Factors contributing to the diagnosis and onset prediction of perennial allergic rhinitis in high-risk children: A sub-analysis of the CHIBA study.

BACKGROUND: This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies. METHODS: Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible. RESULTS: Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years. CONCLUSIONS: Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.

Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber.

BACKGROUND: Immediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis. OBJECTIVE: To examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC). METHODS: Fifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m(3) for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored. RESULTS: The severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased. CONCLUSION: Various mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.

Comparison of the Visual Capabilities of an Amphibious and an Aquatic Goby That Inhabit Tidal Mudflats.

The mudskipper Periophthalmus modestus and the yellowfin goby Acanthogobius flavimanus are gobiid teleosts that both inhabit the intertidal mudflats in estuaries. While P. modestus has an amphibious lifestyle and forages on the exposed mudflat during low tide, the aquatic A. flavimanus can be found at the same mudflat at high tide. This study primarily aimed to elucidate the differential adaptations of these organisms to their respective habitats by comparing visual capacities and motor control in orienting behavior during prey capture. Analyses of retinal ganglion cell topography demonstrated that both species possess an area in the dorsotemporal region of the retina, indicating high acuity in the lower frontal visual field. Additionally, P. modestus has a minor area in the nasal portion of the retina near the optic disc. The horizontally extended specialized area in P. modestus possibly reflects the need for optimized horizontal sight on the exposed mudflat. Behavioral experiments to determine postural and eye direction control when orienting toward the object of interest revealed that these species direct their visual axes to the target situated below eye level just before a rapid approach toward it. A characteristic feature of the orienting behavior of P. modestus was that they aimed at the target by using the specialized retinal area by rotating the eye and lifting the head before jumping to attack the target located above eye level. This behavior could be an adaptation to a terrestrial feeding habitat in which buoyancy is irrelevant. This study provides insights into the adaptive mechanisms of gobiid species and the evolutionary changes enabling them to forage on land.

Visual Capability of the Weakly Electric Fish Apteronotus albifrons as Revealed by a Modified Retinal Flat-Mount Method.

Apteronotus albifrons (Gymnotiformes, Apteronotidae) is well known to have a sophisticated active electrosense system and is commonly described as having poor vision or being almost blind. However, some studies on this species suggest that the visual system may have a role in sensing objects in the environment. In this study, we investigated the visual capabilities of A. albifrons by focusing on eye morphology and retinal ganglion cell distribution. The eyes were almost embedded below the body surface and pigmented dermal tissue covered the peripheral regions of the pupil, limiting the direction of incoming light. The lens was remarkably flattened compared to the almost spherical lenses of other teleosts. The layered structure of the retina was not well delineated and ganglion cells did not form a continuous sheet of cell bodies. A newly modified retinal flat-mount method was applied to reveal the ganglion cell distribution. This method involved postembedding removal of the pigment epithelium of the retina for easier visualization of ganglion cells in small and/or fragile retinal tissues. We found that ganglion cell densities were relatively high in the periphery and highest in the nasal and temporal retina, although specialization was not so high (approx. 3:1) with regard to the medionasal or mediotemporal axis. The estimated highest possible spatial resolving power was around 0.57 and 0.54 cycles/degree in the nasal and temporal retina, respectively, confirming the lower importance of the visual sense in this species. However, considering the hunting nature of A. albifrons, the relatively high acuity of the caudal visual field in combination with electrolocation may well be used to locate prey situated close to the side of the body.

Characteristics of the Chiba environmental challenge chamber.

BACKGROUND: An environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC. METHODS: The stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season. RESULTS: The severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m3. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season. CONCLUSIONS: The ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC.

An unusual configuration of two anomalies in the extensor digitorum profundus complex in a human.

