Novel Function of Ceramide for Regulation of Mitochondrial ATP Release in Astrocytes

We reported that amyloid β peptide (Aβ42) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ42 induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine (pacFACer), a bifunctional ceramide analog, and binding of tubulin to ceramide-linked agarose beads. Ceramide-associated tubulin (CAT) translocated from the perinuclear region to peripheral CEMAMs and mitochondria, which was prevented in nSMase2-deficient or FB1-treated astrocytes. Proximity ligation and coimmunoprecipitation assays showed that ceramide depletion reduced association of tubulin with voltage-dependent anion channel 1 (VDAC1), an interaction known to block mitochondrial ADP/ATP transport. Ceramide-depleted astrocytes contained higher levels of ATP, suggesting that ceramide-induced CAT formation leads to VDAC1 closure, thereby reducing mitochondrial ATP release, and potentially motility and resistance to Aβ42. Our data also indicate that inhibiting ceramide generation may protect mitochondria in Alzheimer’s disease

Burnout and fear of COVID-19 among medical students in Japan: impact of infection history, gender, and social support

The COVID-19 pandemic caused significant changes in medical students' lives and study methods, with online learning replacing in-person classes and limited opportunities for clinical practice. However, there are few studies about burnout and fear of COVID-19 among medical students, especially in East Asia, and a need for research investigating the impact of gender, a history of COVID-19 infection, and social support. In March 2022, we conducted a cross-sectional web-based survey of 4th/5th year medical students who completed a clinical clerkship in Japan. Our survey included the Japan Burnout Scale (JBS, range 5-85, comprising of emotional exhaustion, depersonalization and reduced personal accomplishment), fear of COVID-19 scale (range, 1-4), gender, school year, COVID-19 history, household composition, online education use, and financial burden. There were 343 respondents and 42.4% were women. Multivariable adjusted linear regression analyses showed that students with a COVID-19 infection history had significantly higher overall burnout, depersonalization, reduced personal accomplishment, and lower fear of COVID�19. Students with low social support (living alone and greater financial burden) had higher overall burnout, emotional exhaustion, and depersonalization. Gender had no significant effect on burnout (mean JBS among women was 38.6 versus 39.3 among men). Gender significantly predicted fear of COVID-19, with women scoring higher (1.60 versus 1.50). The findings of the present study have implications that medical schools should provide pastoral care for their students according to students’ circumstances, especially those who live alone, have a high financial burden, and/or were infected with COVID-19

Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute: Good outcome in 43 patients followed for a mean of 2 years

Background and purpose One of the greatest problems of revision hip arthroplasty is dealing with lost bone stock. Good results have been obtained with impaction grafting of allograft bone. However, there have been problems of infection, reproducibility, antigenicity, stability, availability of bone, and cost. Thus, alternatives to allograft have been sought. BoneSave is a biphasic porous ceramic specifically designed for use in impaction grafting. BoneSave is 80% tricalcium phosphate and 20% hydroxyapatite. Previous in vitro and in vivo studies have yielded good results using mixtures of allograft and BoneSave, when compared with allograft alone. This study is the first reported human clinical trial of BoneSave in impaction grafting

A review of symptomatic leg length inequality following total hip arthroplasty

Leg length inequality (LLI) following total hip replacement is a complication which features increasingly in the recent literature. The definition of LLI is complicated by lack of consensus regarding radiological measurement, clinical measurement and the incomplete relationship between LLI and associated symptoms. This paper reviews 79 reports relating to LLI post hip replacement, detailing definitions and classification and highlighting patient populations prone to symptomatic LLI. While there is no universal definition of LLI, there is a broad consensus that less than 10 mm of difference on AP view plain radiographs is clinically acceptable. There are few techniques described that consistently produce a postoperative LLI of less than this magnitude. Where postoperative LLI exists, lengthening appears to cause more problems than shortening. In cases of mild LLI, non-surgical management produces adequate outcomes in the majority of cases, with functional LLI cases doing better than those with true LLI. Operative correction is effective in half of cases, even where nerve palsy is present, and remains an important option of last resort. Poor outcomes in patients with LLI may be minimised if individuals at risk are identified and counselled appropriately

Quantification of iodine in porous hydroxyapatite matrices for application as radioactive sources in brachytherapy

In this study, non-radioactive iodine was incorporated in two types of biodegradable hydroxyapatite-based porous matrices (HA and HACL) through impregnation process from sodium iodine aqueous solutions with varying concentrations (0.5 and 1.0 mol/L) . The results revealed that both systems presented a high capacity of incorporating iodine into their matrices. The quantity of incorporated iodine was measured through Neutron Activation Analysis (NAA). The porous ceramic matrices based on hydroxyapatite demonstrated a great potential for uses in low dose rate (LDR) brachytherapy.<br>Materiais cerâmicos porosos à base de compostos de fosfatos de cálcio (CFC) vêm sendo estudados e desenvolvidos para várias aplicações biomédicas tais como implantes, sistemas para liberação de drogas e fontes radioativas para braquiterapia. Dois tipos de matrizes porosas biodegradáveis de hidroxiapatita (HA e HACL) foram avaliadas em termos da capacidade de incorporação de iodo em suas estruturas. Resultados revelaram que as matrizes porosas a base de hidroxiapatita apresentaram alta capacidade de incorporar iodo em sua estrutura. A quantidade de iodo foi mensurada através da técnica de Análise por Ativação Nêutronica (AAN). As matrizes cerâmicas porosas à base de hidroxiapatita demostraram ter grande potencial para aplicação em braquiterapia de baixa taxa de dose (LDR - Low Dose Rate)