Peripheral Pathways Research Articles

Analgesic Activity of the Kappa Opioid Receptor Agonist RU-1205 in Rats

Introduction: Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. However, side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. Currently, the kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. The purpose of this study was to evaluate the antinociceptive effect of the novel compound - RU-1205. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Results: RU-1205 exhibited highly potent antinociceptive effects in rodent models of acute pain with ED50 values of 0.002 - 0.49 mg /kg. Pretreatment with the κ-opioid receptor antagonist norBinaltorphimine significantly attenuated the analgesic activity of investigated substance in a hot plate test. Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205.

Stimulus dynamics-dependent information transfer of olfactory and vomeronasal sensory neurons in mice

The parallel processing of chemical signals by the main olfactory system and the vomeronasal system has been known to control animal behavior. The physiological significance of peripheral parallel pathways consisting of olfactory sensory neurons and vomeronasal sensory neurons is not well understood. Here, we show complementary characteristics of the information transfer of the olfactory sensory neurons and vomeronasal sensory neurons. A difference in excitability between the sensory neurons was revealed by patch-clamp experiments. The olfactory and vomeronasal sensory neurons showed phasic and tonic firing, respectively. Intrinsic channel kinetics determining firing patterns was demonstrated by a Hodgkin-Huxley-style computation. Our estimation of the information carried by action potentials during one cycle of sinusoidal stimulation with variable durations revealed distinct characteristics of information transfer between the sensory neurons. Phasic firing of the olfactory sensory neurons was suitable to carry information about rapid changes in a shorter cycle (<200 ms). In contrast, tonic firing of the vomeronasal sensory neurons was able to convey information about smaller stimuli changing slowly with longer cycles (>500 ms). Thus, the parallel pathways of the two types of sensory neurons can convey information about a wide range of dynamic stimuli. A combination of complementary characteristics of olfactory information transfer may enhance the synergy of the interaction between the main olfactory system and the vomeronasal system.

Anti-cholinergics mecamylamine and scopolamine alleviate motion sickness-induced gastrointestinal symptoms through both peripheral and central actions

Enhanced cholinergic activity contributes to the production of complex autonomic manifestations of motion sickness (MS). However, whether anti-cholinergics exert their anti-MS effects through central or peripheral actions remained unclarified. In the present study, we investigated the effects of mecamylamine (MEC) and scopolamine (SCOP) on rotation-induced gastrointestinal symptoms (conditioned gaping and defecation), locomotion disturbances (hypoactivity and impaired balance performance), hypothermia as well as Fos expression in vestibulo-autonomic regions in rats. We also observed the effects of hexamethonium (HEX) and methyl scopolamine (MSCP) on those MS behavioral responses. The efficacy of all these drugs on rotation-induced emesis and other MS symptoms in cats was also examined. We found that intragastric administration of MEC and SCOP inhibited rotation-induced gaping and defecation in rats, but only MEC showed a dose-dependent manner. MEC aggravated rotation-induced balance disorder and failed to attenuate rotation-induced hypothermia as the SCOP did. MEC was more effective for inhibiting Fos expression in the caudal vestibular nucleus and nucleus of solitary tract than SCOP. Intraperitoneal injection of HEX and MSCP also significantly alleviated rotation-induced gastrointestinal symptoms, and showed benefit to balance performance in rats. In cats, MEC, SCOP and HEX had prophylactic effects against rotation-induced emesis and salivation, and deceased non-retching/vomiting symptoms, but MSCP only attenuated emesis. It suggested that MEC and SCOP might alleviate gastrointestinal symptoms of MS via inhibiting peripheral autonomic nervous system and central vestibulo-autonomic pathways. The nicotinic acetylcholine receptor inhibitors like MEC might be new candidates against gastrointestinal symptoms induced by MS or other vestibular disorders.

Mechanistic pain profiling as a tool to predict the efficacy of 3-week nonsteroidal anti-inflammatory drugs plus paracetamol in patients with painful knee osteoarthritis.

