Publications by authors named "Daniela Matei"

139 Publications

Interaction between decadal-to-multidecadal oceanic variability and sudden stratospheric warmings.

Ann N Y Acad Sci 2021 Jul 11. Epub 2021 Jul 11.

Max-Planck-Institut für Meteorologie, Hamburg, Germany.

Major sudden stratospheric warmings (SSWs) are the most important phenomena of the wintertime boreal stratospheric variability. During SSWs, the polar temperature increases abruptly, and easterlies prevail in the stratosphere. Their effects extend farther from the polar stratosphere, affecting near-surface circulation. According to observations, SSWs are not equally distributed in time, with decades experiencing very few events, while others experiencing SSWs almost every winter. Some sources of this SSW multidecadal variability can be traced back to sea surface temperature changes. Here, we investigate the effects of Pacific decadal variability (PDV) and Atlantic multidecadal variability (AMV) on SSWs. We use for the first time a large ensemble of historical experiments to examine the modulation of the frequency, tropospheric precursors, and impact of SSWs by the PDV and AMV. We find a strong impact of the PDV on the occurrence of SSWs, with a higher SSW frequency for the positive phase of the PDV. This PDV influence is mediated by constructive interference of PDV anomalies with tropospheric stationary waves. The main effect of AMV is, instead, a modulation of the tropospheric response to SSWs, a finding that can be useful for predicting the tropospheric fingerprint of SSWs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nyas.14663DOI Listing
July 2021

The ratio of toxic-to-nontoxic microRNAs predicts platinum sensitivity in ovarian cancer.

Cancer Res 2021 Jun 15. Epub 2021 Jun 15.

Medicine, Northwestern University Feinberg School of Medicine

Ovarian cancer remains one of the deadliest gynecologic malignancies affecting women, and development of resistance to platinum remains a major barrier to achieving a cure. Multiple mechanisms have been identified to confer platinum resistance. Numerous microRNAs (miRNAs) have been linked to platinum sensitivity and resistance in ovarian cancer. miRNA activity occurs mainly when the guide strand of the miRNA, with its seed sequence at position 2-7/8, is loaded into the RNA-induced silencing (RISC) complex and targets complementary short seed matches in the 3' untranslated region of mRNAs. Toxic 6mer seeds, which target genes critical for cancer cell survival, have been found in tumor suppressive miRNAs. Many small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) can also kill cancer cells via toxic seeds, the most toxic of which carry G-rich 6mer seed sequences. We showed here that treatment of ovarian cancer cells with platinum led to increased RISC-bound miRNAs carrying toxic 6mer seeds and decreased miRNAs with nontoxic seeds. Platinum-tolerant cells did not exhibit this toxicity shift but retained sensitivity to cell death mediated by siRNAs carrying toxic 6mer seeds. Analysis of RISC-bound miRNAs in ovarian cancer patients revealed that the ratio between miRNAs with toxic versus nontoxic seeds was predictive of treatment outcome. Application of the 6mer seed toxicity concept to cancer relevant miRNAs provides a new framework for understanding and predicting cancer therapy responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-21-0953DOI Listing
June 2021

Immunotherapy in ovarian cancer: we are not there yet.

Lancet Oncol 2021 07 15;22(7):903-905. Epub 2021 Jun 15.

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Jesse Brown VA Medical Center, Chicago, IL, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(21)00303-XDOI Listing
July 2021

The circadian rhythm of arterial blood pressure in Alzheimer's disease and vascular dementia.

Acta Neurol Belg 2021 May 27. Epub 2021 May 27.

Neurology Department, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", Iasi, Romania.

Hypertension is considered a risk factor for stroke and dementia. Ambulatory blood pressure monitoring (ABPM) is a useful tool in the diagnosis and treatment of hypertension. This study aimed to evaluate blood pressure using ABPM, in 30 Alzheimer's disease (AD) patients and 30 vascular dementia (VaD) patients in comparison with 30 healthy controls. BP was recorded every 15 min from 6 AM to 10 PM, and every 30 min from 10 PM to 6 AM. Mean systolic (SBP) and diastolic (DBP) blood pressure during daytime, nighttime, diurnal index, pulse pressure, and heart rate were extracted from the ABPM recordings. VaD patients presented higher SBP values compared to AD patients and healthy controls. DBP values in the AD group were the lowest, while VaD patients presented the highest DBP values, including day and nighttime. Mean arterial pressure values were also the highest in the VaD group, while AD patients had similar values with the control group. The VaD patients presented the lowest systolic diurnal index compared to AD patients and controls. The mean pulse pressure and nighttime pulse pressure values were higher in both groups of dementia patients when compared with the control group. Increased SBP, pulse pressure, and alteration in the circadian pattern with the highest incidence of the non-dipper and reverse dipper patterns were found in patients with dementia when compared with the healthy elderly. Also, decreased values of DBP were found in AD patients, especially during the night period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-021-01664-8DOI Listing
May 2021

Ultrasensitive Vibrational Imaging of Retinoids by Visible Preresonance Stimulated Raman Scattering Microscopy.

