Preclinical Female Model of Urogenital Dysfunction and Pathophysiological Changes After Pelvic Radiation Therapy.

Introduction Radiation therapy (RT) is the gold standard for many pelvic cancers and improves overall patient survival. However, pelvic RT is associated with increased sexual dysfunction and urinary incontinence. Although the side effects of pelvic RT are well-documented, the pathological mechanisms leading to pelvic organ dysfunction are unknown, and a preclinical model has not been established.

A Case of Combined Infection with Tick-Borne Encephalitis and Lyme Borreliosis with Severe Meningoencephalitis and Complete Recovery.

Here, we present a case of severe meningoencephalitis caused by combined infection with tick-borne encephalitis (TBE) and Lyme borreliosis (LB) in a 25-year-old woman in a rural area of Zhambyl region, Kazakhstan. She presented with fever, nausea, vomiting, weakness, sweating, severe headache, arthralgia, and malaise. The course of illness was further complicated by encephalitis with symmetric lesions of the midbrain cerebral peduncles and serous meningitis.

Paternal Western diet causes transgenerational increase in food consumption in Drosophila with parallel alterations in the offspring brain proteome and microRNAs.

Several lines of evidence indicate that ancestral diet might play an important role in determining offspring's metabolic traits. However, it is not yet clear whether ancestral diet can affect offspring's food choices and feeding behavior. In the current study, taking advantage of Drosophila model system, we demonstrate that paternal Western diet (WD) increases offspring food consumption up to the fourth generation.

In vitro high glucose increases apoptosis, decreases nerve outgrowth, and promotes survival of sympathetic pelvic neurons.

Background: Diabetes mellitus (DM) is a common cause of erectile dysfunction (ED), yet the molecular basis of DM neurogenic ED remains unknown.

Aim: In this study we examined the impact of high glucose on survival and growth of primary cultured pelvic neurons in a rat model and assessed whether coculturing with healthy Schwann cells (SCs) can rescue pelvic neuron growth in patients with DM.

Methods: Major pelvic ganglia (MPGs) from adult male Sprague Dawley rats ( = 8) were dissociated and plated on coverslips.

Cocultured Schwann Cells Rescue Irradiated Pelvic Neuron Outgrowth and Increase Survival.

Background: Prostatic radiation therapy (RT) leads to erectile dysfunction by damaging peri-prostatic pro-erectile nerves of the pelvic ganglion. Schwann cells (SC) facilitate neuronal repair after mechanical injury, however, their role in repair of pelvic neurons post-radiation hasn't been explored.

Aim: To determine if SCs cocultured with primary pelvic neurons can rescue neuronal survival and growth after ex vivo RT.

Safety and Feasibility of Research Lumbar Puncture in Huntington's Disease: The HDClarity Cohort and Bioresource.

Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington's disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain.

Objective: To investigate the safety and feasibility of research lumbar punctures (LP) in HD.

Drosophila Passive Avoidance Behavior as a New Paradigm to Study Associative Aversive Learning.

This protocol describes a new paradigm for analyzing aversive associative learning in adult flies (Drosophila melanogaster). The paradigm is analogous to passive avoidance behavior in laboratory rodents in which animals learn to avoid a compartment where they have previously received an electric shock. The assay takes advantage of negative geotaxis in flies, which manifests as an urge to climb up when they are placed on a vertical surface.

Ex vivo Akt inhibition reverses castration induced internal pudendal artery and penile endothelial dysfunction.

Aims: Androgen deprivation therapy is a common prostate cancer treatment which causes men to have castrate levels of testosterone. Unfortunately, most testosterone deficient patients will suffer severe erectile dysfunction (ED) and have no effective ED treatment options. Testosterone deficiency causes endothelial dysfunction and impairs penile vasodilation necessary to maintain an erection.

Prediction of Prognosis in Glioblastoma Using Radiomics Features of Dynamic Contrast-Enhanced MRI.

Objective: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma.

Materials And Methods: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.

Impact of prostatic radiation therapy on bladder contractility and innervation.

Aims: To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.

Methods: Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2- and 10-weeks post-RT.

High-fat diet induces obesity in adult mice but fails to develop pre-penile and penile vascular dysfunction.

Obesity can lead to cardiovascular disease, diabetes, and erectile dysfunction (ED), which decreases overall quality of life. Mechanisms responsible for obesity-induced ED are unknown. Current mouse models of high-fat diet (HFD)-induced obesity yield conflicting results.

Preference and detrimental effects of high fat, sugar, and salt diet in wild-caught Drosophila simulans are reversed by flight exercise.

High saturated fat, sugar, and salt contents are a staple of a Western diet (WD), contributing to obesity, metabolic syndrome, and a plethora of other health risks. However, the combinatorial effects of these ingredients have not been fully evaluated. Here, using the wild-caught Drosophila simulans, we show that a diet enriched with saturated fat, sugar, and salt is more detrimental than each ingredient separately, resulting in a significantly decreased lifespan, locomotor activity, sleep, reproductive function, and mitochondrial function.

Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons.

