes preceding seizures. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were co‐registered with electroencephalography (EEG) to determine the location of the seizure‐onset zone (SOZ).ResultsChanges in IIS shape and relative synchrony were observed on a subset of macroelectrodes minutes before seizure onset, and these changes were reactivated preferentially during postseizure SWS. Changes in synchrony were greatest for pairs of electrodes where at least one electrode was located in the SOZ.SignificanceThese data suggest preseizure changes in neural activity and their subsequent reactivation occur across a broad spatiotemporal scale: from single neurons to LFPs, both within and outside the SOZ. The preferential reactivation of seizure‐related changes in IISs during postseizure SWS adds to a growing body of literature suggesting that pathologic neural processes may utilize physiologic mechanisms of synaptic plasticity.

ABSTRACTObjectivesPre‐eclampsia (PE) is a pregnancy‐specific hypertensive disorder that has been associated with cardiovascular risk factors and vascular changes, such as acute atherosis in placental blood vessels, similar to early‐stage atherosclerosis. The objective of this study was to determine whether women with PE have increased atherosclerotic burden, as determined by the carotid intima–media thickness (CIMT), compared with women without PE.MethodsWe conducted a systematic review and meta‐analysis of studies that reported CIMT, a non‐invasive, ultrasound‐based measure of subclinical atherosclerosis, in women who did vs those who did not have PE. Studies were eligible if they had been conducted during pregnancy or during the first decade postpartum, and if CIMT was measured in the common carotid artery. Studies published before 7 March 2016 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full‐text screening, data abstraction and quality assessment. Heterogeneity was assessed using the I2 statistic. Standardized mean difference (SMD) was used as a measure of effect size.ResultsFourteen studies were included in the meta‐analysis. Seven studies were carried out during pregnancy complicated by PE, 10 were carried out up to 10 years postpartum and three included measurements obtained at both time periods. Women who had PE had significantly higher CIMT than did those who did not have PE, both at the time of diagnosis (SMD, 1.10 (95% CI, 0.73–1.48); P < 0.001) and in the first decade postpartum (SMD, 0.58 (95% CI, 0.36–0.79); P < 0.001).ConclusionsAtherosclerotic load is present at the time of PE and may be a mechanism associated with the disease. Measurement of CIMT may offer an opportunity for the early identification of premenopausal women with atherosclerotic burden after a PE pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.RESUMENObjetivosLa preeclampsia (PE) es un trastorno hipertensivo específico del embarazo que ha sido asociada con factores de riesgo cardiovascular y cambios vasculares, tales como aterosis aguda en los vasos sanguíneos de la placenta, similares a las primeras etapas de la aterosclerosis. El objetivo de este estudio fue determinar si las mujeres con PE han aumentado la carga aterosclerótica, según lo determinado por el espesor del complejo íntima‐media de la arteria carótida (CIMT, por sus siglas en inglés), en comparación con las mujeres sin PE.MétodosSe realizó una revisión sistemática y un metaanálisis de estudios que reportaron el CIMT, una medida no invasiva de la aterosclerosis subclínica obtenida mediante ecografía, comparando mujeres con PE y mujeres sin ella. Solo se incluyeron estudios llevados a cabo durante el embarazo o durante la primera década después del parto, y en los que se midió el CIMT en la arteria carótida común. Se usaron las bases de datos de PubMed, EMBASE y Web of Science para identificar estudios publicados antes del 7 marzo de 2016. Dos revisores utilizaron formularios y protocolos preestablecidos para evaluar de forma independiente la elegibilidad de los estudios, a partir de los títulos y los resúmenes, y para realizar un cribado del texto completo, un resumen de los datos y una evaluación de calidad. La heterogeneidad se evaluó mediante el test estadístico I2. Se usó la diferencia de medias estandarizada (SMD, por sus siglas en inglés) como una medida de la magnitud del efecto.ResultadosEn el metaanálisis se incluyeron catorce estudios. Siete de los estudios se llevaron a cabo durante embarazos complicados por PE, 10 se realizaron hasta 10 años después del parto y tres incluyeron mediciones tomadas en ambos períodos. Las mujeres con PE tuvieron un CIMT significativamente mayor que aquellas que no la tenían, tanto en el momento del diagnóstico (SMD 1,10 (I 95%, 0,73‐1,48), P <0,001) como en la primera década después del parto (SMD 0,58 (IC 95%, 0,36‐0,79), P <0,001).ConclusionesLa carga aterosclerótica está presente en el momento de la PE y podría ser un mecanismo asociado con esta enfermedad. La medición del CIMT puede ofrecer una oportunidad para la identificación temprana de mujeres premenopáusicas con carga aterosclerótica después de un embarazo con PE.目的子痫前期(pre‐eclampsia,PE)是一种妊娠期特发的高血压疾病,与心血管危险因素和血管改变有关,如胎盘血管急性动脉粥样硬化,与早期动脉粥样硬化相似。本研究的目的是通过检测颈动脉内—中膜厚度(carotid intima–media thickness,CIMT),确定妊娠合并PE与无合并PE患者相比,动脉粥样硬化负担是否增加。方法我们对报道PE患者与无PE患者相比CIMT的研究进行系统综述和meta分析,CIMT为无创性、基于超声的亚临床动脉粥样硬化检测方法。纳入标准为:研究在妊娠期间或产后头10年进行并检测颈总动脉的CIMT。检索PubMed、EMBASE和Web of Science中发表的研究,时间截止至2016年3月7日。由两名人员根据预定的格式和方案,通过题目和摘要独立评估符合纳入标准的研究,并进行全文筛查、数据提取和质量评估。采用I2检验评估异质性。采用标准化均数差(SMD)检测效应量。结果meta分析中纳入14项研究。7项研究在妊娠合并PE时进行,10项研究在产后10年进行,3项研究在两个时间段均进行了检测。PE患者与无合并PE患者相比,确诊时[SMD,1.10(95% CI,0.73~1.48);P<0.001]以及产后头10年[SMD,0.58(95% CI,0.36~0.79);P<0.001] CIMT均明显较高。结论PE时存在动脉粥样硬化负担,它可能与疾病发病机制有关。通过检测CIMT,可以早期识别PE妊娠后存在动脉粥样硬化负担的绝经前女性。