Adv Sci (Weinh) 2021 05 8;8(9):2003136. Epub 2021 Feb 8.

Department of Biomedical Engineering Boston University Boston MA 02215 USA.

High-sensitivity chemical imaging offers a window to decipher the molecular orchestra inside a living system. Based on vibrational fingerprint signatures, coherent Raman scattering microscopy provides a label-free approach to map biomolecules and drug molecules inside a cell. Yet, by near-infrared (NIR) pulse excitation, the sensitivity is limited to millimolar concentration for endogenous biomolecules. Here, the imaging sensitivity of stimulated Raman scattering (SRS) is significantly boosted for retinoid molecules to 34 micromolar via electronic preresonance in the visible wavelength regime. Retinoids play critical roles in development, immunity, stem cell differentiation, and lipid metabolism. By visible preresonance SRS (VP-SRS) imaging, retinoid distribution in single embryonic neurons and mouse brain tissues is mapped, retinoid storage in chemoresistant pancreatic and ovarian cancers is revealed, and retinoids stored in protein network and lipid droplets of are identified. These results demonstrate VP-SRS microscopy as an ultrasensitive label-free chemical imaging tool and collectively open new opportunities of understanding the function of retinoids in biological systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202003136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097318PMC
May 2021

Cytokines, paraoxonase-1, periostin and non-invasive liver fibrosis scores in patients with non-alcoholic fatty liver disease and persistently elevated aminotransferases: A pilot study.

Exp Ther Med 2021 May 23;21(5):533. Epub 2021 Mar 23.

Doctoral School, 'Iuliu Haţieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The aim of this study was to evaluate the possible association between paraoxonase-1 (PON1), periostin (POSTN), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 serum concentration with non-invasive liver fibrosis scores, in a cohort of patients with NAFLD. We studied a cohort of 52 patients diagnosed with NAFLD. The NAFLD fibrosis score (NFS), Fibrosis-4 Index (FIB-4), AST to platelet ratio index (APRI) and BARD scores were calculated for each patient. We determined the PON1, POSTN, TNF-α, IL-6, and IL-10 serum values using ELISA kits. There was no correlation between PON1 or POSTN serum levels and non-invasive liver fibrosis. The TNF-α serum values were independently associated with the liver fibrosis scores (P=0.02 for NFS and P=0.002 for FIB-4). Age and metabolic syndrome were also independently linked to the fibrosis scores. In conclusion, serum levels of TNF-α, age and metabolic syndrome were associated with the non-invasive liver fibrosis scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.9965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014973PMC
May 2021

A nontraumatic myositis ossificans case of the forearm: Case report and literature review.

Exp Ther Med 2021 May 23;21(5):531. Epub 2021 Mar 23.

Department of Physical and Rehabilitation Medicine, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania.

Myositis ossificans (MO) is a rare, benign ossifying lesion characterized by focal formation of heterotopic bone and cartilage in extraskeletal soft-tissue that most commonly occurs in young adults. In most cases, no causative factor can be identified. The diagnosis of MO is usually based on the patient's history of trauma, clinical signs, on imaging appearance and histological examination. We present a non-traumatic MO case of the forearm in a 40-year-old man with weakness in left finger motion, a decrease in prehension for more than three weeks, without any weight loss, malaise, anorexia or fever. The clinical symptoms and radiological findings can be easily confused with malignant lesions. Treatment is usually conservative but, due to the limited strength and range of motion of the left hand, the tumor was extirpated and the diagnosis of MO was made by biopsy. The patient had no neurological deficits after surgical treatment and was discharged on the fifth day after the surgery in good condition with the recommendation to begin a rehabilitation program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.9963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014871PMC
May 2021

Influence of multidisciplinary therapeutic approach on fibromyalgia patients.

Exp Ther Med 2021 May 22;21(5):528. Epub 2021 Mar 22.

Department of Physical and Rehabilitation Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.

There is no specific cure for fibromyalgia (FM), but combined non-pharmacologic and pharmacologic treatments may mitigate symptoms and improve quality of life in patients. The aim of the present study was to monitor patient response to several types of therapy, including cognitive-behavioral and occupational therapy, and kinetic therapy, as compared to a control group that was not subjected to any form of therapy. The study included 98 FM patients, all women, out of which 32 received cognitive-behavioral therapy and occupational therapy (CBT+OT), 34 kinetic therapy (KT) and 32 participated as controls. The evaluation protocol comprised two questionnaires developed in order to assess the patient's condition as fully as possible: Fibromyalgia Impact Questionnaire (FIQ) and Fibro Fatigue (FF) scale. At the pre-evaluation there were no significant inter-group differences. At post-evaluation significant differences were observed between the control sample and the group subjected to kinetic therapy (P<0.05). FIQ scores decreased in the CBT+OT group too, but less than that in the KT group. The FF scale registered notable evolutions in time for the group subjected to kinetic therapy. In order to control and improve most of the FM symptoms, besides proper medication, we suggest an interdisciplinary intervention mainly focusing on long-term individualized kinetic therapy. The simultaneous integration of a cognitive-behavioural and occupational therapy intervention could be the element that completes the complex treatment of FM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.9960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014964PMC
May 2021

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2021 02 2;19(2):191-226. Epub 2021 Feb 2.

Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2021.0007DOI Listing
February 2021

Methylomic Signatures of High Grade Serous Ovarian Cancer.

Epigenetics 2020 Dec 8:1-16. Epub 2020 Dec 8.

Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN, USA.

High-grade serous ovarian cancer (HGSOC) harbours aberrant epigenetic features, including DNA methylation. In this study we delineate pathways and networks altered by DNA methylation and associated with HGSOC initiation and progression to a platinum-resistant state. By including tumours from patients who had been treated with the hypomethylating agent (HMA) guadecitabine, we also addressed the role of HMAs in treatment of HGSOC. Tumours from patients with primary (platinum-naïve) HGSOC (n = 20) were compared to patients with recurrent platinum-resistant HGSOC and enrolled in a recently completed clinical trial (NCT01696032). Human ovarian surface epithelial cells (HOSE; n = 5 samples) served as normal controls. Genome-wide methylation profiles were determined. DNA methyltransferase (DNMT) expression levels were examined by immunohistochemistry and correlated with clinical outcomes. Cancer-related and tumorigenesis networks were enriched among differentially methylated genes (DMGs) in primary OC vs. HOSE. When comparing platinum-resistant and primary tumours, 452 CpG island (CGI)-containing gene promoters acquired DNA methylation; of those loci, decreased (P < 0.01) methylation after HMA treatment was observed in 42% (n = 189 CGI). Stem cell pluripotency and cytokine networks were enriched in recurrent platinum-resistant OC tumours, while drug metabolism and transport-related networks were downregulated in tumours from HMA-treated patients compared to HOSE. Lower DNMT1 and 3B protein levels in pre-treatment tumours were associated with improved progression-free survival. The findings provide important insight into the DNA methylation landscape of HGSOC tumorigenesis, platinum resistance and epigenetic resensitization. Epigenetic reprogramming plays an important role in HGSOC aetiology and contributes to clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15592294.2020.1853402DOI Listing
December 2020

Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis.

Cancer Res 2021 01 10;81(2):384-399. Epub 2020 Nov 10.

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Defining traits of platinum-tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum-tolerant cells and tumors were identified using and ovarian cancer models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were enriched in ALDH cells, formed more spheroids, and expressed increased levels of stemness-related transcription factors compared with parental cells. Additionally, platinum-tolerant cells and tumors exhibited expression of the Wnt receptor (). Knockdown of FZD7 improved sensitivity to platinum, decreased spheroid formation, and delayed tumor initiation. The molecular signature distinguishing FZD7 from FZD7 cells included epithelial-to-mesenchymal (EMT), stemness, and oxidative phosphorylation-enriched gene sets. Overexpression of FZD7 activated the oncogenic factor , driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. , and glutathione metabolism gene sets were strongly correlated in the ovarian cancer Tumor Cancer Genome Atlas (TCGA) database and in residual human ovarian cancer specimens after chemotherapy. These results support the existence of a platinum-tolerant cell population with partial cancer stem cell features, characterized by FZD7 expression and dependent on the FZD7-β-catenin-Tp63-GPX4 pathway for survival. The findings reveal a novel therapeutic vulnerability of platinum-tolerant cancer cells and provide new insight into a potential "persister cancer cell" phenotype. SIGNIFICANCE: Frizzled-7 marks platinum-tolerant cancer cells harboring stemness features and altered glutathione metabolism that depend on GPX4 for survival and are highly susceptible to ferroptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-1488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855035PMC
January 2021

Predictive Value of HPV, p53, and p16 in the Post-Treatment Evolution of Malignant Tumors of the Oropharynx and Retromolar Trigone-Oropharynx Junction.

Medicina (Kaunas) 2020 Oct 15;56(10). Epub 2020 Oct 15.

Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.

Knowledge of the interactions and influences of infectious, genetic, and environmental factors on the evolution and treatment response of malignant tumors is essential for improving the management of the disease and increasing patient survival. The objective of this study was to establish the contribution of human papillomavirus (HPV), as well as p53 and p16 tumor markers, alongside associated factors (smoking and alcohol consumption), in the progression of malignancies located in the oropharynx and at the retromolar trigone-oropharyngeal junction. We performed a prospective study including 50 patients with malignant tumors of the oropharynx and retromolar trigone-oropharyngeal junction. In all patients, the presence and type of HPV were determined, as well as the status of the tumor markers p53 and p16. The associated risk factors, biopsy results, treatment method, and post-treatment evolution were all documented. Statistical analyses were performed to evaluate the correlations between the determining factors and their influence on the post-treatment evolution. An overall increased survival rate was found in HPV(+) patients. Our study outlined the prevalence of different high-risk subtypes of HPV from the ones presented by other studies, suggesting a possible geographic variation. Correlations between the p53 and p16 statuses and patient survival could be established. The association of smoking and alcohol consumption strongly correlated with an unfavorable evolution. Awareness of the differences in the post-treatment evolution of the patients in relation to the presence of the factors determined in our study could change the future management of such cases for ensuring improved treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina56100542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602815PMC
October 2020

Intracellular optical doppler phenotypes of chemosensitivity in human epithelial ovarian cancer.