The extensor digitorum profundus complex underwent degeneration of the ulnar segments during primate adaptation and evolution. This process resulted in the preservation of only the extensor pollicis longus and extensor indicis in some apes, including humans. Consequently, anatomical variations within the digitorum profundus complex in modern humans have been well-documented, with detailed reports on their frequency and patterns in previous studies. Here, we report an unusual arrangement involving two anomalies in the extensor digitorum profundus complex, identified in a 66-year-old Japanese male cadaver. In this cadaver, two accessory muscles differentiated from both the extensor pollicis longus and extensor indicis. Notably, the latter muscle featured a tendon bifurcating towards both the thumb and index fingers, referred to as the extensor pollicis et indicis communis. Under the extensor retinaculum, the tendon of the accessory extensor pollicis longus passed through an independent compartment, whereas that of the extensor pollicis et indicis communis traversed a compartment shared by the extensor indicis and the extensor digitorum communis. Both muscles were innervated by the posterior interosseous nerve. Previous studies have reported that the accessory slip of the extensor pollicis longus and extensor pollicis et indicis communis appear at frequencies of 0.6% and 0.4-1.4%, respectively. However, to the best of our knowledge, a configuration in which both appear simultaneously has not been reported. The data from this case could provide essential insights into the variations in the extensor digitorum profundus complex in humans and non-human primates.

A candidate of organum vasculosum of the lamina terminalis with neuronal connections to neurosecretory preoptic nucleus in eels.

Systemic angiotensin II (Ang II) is a dipsogen in terrestrial vertebrates and seawater teleosts. In eels, Ang II acts on the area postrema, a sensory circumventricular organ (CVO) and elicits water intake but other sensory CVOs have not yet been found in the eel forebrain. To identify sensory CVOs in the forebrain, eels were peripherally injected with Evans blue, which immediately binds to albumin, or a rabbit IgG protein. Extravasation of these proteins, which cannot cross the blood­brain barrier (BBB), was observed in the brain parenchyma of the anteroventral preoptic recess (PR) walls. Fenestrated capillaries were observed in the parenchymal margin of the ventral wall of the PR, confirming a deficit of the BBB in the eel forebrain. Immunostaining for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) detected neurons in the lateral region of the anterior parvocellular preoptic nucleus (PPa), which were strongly stained by BBB-impermeable N-hydroxysulfosuccinimide. In the periventricular region of the PPa, many neurons incorporated biotinylated dextran amine conjugated to fluorescein, a retrograde axonal tracer, injected into the magnocellular preoptic nucleus (PM), indicating neuronal connections from the PPa to the PM. The mammalian paraventricular and supraoptic nuclei, homologous to the teleost PM, receive principal neuronal projections from the organum vasculosum of the lamina terminalis (OVLT). These results strongly suggest that the periventricular subpopulation of the PPa, which is most likely to be a component of the OVLT, serves as a functional window of access for systemic signal molecules such as Ang II.

Toxic epidermal necrolysis associated with nivolumab treatment for head and neck cancer.

This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.

Constitutive accessibility of circulating proteins to hippocampal neurons in physiologically normal rats.

INTRODUCTION: Although the hippocampus (HIP) is thought impermeable to blood-borne proteins because of the integrity of the blood-brain barrier (BBB), it was recently suggested to be susceptible to hydrophilic hormones. The present study determined the accessibility of blood-borne signal molecules such as hormones to hippocampal neurons in physiologically normal rats. METHODS: As a probe for accessibility, Evans blue dye (EB) that rapidly binds to albumin (Alb), which is impermeable to the BBB, was injected intravenously. To increase the vascular permeability of the BBB, a daily single administration of angiotensin II (Ang II) was applied intravenously for seven consecutive days. RESULTS: Fifteen minutes after the injection of EB, histological observation revealed that a number of neurons had entrapped and accumulated EB into their cell bodies in the hippocampal dentate gyrus in all rats. Of these, relatively large oval neurons (>15 µm) in the hilus and molecular layer showed parvalbumin immunopositivity, indicating they are GABAergic interneurons. The population of EB-accumulating neurons (approximately 10 µm) were localized in the inner margin of the granule cell layer, suggesting they were granule cells. However, the number of EB-positive neurons did not change in rats treated with Ang II compared with vehicle injection. CONCLUSIONS: These findings suggest an intriguing possibility that blood-derived proteins such as hormones have access to hippocampal neurons constitutively in the absence of stimuli that increase the vascular permeability of the BBB in a physiologically normal state.

Short-term Heat Exposure Promotes Hippocampal Neurogenesis via Activation of Angiotensin II Type 1 Receptor in Adult Rats.