Joint inflammation is present in a subpopulation of knee osteoarthritis (OA) patients. Proinflammatory cytokines are known to sensitize the peripheral and central pain pathways. This can be mechanistically assessed by pressure pain thresholds and temporal summation of pain (TSP). Nonsteroidal anti-inflammatory drugs (NSAIDs) combined with paracetamol are recommended as OA treatment. The current study hypothesized that evidence of central sensitization would predict poor responses to peripherally directed therapies in knee OA and therefore aimed to investigate the value of mechanistic pain profiling for predicting pain outcome of treatment with NSAIDs plus paracetamol. One hundred thirty-two patients received ibuprofen 1200 mg/daily, paracetamol 3 g/daily, and pantoprazole 20 mg/daily for 3 weeks. Before administration, cuff pain detection, tolerance threshold, and TSP were assessed. Worst pain within the last 24 hours and pain during activity (visual analogue scales) were assessed before and after treatment. Facilitated TSP was found at baseline in the nonresponders to the 3-weeks treatment as compared to responders for both the 30% and 50% pain alleviation criteria (P < 0.02). Linear regression models identified facilitated TSP (P < 0.01) and low clinical pain scores (P < 0.001) as independent factors for prediction of poor pain alleviation by the treatment. In conclusion, this study found that mechanistic pain profiling can predict pain alleviation of NSAIDs and paracetamol. Facilitated TSP and low clinical pain scores before treatment are independent predictors of poor pain alleviation after NSAIDs and paracetamol. This study adds to the growing evidence that a subgroup of knee OA patients with manifested central sensitization may require special management attention.

Homeostatic and neurocognitive control of energy intake in response to exercise in pediatric obesity: a psychobiological framework.

While energy intake and energy expenditure have long been studied independently, the alarming progression of obesity has led to a more integrative approach to energy balance considering their potential interactions. Although the available literature concerned with the effect of chronic and acute exercise on energy intake and appetite control in adults is considerable, these questions remain less explored among children and adolescents. Based on the search of four databases (Medline, Embase, PsycINFO and Cochrane Library; articles published until May 2018), the objective of this review is to summarize and discuss the effect of acute and chronic physical exercise on energy intake and appetite control in children and adolescents with obesity, and to identify the physiological and neurocognitive signals and pathways involved. Evidence suggested that acute intensive exercise has the potential to reduce subsequent energy intake in children and adolescents with obesity but not healthy weight, through both peripheral (mainly gastro-peptides) and neurocognitive (neural responses to food cues) pathways. The nutritional responses to chronic physical activity remain less clear and require further consideration, especially from an anti-obesity perspective.

An overview of energy and metabolic regulation.

The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identifying critical targets for treatment are important research goals. Therefore, the purpose of this article is to describe energy regulation by the central nervous system (CNS) and peripheral humoral pathway. Homeostasis and rewarding are the basis of CNS regulation. Anorexigenic or orexigenic effects reflect the activities of the POMC/CART or NPY/AgRP neurons within the hypothalamus. Neurotransmitters have roles in food intake, and responsive brain nuclei have different functions related to food intake, glucose monitoring, reward processing. Peripheral gut- or adipose-derived hormones are the major source of peripheral humoral regulation systems. Nutrients or metabolites and gut microbiota affect metabolism via a discrete pathway. We also review the role of peripheral organs, the liver, adipose tissue, and skeletal muscle in peripheral regulation. We discuss these topics and how the body regulates metabolism.

Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS.

Neuroinflammation is a recognized pathogenic mechanism underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but the inflammatory mechanisms influencing peripheral motor axon degeneration remain largely unknown. A recent report showed a pathogenic role for c-Kit-expressing mast cells mediating inflammation and neuromuscular junction denervation in muscles from SOD1G93A rats. Here, we have explored whether mast cells infiltrate skeletal muscles in autopsied muscles from ALS patients. We report that degranulating mast cells were abundant in the quadriceps muscles from ALS subjects but not in controls. Mast cells were associated with myofibers and motor endplates and, remarkably, interacted with neutrophils forming large extracellular traps. Mast cells and neutrophils were also abundant around motor axons in the extensor digitorum longus muscle, sciatic nerve, and ventral roots of symptomatic SOD1G93A rats, indicating that immune cell infiltration extends along the entire peripheral motor pathway. Postparalysis treatment of SOD1G93A rats with the tyrosine kinase inhibitor drug masitinib prevented mast cell and neutrophil infiltration, axonal pathology, secondary demyelination, and the loss of type 2B myofibers, compared with vehicle-treated rats. These findings provide further evidence for a yet unrecognized contribution of immune cells in peripheral motor pathway degeneration that can be therapeutically targeted by tyrosine kinase inhibitors.