Sci Rep 2020 10 15;10(1):17354. Epub 2020 Oct 15.

Department of Physics and Astronomy, Purdue University, West Lafayette, IN, USA.

Development of an assay to predict response to chemotherapy has remained an elusive goal in cancer research. We report a phenotypic chemosensitivity assay for epithelial ovarian cancer based on Doppler spectroscopy of infrared light scattered from intracellular motions in living three-dimensional tumor biopsy tissue measured in vitro. The study analyzed biospecimens from 20 human patients with epithelial ovarian cancer. Matched primary and metastatic tumor tissues were collected for 3 patients, and an additional 3 patients provided only metastatic tissues. Doppler fluctuation spectra were obtained using full-field optical coherence tomography through off-axis digital holography. Frequencies in the range from 10 mHz to 10 Hz are sensitive to changes in intracellular dynamics caused by platinum-based chemotherapy. Metastatic tumor tissues were found to display a biodynamic phenotype that was similar to primary tissue from patients who had poor clinical outcomes. The biodynamic phenotypic profile correctly classified 90% [88-91% c.i.] of the patients when the metastatic samples were characterized as having a chemoresistant phenotype. This work suggests that Doppler profiling of tissue response to chemotherapy has the potential to predict patient clinical outcomes based on primary, but not metastatic, tumor tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74336-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562924PMC
October 2020

Phase I, Pharmacogenomic, Drug Interaction Study of Sorafenib and Bevacizumab in Combination with Paclitaxel in Patients with Advanced Refractory Solid Tumors.

Mol Cancer Ther 2020 10 26;19(10):2155-2162. Epub 2020 Aug 26.

Northwestern University, Chicago, Illinois.

VEGF blockade does not uniformly result in clinical benefit. We evaluated safety, dose-limiting toxicities (DLT), recommended phase II dose (RP2D), antitumor efficacy, and exploratory biomarkers including pharmacogenomics and pharmacokinetics with sorafenib, bevacizumab, and paclitaxel in patients with refractory cancers. The study had a "3 + 3" design, using paclitaxel 80 mg/m every week for 3 weeks, in every 4 week cycles, bevacizumab 5 mg/kg every 2 weeks, and sorafenib 200 or 400 mg twice a day, 5 or 7 days/week (5/7, 7/7). The MTD cohort was expanded. Twenty-seven patients enrolled in 3 cohorts: sorafenib 200 mg twice a day 5/7, 200 mg twice a day 7/7, and 400 mg twice a day 5/7. DLTs were grade 3 neutropenia >7 days (cohort 1, 1), grade 3 hypertension (cohort 2, 1), grade 3 hand-foot skin reaction (HFSR; cohort 3, 2). MTD was sorafenib 200 mg twice a day 7/7. Six DLTs occurred in cohort 2 expansion: grade 3 HFSR (2), grade 2 HFSR with sorafenib delay >7 days (2), grade 4 cerebrovascular accident (1), grade 3 neutropenia >7 days (1). RP2D was sorafenib 200 mg twice a day 5/7. Most patients (62%) dose reduced sorafenib to 200 mg daily 5/7 after a median 3 (range, 2-17) cycles. Response rates were 48% overall (27) and 64% for ovarian cancers (14). -1154AA and -7TT recessive homozygous genotypes conferred worse overall survival versus alternative genotypes (7 vs. 22 months). Intermittent, low-dose sorafenib (200 mg twice a day 5/7) combined with bevacizumab and paclitaxel was tolerable and had high antitumor efficacy in patients with refractory cancer (NCT00572078).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-20-0277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541675PMC
October 2020

Quantification of the Arctic Sea Ice-Driven Atmospheric Circulation Variability in Coordinated Large Ensemble Simulations.

Geophys Res Lett 2020 Jan 17;47(1):e2019GL085397. Epub 2020 Jan 17.

Danish Meteorological Institute Copenhagen Denmark.

A coordinated set of large ensemble atmosphere-only simulations is used to investigate the impacts of observed Arctic sea ice-driven variability (SIDV) on the atmospheric circulation during 1979-2014. The experimental protocol permits separating Arctic SIDV from internal variability and variability driven by other forcings including sea surface temperature and greenhouse gases. The geographic pattern of SIDV is consistent across seven participating models, but its magnitude strongly depends on ensemble size. Based on 130 members, winter SIDV is ~0.18 hPa for Arctic-averaged sea level pressure (~1.5% of the total variance), and ~0.35 K for surface air temperature (~21%) at interannual and longer timescales. The results suggest that more than 100 (40) members are needed to separate Arctic SIDV from other components for dynamical (thermodynamical) variables, and insufficient ensemble size always leads to overestimation of SIDV. Nevertheless, SIDV is 0.75-1.5 times as large as the variability driven by other forcings over northern Eurasia and Arctic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1029/2019GL085397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375043PMC
January 2020

FTO-Dependent -Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.

