Publications by authors named "Eleonora Russo"

111 Publications

Coordinated prefrontal state transition leads extinction of reward-seeking behaviors.

J Neurosci 2021 Feb 1. Epub 2021 Feb 1.

Physiology of Neural Networks, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68159, Germany.

Extinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Abrupt transitions in mPFC activity anticipate changes in conditioned responses to altered contingencies. It remains however unknown if such transitions are driven by the extinction of old behavioral strategies or by the acquisition of new competing ones. Using multiple single-unit recordings of mPFC in male rats, we studied the relationship between single-unit and population dynamics during extinction learning, employing alcohol as a positive reinforcer in an operant conditioning paradigm. To examine the fine temporal relation between neural activity and behavior, we developed a novel behavioral model that allowed us to identify in each animal's behavior the number, onset and duration of extinction-learning episodes. We found that single-unit responses to conditioned stimuli changed even under stable experimental conditions and behavior. However, when behavioral responses to task contingencies had to be updated, unit-specific modulations became coordinated across the whole population, pushing the network into a new stable attractor state. Thus, extinction learning is not associated with suppressed mPFC responses to conditioned stimuli, but is anticipated by single-unit coordination into population-wide transitions of the animal's internal state.The ability to suppress conditioned behaviors when no longer beneficial is fundamental for the survival of any organism. While pharmacological and optogenetic interventions have shown a critical involvement of the mPFC in the suppression of conditioned responses, the neural dynamics underlying such a process is still largely unknown. Combining novel analysis tools to describe behavior, single-neuron response and population activity, we found that widespread changes in neuronal firing temporally coordinate across the whole mPFC population in anticipation of behavioral extinction. This coordination leads to a global transition in the internal state of the network, driving extinction of conditioned behavior.
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http://dx.doi.org/10.1523/JNEUROSCI.2588-20.2021DOI Listing
February 2021

Advantages of robotic surgery in the treatment of complex pelvic organs prolapse.

Updates Surg 2021 Jan 2. Epub 2021 Jan 2.

Department of Gynecology and Obstetrics, Santa Chiara University Hospital, Pisa, Italy.

Robot-assisted surgery is safe and effective to treat the complex pelvic organs prolapse (C-POP). The present study analyzes all the robotic procedures and their advantages in the treatment of C-POP performed in a Proctologic and Pelvic Floor Clinical Centre. All the patients affected by C-POP who had robot-assisted surgery were retrospective analyzed. The anatomical and functional outcomes were respectively evaluated through POP-Q grading system and Wexner score about constipation and incontinence. The satisfaction rate was investigated using a five-point scale. From September 2014 to December 2018, 229 women underwent robotic surgery. The follow-up was 12 months. There were no robot-related complications. One hematoma (4.5%) of the recto-vaginal space occurred after Robotic Ventral Rectopexy with Folded Mesh (R-VRP-FM). In the robotic assisted lateral suspension (R-ALS) group there was one case of anterior vaginal wall mesh exposure (0.9%). After the robotic ventral rectopexy (R-VRP) the recurrence rate of external rectal prolapse, internal rectal prolapse, rectocele and enterocele was respectively 6.6, 9.5, 7.4 and 9.5%. After R-VRP-FM only one cystocele (14%) and one partial rectal prolapse (25%) recurred. Vaginal bulge symptoms resolution rate was 95.4%. The mean Wexner constipation score significantly decreased after R-VRP and R-VRP-FM. Vaginal bulge symptoms improved in 98.3% of cases with any apical prolapse recurrence after robotic abdominal colposacropexy. Success rate after R-ALS was 99.1% and 96.4% for apical and anterior prolapse respectively. Robotic assistance makes some surgical steps easier and more precise and this may result in less morbidity and better results.
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http://dx.doi.org/10.1007/s13304-020-00913-4DOI Listing
January 2021

Female urine incontinence: (VEL) effectiveness and safety.

Horm Mol Biol Clin Investig 2020 Oct 30;41(4). Epub 2020 Oct 30.

Vaginal Erbium Laser Academy Italia, Livorno, Italy.

Urinary incontinence is a common health problem that impacts the quality of life of women at different ages. Its physiopathology is not unequivocal, and it is necessary to consider the stress urinary incontinence (SUI), the overactive bladder syndrome and the mixed incontinence (MUI). According to the type of incontinence, its impact on the quality of life and age of the patients, therapeutic strategies are currently summarized in physiotherapy, surgery and drug treatments. We already know the benefit/risk ratio of each of these strategies. Our objective is to evaluate the potential effectiveness and safety of the VEL, an innovative vaginal laser technique (VEL - Vaginal Erbium Laser, erbium yttrium-aluminum-garnet -Er: YAG) a non-invasive laser proposed as a treatment for SUI, overactive bladder syndrome and MUI. The mechanisms of action of lasers are discussed in general and those of VEL in particular with the description of the Smooth® mode. To do this, we have collected the 21 published studies including the first randomized vs. placebo and two pilot studies of intra-urethral VEL. In conclusion: VEL procedures already have their place between the rehabilitation of the perineal floor and surgery. Further properly sized, randomized studies are needed to evaluate the laser treatments in comparison with other therapies, as well as to assess the duration of the therapeutic effects and the safety of repeated applications.
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http://dx.doi.org/10.1515/hmbci-2020-0012DOI Listing
October 2020

Management of urinary incontinence in postmenopausal women: An EMAS clinical guide.

Maturitas 2021 Jan 30;143:223-230. Epub 2020 Sep 30.

Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100, Pisa, Italy. Electronic address:

Introduction: The prevalence of urinary incontinence and of other lower urinary tract symptoms increases after the menopause and affects between 38 % and 55 % of women aged over 60 years. While urinary incontinence has a profound impact on quality of life, few affected women seek care.

