Paradoxical adipose hyperplasia is a rare adverse event associated with cryolipolysis. No evidence of spontaneous resolution has been described and little has been written about its treatment. The ...purpose of this report is to share the authors' experience treating patients with paradoxical adipose hyperplasia after cryolipolysis. A retrospective chart review was performed for all paradoxical adipose hyperplasia patients seen in the authors' practice between May of 2013 and May of 2016. The treatment parameters, demographics, onset of findings, and subsequent treatment were chronicled. Eleven cases of paradoxical adipose hyperplasia were identified (eight men and three women). All patients were of Hispanic background. Seven patients were treated surgically (six cases of liposuction alone and one case of liposuction and abdominoplasty). Average follow-up was 9.6 months (range, 2 to 32 months). Three of the patients treated with liposuction required a secondary procedure. All surgically treated patients were very satisfied with their final appearance. Paradoxical adipose hyperplasia is a rare complication of cryolipolysis that may occur more frequently than in the manufacturer's reported data. Treatment is best delayed until the affected area has softened, which normally occurs in 6 to 9 months after the initial cryolipolysis procedure. Power-assisted liposuction is the preferred method of treatment, but in some cases, abdominoplasty may be necessary. Secondary treatments might be needed for recurrence or persistent bulge. One must be sensitive to heightened patient concerns when offering an invasive procedure to correct the complications from a noninvasive one.
Therapeutic, IV.
Optimal treatment of brain metastases is often hindered by limitations in diagnostic capabilities. To meet this challenge, here we profile DNA methylomes of the three most frequent types of brain ...metastases: melanoma, breast, and lung cancers (n = 96). Using supervised machine learning and integration of DNA methylomes from normal, primary, and metastatic tumor specimens (n = 1860), we unravel epigenetic signatures specific to each type of metastatic brain tumor and constructed a three-step DNA methylation-based classifier (BrainMETH) that categorizes brain metastases according to the tissue of origin and therapeutically relevant subtypes. BrainMETH predictions are supported by routine histopathologic evaluation. We further characterize and validate the most predictive genomic regions in a large cohort of brain tumors (n = 165) using quantitative-methylation-specific PCR. Our study highlights the importance of brain tumor-defining epigenetic alterations, which can be utilized to further develop DNA methylation profiling as a critical tool in the histomolecular stratification of patients with brain metastases.
Stroke represents a core area of study in neurosciences and public health due to its global contribution toward mortality and disability. The intricate pathophysiology of stroke, including ischemic ...and hemorrhagic events, involves the interruption in oxygen and nutrient delivery to the brain. Disruption of these crucial processes in the central nervous system leads to metabolic dysregulation and cell death. Fourier transform infrared (FTIR) spectroscopy can simultaneously measure total protein and lipid content along with a number of key biomarkers within brain tissue that cannot be observed using conventional techniques. FTIR imaging provides the opportunity to visualize this information in tissue which has not been chemically treated prior to analysis, thus retaining the spatial distribution and in situ chemical information. Here we present a review of FTIR imaging methods for investigating the biomarker responses in the post-stroke brain.
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•FTIR spectroscopic imaging is presented as a versatile tool for characterizing the neurovascular unit.•Methods for biomarker preservation are presented and contrasted with conventional tissue preparation.•A comprehensive characterization of the mouse brain is presented using FTIR imaging.•Biomarkers and metabolic changes in ischemic and hemorrhagic stroke, as well as hemorrhagic transformation, are presented.•Data processing methods for FTIR imaging of brain tissue are presented which aid differentiation and characterization.
Cardiac tissue engineering aims to develop engineered constructs for myocardial infarction repair, where a challenge is the control of growth factor (GF) sequential release. Herein, bilayer polymeric ...nanoparticles composed of a GF-encapsulating core surrounded by rate-regulating shell were developed for sequential GF release.
Single and bilayer polymeric nanoparticles were fabricated, characterized and biologically assessed. A novel 'Geno-Neural model' was developed and validated for rate-programming of the nanoparticles.
The bilayer nanoparticles featured low burst effect and time-delayed release, and allowed for sequential release of PDGF following co-release of VEGFand bFGF, which promoted angiogenesis.