Cancer Res 2020 08 30;80(16):3200-3214. Epub 2020 Jun 30.

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

-Methyladenosine (mA) is the most abundant modification of mammalian mRNAs. RNA methylation fine tunes RNA stability and translation, altering cell fate. The fat mass- and obesity-associated protein (FTO) is an mA demethylase with oncogenic properties in leukemia. Here, we show that expression is suppressed in ovarian tumors and cancer stem cells (CSC). FTO inhibited the self-renewal of ovarian CSC and suppressed tumorigenesis , both of which required FTO demethylase activity. Integrative RNA sequencing and mA mapping analysis revealed significant transcriptomic changes associated with overexpression and mA loss involving stem cell signaling, RNA transcription, and mRNA splicing pathways. By reducing mA levels at the 3'UTR and the mRNA stability of two phosphodiesterase genes ( and ), FTO augmented second messenger 3', 5'-cyclic adenosine monophosphate (cAMP) signaling and suppressed stemness features of ovarian cancer cells. Our results reveal a previously unappreciated tumor suppressor function of FTO in ovarian CSC mediated through inhibition of cAMP signaling. SIGNIFICANCE: A new tumor suppressor function of the RNA demethylase FTO implicates mA RNA modifications in the regulation of cyclic AMP signaling involved in stemness and tumor initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-19-4044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442742PMC
August 2020

Cardiac autonomic modulation in drug-resistant epilepsy patients after vagus nerve stimulation therapy.

Neurol Neurochir Pol 2020 18;54(4):329-336. Epub 2020 Jun 18.

University of Medicine and Pharmacy, Universitatii street No 16, 700115 Iasi, Romania.

The positive effect of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy is considered to be mediated by the afferent pathways of the vagus nerve, but the efferent pathways may influence the cardiac autonomic activity.

Aim Of The Study: To assess the effects of VNS on cardiac autonomic modulation in epilepsy patients, over three months of neurostimulation.

Clinical Rationale For The Study: Linear and non-linear heart rate variability (HRV) analysis can provide information on the sympathovagal balance and reveal particularities of the central control of the autonomic cardiovascular function.

Materials And Methods: Using Biopac Acquisition System, we analysed HRV parameters in resting condition and during sympathetic and parasympathetic activation tests in five patients with drug-resistant epilepsy, who underwent VNS procedure.

Results: During the sympathetic and vagal activation tests, all five patients presented normal responses of cardiac autonomic activity, reflected in RMSSD, HFnu and LF/HF dynamics in both HRV evaluations. No bradycardia, cardiac arrhythmia or orthostatic hypotension was registered during the two evaluations.

Conclusions: Our results indicate that VNS appears not to alter the cardiac autonomic function after three months of neurostimulation. HRV analysis is a useful tool for evaluating cardiac autonomic modulation in epilepsy patients during VNS therapy.

Clinical Implications: Patients with decreased HRV should be periodically monitored. Cardiac changes in patients with epilepsy are important because of the additional risk of arrhythmias mediated through the autonomic dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/PJNNS.a2020.0044DOI Listing
October 2020

Epigenetic Attire in Ovarian Cancer: The Emperor's New Clothes.

Cancer Res 2020 09 7;80(18):3775-3785. Epub 2020 May 7.

Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana.

Ovarian cancer is an aggressive epithelial tumor that remains a major cause of cancer morbidity and mortality in women. Epigenetic alterations including DNA methylation and histone modifications are being characterized in ovarian cancer and have been functionally linked to processes involved in tumor initiation, chemotherapy resistance, cancer stem cell survival, and tumor metastasis. The epigenetic traits of cancer cells and of associated tumor microenvironment components have been shown to promote an immunosuppressive tumor milieu. However, DNA methylation and histone modifications are reversible, and therapies targeting the epigenome have been implicated in potential reinvigoration of the antitumor immunity. In this review, we provide an overview specifically of DNA methylation and histone modifications as "clothes of the ovarian cancer genome" in relationship to their functional effects and highlight recent developments in the field. We also address the clinical implications of therapeutic strategies to remove or alter specific articles of genomic "clothing" and restore normal cellular function. As the clothes of the genome continue to be deciphered, we envision that the epigenome will become an important therapeutic target for cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-19-3837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501210PMC
September 2020

Heart Rate Variability Analysis: A Useful Tool to Assess Poststroke Cardiac Dysautonomia.

Neurologist 2020 May;25(3):49-54

Neurology Department, Faculty of Medicine.

Background: Neurogenic heart syndrome represents a phenomenon often encountered in clinical practice after ischemic stroke. Further poststroke cardiovascular complications are possibly related to cardiac autonomic dysregulation. Multiple Trigonometric Regressive Spectral (MTRS) analysis of the heart rate variability (HRV) allows a precise evaluation of cardiovascular modulation under different conditions.