Purpose of reviewDetection of endometrial cancer at an early stage leads to better oncologic outcomes. To date, a screening test for endometrial cancer does not exist.Recent findingsEvolving knowledge of molecular changes involved in endometrial cancer carcinogenesis paired with sensitive and high-throughput technological advancements are a promising combination that can be leveraged to detect tumor DNA and proteins. These molecular biomarkers can be identified in biospecimens collected via minimally invasive and noninvasive approaches. Exploiting lower genital tract secretions as a biospecimen also allows for patient self-sampling.SummarySuccessful development of a screening test for endometrial cancer using self-collected lower genital tract biospecimens has the potential to increase accessibility to care and improve patient compliance.

Background and objectives ESRD requiring dialysis is associated with increased morbidity and mortality rates, including increased rates of cognitive impairment, compared with the general population. About one quarter of patients receiving dialysis choose to discontinue dialysis at the end of life. Advance directives are intended to give providers and surrogates instruction on managing medical decision making, including end of life situations. The prevalence of advance directives is low among patients receiving dialysis. Little is known about the contents of advance directives among these patients with advance directives. Design, setting, participants, & measurements We retrospectively reviewed the medical records of all patients receiving maintenance in–center hemodialysis at a tertiary academic medical center between January 1, 2007 and January 1, 2012. We collected demographic data, the prevalence of advance directives, and a content analysis of these advance directives. We specifically examined the advance directives for instructions on management of interventions at end of life, including dialysis. Results Among 808 patients (mean age of 68.6 years old; men =61.2%), 49% had advance directives, of which only 10.6% mentioned dialysis and only 3% specifically addressed dialysis management at end of life. Patients who had advance directives were more likely to be older (74.5 versus 65.4 years old; P <0.001) and have died during the study period (64.4% versus 46.6%; P <0.001) than patients who did not have advance directives. Notably, for patients receiving dialysis who had advance directives, more of the advance directives addressed cardiopulmonary resuscitation (44.2%), mechanical ventilation (37.1%), artificial nutrition and hydration (34.3%), and pain management (43.4%) than dialysis (10.6%). Conclusions Although one-half of the patients receiving dialysis in our study had advance directives, end of life management of dialysis was rarely addressed. Future research should focus on improving discernment and documentation of end of life values, goals, and preferences, such as dialysis–specific advance directives, among these patients.

Neuroendocrine tumors (NETs) are rare neoplasms that can arise from any tissue. They are classified based on embryonic gut derivative (i.e. foregut, midgut and hindgut) with midgut tumors being the most common (e.g. gastrointestinal NET). The second most common category of NETs is that which arises from the lung. In fact, 25% of primary lung cancers are NETs, including small cell lung cancer (SCLC), which comprises 20% of all lung cancers. The remaining 5% are large cell neuroendocrine cancer (LCNEC, 3%), typical carcinoids (TCs, 1.8%), and atypical carcinoids (ACs, 0.2%). The less common TCs/ACs are well differentiated lung NETs. Their incidence has been increasing in more recent years and although these tumors are slow growing, advanced disease is associated with poor survival. There have been advances in classification of lung NETs that have allowed for more appropriate management upfront. They are cured by surgical resection when disease is limited. However, advanced and metastatic disease requires medical therapy that is ever changing and expanding. In this review, the aim is to summarize the current understanding and classification of well differentiated lung NETs (i.e. TCs and ACs), and focus on recent updates in medical management of advanced disease, along with a brief discussion on potential future discoveries.

In this review, we highlight that the relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure is complex, differs by sex, and changes with age. In young men there is an inverse relationship between MSNA and cardiac output where high MSNA is compensated for by low cardiac output. This inverse relationship is not seen in older men. In young women sympathetic vasoconstriction is offset by β-adrenoreceptor mediated vasodilation, limiting the ability of young women to maintain blood pressure in response to orthostatic stress. However, β-mediated dilation in women is attenuated with age, leading to unopposed α-adrenergic vasoconstriction and a rise in the direct transduction of MSNA into increases in blood pressure. We propose that these changes with age and menopausal status are major contributing factors in the increased prevalence of hypertension in older women. In addition to aging, we highlight that changes in sex hormones in young women (across the menstrual cycle, with oral contraceptive use, or with pregnancy) influence MSNA and the transduction of MSNA into increases in blood pressure. It is likely that the β-adrenergic receptors and/or changes in baroreflex sensitivity play a large role in these sex differences and changes with alterations in sex hormones.

Key Points Mass spectrometry is a high-throughput, low-resource technique that can identify immunoglobulin variable region gene from tissue specimens. IGVL gene usage is restricted and different between systemic and localized AL and only partially explains organ tropism in this disease.