The nanoparticulate delivery system, along with the Geno-Neural model, offers great potential for spatiotemporal control of GF release for cardiovascular regenerative medicine.
Summary Background Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ...ischaemic brain damage in human beings. Methods For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12–95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov , number NCT00728182. Findings Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment—12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38–0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42–0·83). Interpretation Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. Funding NoNO Inc and Arbor Vita Corp.
The conjunctiva contains a specialized population of lymphocytes that reside in the epithelium, named intraepithelial lymphocytes (IEL).
Here we characterized the IEL population prior to and after ...experimental desiccating stress (DS) for 5 or 10 days (DS5, DS10) and evaluated the effect of NK depletion on DS. The frequency of IELs in normal murine conjunctiva was CD3(+)CD103(+) (~22%), CD3(+)γδ(+) (~9.6%), CD3(+)NK(+) (2%), CD3(-)NK(+) (~4.4%), CD3(+)CD8α (~0.9%), and CD4 (~0.6%). Systemic depletion of NK cells prior and during DS led to a decrease in the frequency of total and activated DCs, a decrease in T helper-17(+) cells in the cervical lymph nodes and generation of less pathogenic CD4(+)T cells. B6.nude recipient mice of adoptively transferred CD4(+)T cells isolated from NK-depleted DS5 donor mice showed significantly less corneal barrier disruption, lower levels of IL-17A, CCL20 and MMP-3 in the cornea epithelia compared to recipients of control CD4(+)T cells.
Taken together, these results show that the NK IELs are involved in the acute immune response to desiccation-induced dry eye by activating DC, which in turn coordinate generation of the pathogenic Th-17 response.
Baseline CTP sometimes overestimates the size of the infarct core ("ghost core" phenomenon). We investigated how often CTP overestimates infarct core compared with 24-hour imaging, and aimed to ...characterize the patient subgroup in whom a ghost core is most likely to occur.
Data are from the randomized controlled ESCAPE-NA1 trial, in which patients with acute ischemic stroke undergoing endovascular treatment were randomized to intravenous nerinetide or placebo. Patients with available baseline CTP and 24-hour follow-up imaging were included in the analysis. Ghost infarct core was defined as CTP core volume minus 24-hour infarct volume > 10 mL). Clinical characteristics of patients with versus without ghost core were compared. Associations of ghost core and clinical characteristics were assessed by using multivariable logistic regression.
A total of 421 of 1105 patients (38.1%) were included in the analysis. Forty-seven (11.2%) had a ghost core > 10 mL, with a median ghost infarct volume of 13.4 mL (interquartile range 7.6-26.8). Young patient age, complete recanalization, short last known well to CT times, and possibly male sex were associated with ghost infarct core.
CTP ghost core occurred in ∼1 of 10 patients, indicating that CTP frequently overestimates the infarct core size at baseline, particularly in young patients with complete recanalization and short ischemia duration.
Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so ...reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003-2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10-4 mutations/site/year (95% highest posterior density 4.55 × 10-4 to 5.38 × 10-4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10-4 mutations/site/year, 95% highest posterior density 3.26 × 10-4 to 3.94 × 10-4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.
Ductal carcinoma in situ (DCIS) is a non-obligate precursor, non-invasive malignancy confined within the basement membrane of the breast ductal system. There is a wide variation in the natural ...history of DCIS with an estimated incidence of progression to invasive ductal carcinoma being at least 13%–50% over a range of 10 or more years after initial diagnosis. Regardless of the treatment strategy, long-term survival is excellent. The controversy surrounding DCIS relates to preventing under-treatment, while also avoiding unnecessary treatments. In this article, we review the incidence, presentation, management options and surveillance of DCIS. Furthermore, we address several current controversies related to the management of DCIS, including margin status, sentinel node biopsy, hormonal therapy, the role of radiation in breast conservation surgery, and various risk stratification schemes.
•Incidence of DCIS has increased in the last 20 years with increased use of screening mammography.•Progression from DCIS to IDC is estimated to occur in at least 13%–50% of cases.•Prognostic variables including genetic profiling, grade, necrosis, morphology, and size.•Evaluation is intended to guide the management of DCIS as well as minimize over-treatment.•Definitive predictive tools to identify patients who will proceed to invasive carcinoma remain elusive.
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