Angiotensin II (Ang II) synthesized in response to body fluid loss caused by actions such as sweating and breathing is today considered as one of the essential factors for promoting hippocampal neurogenesis. Because heat stimuli, along with exercise, increase systemic levels of Ang II, the effects of short-term heat exposure on hippocampal neurogenesis were examined in adult male rats. When rats were exposed daily to a 1-h heat treatment (36.0 ±â€¯0.1 °C) during a 7-d experimental period, the number of doublecortin-immunoreactive newborn cells in the hippocampal dentate gyrus was increased approximately 1.4-fold compared with that in controls that were exposed to a normothermic environment (25.0 ±â€¯0.8 °C). No significant change was observed in the number of Ki-67-immunoreactive stem cells. Western blot and immunohistochemical analyses revealed an enhancement of vascular endothelial growth factor (VEGF) expression in hippocampal astrocytes following short-term heat exposure. These beneficial effects of short-term heat exposure were prevented when an antagonist for Ang II type 1 receptor (AT1R), candesartan, was given orally. These results indicate that short-term heat exposure enhances adult neurogenesis via activation of AT1R in the hippocampal dentate gyrus, in which VEGF may participate by promoting cell proliferation and/or newborn neuron survival.

Descending necrotizing mediastinitis with Lemierre's syndrome.

Descending necrotizing mediastinitis is a severe infection of the mediastinum. Lemierre's syndrome manifests as thrombophlebitis in the cervical veins, which is caused by a neck infection. A 50-year-old woman had a fever with a 13-day history of neck pain. CT showed a deep neck abscess with vertebral vein thrombosis and mediastinal abscesses. Multiple small pulmonary nodules were found, suggesting septic pulmonary embolism. Emergency surgery for bilateral cervical and mediastinal drainage was performed, and antibiotics and anticoagulation agent was administered. Edoxaban was required to clear vein thrombosis and pulmonary embolization.

Impact of dehydration on the forebrain preoptic recess walls in the mudskipper, Periophthalmus modestus: a possible locus for the center of thirst.

The forebrain lamina terminalis has not yet been examined for the role of osmosensing in teleosts, although the thirst center is well known to be present in this vascular permeable forebrain region in mammals. Here, we examined vascular permeability and neuronal responsiveness to dehydration in the lamina terminalis of the mudskipper, a euryhaline goby. Evans blue and N-hydroxysulfosuccinimide-biotin both bind to blood proteins, and are impermeable to the blood-brain barrier. Intraperitoneal injection of these probes stained the walls of the preoptic recess (PR) of the third ventricle, indicating increased vascular permeability in this region. When mudskippers kept in isotonic brackish water (ca. 11 psu) were challenged to seawater (ca. 34 psu) for 3 h, body water content showed a 1 % decrease, compared with mudskippers without hypertonic challenge. Simultaneously, the number of immunohistochemically identified cFos-expressing neurons in the anterior parvocellular preoptic nucleus (PPa) of the PR walls increased in a site-specific manner by approximately 1.6-fold compared with controls. Thus, these findings indicate that PPa neurons are activated, following dehydration in mudskippers. Taken together, the vascularly permeable PR walls may be involved in osmosensing, as in the mammalian thirst center.

Systemic angiotensin II and exercise-induced neurogenesis in adult rat hippocampus.

Physical exercise is a robust stimulus that enhances hippocampal neurogenesis via cell proliferation in rodents. We examined the role of systemic angiotensin (Ang) peptides in exercise-dependent enhancement of neurogenesis in the adult rat hippocampus. Plasma angiotensin peptide concentration increased rapidly in response to 30 min of treadmill exercise. After undertaking this exercise once daily for a week, the number of proliferating cells in the hippocampus, identified by 5-bromo-2'-deoxyuridine (BrdU) incorporation, had increased compared with controls. To mimic the increase in plasma Ang peptide concentrations brought about by exercise, rats were injected with 10(-5)M Ang II once daily for a week. The number of BrdU-incorporating cells and of doublecortin (DCX)-expressing immature neurons in the hippocampus rose approximately 1.5 and 1.9-fold compared with controls, respectively. The effects were completely abolished by an Ang II receptor subtype 1 antagonist losartan. These findings, taken together, suggest that an increased concentrations of Ang peptides in the systemic circulation during exercise may promote neurogenesis in the adult rat hippocampus.