The Reliability of Neurological Measurement in the Vastus Medialis: Implications for Research and Practice.

The integrity of the corticomotor pathway is paramount in the optimal functioning of skeletal muscle. However, variability of neurophysiological assessment via peripheral nerve and transcranial magnetic stimulation can render interpretation difficult. Seldom evidence exists regarding the reliability of such measurements in the leg extensors, which have important locomotive and functional roles. This study aimed to assess the test-retest reliability of peripheral, corticospinal and intracortical responses in the vastus medialis. Transcranial magnetic and direct current electrical nerve stimulation were delivered to sixteen healthy young adults (8M and 8F) on two separate occasions. The Hoffmann reflex, maximal compound wave, motor evoked potential, corticospinal silent period, intracortical facilitation, and short-interval intracortical inhibition were recorded from the vastus medialis at rest, and during controlled submaximal voluntary contraction. Relative reliability was quantified using intra-class correlation coefficient (ICC2,1). Absolute reliability was quantified using standard error of measurement (SEm) and minimal detectable change (MDC). Corticospinal silent period, corticospinal silent period/motor evoked potential ratio, active motor evoked potential, maximal Hoffman reflex, and passive short-interval intracortical inhibition demonstrated “good to excellent” relative reliability (ICC ≥ 0.643). Intracortical facilitation demonstrated the lowest relative reliability (ICC = 0.420–0.908). Corticospinal silent period displayed the lowest absolute reliability (SEm ≤ 18.68%). Good reliability of the maximal compound wave, Hoffman reflex, motor evoked potential, and corticospinal silent period allow for reliable neurological evaluation of peripheral and corticospinal pathways in the vastus medialis. Future research should investigate reliability of the intracortical (short-interval intracortical inhibition and intracortical facilitation) measures by using different paired-pulse stimulus parameters. These findings hold important implications for neurophysiological assessment conducted in the leg extensor group.

Involvement of the Hypothalamic Glutamatergic System in the Development of Radiation-Induced Pica in Rats.

Since the peripheral serotoninergic pathway is involved in the development of radiation-induced nausea and vomiting, referred to as radiation sickness, serotonin 5-HT3 receptor antagonists are used as a preventive measure, although patients still suffer from these symptoms. Glutamate is known as the excitatory neurotransmitter and is involved in various autonomic symptoms. We investigated the effect of radiation on glutamate release in rats, as measured by in vivo brain microdialysis, and the effects of glutamate receptor antagonists on radiation-induced pica, which can be used as a behavioral assessment of radiation sickness in rats. A microdialysis probe was inserted into the hypothalamus of rats that received 4 Gy total-body irradiation (TBI) with or without pretreatment of 5-HT3 receptor antagonist (granisetron, 0.1 mg/kg, i.p.), and dialysates were collected for 3 h after TBI and subjected to HPLC assay of glutamate. In addition, rats were intracerebroventricularly injected with NMDA receptor antagonist (MK-801: 3 μg/rat) or AMPA receptor antagonist (CNQX: 1 μg/rat) before TBI, and radiation-induced pica was determined. An increase in glutamate release was observed within 1 h postirradiation. The increased glutamate release was suppressed by granisetron. We also found that CNQX, but not MK-801, effectively inhibited radiation-induced pica. These results indicate that the hypothalamic glutamatergic system contributes to radiation-induced pica through the AMPA receptors.