Objectives: This research aims to evaluate the impact of the middle cerebral artery (MCA) ischemic stroke on cardiac autonomic function, using the MTRS analysis of HRV, during sympathetic and parasympathetic activation tests.

Methods: The authors analyzed HRV parameters in 20 patients who had a right and 20 who had a left MCA ischemic stroke, under rest condition and during autonomic activation tests (deep breathing and standing tests). Data were compared with 20 age-matched and sex-matched healthy controls.

Results: Patients who had a right MCA ischemic stroke presented a decreased vagal modulation of the heart rate compared with healthy controls and patients who had a left MCA ischemic stroke, in resting state and during autonomic activation tests. Decreased root mean square of the successive differences, pNN50, high frequency, and high-frequency normalized units values (P<0.05) and increased low frequency/high frequency ratio (P<0.05) in resting state and during autonomic activation tests in patients who had a right MCA stroke indicate a sympathetic predominance in the control of the heart rate. The parasympathetic activation test did not change the sympathovagal balance in this group of patients.

Conclusions: The autonomic nervous system represents an attractive target for the therapeutic approach. As MCA ischemic stroke, especially in the right hemisphere, seems to cause significant long-lasting autonomic dysregulation, implementing early pharmacological or nonpharmacological intervention for autonomic restoration may improve the outcome of patients who had an ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NRL.0000000000000270DOI Listing
May 2020

MicroRNA-155 Implication in M1 Polarization and the Impact in Inflammatory Diseases.

Front Immunol 2020 15;11:625. Epub 2020 Apr 15.

"Octavian Fodor" Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania.

Macrophages are known to have an impact in cytokine signaling in the myriad of organs in which they reside and are classically known to be either pro-inflammatory (M1), anti-inflammatory (M2). Different classes of signaling molecules influence these states, of which, microRNAs represent key modulators. These are short RNA species approximately 21 to 23 nucleotides long that generally act by binding to the 3' untranslated region of mRNAs, regulating their translation, and, thus, the quantity of protein they encode. From these species, microRNA-155 was observed to be of great importance for M1 polarization. Because of it's major implication in M1 polarization microRNA-155 was shown to be implicated in different inflammatory diseases. To name a few, microRNA-155 was shown to be modified in patients with asthma and to correlate with asthma symptoms in mouse model; it has been shown to modulate the activity of foam cells and influence the dimensions of the atherosclerotic plaque and it has also been shown to be of crucial influence in transducing the signal of LPS in septic shock. Because of this, the current review aims to offer an overview of the role of microRNA-155 in M1 polarization, the implication that this poses for the pathophysiology of inflammatory diseases and the potential therapeutic possibilities that this knowledge might bring. Currently, microRNA-155 has been used in clinical trials as a marker of inflammation, but the question remains if it's inhibition will be useful in inflammatory diseases, as other products might have a better cost/benefit ratio.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174664PMC
March 2021

Bleeding after Microwave Ablation in Hepatocellular Carcinoma: Successful Treatment with Percutaneous Ultrasound-Guided Cyanoacrylate Glue Embolization.

Ultraschall Med 2021 04 4;42(2):202-203. Epub 2020 Mar 4.

3rd Surgical Department, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1049-0090DOI Listing
April 2021

The Clinical Impact of Cancer Stem Cells.

Oncologist 2020 02 17;25(2):123-131. Epub 2019 Dec 17.

Department of Obstetrics and Gynecology and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Patients with cancer can go though many stages in their disease, including diagnosis, recurrence, metastasis, and treatment failure. Cancer stem cells (CSCs) are a subgroup of cells within tumors that may explain the mechanism by which tumors recur and progress. CSCs can both self-renew and produce progenitor cells of more differentiated cancer cells as well as heterogeneously demonstrate resistance and the abilities to migrate and metastasize. These "stemness" characteristics are often the result of dysregulation of one or more pathways, which can be detected by various biomarkers. Although there has been considerable laboratory research conducted on CSCs, its relevance to the practicing oncologist may seem questionable. We sought to determine the clinical impact of CSCs on patients. A systematic literature search was conducted to identify analyses containing survival information based on the expression of known CSC biomarkers in any cancer. Overall, 234 survival analyses were identified, of which 82% reported that high expression of CSC biomarker(s) resulted in poor overall survival and/or disease-free survival compared with low or no expression of the biomarker. Elevated stemness biomarker levels were also associated with decreased tumor differentiation, altered TNM stage, and increased metastasis. This analysis would suggest that CSCs have a clinical impact on patients and that practicing oncologists need to start considering incorporating CSC-targeting therapies into their patients' treatment regimens. IMPLICATIONS FOR PRACTICE: Cancer stem cells (CSCs) may occur at any stage of cancer and are implicated in the occurrence of resistance, recurrence, and metastasis. A systematic literature analysis has shown that the presence of CSCs, identified via the upregulation of stemness pathway biomarkers, results in reduced survival across all cancers studied. Several CSC-targeting agents are currently approved, and several others are in clinical trials. Future treatment regimens will likely include CSC-targeting agents to enable the elimination of these holdouts to current therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011672PMC
February 2020

Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86).

