Restoration of hearing with an auditory brainstem implant in a patient with neurofibromatosis type 2--case report

A 25-year-old male with neurofibromatosis type 2 had hearing restored with an auditory brainstem implant (ABI) after removal of an acoustic schwannoma. The ABI allows the patient to discern many different environment sounds and is a significant adjunct to lip-reading, enabling conversation with people who have clear pronunciation without the necessity for writing.     

Patent ductus venosus with a hypoplastic intrahepatic portal system presenting intrapulmonary shunt: a case treated with banding of the ductus venosus

A case of patent ductus venosus (PDV) presenting intrapulmonary shunting is described. Although retrograde venography of ductus venosus showed few intrahepatic branches, banding of PDV resulted in increased intrahepatic portal branches and disappearance of symptoms 10 months after the operation. Banding of the ductus venosus may be effective in PDV even with hypoplastic intrahepatic portal system.     

Left Ventricular Abnormality and Covert Atrial Fibrillation in Embolic Stroke of Undetermined Source

Aims: The relationship between left ventricular (LV) function and AF detection in embolic stroke of undetermined source (ESUS) patients with insertable cardiac monitors (ICMs) remains unclear. We investigated the association between LV function and AF detection in patients with ESUS after ICMs implantation. Methods: We enrolled patients with ESUS who underwent ICMs implantation from September 2016 to September 2020 using a single-center, prospective registry. LV systolic and diastolic functions were assessed on precordial echocardiography by LV fractional shortening (LVFS) and average E/e’, respectively. Associations between characteristics of LV function and detection of AF by ICMs were analyzed. Results: Participants comprised 101 patients (median age, 74 years; male, 62%). During a median follow-up period of 442 days (interquartile range (IQR), 202–770 days), AF was detected in 24 patients (24%). Median duration from ICMs implantation to AF detection was 71 days (IQR, 13–150 days). When LVFS and E/e’ were dichotomized by cutoff value, each of low LVFS (＜35.5%; adjusted hazard ratio (HR), 4.77; 95% confidence interval (CI), 1.77–12.9) and high E/e’ (≥ 8.65; adjusted HR, 4.56; 95%CI, 1.17–17.7) were independently associated with AF detection after adjusting for age and sex. When patients were divided into four groups according to dichotomized LVFS and E/e’, the combination of low LVFS and high E/e’ was independently associated with AF. Conclusions: In patients with ESUS after ICMs implantation, the LV characteristics of low LVFS and high E/e’ were associated with AF detection.     

Effect of Host Structure on Optical Freedericksz Transition in Dye-Doped Liquid Crystals

The optical Freedericksz transition (OFT) can reversibly control the molecular orientation of liquid crystals (LCs) only by light irradiation, leading to the development of all-optical devices, such as smart windows. In particular, oligothiophene-doped LCs show the highly sensitive OFT due to the interaction between dyes and an optical-electric field. However, the sensitivity is still low for the application to optical devices. It is necessary to understand the factors in LCs affecting the OFT behavior to reduce the sensitivity. In this study, we investigated the effect of the host LC structure on the OFT in oligothiophene-doped LCs. The threshold light intensity for the OFT in trifluorinated LCs was 42% lower than that in LCs without fluorine substituents. This result contributes to the material design for the low-threshold optical devices utilizing the OFT of dye-doped LCs.     

Vesicular nucleotide transporter is a molecular target of eicosapentaenoic acid for neuropathic and inflammatory pain treatment

Eicosapentaenoic acid (EPA), an omega-3 (ω-3) polyunsaturated fatty acid, is an essential nutrient that exhibits antiinflammatory, neuroprotective, and cardiovascular-protective activities. Although EPA is used as a nutrient-based pharmaceutical agent or dietary supplement, its molecular target(s) is debatable. Here, we showed that EPA and its metabolites strongly and reversibly inhibit vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and release of adenosine triphosphate (ATP) in purinergic chemical transmission. In vitro analysis showed that EPA inhibits human VNUT-mediated ATP uptake at a half-maximal inhibitory concentration (IC₅₀) of 67 nM, acting as an allosteric modulator through competition with Cl⁻. EPA impaired vesicular ATP release from neurons without affecting the vesicular release of other neurotransmitters. In vivo, VNUT^−/− mice showed a delay in the onset of neuropathic pain and resistance to both neuropathic and inflammatory pain. EPA potently attenuated neuropathic and inflammatory pain in wild-type mice but not in VNUT^−/− mice without affecting the basal nociception. The analgesic effect of EPA was canceled by the intrathecal injection of purinoceptor agonists and was stronger than that of existing drugs used for neuropathic pain treatment, with few side effects. Neuropathic pain impaired insulin sensitivity in previous studies, which was improved by EPA in the wild-type mice but not in the VNUT^−/− mice. Our results showed that VNUT is a molecular target of EPA that attenuates neuropathic and inflammatory pain and insulin resistance. EPA may represent a unique nutrient-based treatment and prevention strategy for neurological, immunological, and metabolic diseases by targeting purinergic chemical transmission.

Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are essential nutrients that contain multiple double bonds. PUFAs can be classified into ω-3 and ω-6 depending on the position of the bonds. As humans cannot produce PUFAs, they must be acquired from the diet to maintain homeostasis. Omega-3 PUFAs, such as eicosapentaenoic acid (EPA), are abundantly present in fish and linseed oil and exhibit antiinflammatory, neuroprotective, and cardiovascular-protective activities via the competitive inhibition of cyclooxygenase (COX)-2 in eicosanoid production (1–3). Danish and Greenland Inuit epidemiological studies have reported that EPA reduces the risk of death after myocardial infarction (4, 5), and other studies have reported its influence on analgesia, neuroinflammatory disease (Parkinson’s disease, Alzheimer’s disease, and depression) improvement, platelet aggregation inhibition, decrease in blood triglyceride and glucose levels, and improved insulin resistance (1, 6–11). Omega-3 fatty acid supplementation in COVID-19 patients showed a beneficial effect in managing the cytokine storm (12). Conversely, omega-6 fatty acids, such as arachidonic acid, produce inflammatory eicosanoids and play central roles in the initial stage of inflammatory responses (13). Although arachidonic acid has also been reported to produce antiinflammatory metabolites, omega-6 PUFA-derived linoleate diols have a harmful effect and are biomarkers for severe COVID-19 infection (14). An omega-6 PUFA-enriched Western-style diet, which abundantly contains linoleate, causes neuropathy and chronic pain, but an omega-3 PUFA-enriched diet attenuates these pathological conditions (15).All therapeutic effects of EPA cannot be explained by COX-2 inhibition alone (16). Typically, COX-2 inhibitors (nonsteroidal antiinflammatory druga [NSAIDs]) are effective for inflammatory pain but ineffective for neuropathic pain (16). However, EPA significantly attenuates both inflammatory and neuropathic pain, which strongly suggests another important molecular target of EPA related to neuropathy (7, 8). Although chronic pain is coincidentally caused by inflammation and neuropathy, there is no therapeutic drug with few side effects to attenuate both inflammatory and neuropathic pain (17–20). In this situation, EPA may affect the key signaling molecule(s) in neurological, metabolic, and immunological functions.Purinergic chemical transmission is involved in neurological, metabolic, and immunological disruptions and functions, including neuropathic and inflammatory pain, depression, inflammation, increase in blood triglyceride and glucose levels, insulin resistance, and blood coagulation (21, 22). The released adenosine triphosphate (ATP) and degraded adenosine diphosphate (ADP) or adenosine binds to many types of purinoceptors that are intricately involved in biological and pathological processes. In pain perception, ATP and ADP bind to P2X and P2Y receptors and thereby exacerbate neuropathic and inflammatory pain (23). Adenosine binds to P1 receptors and thereby attenuates neuropathic and inflammatory pain (24). However, a vesicular nucleotide transporter (VNUT/SLC17A9) is localized in the secretory vesicles of neuronal, endocrine, and immune cells. It plays an essential role in vesicular ATP storage in a Δψ- and Cl^–-dependent manner in the purinergic chemical transmission, which leads to vesicular ATP release (25, 26). Thus, VNUT is a key molecule in the initiation of purinergic signaling for neurological, metabolic, and immunological disruptions and functions. Interestingly, the observed effects of the VNUT inhibitor and phenotypes of VNUT^−/− mice were consistent with the above-mentioned therapeutic effects of EPA (27–31). Therefore, we hypothesized that VNUT serves as a molecular target of EPA to attenuate neuropathic and inflammatory pain.Here, we demonstrated that a low concentration of EPA and its metabolites, but not docosahexaenoic acid (DHA), are potent and selective physiological inhibitors of vesicular ATP release via the blockade of purinergic chemical transmission, which improved neuropathic and inflammatory pain and insulin resistance. Furthermore, EPA is more effective for neuropathic and inflammatory pain and has fewer side effects than existing drugs.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Nonfunctional pituitary macroadenoma manifested as muscular symptoms

A 75-year-old man with a large pituitary adenoma presented with general muscular weakness, including difficulty in rising in the morning and forceless defecation and urination, and muscular pain, numbness and atrophy in the shoulder, neck and thigh. Testosterone replacement and subsequent resection of the pituitary tumor resulted in resolution of the symptoms. The value of pituitary imaging tests for men with hypogonadotropic hypogonadism is discussed.     

An Analytical Model / Emotional Intelligence Quotient and QOL in Mothers with Infants in Japan

Objective: The purpose of this study was to examine the relationship betweenthe emotional intelligence quotient and health-related quality of life using structuralequation modeling.Methods: A self-administered questionnaire survey was conducted among 1,911mothers who visited the Health Center for an infant medical examination. A hypotheticalmodel was constructed using variables of the emotional intelligence quotient, socialsupport, coping, parenting stress, and perceived health competence.Result: There were a total of 1,104 valid responses (57.8%). Significantstandardized estimates were obtained, confirming the goodness of fit issues with themodel. The emotional intelligence quotient had a strong impact on physical andpsychological quality of life, and showed the greatest association with coping. This studydiffered from previous studies in that, due to the inclusion of social support andexplanatory variables in coping, an increase in coping strategies was more highlyassociated with emotional intelligence quotient levels than with social support.Conclusion: An enhanced emotional intelligence quotient should be considereda primary objective to promote the health of mothers with infant children.