Rationale for electrical parameter determination in external trigeminal nerve stimulation (eTNS) for migraine: A narrative review

Migraine is a primary headache disorder involving dysregulation of central and peripheral pain pathways. Medical treatment is often limited by drug side effects, comorbidities and poor compliance. This makes neuromodulation an ideal option for migraine treatment. Cefaly® is a transcutaneous electrical neurostimulator designed specifically for migraine treatment. It results in external trigeminal nerve stimulation of the supraorbital and supratrochlear nerves. External trigeminal nerve stimulation is effective for acute and preventive migraine treatment and may result in normalization of dysregulated pain pathways. Our objective was to provide a narrative review of the neuroanatomical and pathophysiological basis of external trigeminal nerve stimulation for migraine treatment and to provide the rationale behind the choice of the electrical parameters used for external trigeminal nerve stimulation. We reviewed external trigeminal nerve stimulation clinical trial publications, basic science neurostimulation literature, publications describing pathophysiological mechanisms in migraine, and documentation used in the application for the Food and Drug Administration approval of external trigeminal nerve stimulation. The electrical parameters used for external trigeminal nerve stimulation were chosen to maximize safety and efficacy. Critical parameters include generator characteristics, pulse shape, pulse duration, pulse frequency and session duration and frequency. We explain the rationale behind determination of each parameter. There is evidence of dysregulated central and peripheral pathways in migraine and evidence that external trigeminal nerve stimulation may normalize function of these pathways. External trigeminal nerve stimulation is a safe and effective Food and Drug Administration-approved option for the acute and preventive treatment of migraine. The electrical parameters were optimized specifically for external stimulation of the trigeminal nerve to maximum safety, comfort and efficacy.

Pathophysiology of cation channels in pain: Focus on TRP Channels

In neurons such as dorsal root ganglion (DRG) and trigeminal ganglia, calcium (Ca2+) and sodium ion concentrations are higher in in outside than in cytosol, although potassium ion concentration was higher in inside of the neurons than outside of the neurons. Within the ions, it has been suggested that a dysregulation of Ca2+ homeostasis acts a key role in the pathogenesis of oxidative stress associated nerve damage. Ca2+ is a main intracellular messenger involved in several physiological functions of neurons such survival, death, synaptic plasticity and neurotransmitter release. It has specific role in induction of peripheral pain. Ca2+ passes cell membrane via different channels such as chemical and voltage gated channels. Apart from the well-known cation channels, there is recently discovered channels namely transient receptor potential (TRP) family. The TRP superfamily is containing 6 subfamilies with 28 members in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the voltage gated calcium channels. Some TRP channels such as TRP melastatin 2 (TRPM2), melastatin 7 (TRPM7) and TRP ankyrin 1 (TRPA1) are activated by oxidative stress. Expression levels of TRPA1, TRPM2 and TRPM7 are high in DRG, phagocytic cells and hippocampus, respectively. Therefore, TRPM2 is important channels in physiological activity of phagocytic cells such as neutrophil and monocytes (Heiner et al. 2006). TRPM7 and TRPA1 have main roles in cerebral ischemia and peripheral pain molecular pathways, respectively (Carrasco et al. 2018; Sun, 2017). Till today specific antagonists of most TRP channels have not been discovered yet and they have potential targets for discovering drugs in neuroscience. In pain etiology, Ca2+ is important and it has been demonstrated in some studies that the administration of an antagonist to Ca2+ channels induces a reduction in chemotherapeutic&amp;nbsp;&amp;nbsp;agents-induced neuropathic pain.&amp;nbsp; In the presentation, I discussed novel results of Ca2+ on the peripheral pain by the regulation of TRP channels.&amp;nbsp; I concluded that the results of recent studies suggest that increased cytosolic Ca2+ has through inhibition of TRP channels main role in etiology of peripheral pain. It seems to that the TRP channels are potential target for treatment of peripheral pain.&amp;nbsp;

A chronic LPS-induced low-grade inflammation fails to reproduce in lean mice the impairment of preference for oily solution found in diet-induced obese mice