Background: Prostatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies.

Aim: To determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture.

Methods: MPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats.

Chronic high-fat diet decreased detrusor mitochondrial respiration and increased nerve-mediated contractions.

Aims: To assess the impact of chronic high-fat diet (HFD) on behavioral voiding patterns, detrusor contractility, and smooth muscle mitochondrial function in male mice.

Materials And Methods: Male C57BL/6J mice (6 weeks) were fed a control or HFD for 20 weeks. Bladder function was assessed by void spot assays.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth.

Background: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated.

Aim: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model.

Clarifying the Relative Impacts of Vascular and Nerve Injury That Culminate in Erectile Dysfunction in a Pilot Study Using a Rat Model of Prostate Irradiation and a Thrombopoietin Mimetic.

Purpose: Radiation therapy (RT) offers an important and curative approach to treating prostate cancer, but it is associated with a high incidence of erectile dysfunction (ED). It is not clear whether the etiology of radiation-induced ED (RI-ED) is driven by RT-mediated injury to the vasculature, the nerves, or both. This pilot study sought to distinguish the effects of vascular and nerve injury in RI-ED by applying a vascular radioprotectant in a rat model of prostate RT.

miRNA-431 Prevents Amyloid-β-Induced Synapse Loss in Neuronal Cell Culture Model of Alzheimer's Disease by Silencing Kremen1.

Synapse loss is well regarded as the underlying cause for the progressive decline of memory function over the course of Alzheimer's disease (AD) development. Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf-1 (Dkk1) in the AD brain plays a critical role in triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block the Wnt/β-catenin signaling pathway.

Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries.

Background: The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA.

Aim: To examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone.

NLRP3/IL-1β mediates denervation during bladder outlet obstruction in rats.

Aims: Denervation of the bladder is a detrimental consequence of bladder outlet obstruction (BOO). We have previously shown that, during BOO, inflammation triggered by the NLRP3 inflammasome in the urothelia mediates physiological bladder dysfunction and downstream fibrosis in rats. The aim of this study was to assess the effect of NLRP3-mediated inflammation on bladder denervation during BOO.

Membrane Distribution and Activity of a Neuronal Voltage-Gated K+ Channel is Modified by Replacement of Complex Type N-Glycans with Hybrid Type.

Abnormal modifications in N-glycosylation processing are commonly associated with neurological disorders, although the impact of specific N-glycans on neuronal excitability is unknown. By replacement of complex types of N-glycans with hybrid types in neuroblastoma cells, we provide the first study that addresses how distinct N-glycan types impact neuronal excitability. Using CRISPR/Cas9 technology, NB_1, a clonal cell line derived from rat neuroblastoma cells (NB), was modified to create an N-glycosylation mutant cell line, NB_1 (-Mgat2), which expresses predominantly hybrid type N-glycans.

Paternal long-term exercise programs offspring for low energy expenditure and increased risk for obesity in mice.

Obesity has more than doubled in children and tripled in adolescents in the past 30 yr. The association between metabolic disorders in offspring of obese mothers with diabetes has long been known; however, a growing body of research indicates that fathers play a significant role through presently unknown mechanisms. Recent observations have shown that changes in paternal diet may result in transgenerational inheritance of the insulin-resistant phenotype.

Neurogenic potential of spinal cord organotypic culture.

There are several neurogenic niches in the adult mammalian central nervous system. In the central nervous system, neural stem cells (NSC) localize not only to the periventricular area, but are also diffusely distributed in the parenchyma. Here, we assessed neurogenic potential of organotypic cultures prepared from adult mouse spinal cord.

Dicer-microRNA pathway is critical for peripheral nerve regeneration and functional recovery in vivo and regenerative axonogenesis in vitro.

Both central and peripheral axons contain pivotal microRNA (miRNA) proteins. While recent observations demonstrated that miRNA biosynthetic machinery responds to peripheral nerve lesion in an injury-regulated pattern, the physiological significance of this phenomenon remains to be elucidated. In the current paper we hypothesized that deletion of Dicer would disrupt production of Dicer-dependent miRNAs and would negatively impact regenerative axon growth.

Multi-walled carbon nanotubes inhibit regenerative axon growth of dorsal root ganglia neurons of mice.

Recent observations have demonstrated that nanomaterials may be toxic to human tissue. While the ability of nano-scaled particulate matter is known to cause a range of problems in respiratory system, recent observations suggest that the nervous system may be vulnerable as well. In the current paper we asked whether exposure of primary neuronal cell cultures to nanoparticles might compromise regenerative axon growth.

Embryonic stem cells inhibit expression of erythropoietin in the injured spinal cord.

Recent observations have demonstrated neuroprotective role of erythropoietin (Epo) and Epo receptor in the central nervous system. Here we examined Epo function in the murine spinal cord after transplantation of pluripotent mouse embryonic stem (ES) cells pre-differentiated towards neuronal type following spinal cord injury. Expression of Epo was measured at both mRNA and protein levels in the ES cells as well as in the spinal cords after 1 and 7 days.