Severe acute respiratory syndrome coronavirus 2, primary varicella zoster virus coinfection, and a polymicrobial ventilator-associated tracheobronchitis in an adult immunocompetent male: a case report

BACKGROUND: The spectrum of clinical manifestations and differential diagnosis associated with coronavirus disease 2019 is broad, ranging from fever and cutaneous eruptions to respiratory distress or even neurological disorders. Coexisting multipathogen infections significantly increase the complexity of the proper diagnostic and therapeutic approach and correlate with the rate of intensive care unit admissions and in-hospital mortality. CASE PRESENTATION: We present a case of multipathogen respiratory infection with severe acute respiratory syndrome coronavirus 2, varicella zoster virus, and polymicrobial tracheobronchitis in a 48-year-old Caucasian male hospitalized after traumatic brain injury. The patient tested positive for severe acute respiratory syndrome coronavirus 2 infection upon admission. During his stay in the intensive care unit, the patient developed a vesicular exanthema along with respiratory failure and signs of septic shock. CONCLUSION: This case of an adult presenting with severe acute respiratory syndrome coronavirus 2 infection and simultaneous primary varicella zoster virus infection illustrates the importance of considering coinfections in patients with coronavirus disease 2019 with unusual clinical manifestations

KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages

Among the strategies adopted by glioma to successfully invade the brain parenchyma is turning the infiltrating microglia/macrophages (M/MΦ) into allies, by shifting them toward an anti-inflammatory, pro-tumor phenotype. Both glioma and infiltrating M/MΦ cells express the Ca(2+)-activated K(+) channel (KCa3.1), and the inhibition of KCa3.1 activity on glioma cells reduces tumor infiltration in the healthy brain parenchyma. We wondered whether KCa3.1 inhibition could prevent the acquisition of a pro-tumor phenotype by M/MΦ cells, thus contributing to reduce glioma development. With this aim, we studied microglia cultured in glioma-conditioned medium or treated with IL-4, as well as M/MΦ cells acutely isolated from glioma-bearing mice and from human glioma biopsies. Under these different conditions, M/MΦ were always polarized toward an anti-inflammatory state, and preventing KCa3.1 activation by 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), we observed a switch toward a pro-inflammatory, antitumor phenotype. We identified FAK and PI3K/AKT as the molecular mechanisms involved in this phenotype switch, activated in sequence after KCa3.1. Anti-inflammatory M/MΦ have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition. In line with these findings, TRAM-34 treatment, in vivo, significantly reduced the size of tumors in glioma-bearing mice. Our data indicate that KCa3.1 channels are involved in the inhibitory effects exerted by the glioma microenvironment on infiltrating M/MΦ, suggesting a possible role as therapeutic targets in glioma

Close similarities between Cherry chlorotic rusty spot disease from Italy and Cherry leaf scorch from Spain

Cherry chlorotic rusty spot (CCRS), a disease affecting sweet and sour cherry in Southern Italy was regularly found associated with an unidentified fungus and with a complex pattern of viral-like double-stranded RNAs as well as with two small circular RNAs (cherry small circular RNAs, cscRNAs). Further studies revealed that i) the ds-RNAs correspond to the genome of different mycoviruses belonging to the genera Chrysovirus, Partitivirus and Totivirus and ii) the two viroid-like RNAs consist of two groups of variants with similar sequences but differing in size (394–415 and 372–377 nt for cscRNA1 and cscRNA2, respectively). Here we report that the dsRNAs of Chrysovirus and Partitivirus have been detected by RT-PCR analysis with CCRS specific primers in nucleic acid preparations from cherry leaves affected by cherry leaf scorch (CLS) in Spain, a disease whose etiological agent is the ascomycetes Apiognomonia erythrostoma, order Diaporthales. Moreover, Northern-blot hybridization assays showed that a viroid-like RNA comigrating and sharing high sequence similarity with the cscRNA1 previously reported in Italy, accumulate in leaves from CLS affected trees in Spain. These data, together with other evidence showing similar symptoms, disease cycle and fungal fructifications in CCRS and CLS affected trees, suggest a close relationship between the two cherry disorders.Keywords: dsRNAs, cscRNAs, Apiognomonia erythrostoma, Diaporthale

Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders

Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD

Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer’s disease patients, possible biomarkers for early diagnosis

Alzheimer's disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid-beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non-invasive technologies to measure neuropathological changes in vivo at pre-symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non-invasive rapid detection of AD biomarkers. Here, we report the presence of amyloid beta plaques, tau tangles, neurodegeneration and detrimental astrocyte and microglia activation according to a disease associated microglia phenotype (DAM). Thus, we propose the human retina as a useful site for the detection of cellular and molecular changes associated with Alzheimer's disease