Investigation of Receptor-Mediated Cyanocobalamin (Vitamin B12) Transport across the Inner Blood-Retinal Barrier Using Fluorescence-Labeled Cyanocobalamin.

The blood-to-retina supply of cyanocobalamin (vitamin B12) across the blood-retinal barrier (BRB) was investigated by synthesizing a fluorescence-labeled cyanocobalamin (Cy5-cyanocobalamin). In the in vivo analysis following internal jugular injection of Cy5-cyanocobalamin, confocal microscopy showed the distribution of Cy5-cyanocobalamin in the inner plexiform layer (IPL), the outer plexiform layer (OPL), and the retinal pigment epithelium (RPE). In the in vitro analysis with TR-iBRB2 cells, an in vitro model cell line of the inner BRB, Cy5-cyanocobalamin uptake by TR-iBRB2 cells exhibited a time-dependent increase after preincubation with transcobalamin II (TCII) protein, during its residual uptake without preincubation with TCII protein. The Cy5-cyanocobalamin uptake by TR-iBRB2 cells was significantly reduced in the presence of unlabeled cyanocobalamin, chlorpromazine, and chloroquine and was also significantly reduced under Ca2+-free conditions. Confocal microscopy of the TR-iBRB2 cells showed fluorescence signals of Cy5-cyanocobalamin and GFP-TCII protein, and these signals merged with each other. The RT-PCR, Western blot, and immunohistochemistry clearly suggested the expression of TCII receptor (TCII-R) in the inner and outer BRB. These results suggested the involvement of receptor-mediated endocytosis in the blood-to-retina transport of cyanocobalamin at the inner BRB with implying its possible involvement at the outer BRB.

A review of toxic epidermal necrolysis management in Japan.

Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction characterized by necrosis of the epidermis. Its incidence is approximately 1 per million a year and average mortality rate is high at 25-50%. TEN has a flu-like prodrome, followed by atypical, targetoid erythematous or purpuric macules on the skin. These macules coalesce to form flaccid blisters that slough off as areas of epidermal necrosis. Drugs such as allopurinol, sulfonamides, and carbamazepine are the most common causes. The human leukocyte antigen (HLA)-B*15:02 in Asians being administered carbamazepine and the HLA-B*58:01 antigen in patients of all ethnicities being administered allopurinol are known to be high-risk factors. Rapid diagnosis, discontinuation of the causative drug, and supportive treatment are essential for better prognosis and improvement of sequelae. Till now, systemic corticosteroids and intravenous immunoglobulins have been used as the most common active interventions; however, no gold standard has been established. In Japan, physicians follow a unique diagnostic criteria and treatment guideline to improve the diagnosis rate and streamline treatments. This may be a contributing factor for the lower mortality rate (14.3%). The efficacy of systemic corticosteroids, immunoglobulins, and plasmapheresis may have been beneficial as well. In Japan, TEN is defined as an epidermal detachment of over 10% of the body surface area (BSA), while the globally accepted definition established by Bastuji-Garin describes it as an epidermal detachment of over 30% of the BSA. In Japanese individuals, HLA-A*02:06, HLA-A*02:07, HLA-A*31:01 and HLA-B*51:01 may be linked to higher risks of TEN.

Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

[Two cases of allergies due to Anisakis simplex, positive to specific IgE for Ani s 12 allergen].

We report 2 cases of immediate allergies to Anisakis after ingestion of seafood. In case 1, after ingestion of flatfish, sea bream and mackerel, wheals and dyspnea occurred. Result of ImmunoCAP was class 5 for Anisakis. ELISA for specific IgE showed that the patient serum strongly reacted to Ani s 12. In case 2, after ingestion of flatfish and yellowtail, pruritus and dyspnea occurred. Result of ImmunoCAP was class 6 for Anisakis. ELISA for specific IgE showed that the patient serum reacted to Ani s 1, 4, 6 and 12. In both cases, skin prick tests were negative for suspected seafoods. These data suggests the possibility Ani s 12 is a major allergen of Anisakis allergy besides Ani s 1, 2 and 7. Ani s 12 is an allergen that was first reported in 2011. The reactivity of Ani s 12 specific IgE with ELISA may become useful for the diagnosis of Anisakis allergy.

A Retrospective Study of the Clinicopathological Characteristics of Approximately 1,600 Pilomatricomas Treated at a Single Institution.

