Repeated Vaginal Exposures to the Common Cosmetic and Household Preservative Methylisothiazolinone Induce Persistent, Mast Cell-Dependent Genital Pain in ND4 Mice.

A history of allergies doubles the risk of vulvodynia-a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)-a biocide preservative ubiquitous in cosmetics and cleaners-dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of Δ9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.

Introduction: Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. Methods: Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. Results: Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. Discussion: Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.

Corrigendum: Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.

[This corrects the article DOI: 10.3389/fimmu.2023.1101808.].

Neural substrates of affective face recognition in alexithymia: a functional magnetic resonance imaging study.

BACKGROUND: Alexithymia is a condition characterized by deficits in cognitive processing and the regulation of emotions. Several theories have been proposed for the underlying neurobiology, but the etiology of alexithymia remains unclear. METHODS: Using functional magnetic resonance imaging, we investigated brain activation measured on the scale of alexithymia in 38 individuals who were presented with neutral, sad, or angry affective facial stimuli. RESULTS: We found significant inverse correlations between the degree of alexithymia represented by the Korean version of the Toronto Alexithymia Scale (TAS-20K) and the intensity of the neural response to angry facial stimuli over neutral facial stimuli in the right caudate. This result was mainly due to the activations in factor 2 (difficulty describing feelings) in TAS-20K scale. CONCLUSIONS: The results suggest that functional impairments in the caudate of the fronto-striatal circuitry may play important roles in the pathophysiology of alexithymia.

A Room-Temperature Ferroelectric Ferromagnet in a 1D Tetrahedral Chain Network.

Ferroelectricity occurs in crystals with broken spatial inversion symmetry. In conventional perovskite oxides, concerted ionic displacements within a 3D network of transition-metal-oxygen polyhedra (MOx ) manifest spontaneous polarization. Meanwhile, some 2D networks of MOx foster geometric ferroelectricity with magnetism, owing to the distortion of the polyhedra. Because of the fundamentally different mechanism of ferroelectricity in a 2D network, one can further challenge an uncharted mechanism of ferroelectricity in a 1D channel of MOx and estimate its feasibility. Here, ferroelectricity and coupled ferromagnetism in a 1D FeO4 tetrahedral chain network of a brownmillerite SrFeO2.5 epitaxial thin film are presented. The result provides a new paradigm for designing low-dimensional MOx networks, which is expected to benefit the realization of macroscopic ferro-ordering materials including ferroelectric ferromagnets.

Acupuncture and spontaneous regression of a radiculopathic cervical herniated disc.

The spontaneous regression of herniated cervical discs is not a well-established phenomenon. However, we encountered a case of a spontaneous regression of a severe radiculopathic herniated cervical disc that was treated with acupuncture, pharmacopuncture, and herb medicine. The symptoms were improved within 12 months of treatment. Magnetic resonance imaging (MRI) conducted at that time revealed marked regression of the herniated disc. This case provides an additional example of spontaneous regression of a herniated cervical disc documented by MRI following non-surgical treatment.

Occurrence of diverse dsRNA in a Korean population of the chestnut blight fungus, Cryphonectria parasitica.

We analysed 676 isolates from 33 Korean Cryphonectria parasitica subpopulations in Korea for dsRNA incidence and diversity. dsRNA was detected in 84 isolates. Although the dsRNA banding patterns varied in several minor bands, infected isolates could be categorized into two groups. The most common banding pattern occurred in 77 isolates and contained a 12.7-kb band indicative of Cryphonectria hypovirus 1 (CHV1), and several accompanying minor bands with sizes ranging from 0.9-5kb. Northern blot analysis revealed that all 12.7-kb fragments in the dsRNA-containing isolates hybridized to probes corresponding to open reading frames (ORFs) A and B from the reference CHV1 strain (GenBank accession no. M57938). In addition, the sequence of a 1.4-kb cDNA fragment from a representative isolate of the most common group showed 99% sequence similarity to ORF A of CHV1. However, the other group of seven isolates had distinctive bands of 3.5 and 3.3kb, but not the 12.7-kb band. Sequence comparison showed that cloned fragments of these dsRNAs were similar to those of the coat protein and RNA-dependent RNA polymerase genes of chrysovirus, which indicates the occurrence of chrysovirus in the Korean population. Fungal strain identity was assessed via RFLP analysis of the ITS regions. Among the 84 tested isolates, six had different ITS-RFLP patterns (RFLP-II) from that (RFLP-I) of C. parasitica, and are believed to be C. nitschkei, a sympatric species reported on chestnut trees in Japan. The chrysovirus and CHV1 were detected in strains showing both RFLP patterns. However, the chrysovirus was more frequent in the RFLP-II group.

[Quality of life and its associated factors among some elderly residents using a hall for the aged in a community].

OBJECTIVES: This study was performed to investigate the level of quality of life (QOL) and to identify its related factors among the elderly using a hall for the aged. METHODS: The study subjects were 350 elderly people living in Nam Gu, Gwangju City. They were interviewed by questionnaire to collect information on social-demographic characteristics, health behaviors, health-related characteristics and QOL. We used statistical analysis methods such as T-test, ANOVA and multiple regression analysis to find which factors affected QOL. RESULTS: The characteristics relating to physical functions were as follows: presence of spouse, education, alcohol drinking, teeth condition, arthritis, frequency of visiting the hall for the aged, and depression. Age, arthritis and depression were significantly related to role limitation due to physical problems. General health was related to gender, age, and depression, and vitality was related to education, frequency of visiting the hall, and depression. Role limitation due to emotional problems was related to age and depression, and mental health was related to age, hypertension, arthritis and depression. CONCLUSIONS: This study showed QOL of the elderly was significantly influenced by socio-demographic factors, and physical or emotional conditions. To improve QOL of the elderly, we need to develop programs to promote health and to manage chronic diseases of the elderly.

A gene encoding phosphatidyl inositol-specific phospholipase C from Cryphonectria parasitica modulates the lac1 expression.

Hypovirus infection of the chestnut blight fungus Cryphonectria parasitica is known to downregulate the fungal laccase1 (lac1), the modulation of which is tightly governed by the inositol triphosphate (IP(3)) and calcium second messenger system in a virus-free strain. We cloned the gene cplc1 encoding a phosphatidyl inositol-specific phospholipase C (PLC), to investigate the regulation of lac1 expression and to better characterize fungal gene regulation by hypovirus. Sequence analysis of the cplc1 gene indicated that the protein product contained both the X and Y domains, which are the two conserved regions found in all known PLCs, with a 133 amino acid extension between the 2nd beta-strand and the alpha-helix in the X domain. In addition, the gene organization appeared to be highly similar to that of a delta-type PLC. Disruption of the cplc1 gene resulted in slow growth and produced colonies characterized by little aerial mycelia and deep orange in color. Accordingly, reduced virulence of the cplc1-null mutant as compared to the wild-type was observed, which can be ascribed to the growth defect. However, other PLC-associated characteristics including temperature sensitivity and osmosensitivity did not differ from the wild-type strain. Northern blot analysis revealed no accumulation of the lac1 gene transcript due to the disruption of the cplc1 gene. Functional complementation of the cplc1-null mutant with the PLC1 gene from Saccharomyces cerevisiae restored lac1 expression, which suggests that the cloned gene encodes PLC activity. The present study indicates that the cplc1 gene is required for normal mycelial growth rate and colony morphology, and that it regulates the lac1 expression, which is also modulated by the hypovirus. Although several PLC genes have been identified in various simple eukaryotic organisms, the deletion analysis of the cplc1 gene in this study appears to be the first report on the functional analysis of PLC in filamentous fungi.