Aim: The aim of this clinical guide is to provide an evidence-based approach to the management of urinary incontinence in postmenopausal women.

Materials And Methods: Literature review and consensus of expert opinion.

Summary Recommendations: Healthcare professionals should consider urinary incontinence a clinical priority and develop appropriate diagnostic skills. They should be able to identify and manage any relevant modifiable factors that could alleviate the condition. A wide range of treatment options is available. First-line management includes lifestyle and behavioral modification, pelvic floor exercises and bladder training. Estrogens and other pharmacological interventions are helpful in the treatment of urgency incontinence that does not respond to conservative measures. Third-line therapies (e.g. sacral neuromodulation, intravesical onabotulinum toxin-A injections and posterior tibial nerve stimulation) are useful in selected patients with refractory urge incontinence. Surgery should be considered in postmenopausal women with stress incontinence. Midurethral slings, including retropubic and transobturator approaches, are safe and effective and should be offered.
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http://dx.doi.org/10.1016/j.maturitas.2020.09.005DOI Listing
January 2021

Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design.

J Interv Card Electrophysiol 2020 Aug 24. Epub 2020 Aug 24.

Heart Rhythm Center, Centro Cardiologico Monzino IRCCS, Milan, Italy.

Purpose: Catheter ablation (CA) procedures are characterized by exposure to ionizing radiations (IR). IR can cause DNA damage and may lead to carcinogenesis if not efficiently repaired. The primary endpoint of this study is to investigate whether intravenous administration of N-acetylcysteine prior to CA procedure may prevent systemic oxidative stress and genomic DNA damage induced by exposure to IR.

Methods: The "Cardiac Arrhythmia catheter ablation procedures guided by x-Ray imaging: N-Acetylcysteine Protection Against radiation induced Cellular damagE" (CARAPACE) study is a prospective, randomized, single-blinded, parallel-arm monocenter study enrolling 550 consecutive patients undergoing CA at the Arrhythmology Unit of Centro Cardiologico Monzino (CCM). Inclusion criteria are age ≥ 18, indication for CA procedure guided by IR imaging, and written informed consent. IR levels will be measured via fluoroscopy time, effective dose, and dose area product. Glutathione and glutathione disulfide concentrations will be measured, and urinary levels of 8-iso-prostaglandin-F and 8-hydroxy-2-deoxyguanosine will be quantified. The enrolled patients will be randomized 1:1 to the N-acetylcysteine group or to the control group.

Results: We expect that pre-operative administration of N-acetylcysteine will prevent IR-induced systemic oxidative stress. The study will provide data on oxidative DNA damage assessed by urinary 8-hydroxy-2-deoxyguanosine levels and direct evidence of genomic DNA damage in blood cells by comet assay.

Conclusion: Catheter ablation procedures can lead to IR exposure and subsequent DNA damage. N-acetylcysteine administration prior to the procedure may prevent them and therefore lead to less possible complications.

Trial Registration: www.clinicaltrials.gov (NCT04154982).
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http://dx.doi.org/10.1007/s10840-020-00853-4DOI Listing
August 2020

Tumor inhibition or tumor promotion? The duplicity of CXCR3 in cancer.

J Leukoc Biol 2020 08;108(2):673-685

Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Institute Pasteur-Italia, Rome, Italy.

Tumor tissue includes cancer cells and normal stromal cells such as vascular endothelial cells, connective tissue cells (cancer associated fibroblast, mesenchymal stem cell), and immune cells (tumor-infiltrating lymphocytes or TIL, dendritic cells, eosinophils, basophils, mast cells, tumor-associated macrophages or TAM, myeloid-derived suppressor cells or MDSC). Anti-tumor activity is mainly mediated by infiltration of NK cells, Th1 and CD8 T cells, and correlates with expression of NK cell and T cell attracting chemokines. Nevertheless, cancer cells hijack tissue homeostasis through secretion of cytokines and chemokines that mediate not only the induction of an inflamed status that supports cancer cell survival and growth, but also the recruitment and/or activation of immune suppressive cells. CXCL9, CXCL10, and CXCL11 are known for their tumor-inhibiting properties, but their overexpression in several hematologic and solid tumors correlates with disease severity, suggesting a role in tumor promotion. The dichotomous nature of CXCR3 ligands activity mainly depends on several molecular mechanisms induced by cancer cells themselves able to divert immune responses and to alter the whole local environment. A deep understanding of the nature of such phenomenon may provide a rationale to build up a CXCR3/ligand axis targeting strategy. In this review, we will discuss the role of CXCR3 in cancer progression and in regulation of anti-tumor immune response and immunotherapy.
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http://dx.doi.org/10.1002/JLB.5MR0320-205RDOI Listing
August 2020

Phasic dopamine reinforces distinct striatal stimulus encoding in the olfactory tubercle driving dopaminergic reward prediction.

Nat Commun 2020 07 10;11(1):3460. Epub 2020 Jul 10.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany.

The learning of stimulus-outcome associations allows for predictions about the environment. Ventral striatum and dopaminergic midbrain neurons form a larger network for generating reward prediction signals from sensory cues. Yet, the network plasticity mechanisms to generate predictive signals in these distributed circuits have not been entirely clarified. Also, direct evidence of the underlying interregional assembly formation and information transfer is still missing. Here we show that phasic dopamine is sufficient to reinforce the distinctness of stimulus representations in the ventral striatum even in the absence of reward. Upon such reinforcement, striatal stimulus encoding gives rise to interregional assemblies that drive dopaminergic neurons during stimulus-outcome learning. These assemblies dynamically encode the predicted reward value of conditioned stimuli. Together, our data reveal that ventral striatal and midbrain reward networks form a reinforcing loop to generate reward prediction coding.
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http://dx.doi.org/10.1038/s41467-020-17257-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351739PMC
July 2020

Long-Term Arrhythmic Risk Assessment in Biopsy-Proven Myocarditis.