Clin Cancer Res 2020 06 28;26(11):2477-2486. Epub 2020 Jan 28.

Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Purpose: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease.

Patients And Methods: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort.

Results: A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand-foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent and mutations (three PRs in 12 patients, median PFS 5.9 months).

Conclusions: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-19-2576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269808PMC
June 2020

The Clinical Impact of Cancer Stem Cells.

Oncologist 2019 Dec 17. Epub 2019 Dec 17.

Department of Obstetrics and Gynecology and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Patients with cancer can go though many stages in their disease, including diagnosis, recurrence, metastasis, and treatment failure. Cancer stem cells (CSCs) are a subgroup of cells within tumors that may explain the mechanism by which tumors recur and progress. CSCs can both self-renew and produce progenitor cells of more differentiated cancer cells as well as heterogeneously demonstrate resistance and the abilities to migrate and metastasize. These "stemness" characteristics are often the result of dysregulation of one or more pathways, which can be detected by various biomarkers. Although there has been considerable laboratory research conducted on CSCs, its relevance to the practicing oncologist may seem questionable. We sought to determine the clinical impact of CSCs on patients. A systematic literature search was conducted to identify analyses containing survival information based on the expression of known CSC biomarkers in any cancer. Overall, 234 survival analyses were identified, of which 82% reported that high expression of CSC biomarker(s) resulted in poor overall survival and/or disease-free survival compared with low or no expression of the biomarker. Elevated stemness biomarker levels were also associated with decreased tumor differentiation, altered TNM stage, and increased metastasis. This analysis would suggest that CSCs have a clinical impact on patients and that practicing oncologists need to start considering incorporating CSC-targeting therapies into their patients' treatment regimens. IMPLICATIONS FOR PRACTICE: Cancer stem cells (CSCs) may occur at any stage of cancer and are implicated in the occurrence of resistance, recurrence, and metastasis. A systematic literature analysis has shown that the presence of CSCs, identified via the upregulation of stemness pathway biomarkers, results in reduced survival across all cancers studied. Several CSC-targeting agents are currently approved, and several others are in clinical trials. Future treatment regimens will likely include CSC-targeting agents to enable the elimination of these holdouts to current therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0517DOI Listing
December 2019

Paraoxonase-1 Serum Concentration and Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease.

J Clin Med 2019 Dec 13;8(12). Epub 2019 Dec 13.

Doctoral School, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

Background: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and gene polymorphisms in patients with NAFLD.

Materials And Methods: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the gene polymorphisms L55M, Q192R, and C-108T.

Results: There was a significant difference ( < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group ( < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration ( < 0.001).

Conclusions: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8122200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947206PMC
December 2019

Interferon-γ signaling is associated with loss-of-function mutations in high grade serous ovarian cancer.

NPJ Precis Oncol 2019 6;3:32. Epub 2019 Dec 6.

1Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL USA.

Loss-of-function mutations of the breast cancer type 1 susceptibility protein (BRCA1) are associated with breast (BC) and ovarian cancer (OC). To identify gene signatures regulated by epigenetic mechanisms in OC cells carrying BRCA1 mutations, we assessed cellular responses to epigenome modifiers and performed genome-wide RNA- and chromatin immunoprecipitation-sequencing in isogenic OC cells UWB1.289 (carrying a BRCA1 mutation, BRCA1-null) and UWB1.289 transduced with wild-type BRCA1 (BRCA1+). Increased sensitivity to histone deacetylase inhibitors (HDACi) was observed in BRCA1-null vs. BRCA1+ cells. Gene expression profiles of BRCA1-null vs. BRCA1+ cells and treated with HDACi were integrated with chromatin mapping of histone H3 lysine 9 or 27 acetylation. Gene networks activated in BRCA1-null vs. BRCA1 + OC cells related to cellular movement, cellular development, cellular growth and proliferation, and activated upstream regulators included , and . The IFN-γ pathway was altered by HDACi in BRCA1+ vs. BRCA1-null cells, and in BRCA1-mutated/or low vs. BRCA1-normal OC tumors profiled in the TCGA. Key IFN-γ-induced genes upregulated at baseline in BRCA1-null vs. BRCA1+OC and BC cells included , and . Increased localization of STAT1 in the promoters of these genes occurred in BRCA1-null OC cells, resulting in diminished responses to IFN-γ or to STAT1 knockdown. The IFN-γ signature was associated with improved survival among OC patients profiled in the TCGA. In all, our results support that changes affecting IFN-γ responses are associated with inactivating BRCA1 mutations in OC. This signature may contribute to altered responses to anti-tumor immunity in BRCA1-mutated cells or tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41698-019-0103-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897992PMC
December 2019

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

Clin Cancer Res 2020 03 12;26(5):1009-1016. Epub 2019 Dec 12.

Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.