BACKGROUND: First reported by Malherbe in 1880, pilomatricoma is a common benign skin tumor generally believed to occur mainly in children and adolescents. We conducted this study to better define the characteristics of pilomatricoma and compare our findings with current knowledge. METHODS: Patients diagnosed pathologically with pilomatricoma from 2016 through 2020 at Nippon Medical School Musashi Kosugi Hospital were included (1,559 patients, 1,590 tumors). Clinicopathological characteristics were analyzed. RESULTS: The male to female ratio was 1:1.6, and the most common tumor site was the upper limbs (33.7%). Preoperative diagnosis was correct in 48.5% of the patients, and their average age at resection was 33.5 years. Resection was carried out in 70% of the patients within 1 year, but time to resection was more than 1 year in the other 30%. Pathologically, squamous stratifying keratinocytes were observed in 41.7% of the patients, cells with a large pale pink cytoplasm in 38.9%, hair papilla-like structures in 33.9%, ossification in 15.7%, trichohyalin granules in 11.9%, and aggregations of follicular germinative cells in 7.8%. Of the chronological and morphological stages proposed by Kaddu (stage 1: early, stage 2: fully developed, stage 3: early regressive, stage 4: late regressive), stage 3 was the most common (70.6%). CONCLUSION: Pilomatricoma is more common in females, regardless of ethnicity or age, but the tumor location in the upper limbs commonly observed in Japanese patients may indicate ethnic differences. Pathologically, the fact that cells linked to follicular differentiation are observed suggests that pilomatricoma is a complex panfollicular neoplasm. Time to resection appears to correlate with Kaddu stages. Factors such as age, location, sex, depth, and stage may affect the pathological features of this tumor.

A cephalometric analysis of the antegonial notch in relation to the direction of mandibular growth.

Masticatory muscle forces influence craniofacial morphology development. The antegonial notch (Notch) is a bony concavity on the inferior border of the mandible. Considering the Notch is located anteriorly to the insertion of the masseter muscle and varies among individuals, we hypothesised that these muscles influence the formation of the Notch. Therefore, this study aimed to investigate the correlation between mandible morphology and Notch formation. Sixty Japanese patients who visited the Department of Orthodontics at our university hospital were retrospectively evaluated. Morphological and morphometric analyses of the Notch and related craniofacial parameters were conducted using lateral cephalograms taken at the patients' initial visits. Standard values for the Notch area and depth were determined, and the morphology of the Notch and mandible was analysed using Spearman's rank correlation coefficient (p < 0.05). The mean Notch area and depth was 78.71 ± 36.54 mm2 and 3.11 ± 1.09 mm, respectively. The Notch area was significantly correlated with ramus inclination (p = 0.044, r = 0.261) and with the Y-axis (p = 0.039, r = 0.267). This study indicated that both the masticatory muscles and mandibular growth could contribute to the Notch formation.

Community resilience through partnership after the Great East Japan Earthquake: cooking classes by Iwate Co-op and a food company.

Introduction: This case study aimed to demonstrate how cooking class activities held in collaboration with the Ajinomoto Foundation (TAF) and a consumer cooperative after the Great East Japan Earthquake contributed to the resilience of the affected community. Methods: With reference to the logic model, evaluation indicators for the case study were established. We focused on the Iwate Seikatsu Kyodo Kumiai (Iwate Co-op). We organized 120 continuation cases out of the eight-and-a-half-year activity records of the project owned by TAF (April 2012 to March 2020). The Iwate Co-op was one of the 120 continuing cases and had special features, including awareness that its members were responsible for the community. Results: The collaboration revealed three effects. First, owing to the encounter and collaboration with TAF, the cooking class was continuously conducted even after TAF withdrew from the disaster-affected areas. Second, the Iwate Co-op trained some of its members as food support staff to run the cooking class independently and was actively involved in obtaining the necessary budget for the operation, consequently leading to the independent activation of member activities. Third, they developed a cooking class project in inland areas other than disaster-stricken areas, assuming that they could incorporate the project into their existing activities, as food problems affected people beyond disaster victims. Conclusion: The collaborative food support project of the Iwate Co-op and TAF contributed to the resilience of the affected people and communities by strengthening bonds and solidarity among residents and organizations. The key to success was the fusion of a traditional sense of independence in the co-op with TAF's mission and technical know-how. The partnership between the Iwate Co-op and TAF allowed the former to aim toward developing food support activities in the affected areas, accelerating the resilience of the community in the Iwate Prefecture.

Idobata-Nagaya: a community housing solution for socially isolated older adults following the great East Japan earthquake.