JACC Clin Electrophysiol 2020 05 26;6(5):574-582. Epub 2020 Feb 26.

Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy.

Objectives: This study sought to assess long-term arrhythmic risk in patients with myocarditis who received an implantable cardioverter-defibrillator (ICD).

Background: The arrhythmic risk of patients with myocarditis overtime remains poorly known.

Methods: The study enrolled 56 patients with biopsy-proven myocarditis who received an ICD for either primary (57%) or secondary prevention (43%) according to current guidelines. Clinical characteristics, biopsy findings, electrophysiological data from endocardial 3-dimensional electroanatomic voltage mapping, and device interrogation data were analyzed to detect arrhythmic events overtime. Coronary angiography excluded significant coronary artery disease in all patients.

Results: At a mean follow-up of 74 ± 60 months (median 65 months), 25 (45%) patients had major ventricular arrhythmias treated by ICD intervention (76% being terminated by ICD shock and 24% by antitachyarrhythmia burst pacing). At multivariable analysis, the presence of sustained ventricular tachycardia on admission (hazard ratio: 13.0; 95% confidence interval: 2.0 to 35.0; p = 0.032) and the extension of the areas of low potentials at the bipolar endocardial mapping (hazard ratio: 1.19; 95% confidence interval: 1.04 to 1.37; p = 0.013) were the only independent predictors of appropriate ICD interventions. A cutoff value of 10% of abnormal bipolar area at electroanatomical ventricular mapping discriminated patients with appropriate ICD interventions with a sensitivity of 89% and a specificity of 85%.

Conclusions: The study demonstrates that the prevalence of life-threatening ventricular arrhythmias in patients with myocarditis receiving an ICD according to current guidelines is high and the arrhythmic risk persists late overtime. Electroanatomical ventricular mapping may be a useful tool to identify patients at greater arrhythmic risk.
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http://dx.doi.org/10.1016/j.jacep.2019.12.010DOI Listing
May 2020

Energy Metabolism Analysis of Three Different Mesenchymal Stem Cell Populations of Umbilical Cord Under Normal and Pathologic Conditions.

Stem Cell Rev Rep 2020 06;16(3):585-595

Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a pivotal source of therapeutically active cells for regenerative medicine due to their multipotent differentiation potential, immunomodulatory and anti-inflammatory proprieties, as well as logistical collection advantages without ethical concerns. However, it remains poorly understood whether MSCs from different compartments of the human umbilical cord are therapeutically superior than others. In this study, MSCs were isolated from Wharton's jelly (WJ-MSCs), perivascular region (PV-MSCs) and cord lining (CL-MSCs) of hUC. These cells expressed the mesenchymal markers (CD90, CD73), stemness marker (OCT4), endothelial cell adhesion molecular marker (CD146), and the monocyte/macrophage marker (CD14) found within the MSC population implicated as a key regulator of inflammatory responses to hypoxia, was displayed by WJ-, PV-, and CL-MSCs respectively. A direct consequence of oxygen and glucose deprivation during stroke and reperfusion is impaired mitochondrial function that contributes to cellular death. Emerging findings of mitochondria transfer provide the basis for the replenishment of healthy mitochondria as a strategy for the treatment of stroke. Cell Energy Phenotype and Mito Stress tests were performed the energy metabolic profile of the three MSC populations and their mitochondrial function in both ambient and OGD cell culture conditions. PV-MSCs showed the highest mitochondrial activity. CL-MSCs were the least affected by OGD/R condition, suggesting their robust survival in ischemic environment. In this study, MSC populations in UC possess comparable metabolic capacities and good survival under normal and hypoxic conditions suggesting their potential as transplantable cells for mitochondrial-based stem cell therapy in stroke and other ischemic diseases.
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http://dx.doi.org/10.1007/s12015-020-09967-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253397PMC
June 2020

Genitourinary syndrome of menopause (GSM) and laser VEL: a review.

Horm Mol Biol Clin Investig 2019 Dec 19;41(1). Epub 2019 Dec 19.

Vela-Italia (Vaginal Erbium Laser Academy Italia), Pisa, Italy.

The purpose of this publication is to summarize the results of the vaginal erbium:yttrium-aluminum-garnet (Er:YAG) Smooth® laser (VEL) on the vaginal atrophy component of the genitourinary syndrome of menopause (GSM). GSM has two categories of clinical signs related to estrogen deficiency: symptoms of vulvovaginal atrophy (VVA) and urinary symptoms. This symptomatology is chronic, progressive over the years and affects a majority of women concerned by natural menopause but not exclusively: we must also consider the growing number of survivors of gynecological or non-gynecological cancers (breast, cervix, uterus, vagina, anus, etc.). At a time when hormonal treatment of menopause is contested as is the installation of under urethra prosthesis, the innovation provided by the VEL technology has the merit of offering the women concerned an effective therapeutic alternative with the security of a patent. The VEL technology has an original and unique process: acting only by thermal effect and not by ablation on tissue, VEL is a safe solution in terms of side effects and potential complications. Studies have been increasing since 2012 and all demonstrate a significant improvement in the GSM signs and symptoms, as well as an improved sexual life after VEL treatment. Double-blind, placebo-controlled, randomized studies are expected in order to ultimately confirm the safety and effectiveness of VEL.
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http://dx.doi.org/10.1515/hmbci-2019-0024DOI Listing
December 2019

Poloxamer Hydrogels for Biomedical Applications.