Patients And Methods: Patients received either G+C (guadecitabine 30 mg/m s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS).

Results: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group.

Conclusions: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-19-1638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056559PMC
March 2020

Ovarian Cancer-Why Lipids Matter.

Cancers (Basel) 2019 Nov 26;11(12). Epub 2019 Nov 26.

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA, (G.Z.).

This review highlights recent advances in the understanding of the relevance of altered lipid metabolic pathways contributing to the poor prognosis of high grade serous ovarian cancer, as they relate to cancer metastasis and cancer stemness. Increased lipid uptake regulated by the receptor CD36 and the transport protein FABP4 has been implicated in ovarian cancer metastasis. The symbiotic relationship between ovarian cancer cells and adipocytes was shown to be important for sustaining widespread peritoneal and omental metastasis. Increased lipogenesis dependent on the fatty acid desaturase SCD1 was detected in ovarian cancer stem cells. Furthermore, response to therapy, specifically to platinum, was linked to increased fatty acid biogenesis, while the survival of drug tolerant cells was shown to depend on lipid peroxidation. These recent findings suggest that lipids are necessary elements supporting oncogenic signaling and the energetic needs of rapidly proliferating cancer cells. New strategies targeting key enzymes involved in lipid uptake or utilization in cancer cells have been shown to exert anti-tumor effects and are being developed as cancer interventions in combination with chemotherapy or immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11121870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966536PMC
November 2019

Heart rate variability analysis and cardiac dysautonomia in ischemic stroke patients.

Clin Neurol Neurosurg 2019 Nov 17;186:105528. Epub 2019 Sep 17.

Department of Neurology, Faculty of Medicine, University of Medicine and Pharmacy Iasi, Romania Address: No 16, University Street, Iasi, 700115, Romania.

Objectives: Autonomic nervous system dysfunction after ischemic stroke predisposes to cardiovascular complications. We aimed to investigate cardiac autonomic activity in ischemic stroke patients using heart rate variability analysis, illustrating the sympathovagal balance at different sympathetic and parasympathetic activation tests.

Patients And Methods: We studied the dynamics of the linear and non-linear heart rate variability parameters in 31 left and 40 right middle cerebral artery ischemic stroke patients in rest condition and during autonomic activation tests (handgrip, standing, deep breathing and Valsalva maneuver). Data were compared with 30 age- and sex-matched healthy controls.

Results: We found different responses after autonomic activation tests in stroke patients depending on the cortical lateralization of the ischemic lesion. In resting state, left hemisphere stroke patients presented enhanced parasympathetic modulation of the heart rate (higher values for RMSSD, pNN50, HF and SD1, p < 0.05), comparing to right hemisphere stroke patients. This second group displayed a reduced cardiac parasympathetic control in resting state and during autonomic activation tests (handgrip and standing tests) compared to the left hemisphere stroke group and controls. Non-linear parameters SD1 and DFA α1 showed a decrease of variability and complexity of the heart rate in right hemisphere stroke patients, ameliorated during vagal activation tests.

Conclusion: To prevent possible complications with vital risk, assessment of cardiovascular autonomic activity becomes a necessary stage in stroke patient management, facilitating immediate implementation of preventive and therapeutic strategies. Heart rate variability analysis in resting state and during autonomic activation tests allows identifying patients prone to sympathetic hyperactivity. New therapeutic perspectives for stroke management may emerge founded on the modulation of the autonomic nervous system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clineuro.2019.105528DOI Listing
November 2019

Heart Rate Variability and Vagus Nerve Stimulation in Epilepsy Patients.

Transl Neurosci 2019 24;10:223-232. Epub 2019 Aug 24.

Neurology Department, Faculty of Medicine, University of Medicine and Pharmacy Iasi, Iasi Romania.

Background: Vagus nerve stimulation (VNS) exerts a cortical modulating effect through its diffuse projections, especially involving cerebral structures related to autonomic regulation. The influence of VNS on cardiovascular autonomic function in drug-resistant epilepsy patients is still debated. We aimed to evaluate the impact of VNS on cardiovascular autonomic function in drug-resistant epilepsy patients, after three months of neurostimulation, using the heart rate variability (HRV) analysis.

Methodology: Multiple Trigonometric Regressive Spectral analysis enables a precise assessment of the autonomic control on the heart rate. We evaluated time and frequency-domain HRV parameters in resting condition and during sympathetic and parasympathetic activation tests in five epilepsy patients who underwent VNS procedure.

Results: We found appropriate cardiac autonomic responses to sympathetic and parasympathetic activation tests, described by RMSSD, pNN50, HF and LF/HF dynamics after three months of VNS. ON period of the neurostimulation may generate a transient vagal activation reflected on heart rate and RMSSD values, as observed in one of our cases.

Conclusion: VNS therapy in epilepsy patients seems not to disrupt the cardiac autonomic function. HRV represents a useful tool in evaluating autonomic activity. More extensive studies are needed to further explore cardiac autonomic response after neurostimulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/tnsci-2019-0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708288PMC
August 2019
-->