Antifungal Metabolites as Food Bio-Preservative: Innovation, Outlook, and Challenges

Perishable food spoilage caused by fungi is a major cause of discomfort for food producers. Food sensory abnormalities range from aesthetic degeneration to significant aroma, color, or consistency alterations due to this spoilage. Bio-preservation is the use of natural or controlled bacteria or antimicrobials to enhance the quality and safety of food. It has the ability to harmonize and rationalize the required safety requirements with conventional preservation methods and food production safety and quality demands. Even though synthetic preservatives could fix such issues, there is indeed a significant social need for “clean label” foods. As a result, consumers are now seeking foods that are healthier, less processed, and safer. The implementation of antifungal compounds has gotten a lot of attention in recent decades. As a result, the identification and characterization of such antifungal agents has made promising advances. The present state of information on antifungal molecules, their modes of activity, connections with specific target fungi varieties, and uses in food production systems are summarized in this review.

Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with fragile X syndrome

Background Disturbances in sensory function are an important clinical feature of neurodevelopmental disorders such as fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS; thus, positioning sensory function as a potential clinical target for the development of new therapeutics. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the presence of sensory deficits in the visual system of the Fmr1−/y genetic mouse model of FXS. The goals of the current study were two-folds: (1) to assess the feasibility of measuring ERG and CS as a biomarker of sensory deficits in individuals with FXS, and (2) to investigate whether the deficits revealed by ERG and CS in Fmr1−/y mice translate to humans with FXS. Methods Both ERG and CS were measured in a cohort of male individuals with FXS (n = 20, 18–45 years) and age-matched healthy controls (n = 20, 18–45 years). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full-field flash ERG device (RETeval®, LKC Technologies Inc., Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA). Results Data recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1−/y genetic mouse model, individuals with FXS were found to exhibit reduced b-wave and flicker amplitude in ERG and an impaired ability to discriminate contrasts compared to healthy controls. Conclusions This study demonstrates the feasibility of using ERG and CS for assessing visual deficits in FXS and establishes the translational validity of the Fmr1−/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complementary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS. Trial registration ID-RCB number 2019-A01015-52 registered on the 17 May 2019.

Myelopathies from Neoplasms

Benign and malignant tumors can be an important cause of myelopathy. Patients may present with a wide range of neurologic symptoms including back and neck pain, weakness, sensory abnormalities, and bowel and bladder dysfunction. Management can be challenging depending on the location and underlying biology of the tumor. Neuroimaging of the spine is an important component of diagnostic evaluation and patient management both during initial evaluation and when monitoring after treatment. This article provides a systematic and practical review of neoplasms that can cause myelopathy. Unique imaging and biological features of distinct tumors are discussed, and their management strategies are reviewed.

Contralateral Sensory and Pain Perception Changes in Patients With Unilateral Neuropathy

Objective:To test whether contralateral sensory abnormalities in the clinically unaffected area of patients with unilateral neuropathic pain are due to the neuropathy or pain mechanisms.Methods:We analyzed the contralateral clinically unaffected side of patients with unilateral painful or painless neuropathy (peripheral nerve injury, PNI; postherpetic neuropathy, PHN; radiculopathy) by standardized quantitative sensory testing following a validated protocol. Primary outcome was the independent contribution of the following variables on the contralateral sensory function using generalized linear regression models: pain intensity, disease duration, etiology, body area, and sensory patterns in the most painful area.Results:Among 424 patients (PNI: n=256; PHN: n=78, radiculopathy: n=90) contralateral sensory abnormalities were frequent in both painful (n=383) and painless (n=41) unilateral neuropathy, demonstrating sensory loss for thermal and mechanical non-painful stimuli and both sensory loss and gain for painful test stimuli. Analysis by etiology revealed contralateral pinprick hyperalgesia in PHN and PNI. Analysis by ipsilateral sensory phenotype demonstrated mirror-image pinprick hyperalgesia in both mechanical and thermal hyperalgesia phenotypes. Pain intensity, etiology and affected body region predicted changes in only single contralateral somatosensory parameters. Disease duration had no impact on the contralateral sensory function.Conclusion:Mechanisms of sensory loss seems to spread to the contralateral side in both painful and painless neuropathies. Contralateral spread of pinprick hyperalgesia was restricted to the two ipsilateral phenotypes that suggest sensitization; this suggest a contribution of descending net facilitation from supraspinal areas, which was reported in rodent models of neuropathic pain, but not yet in human patients.

Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with Fragile X Syndrome

Background: Disturbances in sensory function are considered as an important clinical feature of individuals with neurodevelopmental disorders such as Fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS, thus elevating interest in sensory function as a clinical target for therapeutics development. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the presence of sensory deficits in the visual system of the Fmr1-/y genetic mouse model of FXS. The goals of this study were two-fold: 1) assess the feasibility of measuring ERG and CS as a biomarker in individuals with FXS, and 2) investigate whether the deficits in ERG and CS originally discovered in Fmr1-/y mice were translatable to humans with FXS. Methods: Both ERGs and CS were measured in a cohort of individuals with FXS (n=20, 18-45 yrs) and age-matched healthy controls (n=20, 18-45 yrs). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full field flash ERG device (RETeval®, LKC Technologies Inc, Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA). Results: Data recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1-/y genetic mouse model of FXS, abnormalities in both ERG waveform and CS were observed in FXS. Conclusions: This study demonstrates the feasibility of using ERG and CS for assessing the visual system in FXS and establishes the translatability of the Fmr1-/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complimentary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS.Trial Registration: ID-RCB number 2019-A01015-52 registered on the 05/17/2019.

Guillain Barre Syndrome in a Young Man with SARSCoV-2: A Rare Association

Guillain Barre Syndrome (GBS) is usually a post-infectious autoimmune disease that manifests as acute ascending flaccid paralysis. The disease is usually uncommon. However, recently it was reported in a few COVID-19 cases before complete resolution of COVID symptoms. An association between olfactory-gustatory disturbances and sensory abnormalities is frequently observed in GBS with COVID-19. The electrophysiological studies usually reveal a demyelinating pattern. Respiratory involvement, as part of respiratory muscle paralysis or COVID-19 pneumonia, is associated with poor recovery in affected patients. Here, we present a case of a young man, pre-morbid healthy, who presented with GBS with mild COVID-19 infection. He successfully recovered after treatment with Intravenous immunoglobulin IVIg.

Sensory neuronopathies: new genes, new antibodies and new concepts

Degeneration of dorsal root ganglia (DRG) and its central and peripheral projections provokes sensory neuronopathy (SN), a rare disorder with multiple genetic and acquired causes. Clinically, patients with SN usually present with proprioceptive ataxia, patchy and asymmetric sensory abnormalities, widespread areflexia and no weakness. Classic causes of SN include cancer, Sjögren’s syndrome, vitamin deficiency, chemotherapy, mitochondrial disorders and Friedreich ataxia. More recently, new genetic and dysimmune disorders associated with SN have been described, including RFC1 gene-linked cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) and anti-FGFR3 antibodies. In this review, we detail the pathophysiology of DRG degeneration, and the genetic and acquired causes of SN, with a special focus on the recently described CANVAS and anti-FGFR3 antibodies. We also propose a user-friendly and easily implemented SN diagnostic strategy.

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.

Clinical Factors Associated With Chronic Pain in Communicative Adults With Cerebral Palsy: A Cross-Sectional Study

Chronic pain is prevalent in adults with cerebral palsy. We aimed to explore associations between chronic pain and somatosensory, motor, cognitive, etiologic, and environmental factors in adults with cerebral palsy. This cross-sectional study enrolled 17 adult participants with cerebral palsy (mean age 31 years; 8 female; Gross Motor Functional Classification Status levels I-V) able to self-report and 10 neurotypical adult volunteers (mean age 34 years; 9 female). Participants reported pain characteristics, demographics, and affective factors. Physical examination included somatosensory and motor evaluation. Between-group comparisons used a ranksum test, and correlation analyses estimated effect size in terms of shared variance (ρ2). Individuals with cerebral palsy reported greater pain intensity, neuropathic qualities, and nociceptive qualities than control participants. Higher pain intensity was associated with female gender (ρ2 = 16%), anxiety/depression symptoms (ρ2 = 10%), and lower household income (ρ2 = 19%). It was also associated with better communicative ability (ρ2 = 21%), spinothalamic (sharp/temperature) sensory abnormalities (ρ2 = 33%), and a greater degree of prematurity (ρ2 = 17%). This study highlights similarity of chronic pain associations in people with cerebral palsy with patterns seen in other populations with chronic pain. Spinothalamic sensory abnormalities suggest central pain mechanisms.