Pharmaceutics 2019 Dec 10;11(12). Epub 2019 Dec 10.

Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genova, Italy.

This review article focuses on thermoresponsive hydrogels consisting of poloxamers which are of high interest for biomedical application especially in drug delivery for ophthalmic, injectable, transdermal, and vaginal administration. These hydrogels remain fluid at room temperature but become more viscous gel once they are exposed to body temperature. In this way, the gelling system remains at the topical level for a long time and the drug release is controlled and prolonged. Poloxamers are synthetic triblock copolymers of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO), also commercially known as Pluronics, Synperonics or Lutrol. The different poloxamers cover a range of liquids, pastes, and solids, with molecular weights and ethylene oxide-propylene oxide weight ratios varying from 1100 to 14,000 and 1:9 to 8:2, respectively. Concentrated aqueous solutions of poloxamers form thermoreversible gels. In recent years this type of gel has arouse interest for tissue engineering. Finally, the use of poloxamers as biosurfactants is evaluated since they are able to form micelles in an aqueous environment above a concentration threshold known as critical micelle concentration (CMC). This property is exploited for drug delivery and different therapeutic applications.
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http://dx.doi.org/10.3390/pharmaceutics11120671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955690PMC
December 2019

Laparoscopic lateral suspension with mesh for apical and anterior pelvic organ prolapse: A prospective double center study.

Eur J Obstet Gynecol Reprod Biol 2020 Jan 24;244:16-20. Epub 2019 Oct 24.

Department of Obstetrics and Gynecology, University of Pisa, Italy.

Objective: The present study analyzed long-term outcomes and complications of laparoscopic lateral suspension (LLS) with mesh to treat apical and anterior pelvic organ prolapse (POP).

Study Design: A prospective cohort study on 125 patients with vaginal bulge and apical +/- anterior prolapse scheduled for LLS who consecutively underwent LLS between April 2013 and January 2017 in Gynecologic Department of Santa Chiara Hospital in Trento and University of Pisa. The main outcome measure was anatomic and symptomatic POP outcome; the secondary outcomes measures were recurrence, reoperation rate, de novo posterior POP and complications. Percentage distribution of the pre- and postoperative POP-Q stages was compared at mean follow-up. Wilcoxon signed rank sum test was used to compare preoperative POP-Q stage and postoperative POP-Q stage ate mean follow up, for each patient (paired data) and for each type of prolapse.

Results: 120 patients were included in the study. At 2 years 89 % of patients were asymptomatic and anatomic success rate was 94.2 % for the anterior compartment, 94.9 % for the apical compartment. Concerning posterior compartment prolapse 2 (1.7 %) patients referred stage 3 de novo prolapse during follow-up. The complication rate of Clavien-Dindo >3 was 0,8 %. Repeat surgery for POP occurred in 6.4 % of cases. The appearance of POP-Q recurrences was concentrated at 6 months follow-up. BMI > 25 was correlated with de novo posterior compartment appearance during follow-up.

Conclusions: LLS for the treatment of apical and anterior POP is a technique with optimal results in term of safety and effectiveness after 2 years follow-up.
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http://dx.doi.org/10.1016/j.ejogrb.2019.10.026DOI Listing
January 2020

Wharton's Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro.

Stem Cell Rev Rep 2019 12;15(6):900-918

Unit of Histology and Embryology, Department of Biomedicine Neurosciences and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, 90127, Palermo, PA, Italy.

Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of immune-related molecules, such as HLAs, IDO, CD276/B7-H3, and others, both in situ (HUC) and in in vitro-cultured WJ-MSCs. Morphological and biochemical techniques were used to define the expression of such molecules. In addition, we focused on the possible role of CD276/B7-H3 on T cells proliferation inhibition. We assessed CD276/B7-H3 expression by WJ-MSCs both in situ and alongside cell culture. WJ-MSCs were able to suppress T cell proliferation in mixed lymphocyte reaction (MLR). Moreover, we describe for the first time a specific role for CD276/B7-H3, since the immunomodulatory ability of WJ-MSCs was abolished upon anti-CD276/B7-H3 antibody addition to the MLR. These results further detail the immune regulation properties and tolerance induction exerted by human WJ-MSCs, in particular pointing to CD276/B7-H3 as one of the main involved factors. These data further suggest WJ-MSCs as potent tools to modulate local immune response in "support-type" regenerative medicine approaches.
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http://dx.doi.org/10.1007/s12015-019-09907-1DOI Listing
December 2019

Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy.

Stem Cells Transl Med 2020 02 18;9(2):203-220. Epub 2019 Nov 18.

Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida.

The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration. The optimal dose was 7.5 × 10 cells/mL when delivered via the intracarotid artery within 3 days poststroke, although therapeutic effects persisted even when administered at 1 week after stroke. Compared with other mesenchymal stem cells, NCS-01 cells ameliorated both the structural and functional deficits after stroke through a broad therapeutic window. NCS-01 cells secreted therapeutic molecules, such as basic fibroblast growth factor and interleukin-6, but equally importantly we observed for the first time the formation of filopodia by NCS-01 cells under stroke conditions, characterized by cadherin-positive processes extending from the stem cells toward the ischemic cells. Collectively, the present efficacy readouts and the novel filopodia-mediated mechanism of action provide solid lab-to-clinic evidence supporting the use of NCS-01 cells for treatment of stroke in the clinical setting.
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http://dx.doi.org/10.1002/sctm.19-0229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988762PMC
February 2020

Severe bowel incarceration in an eight-millimeter left-lateral trocar site after robot-assisted laparoscopic colposacropexy: A case report.