Diet-induced obesity (DIO) is associated with a decreased oral fat detection in rodents. This alteration has been explained by an impairment of the lipid-mediated signaling in taste bud cells (TBC). However, factors responsible for this defect remain elusive. Diet rich in saturated fatty acids is known to elicit a metabolic inflammation by promoting intestinal permeation to lipopolysaccharides (LPS), Gram-negative bacteria-derived endotoxins. To determine whether a local inflammation of the gustatory tissue might explain the obese-induced impairment of the oro-sensory detection of lipids, mice were subjected to a DIO protocol. Using a combination of behavioral tests, transcriptomic analyses of gustatory papillae and biochemical assays, we have found that i) DIO elicits a pro-inflammatory genic profile in the circumvallate papillae (CVP), known to house the highest density of lingual taste buds, ii) NFkB, a key player of inflammatory process, might play a role in this transcriptomic pattern, iii) plasma LPS levels are negatively correlated with the preference for oily solution, and iv) a chronic infusion of LPS at a level similar to that found in DIO mice is not sufficient to alter the spontaneous preference for fat in lean mice. Taken together these data bring the demonstration that a saturated high fat diet elicits an inflammatory response at the level of peripheral gustatory pathway and a LPS-induced low-grade endotoxemia alone does not explain the change in the preference for dietary lipids observed in DIO mice.

Long-Term Depression Induced by Optogenetically Driven Nociceptive Inputs to Trigeminal Nucleus Caudalis or Headache Triggers.

The peripheral trigeminovascular pathway mediates orofacial and craniofacial pain and projects centrally to the brainstem trigeminal nucleus caudalis (TNc). Sensitization of this pathway is involved in many pain conditions, but little is known about synaptic plasticity at its first central synapse. We have taken advantage of optogenetics to investigate plasticity selectively evoked at synapses of nociceptive primary afferents onto TNc neurons. Based on immunolabeling in the trigeminal ganglia, TRPV1-lineage neurons comprise primarily peptidergic and nonpeptidergic nociceptors. Optical stimulation of channelrhodopsin-expressing axons in the TRPV1/ChR2 mouse in TNc slices thus allowed us to activate a nociceptor-enriched subset of primary afferents. We recorded from lamina I/II neurons in acutely prepared transverse TNc slices, and alternately stimulated two independent afferent pathways, one with light-activated nociceptive afferents and the other with electrically-activated inputs. Low-frequency optical stimulation induced robust long-term depression (LTD) of optically-evoked EPSCs, but not of electrically-evoked EPSCs in the same neurons. Blocking NMDA receptors or nitric oxide synthase strongly attenuated LTD, whereas a cannabinoid receptor 1 antagonist had no effect. The neuropeptide PACAP-38 or the nitric oxide donors nitroglycerin or sodium nitroprusside are pharmacologic triggers of human headache. Bath application of any of these three compounds also persistently depressed optically-evoked EPSCs. Together, our data show that LTD of nociceptive afferent synapses on trigeminal nucleus neurons is elicited when the afferents are activated at frequencies consistent with the development of central sensitization of the trigeminovascular pathway.SIGNIFICANCE STATEMENT Animal models suggest that sensitization of trigeminovascular afferents plays a major role in craniofacial pain syndromes including primary headaches and trigeminal neuralgia, yet little is known about synaptic transmission and plasticity in the brainstem trigeminal nucleus caudalis (TNc). Here we used optogenetics to selectively drive a nociceptor-enriched population of trigeminal afferents while recording from superficial laminae neurons in the TNc. Low-frequency optical stimulation evoked robust long-term depression at TRPV1/ChR2 synapses. Moreover, application of three different headache trigger drugs also depressed TRPV1/ChR2 synapses. Synaptic depression at these primary afferent synapses may represent a newly identified mechanism contributing to central sensitization during headache.

The Impact of Thyroid Disease on Sexual Dysfunction in Men and Women.

