Impact of a worker bee thoracic ganglion RIC-3 variant on the actions of acetylcholine and neonicotinoids on nicotinic receptors in Apis mellifera.

A transmembrane thioredoxin (TMX3) enables the functional expression of insect nicotinic acetylcholine receptors (nAChRs) in Xenopus laevis oocytes, while co-factors RIC-3 and UNC-50 regulate the receptor expression level. RIC-3 (resistant to inhibitors of cholinesterase 3) has been shown to diversify by its differential mRNA splicing patterns. How such diversity influences neonicotinoid sensitivity of nAChRs of beneficial insect species remains poorly understood. We have identified a RIC-3 variant expressed most abundantly in the thoracic ganglia of honeybee (Apis mellifera) workers and investigated its effects on the functional expression and pharmacology of Amα1/Amα8/Amß1 and Amα1/Amα2/Amα8/Amß1 nAChRs expressed in X. laevis oocytes. The AmRIC-3 enhanced the response amplitude to the acetylcholine (ACh) of these A. mellifera nAChRs when its cRNA was injected into oocytes at low concentrations but suppressed the ACh response amplitude at high concentrations. Co-expression of the AmRIC-3 had a minimal impact on the affinity of ACh, but changed the efficacy of imidacloprid and clothianidin, suggesting that the presence and the level of RIC-3 expression can affect the nAChR responses to ACh and neonicotinoids, depending on nAChR subunit composition in honeybees. © 2024 Society of Chemical Industry.

HDR syndrome, detected in the neonatal period by newborn hearing screening.

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.

The Transition of Pediatric Tracheobronchial Foreign Body Cases in the Past 36 Years: A Retrospective Single-Center Study in Japan.

Tracheobronchial foreign bodies (TFBs) are pediatric airway emergencies frequently seen. We aimed to examine the changes in the clinical characteristics of pediatric TFB patients in a single institution within the past 36 years. We retrospectively reviewed the data of 85 patients aged 0-10 years with TFBs lodged in the trachea or bronchus admitted at the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital between 1986 and 2021. We also compared the characteristics, diagnostic methods, and treatments of the previous 64 cases (1986-2005) with those of the recent 21 cases (2006-2021). The number of TFB patients decreased later in this study (3.2 vs. 1.3 patients per year). The proportion of TFB patients aged > 3 years was significantly higher in the later period (6.3% vs. 23.8%, p = 0.038). Peanut was the most common cause of TFBs in both periods, and the overall incidence of peanut aspiration significantly decreased in the later period (68.8% vs. 38.1%, p = 0.019). No patient had an undetected TFB for more than 1 month after the onset of symptoms in the later period. Foreign body extraction using rigid bronchoscopy was performed in all patients earlier, whereas flexible bronchoscopy was used in 14.3% later. Our study revealed a recent trend in the clinical characteristics of pediatric TFB patients in a single institution in Northeast Japan. The prevention and treatment of pediatric TFBs should be considered following the recent trends.

Effects of Unilateral Vagotomy on LPS-Induced Aspiration Pneumonia in Mice.

Respiratory-related dysphagia and aspiration pneumonia can be attributed to multiple causes. However, reproduction of multiple factor-related respiratory distress and aspiration pneumonia in a single animal model is challenging. To validate animals with vagal nerve palsy as novel models for severe aspiration pneumonia associated with respiratory distress, we investigated the effects of unilateral vagotomy on the swallowing function and severity of pneumonia after forced aspiration in mice. Unilateral vagotomy was performed in C57BL6 male mice that subsequently underwent evaluation of swallowing function by videofluoroscopic swallow study (VFSS) and histological assessments for aspiration pneumonia induced by lipopolysaccharide (LPS). VFSS examinations demonstrated that unilateral vagotomy did not cause apparent aspiration in mice, but it resulted in a significant loss of body weight (BW) due to decreased oral intake. In addition, when aspiration pneumonia was induced by forced administration of LPS, significantly prolonged BW loss and severe infiltration of inflammatory cells associated with aspiration pneumonia were observed in the mice that underwent unilateral vagotomy. In conclusion, the vagotomized mice showed appropriate characteristics as a model of aspiration pneumonia caused by multiple factors, including the paralysis of vocal fold movement and respiratory distress. This model can help elucidate the pathogenesis of aspiration pneumonia and the treatment methods for the respiration-compromised model.

Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels.

BACKGROUND/AIMS: Interferon-alfa is widely used for the treatment of chronic hepatitis C, and has been thought to have a preventive effect on the development of hepatocellular carcinoma. Hepatocellular carcinoma develops from chronic liver diseases such as chronic hepatitis C or liver cirrhosis. We studied the effect of interferon for liver cirrhosis with hepatocellular carcinoma after treating hepatocellular carcinoma itself. METHODOLOGY: To evaluate the preventive effect of this drug on local recurrence and/or new development of primary tumor after clearance of hepatitis C virus, 46 patients with hepatocellular carcinoma with low HCV-RNA level were randomized to receive recombinant interferon-alfa 2b (n = 22) or not (n = 24) after being treated by transcatheter arterial chemoembolization and percutaneous ethanol injection therapy. In the interferon-treated group, patients received 3 million international units of interferon-alfa 2b intramuscularly three times a week for 4 months. In both groups, transcatheter arterial chemoembolization followed by percutaneous ethanol injection therapy was performed as an initial treatment and these therapies were repeated every 4-6 months. Serum HCV-RNA levels of all 46 patients were under 0.5 Meq/mL by branched DNA probe assay. RESULTS: In the interferon-treated group, 11 of the 22 (50%) patients were HCV-RNA negative at the 6 months after completing the course of interferon therapy. HCV-RNA was undetectable during the observation period in 2 of the 24 (9.5%) patients in the untreated group. The survival rate in the interferon-treated group was significantly higher than that in the untreated group (P = 0.01 by the log-rank test). Though there was no significant difference in the incidence of local recurrence in both groups, the incidence of secondary hepatocellular carcinoma was significantly lower in the interferon-treated group than that in the untreated group. Cox proportional hazards regression analysis validated interferon treatment as an independent predictor of hepatocellular carcinoma prognosis. CONCLUSIONS: We concluded that, if HCV-RNA level is low, interferon may be a therapy of choice in combination with transcatheter arterial chemoembolization and percutaneous ethanol injection therapy for the treatment of hepatocellular carcinoma.