Case Rep Womens Health 2019 Oct 14;24:e00151. Epub 2019 Oct 14.

Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.

Over the last twenty years, robotic surgery has become an increasingly important form of surgical intervention. However, it can have complications. Trocar site hernia (TSH), also known as port site hernia (PSH), is an uncommon complication, but in the case of bowel incarceration or strangulation it can cause significant morbidity. The lateral trocar sites usually do not need fascial closure, given their low susceptibility to hernia development. In this paper, we present a rare case of an incarcerated TSH from an 8 mm left lateral port after robotic colposacropexy. The patient was a 74-year-old woman with fourth-degree vaginal vault prolapse. She underwent robot-assisted colposacropexy and adnexectomy and was eventually discharged 3 days after surgery, with flatus. A few hours later, the woman developed generalized malaise and acute abdominal pain in the lower left quadrant, with no flatus or bowel movements. CT imaging revealed a small bowel dilatation with a transition point along the left lateral 8 mm trocar site. Laparotomy confirmed an incarcerated ischemic small bowel loop. This required a surgical 40 cm small bowel resection. Although uncommon, TSH is an important clinical entity to recognize after minimally invasive surgery. While it is known that a trocar site port of 10 mm or more does require fascial closure, it is not known whether the same is true of lateral 8 mm sites. Further studies are needed to reconsider the importance of lateral trocar site port fascial closure after robot-assisted surgery.
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http://dx.doi.org/10.1016/j.crwh.2019.e00151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833345PMC
October 2019

Simulation as tool for evaluating and improving technical skills in laparoscopic gynecological surgery.

BMC Surg 2019 Oct 16;19(1):146. Epub 2019 Oct 16.

Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.

Background: Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion.

Methods: Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale.

Results: Senior trainees had better score than junior trainees (p value< 0,005) and after different sessions of simulation scores of both groups significantly improved (p < 0,001), especially for the junior group. All the trainees reported self-assessments that matched with the evaluation of external observers demonstrating the importance of simulation also as auto-evaluation test.

Conclusions: In this study, we demonstrated the role of simulation as powerful tool to evaluate and to self-assess surgical technical skills and to improve own capacities, with the use of a modified OSATs scale adapted to specific exercises.
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http://dx.doi.org/10.1186/s12893-019-0610-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796391PMC
October 2019

Medium-term outcomes after robotic-assisted lateral suspension with mesh for advanced multi-compartmental prolapse.

Int Urogynecol J 2020 08 6;31(8):1647-1653. Epub 2019 Aug 6.

Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.

Introduction And Hypothesis: Robotic abdominal lateral suspension (RALS) is an innovative mini-invasive surgical technique that allows treating apical and anterior prolapse. The safety and efficacy of this strategy have not yet been tested.

Methods: We completed a prospective case series of 115 RALS to treat apical and anterior prolapse stage III or IV, with no or minimal (stage I) posterior defect. Clinical evaluation was performed with a simplified POP quantification system (POP-Q). Mean follow-up was 28 ± 4 months. Primary outcomes were objective and subjective cure; secondary outcomes were reoperation rate for recurrence, erosion rate and complications. Objective cure was defined as POP-Q ≤ 1. Subjective cure was defined as absence of vaginal bulge. Patient's satisfaction was measured using the Patient Global Impression of Improvement Scale (PGI-I).

Results: There was a significant improvement in POP-Q score in all treated compartments with an objective cure rate of 88.7% for the anterior and 93.1% for the apical compartment (p < 0.0001). Subjective cure rate was 82%. The emergence of de novo high rectoceles was not significant in the cohort, as much as the development of de novo stress or urge urinary incontinence. Reoperation rate for POP was 11.3% (8 recurrent cystoceles without apical descent and 5 apical and anterior relapses). No postoperative complications of Clavien-Dindo grade ≥ 3a were seen. Mesh exposure rate was 0.9%; 58.2% patients compiled a PGI-I score at 18-24 months post-surgery, reporting high satisfaction rates.

Conclusions: RALS is highly effective at a mid-term follow-up for the treatment of advanced apical and anterior POP.
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http://dx.doi.org/10.1007/s00192-019-04069-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363728PMC
August 2020

Patient satisfaction and acceptability of an on-demand and on-prophylaxis device for factor VIII delivery in patients with hemophilia A.

Patient Prefer Adherence 2019 31;13:233-240. Epub 2019 Jan 31.

Medical Department, Pfizer srl Rome, Italy.

Background: FuseNGO is a relatively new device consisting of a prefilled dual-chamber syringe (DCS) that was recently introduced for the reconstitution of recombinant factor VIII. Herein, the DCS device was assessed using five questionnaires with the primary aim of evaluating patient perceptions and preferences.

Methods: An observational, non-interventional, longitudinal study on 86 patients with a confirmed diagnosis of hemophilia A was carried out at 21 sites in Italy. Each patient underwent a baseline visit and final study visit within 3-6 months. Patients were administered five questionnaires: HemoPREF; Treatment Satisfaction Questionnaire for Medication (TSQM); VeritasPRO; Hemophilia Well-being Index (HWBI); Work Productivity and Activity Impairment Questionnaire (WPAI) + Classroom Impairment Questions (CIQ): Hemophilia Specific (HS).