Individually, thyroid disease and sexual dysfunction are common conditions that can have a detrimental effect on quality of life. Recent reports have documented an increased prevalence of sexual dysfunction among patients with thyroid disorders. As such, it is important for sexual medicine physicians to be primed on the presentation of patients with overlying sexual and thyroid dysfunction to allow for proper management. To review the available literature exploring the relationship between thyroid disease and sexual dysfunction in men and women. A PubMed review of existing clinical and pre-clinical studies from 1978 through 2018 was performed. The prevalence, symptomatology, pathophysiology, diagnosis and management of patients with sexual dysfunction in the setting of thyroid disease were reviewed. The prevalence of sexual dysfunction in patients with hypothyroid (59-63% and 22-46% in men and women, respectively) and hyperthyroidism (48-77% and 44-60% in men and women, respectively) has been estimated in select populations. Both hypothyroidism and hyperthyroidism were strongly associated with erectile and ejaculatory dysfunction: hypothyroidism with delayed ejaculation, hyperthyroidism with pre-mature ejaculation. Hypothyroidism and hyperthyroidism have been reported to impair libido in men and women; however, evidence of hypothyroidism's impact on male libido is mixed. Hypothyroid and hyperthyroid women demonstrated impairments in desire, arousal/lubrication, orgasm, satisfaction, and pain during intercourse. Mechanistically, hypothyroidism and hyperthyroidism exert effects on circulating sex hormone levels through peripheral and central pathways and can indirectly provoke psychiatric and autonomic dysregulation that can impair sexual function. Correction to euthyroid state was associated with dramatic resolution of sexual dysfunction in both male and female patients with hypothyroidism or hyperthyroidism. By improving awareness of the link between thyroid disease and sexual dysfunction, sexual medicine physicians may sooner identify patients whose sexual symptoms may be remedied by treating an underlying thyroid disorder. Gabrielson AT, Sartor RA, Hellstrom WJG. The Impact of Thyroid Disease on Sexual Dysfunction in Men and Women. Sex Med Rev 2019;7:57-70.

Molecular and clinical aspects of embryotoxicity induced by acetylcholinesterase inhibitors

Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.

Desempeño fonológico y actividad bioeléctrica auditiva en un niño con trastorno fonológico

Introducción. El trastorno fonológico es un déficit en la percepción, organización y producción fonológica del lenguaje. Los potenciales evocados auditivos de tronco cerebral identifican cambios electrofisiológicos generados en la vía auditiva, por tanto, el presente estudio pretende demostrar la utilidad de tales potenciales en la caracterización de los pacientes con trastornos fonológicos, permitiendo así evidenciar una alteración en la actividad bioeléctrica de la vía auditiva.Presentación del caso. Se presenta el caso de un menor con trastorno fonoaudiológico evaluado por medio de potenciales evocados auditivos de tronco cerebral, previa evaluación de la vía auditiva periférica excluyendo patologías adyacentes. El análisis de los resultados verifica que, en tiempo de transmisión del estímulo al recorrer la vía auditiva, se generó un aumento en las latencias absolutas de las ondas I, III y V, con aumento en las desviaciones estándar de la prueba.Conclusiones. Puede existir asociación entre el desarrollo fonológico y la actividad bioeléctrica de la vía auditiva, además, aumentando la muestra se podría generar una evaluación objetiva que valore algunas alteraciones del lenguaje en niños.

Sudden hearing loss as an early detector of multiple sclerosis: a systematic review.

To evaluate whether Sudden Sensorineural Hearing Loss (S-SNHL) may be an early symptom of Multiple Sclerosis (MS). A systematic review was conducted using the following keywords: "Multiple sclerosis, hearing loss, sudden hearing loss, vertigo, tinnitus, magnetic resonance imaging, otoacoustic emission, auditory brainstem responses, white matter lesions, sensorineural hearing loss, symptoms of MS and otolaryngology, nerve disease and MS". Only the articles that included results of at least one auditory test and MRI were considered. We evaluated the prevalence of SNHL in patients with MS, the presence of different forms of SNHL (S-SNHL and Progressive SNHL (P-SNHL)) and their correlation with the stage of MS, the results of electrophysiological tests, and the location (if any) of MS lesions as detected by white matter hyperintensities in the MRI. We reviewed a total of 47 articles, which included 29 case reports, 6 prospective studies, 6 cohort studies, 4 case-control studies, and 2 retrospective studies. 25% of patients suffered from SNHL. S-SNHL typically occurred in the early stage of the disease (92% of patients) and was the only presenting symptom in 43% of female subjects. Instead, P-SNHL occurred in the late stage of MS (88% of patients). Auditory Brainstem Responses (ABR) were abnormal in all MS patients with S-SNHL. When S-SNHL appeared during the early stage of the disease, MS lesions were found in the brain in 60% of patients and in the Internal Auditory Canal in 40% of patients. ABR remained abnormal after recovery. S-SNHL can be an early manifestation of MS and should always be considered in the differential diagnosis of this condition, especially in women. The pathophysiology can be explained by the involvement of microglia attacking the central and/or peripheral auditory pathways as indicated by WMHs.