Introduction: Following the Great East Japan Earthquake, the living environment of socially isolated older adults has become a pressing concern. In response, Nagaya, a collective housing program, was established in Soma City, Fukushima, Japan to address social isolation among older adults and support their long-term health. This study aimed to identify characteristics of individuals in Nagaya and examine the sustainability of this initiative. Methods: We conducted a retrospective analysis of residents who were relocated to Nagaya, emphasizing their characteristics, the continuity of their stay in Nagaya, and their care certification levels, using data up to December 31, 2022. We employed Kaplan-Meier curves to analyze the duration for which residents continued to reside in Nagaya and the time leading up to the requiring care-level certification. Results: Of 65 people who moved to Nagaya after the disaster, 30 people (46.2%) continued to live there, 21 (32.3%) died during their stay, and 14 (21.5%) moved out. The overall duration of occupancy averaged 6.39 years (SD 3.83 years). The proportion of requiring care-level certification occurrences per person-year was 0.0577 for those without care certification and 0.3358 for those with requiring support level at the time of moving in. Conclusion: In summary, Nagaya-style communal housing may offer suitable living environments for older adults with diverse needs during disasters and serve as a valuable tool for developing public policies in aging societies.

Promoting independent living and preventing lonely death in an older adult: Soma Idobata-Nagaya after the 2011 Fukushima disaster.

Contrary to the assumption that older adults are only cared for by their families in rural Japan, this case illustrates that community formation can effectively provide older adult care after an emergency as well. We look at the life of a woman who lived in a housing facility for older adults, Idobata-Nagaya in Soma, Japan, exploring how social housing-which addresses the needs of older adults regarding community, familiarity and socialising-can provide a viable, effective and comfortable environment for older adults to live. In the case of Idobata-Nagaya, not only could older adults take care of one another but they could also share experiences of the Fukushima disaster with each other. This is a qualitative case study which provides a stable foundation for policymakers, healthcare workers and government officials to better understand the effectiveness of housing projects for communities and older adults in Japan and globally.

Older adult living independently in a public rowhouse project after the 2011 Fukushima earthquake: A case report.

We study an older Japanese woman who lived independently with minimal nursing or informal support from others in the rowhouse after the 2011 Fukushima disaster. This case report supports the effectiveness of Idobata nagaya as a measure of the municipality and offers an evidence-based approach to reconstruction after a disaster. Considering the global population aging and isolation trends, the lesson from this case may apply to other settings beyond disasters.

Subjective Wellbeing and Related Factors of Older Adults Nine and a Half Years after the Great East Japan Earthquake: A Cross-Sectional Study in the Coastal Area of Soma City.

This study examined older adults' subjective wellbeing and related factors in the coastal area of Soma City nine and a half years after the Great East Japan Earthquake (GEJE). Data were collected from 65- to 84-year-old residents and 1297 participants via a questionnaire from October to November 2020. The participants were divided into two groups: housing complexes and non-housing complexes. The dependent variable was subjective wellbeing assessed via Lawton's Philadelphia Geriatric Center Morale Scale (PGCMS). Using multivariate regression analysis, the factors most strongly related to a low PGCMS score for both groups were poor health conditions, difficulties resting while asleep, poor financial wellbeing, inability to chew certain foods, and fear of solitary death. The GEJE experience was further distinguished in the housing complex group by the loss of an important non-family individual; for the other group, important factors were female gender, junior high school education level or lower, limited social networks, and deterioration of a family member's health. Older adults' subjective wellbeing in Soma City was low after nine and a half years following the GEJE. For disaster victims and their families in both groups, it is crucial to implement measures such as long-term, continuous physical and mental health support.

Motivation for and Effect of Cooking Class Participation: A Cross-Sectional Study Following the 2011 Great East Japan Earthquake and Tsunami.

We explored the association between the motivation for and effects of cooking class participation in disaster-affected areas following the 2011 Great East Japan Earthquake and Tsunami. We conducted questionnaire surveys in January and February 2020, and applied three Poisson regression models to a cross-sectional dataset of participants, analyzing three perceived participation effects: increase in new acquaintances and friends, increase in excursion opportunities, potential for gaining motivation, and a new sense of life purpose. We also applied the interaction term of motivation variables and usual eating patterns (eating alone or with others). We obtained 257 valid responses from 15 cooking venues. The interaction term for participants' motivation and eating patterns was associated with their perceived participation effects. "Motivation for nutrition improvement × eating alone" was positively associated with an increase in new acquaintances and friends (IRR: 3.05, 95% CI, 1.22-7.64). "Motivation for increasing personal cooking repertoire × eating alone" was positively associated with increased excursion opportunities (IRR: 5.46, 95% CI, 1.41-21.20). In contrast, the interaction effect of "motivation of increasing nutrition improvement × eating alone" was negatively associated with increased excursion opportunities (IRR: 0.27, 95% CI, 0.12-0.69). The results show that the cooking class was effective, as residents' participation improved their nutritional health support and increased their social relationships.