Results: Compared to baseline, scores for HemoPREF were higher at follow-up; significant increases in the percentage of positive responses were seen for all questions regarding the ease of use (<0.05). The mean time needed for the reconstruction of the device at baseline was 11 minutes (range 1-30 minutes), which decreased to 6 minutes (range 30 seconds to 25 minutes) at follow-up. All scores in the TSQM indicated good satisfaction with the device. Patients reported an adherence of >70% in the VeritasPRO questionnaire, and the majority of patients reported in the HWBI that hemophilia A did not affect their lives in a significant way. The perceived level of overall impairment was 30% as reported in the WPAI + CIQ: HS, indicating little impairment. There were no safety concerns.

Conclusion: Considering patient-reported outcomes, the DCS device was associated with easier preparation, storage, disposal of equipment, and overall use. Of particular note, preparation times were reduced by around 50%. The majority of patients were satisfied with the device and overall adherence scores were high. Considering these results, the device has the potential to increase adherence to therapy and, possibly, reduce healthcare costs.
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http://dx.doi.org/10.2147/PPA.S175254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362933PMC
January 2019

Central and Peripheral Secondary Cell Death Processes after Transient Global Ischemia in Nonhuman Primate Cerebellum and Heart.

Methods Mol Biol 2019 ;1919:215-225

Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.

Cerebral ischemia and its pathological sequelae are responsible for severe neurological deficits generally attributed to the neural death within the infarcted tissue and adjacent regions. Distal brain regions, and even peripheral organs, may be subject to more subtle consequences of the primary ischemic event which can initiate parallel disease processes and promote comorbid symptomology. In order to characterize the susceptibility of cerebellar brain regions and the heart to transient global ischemia (TGI) in nonhuman primates (NHP), brain and heart tissues were harvested 6 months post-TGI injury. Immunostaining analysis with unbiased stereology revealed significant cell death in lobule III and IX of the TGI cerebellum when compared to sham cerebellum, coinciding with an increase in inflammatory and apoptotic markers. Cardiac tissue analysis showed similar increases in inflammatory and apoptotic cells within TGI hearts. A progressive inflammatory response and cell death within the cerebellum and heart of chronic TGI NHPs indicate secondary injury processes manifesting both centrally and peripherally. This understanding of distal disease processes of cerebral ischemia underscores the importance of the chronic aberrant inflammatory response and emphasizes the needs for therapeutic options tailored to target these pathways. Here, we discuss the protocols for characterizing the histopathological effects of transient global ischemia in nonhuman primate cerebellum and heart, with an emphasis on the inflammatory and apoptotic cell death processes.
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http://dx.doi.org/10.1007/978-1-4939-9007-8_17DOI Listing
June 2019

Rate and Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation: Current Status.

Curr Cardiol Rev 2019 ;15(3):205-218

Department of Cardiovascular Disease, Division of Cardiac Surgery, Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy.

Transcather aortic valve implantation (TAVI) has become a safe and indispensable treatment option for patients with severe symptomatic aortic stenosis who are at high surgical risk. Recently, outcomes after TAVI have improved significantly and TAVI has emerged as a qualified alternative to surgical aortic valve replacement in the treatment of intermediate risk patients and greater adoption of this procedure is to be expected in a wider patients population, including younger patients and low surgical risk patients. However since the aortic valve has close spatial proximity to the conduction system, conduction anomalies are frequently observed in TAVI. In this article, we aim to review the key aspects of pathophysiology, current incidence, predictors and clinical association of conduction anomalies following TAVI.
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http://dx.doi.org/10.2174/1573403X15666181205105821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719385PMC
July 2019

Healthy mitochondria for stroke cells.

Brain Circ 2018 Jul-Sep;4(3):95-98. Epub 2018 Oct 9.

Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, College of Medicine, University of South Florida, Morsani College of Medicine, Tampa, Florida, USA.

Stroke is a debilitating disease that remains as a significant unmet need. Although our understanding of the disease pathology has advanced over the years, treatment options for stroke are limited. Recent studies have implicated the important role of healthy mitochondria in neuroprotection against stroke. Under the stroke pathological condition, transfer of healthy mitochondria is observed from astrocytes to ischemic neurons. However, without additional therapeutic intervention, such astrocyte-to-neuron transfer of mitochondria may not sufficiently afford a robust and stable therapeutic effect against the devastating primary insult and progressive neurodegeneration associated with stroke. We now explore the concept that transplantation of exogenous stem cells may serve as efficacious sources of healthy mitochondria for ischemic cells, not only neurons but also endothelial cells. This review captures the recent advances on the therapeutic potential of mitochondrial transfer as a novel stroke treatment. This paper is a review article. Referred literature in this article has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed.
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http://dx.doi.org/10.4103/bc.bc_20_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187944PMC
October 2018

Mitochondrial targeting as a novel therapy for stroke.

Brain Circ 2018 Jul-Sep;4(3):84-94. Epub 2018 Oct 9.

Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.

Stroke is a main cause of mortality and morbidity worldwide. Despite the increasing development of innovative treatments for stroke, most are unsuccessful in clinical trials. In recent years, an encouraging strategy for stroke therapy has been identified in stem cells transplantation. In particular, grafting cells and their secretion products are leading with functional recovery in stroke patients by promoting the growth and function of the neurovascular unit - a communication framework between neurons, their supply microvessels along with glial cells - underlying stroke pathology and recovery. Mitochondrial dysfunction has been recently recognized as a hallmark in ischemia/reperfusion neural damage. Emerging evidence of mitochondria transfer from stem cells to ischemic-injured cells points to transfer of healthy mitochondria as a viable novel therapeutic strategy for ischemic diseases. Hence, a more in-depth understanding of the cellular and molecular mechanisms involved in mitochondrial impairment may lead to new tools for stroke treatment. In this review, we focus on the current evidence of mitochondrial dysfunction in stroke, investigating favorable approaches of healthy mitochondria transfer in ischemic neurons, and exploring the potential of mitochondria-based cellular therapy for clinical applications. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed.
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http://dx.doi.org/10.4103/bc.bc_14_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187947PMC
October 2018

Advancing stem cells: New therapeutic strategies for treating central nervous system disorders.