Effect of Leptin on Marrow Adiposity in Ovariectomized Rabbits Assessed by Proton Magnetic Resonance Spectroscopy

Leptin acts to influence bone metabolism through indirect hypothalamic relay and direct peripheral pathways. Leptin enhances the differentiation of mesenchymal stem cells to the osteoblast rather than the adipocyte lineage, but the in vivo impacts of leptin on ovariectomy (OVX)-induced marrow adiposity are poorly understood. In this work, we aimed to address this question. Forty-five female New Zealand rabbits were divided into sham + vehicle, OVX + vehicle, and OVX + leptin for 5 months. Magnetic resonance spectroscopy and dual-energy x-ray absorptiometry were performed to longitudinally evaluate marrow fat fraction and bone density at 0, 2.5, and 5 months, respectively. At the end of experiment, quantitative parameters of marrow adipocytes were assessed by histopathology. Estrogen-deficient rabbits markedly exhibited expansion of marrow fat in a time-dependent manner, with a variation of marrow fat fraction (+19.7%) at 2.5 months relative to baseline conditions, and it was maintained until 5 months (+49.2%; all P < 0.001), which was accompanied by diminished bone density. Adipocyte diameter, density, and adipocytes area percentage in the OVX controls was increased by 50.7%, 76.3%, and 135.5%, respectively, relative to the sham controls (all P < 0.001). These OVX-induced marrow adiposity and bone loss were partly restored by leptin treatment. Treatment with leptin prevented OVX-induced increases in bone turnover in rabbits. Early leptin administration inhibits the adipogenic effect of estrogen deficiency in terms of reverting marrow fat expansion seen in OVX rabbits. Magnetic resonance spectroscopy may be a useful tool for longitudinal and interventional assessments in osteoporosis.

Predicting Likelihood to Pay Attention to Agriculture-Related Issues in the News with Demographic Characteristics

The public has more choices than ever when it comes to choosing media, which has led to gaps in knowledge across members of the public. Investigating motivational differences across demographic groups to pay attention to agriculture-related news could address knowledge gaps related to agriculture-related issues. The Elaboration Likelihood Model (ELM) includes motivation as a precursor to attitude change. Past research has indicated the public utilizes the peripheral processing route of the ELM when presented with agriculture-related messages, which leads to weak changes in attitude. The purpose of this research was to explore how demographic characteristics could predict likelihood to pay attention to agriculture-related news issues. A nationwide survey of United States residents indicated that respondents were likely to pay attention to agriculture-related news topics. A regression analysis found the following to be statistically significant predictors for likelihood to pay attention: marital status, geographic region, age, and political beliefs. However, the model accounted for a small amount of variance in likelihood to pay attention. The results from this study illustrate that while U.S. residents possess the motivation to process agriculture-related news, they may be utilizing the peripheral pathway of the ELM due to a lack in ability to process the communication.

Effect of Phosphate-Solubilizing Bacteria on the Mobility of Insoluble Cadmium and Metabolic Analysis.

Phosphate-solubilizing bacteria (PSB) can promote plant growth by dissolving insoluble phosphate. Therefore, PSB may have the potential to improve the mobility of heavy metals in soils and enhance phytoextraction. This study isolated a few PSB strains that could dissolve CdCO3 and solid Cd in soil. Two typical PSB, namely, high- and low-Cd-mobilizing PSB (Pseudomonas fluorescens gim-3 and Bacillus cereus qh-35, respectively), were selected to analyze the metabolic profiles, metabolic pathways, and mechanisms of mobilization of insoluble Cd. A total of 34 metabolites secreted by the two PSB strains were identified. Gluconic acid was the main contributor to Cd dissolution (42.4%) in high-Cd-mobilizing PSB. By contrast, gluconic acid was not secreted in low-Cd-mobilizing PSB. Metabolic pathway analysis showed that gluconic acid was produced by the peripheral direct oxidation pathway. Hence, PSB with peripheral direct oxidation pathway were likely to have high-Cd-mobilizing capacity.