Effects of uremic serum and uremic toxins on hepatic uptake of digoxin.

Not only the renal clearance but also the hepatic clearance of drugs varies with the progression of renal failure. The aim of this study was to investigate the effects of human uremic serum and various uremic toxins on the hepatic uptake of digoxin (DX), a drug mainly excreted into bile in patients with severe renal failure, using isolated rat and human hepatocytes as model systems. Uremic serum inhibited the uptake of DX into rat hepatocytes in a concentration-dependent manner, whereas normal serum did not affect the uptake. In addition, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid, indole-3-acetic acid, indoxyl sulfate, and p-cresol (PC) concentration dependently inhibited the uptake. CMPF and PC at the concentration of 400 microM, which is within the plasma concentration range attained in patients with renal failure, inhibited the uptake of DX into rat hepatocytes by 27% and 23%, respectively. In human hepatocytes, 10% uremic serum, 400 microM CMPF, and 400 microM PC inhibited the uptake of DX by 23.3%, 23.4%, and 28.2%, respectively. In conclusion, our results suggest that hepatic uptake of DX is likely to be inhibited by uremic toxins, such as CMPF and PC, present in the serum of patients with renal failure.

A Review of the Active Treatments for Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction associated with the separation of skin and mucous membranes at the dermal-epidermal junction. Although it is rare, many treatments have been trialed because of its high mortality rate. Active interventions performed to date include the use of systemic corticosteroids, intravenous immunoglobulins (IVIg), cyclosporine, plasmapheresis, anti-tumor necrosis factor drugs and N-acetylcysteine, but none has been established as the most effective therapy. IVIg and short-term high-dose corticosteroids were regarded as the most promising treatments for TEN in a comprehensive review of all reported TEN cases from 1975-2003. When used with an appropriate dose and timing, the beneficial effects of IVIg can be maximized. Although no randomized controlled trials have been conducted, cyclosporine and plasmapheresis are considered to be beneficial. As no gold standard for active intervention for TEN has been established, the choice of treatment relies partly on the available guidelines and the experience of the dermatologist. There is still much to be investigated regarding the pathogenesis of TEN, and new findings may contribute to the identification of an effective active intervention strategy.

A Review of the Pathogenesis of Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN) is a rare skin condition, most often drug-induced, known for its skin detachment and high mortality. In general, acute TEN is considered a T-cell mediated, type IV hypersensitivity disorder. It mostly results from a cumulative effect of risks from the drug structure, drug metabolism, HLA alleles and T cell clonotypes. However, the precise mechanism of TEN is still unknown. Apoptosis or necroptosis causes keratinocytes to lose their shape and adhesion, and necrosis predominates within a few days. Total epidermal necrosis separates the epidermis from the dermis. TEN is regarded as an immune reaction with predominantly CD8+ T lymphocytes, monocytes/macrophages, and natural killer cells. Impaired regulatory T-cells, T-helper 17 cells, cytotoxic granules such as perforin-granzyme and granulysin, tumor necrosis factor α, annexin, microRNA-18a-5p, and drug metabolites are all thought to be involved. From what is known, it can be assumed their mechanism is complex, and there is still much to be investigated. New findings will contribute to the identification of effective active methods of intervention.

A qualitative study of risk factors related to child malnutrition in Aileu District, Timor-Leste.

Improvement in child nutritional status is one of the major health priorities in Timor-Leste. A qualitative study was conducted in Aileu District, adjacent to the capital of Timor-Leste, Dili, in September 2010 to determine the possible risk factors associated with the high prevalence of child malnutrition. In-depth interviews were conducted to 32 guardians of children aged younger than 5 years. It was observed that early termination of exclusive breast-feeding and a short lactation period along with an unsanitary living environment were associated with the nutritional status of children in the study area. Although previous surveys have reported poor food security conditions in the country, no statements from the subjects supported this contention. The identified possible risk factors for child malnutrition were closely linked to each other and were mostly modifiable.