Brain Circ 2018 Jul-Sep;4(3):81-83. Epub 2018 Oct 9.

Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida, Florida, USA.

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http://dx.doi.org/10.4103/bc.bc_22_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187938PMC
October 2018

May the force be with you: Transfer of healthy mitochondria from stem cells to stroke cells.

J Cereb Blood Flow Metab 2019 02 30;39(2):367-370. Epub 2018 Oct 30.

2 Department of Molecular Biosciences, University of California Davis, Davis, CA, USA.

Stroke is a major cause of death and disability in the United States and around the world with limited therapeutic option. Here, we discuss the critical role of mitochondria in stem cell-mediated rescue of stroke brain by highlighting the concept that deleting the mitochondria from stem cells abolishes the cells' regenerative potency. The application of innovative approaches entailing generation of mitochondria-voided stem cells as well as pharmacological inhibition of mitochondrial function may elucidate the mechanism underlying transfer of healthy mitochondria to ischemic cells, thereby providing key insights in the pathology and treatment of stroke and other brain disorders plagued with mitochondrial dysfunctions.
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http://dx.doi.org/10.1177/0271678X18811277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365599PMC
February 2019

Role of robotic surgery on pelvic floor reconstruction.

Minerva Ginecol 2019 Feb 11;71(1):4-17. Epub 2018 Oct 11.

Division of Obstetrics and Gynecology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Italy -

Over the past two decades, minimally invasive surgery (MIS) abdominal surgery has increasingly been used to treat pelvic organ prolapse. Besides the several advantages associated with minimal invasiveness, this approach bridged the gap between the benefits of vaginal surgery and the surgical success rates of open abdominal procedures. The most commonly performed procedure for suspension of the vaginal apex for postoperative vaginal prolapse by robotic-assisted laparoscopy is the sacrocolpopexy. Conventional laparoscopic application of this procedure was first reported in 1994 by Nezhat et al. and had not gained widespread adoption due to lengthy learning curve associated with laparoscopic suturing. Since FDA approval of the da Vinci® robot for gynecologic surgery in 2005, minimally invasive abdominal surgery for pelvic organ prolapse has become increasingly popular, as robotic-assisted laparoscopic sacrocolpopexy is an option for those surgeons without experience or training in the conventional route. Robotic surgery has made its way into the armamentarium of POP treatment and has allowed pelvic surgeons to adapt the "gold standard" technique of abdominal sacrocolpopexy to a minimally invasive approach with improved intraoperative morbidity and decreased convalescence. In fact, repair of pelvic organ prolapse can be performed robotically, and sometimes surgeons can feel suturing and dissection during the procedures less challenging with the assistance of the robot. However, even if robotic surgery may confer many benefits over conventional laparoscopy, these advantages should continue to be weighed against the cost of the technology. To date, as long-term outcomes, evidence about robotic sacrocolpopexy for a repair of pelvic organ prolapse are not conclusive, and much more investigations are needed to evaluate subjective and objective outcomes, perioperative and postoperative adverse events, and costs associated with these procedures. It is plausible to think that the main advantage is that robotics may lead to a widespread adoption of minimally invasive techniques in the field of pelvic floor reconstructive surgery. The following review will address the development and current state of robotic assistance in treating pelvic floor reconstruction discussing available data about the techniques of robotic prolapse repair as well as morbidity, costs and clinical outcomes.
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http://dx.doi.org/10.23736/S0026-4784.18.04331-9DOI Listing
February 2019

A Dual Role for Hyperbaric Oxygen in Stroke Neuroprotection: Preconditioning of the Brain and Stem Cells.

Cond Med 2018 Jun;1(4):151-166

Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL.

Stroke continues to be an extremely prevalent disease and poses a great challenge in developing safe and effective therapeutic options. Hyperbaric oxygen therapy (HBOT) has demonstrated significant pre-clinical effectiveness for the treatment of acute ischemic stroke, and limited potential in treating chronic neurological deficits. Reported benefits include reductions in oxidative stress, inflammation, neural apoptosis, and improved physiological metrics such as edema and oxygen perfusion, all of which contribute to improved functional recovery. This pre-clinical evidence has failed to translate into an effective evidence-based therapy, however, due in large part to significant inconsistencies in treatment protocols and design of clinical studies. While the medical community works to standardize clinical protocols in an effort to advance HBOT for acute stroke, pre-clinical investigations continue to probe novel applications of HBOT in an effort to optimize stroke neuroprotection. One such promising strategy is HBOT preconditioning. Based upon the premise of mild oxidative stress priming the brain for tolerating the full-blown oxidative stress inherent in stroke, HBOT preconditioning has displayed extensive efficacy. Here, we first review the pre-clinical and clinical evidence supporting HBOT delivery following ischemic stroke and then discuss the scientific basis for HBOT preconditioning as a neuroprotective strategy. Finally, we propose the innovative concept of stem cell preconditioning, in tandem with brain preconditioning, as a promising regenerative pathway for maximizing the application of HBOT for ischemic stroke treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075658PMC
June 2018

An update on intracerebral stem cell grafts.

Expert Rev Neurother 2018 07 13;18(7):557-572. Epub 2018 Jul 13.

a Department of Neurosurgery and Brain Repair , Center of Excellence for Aging and Brain Repair, USF Morsani College of Medicine , Tampa , FL , USA.

Introduction: Primary neurological disorders are notoriously debilitating and deadly, and over the past four decades stem cell therapy has emerged as a promising treatment. Translation of stem cell therapies from the bench to the clinic requires a better understanding of delivery protocols, safety profile, and efficacy in each disease. Areas covered: In this review, benefits and risks of intracerebral stem cell transplantation are presented for consideration. Milestone discoveries in stem cell applications are reviewed to examine the efficacy and safety of intracerebral stem cell transplant therapy for disorders of the central nervous system and inform design of translatable protocols for clinically feasible stem cell-based treatments. Expert commentary: Intracerebral administration, compared to peripheral delivery, is more invasive and carries the risk of open brain surgery. However, direct cell implantation bypasses the blood-brain barrier and reduces the first-pass effect, effectively increasing the therapeutic cell deposition at its intended site of action. These benefits must be weighed with the risk of graft-versus-host immune response. Rigorous clinical trials are underway to assess the safety and efficacy of intracerebral transplants, and if successful will lead to widely available stem cell therapies for neurologic diseases in the coming years.
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http://dx.doi.org/10.1080/14737175.2018.1491309DOI Listing
July 2018

Computed-tomography image segmentation and 3D-reconstruction of the female pelvis for the preoperative planning of sacrocolpopexy: preliminary data.

Int Urogynecol J 2019 05 29;30(5):725-731. Epub 2018 Jun 29.

Department of Clinical Medicine, Division of Obstetrics and Gynecology, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.

Background: Minimally-invasive sacrocolpopexy is the gold standard procedure for advanced apical prolapse. Nonetheless, sacrocolpopexy has potential serious complications leading many surgeons to avoid this excellent surgical procedure. To overcome these limitations, preoperative planning with 3D models of the female pelvis is proposed. The aim of the study is to evaluate the feasibility of pelvic anatomy reconstruction with the ITK-SNAP software and highlight its potential benefits in this intervention.

Methods: Thirty patient-specific 3D models of the female pelvis were created using ITK-SNAP and the EndoCAS Segmentation Pipeline extension for image segmentation: contrast-enhanced computed tomography (CE-CT) data sets of women who underwent examinations for reasons other than prolapse were used. The distances of pelvic structures from the sacral promontory were standardised and measured, and correlations among these distances were evaluated with Spearman's correlation coefficient.

Results: Pelvic anatomy reconstruction was feasible for all CE-CT data sets. A statistically significant correlation was found between the distances of the cava bifurcation and common iliac vessels from the sacral promontory. An area for proximal mesh attachment was defined: it is free from the passage of iliac vessels in 97.5% of cases. A significant statistical correlation was found between the distances of the midpoint of the bispinous diameter and the uterine cervix from the sacral promontory; a process of linear regression showed that the latter measure can be estimated by multiplying the first one by 0.86.

Conclusions: Pre-surgical 3D reconstructions of the female pelvis using ITK-SNAP could help achieve widespread use of sacrocolpopexy: further comparative studies are needed to evaluate the outcomes with and without their use.
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http://dx.doi.org/10.1007/s00192-018-3706-3DOI Listing
May 2019

Amygdala Corticofugal Input Shapes Mitral Cell Responses in the Accessory Olfactory Bulb.

eNeuro 2018 May-Jun;5(3). Epub 2018 Jun 11.

Center for Neuroscience Research, Children's National Health System, Washington, DC 20010.

Interconnections between the olfactory bulb and the amygdala are a major pathway for triggering strong behavioral responses to a variety of odorants. However, while this broad mapping has been established, the patterns of amygdala feedback connectivity and the influence on olfactory circuitry remain unknown. Here, using a combination of neuronal tracing approaches, we dissect the connectivity of a cortical amygdala [posteromedial cortical nucleus (PmCo)] feedback circuit innervating the mouse accessory olfactory bulb. Optogenetic activation of PmCo feedback mainly results in feedforward mitral cell (MC) inhibition through direct excitation of GABAergic granule cells. In addition, LED-driven activity of corticofugal afferents increases the gain of MC responses to olfactory nerve stimulation. Thus, through corticofugal pathways, the PmCo likely regulates primary olfactory and social odor processing.
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http://dx.doi.org/10.1523/ENEURO.0175-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001136PMC
January 2019

Regulatory Actions of LH and Follicle-Stimulating Hormone on Breast Cancer Cells and Mammary Tumors in Rats.

Front Endocrinol (Lausanne) 2018 16;9:239. Epub 2018 May 16.

Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Gonadotrophins are mainly known to influence the body through the formation of gonadal steroids. However, receptors for luteinizing hormone (LH) and follicular-stimulating hormone (FSH) are present in a set of extra-gonadal tissues in humans and animals, but their functional relevance is uncertain. In this article, we present experimental evidence that, in T-47D breast cancer (BC) cells, FSH, and LH alter the expression of genes involved in adhesion, motility, and invasion through the activation of their receptors. Using miniarray technology we also found that LH influences the expression of a broad set of genes involved in cancer biology in T-47D cells. Interestingly, the regulatory actions of FSH and LH depend on the modality of exposure, with significant differences between pre-pubertal-like vs. post-menopausal-like amounts of gonadotrophins, but not after intermittent administration, representative of fertile life. We also studied the modulation of the circulating levels of gonadotrophins in an rat model of BC progression and observed a direct correlation with the extent of cancer growth. These results support the hypothesis that gonadotrophins may have direct effects on extra-gonadal tissues. They also highlight that gonadotrophins could potentially contribute to BC progression, particularly in post-menopausal women who typically have higher gonadotrophin levels. This research may ultimately lead to testing the use of gonadotrophin-modulating drugs in BC patients.
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http://dx.doi.org/10.3389/fendo.2018.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964138PMC
May 2018