A Patient with Mitochondrial Disease on Dialysis with Long-term Follow-up of Cardiomyopathy: An Autopsy Case Report.

A 59-year-old man developed diabetes at 24 years old and underwent hemodialysis at 42 years old. At 54 years old, cardiac dysfunction with left ventricular hypertrophy was detected, followed by complete atrioventricular block at 57 years old. The patient was diagnosed with mitochondrial disease based on a myocardial biopsy and the presence of a mitochondrial DNA mutation (3243A>G). He died of septic shock at 59 years old, and an autopsy confirmed mitochondrial cardiomyopathy. If progressive cardiac hypertrophy and conduction disturbances are observed in patients with diabetes mellitus on long-term hemodialysis, mitochondrial disease needs to be considered.

Usefulness of a new DUV-LED device for the control of infection by Escherichia coli, Staphylococcus aureus, mycobacteria and spore-forming bacteria.

Reliable disinfection and sterilization technologies are needed to deal with the various infectious diseases spreading around the world. Furthermore, bacteria that are difficult to eliminate by ordinary disinfection are also a problem in the medical environment. We examined the germicidal effect of a newly developed deep-ultraviolet light-emitting diode (DUV-LED) prototype device (wavelength of 280 ± 5 nm; power of 0.9 to 1.4 mW/cm2) for floor sterilization against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium gordonae (M. gordonae), and Bacillus subtilis (B. subtilis). This prototype device is equipped with highly practical DUV-LEDs with a high output efficiency and a long life, and was designed with consideration of the irradiation distance and the angle of the DUV-LEDs to provide a uniform irradiation rate. We found a statistically significant reduction of ≥90% in the infectious titers of both E. coli and S. aureus after irradiation for 2 s. Although acid-fast bacilli and spore-type bacilli are generally thought to be resistant to UV light irradiation compared to general bacteria, the acid-fast bacillus M. gordonae was inactivated after irradiation for 10 s, and spore-type cells of the bacillus B. subtilis were inactivated by ≥90% after irradiation for 30 s. We also found that the effects were cumulative when irradiation was performed at intervals. In the future, the usefulness of this device as an infection control measure will be evaluated in daily medical practice.

Rapid inactivation of Dabie bandavirus (SFTSV) by irradiation with deep-ultraviolet light-emitting diode.

Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (SFTSV) is a serious public health concern in endemic areas, particularly in Asian and Southeast Asian countries. SFTSV is transmitted by direct contact with body fluids from infected humans and animals. Therefore, environmental hygiene in hospitals and veterinary clinics in SFTSV-endemic areas is highly important. This study assessed the effects of continuous and intermittent irradiation with deep-ultraviolet light-emitting diode (DUV-LED) on SFTSV. Evaluation was performed by conducting plaque assay in which SFTSV irradiated with deep-ultraviolet (DUV; 280 ± 5 nm) was inoculated onto Vero cells. The results showed that continuous and intermittent irradiation for 5 s, resulting in 18.75 mJ/cm2 of cumulative UV exposure, led to a >2.7 and >2.9 log reduction, respectively, corresponding to a >99.8% reduction in infectivity. These results demonstrate that DUV can be utilized for inactivation of SFTSV to maintain environmental hygiene in hospitals and veterinary clinics in endemic countries.

Rapid Inactivation of SARS-CoV-2 Variants by Continuous and Intermittent Irradiation with a Deep-Ultraviolet Light-Emitting Diode (DUV-LED) Device.

More than 1 year has passed since social activities have been restricted due to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More recently, novel SARS-CoV-2 variants have been spreading around the world, and there is growing concern that they may have higher transmissibility and that the protective efficacy of vaccines may be weaker against them. Immediate measures are needed to reduce human exposure to the virus. In this study, the antiviral efficacy of deep-ultraviolet light-emitting diode (DUV-LED) irradiation (280 ± 5 nm, 3.75 mW/cm2) against three SARS-CoV-2 variants was evaluated. For the B.1.1.7, B.1.351, and P.1 variant strains, irradiation of the virus stocks for 1 s resulted in infectious titer reduction rates of 96.3%, 94.6%, and 91.9%, respectively, and with irradiation for 5 s, the rates increased to 99.9%, 99.9%, and 99.8%, respectively. We also tested the effect of pulsed DUV-LED irradiation (7.5 mW/cm2, duty rate: 50%, frequency: 1 kHz) under the same output conditions as for continuous irradiation and found that the antiviral efficacy of pulsed and continuous irradiation was the same. These findings suggest that by further developing and optimizing the DUV-LED device to increase its output, it may be possible to instantly inactivate SARS-CoV-2 with DUV-LED irradiation.

Concurrent minimal change nephrotic syndrome and type 1 diabetes mellitus in an adult Japanese woman: a case report.

BACKGROUND: Concurrent type 1 diabetes mellitus (T1DM) and idiopathic nephrotic syndrome is rare, and most previously reported cases were in children. We report the case of an adult woman who developed T1DM and minimal change nephrotic syndrome (MCNS) nearly simultaneously. CASE PRESENTATION: A 24-year-old woman had first presented to another hospital with nausea, vomiting, and fatigue. She was diagnosed with diabetic ketoacidosis and T1DM on the basis of her hyperglycemia, ketoacidosis, and positive anti-glutamic acid decarboxylase antibody test result. Rapid infusion of normal saline and insulin administration alleviated hyperglycemia and ketoacidosis. Two weeks after admission, however, she developed nephrotic syndrome (NS) with rapidly decreasing urine volume. She was referred to our hospital with a diagnosis of acute kidney injury. Although she temporarily required dialysis and high doses of insulin, within 1 month NS and acute kidney injury had been alleviated by oral prednisolone and low-density lipoprotein apheresis. Renal biopsy showed minor glomerular abnormalities without diabetic nephropathy, so we diagnosed her with MCNS. Seven weeks after the discharge, NS relapsed, and cyclosporine was added to prednisolone. However, NS relapsed twice within the next 4 months, so we started her on rituximab. At 6 months after initiating rituximab therapy, she remained in complete remission. Her mother also had T1DM but not MCNS. The patient had HLA-DRB1*09:01/09:01, DQB1*03:03/03:03, and her mother had HLA-DRB1*04:05/09:01, DQB1*03:03/04:01. CONCLUSIONS: Concurrent T1DM and MCNS is rare and their coexistence might be coincidental. Alternatively, they might have been caused by an underlying, unidentified genetic predisposition. Previous reports and our patient's findings suggest that specific HLA alleles and haplotypes or a Th1/Th2 imbalance might be associated with T1DM and MCNS that occurred nearly simultaneously.

Rapid inactivation of SARS-CoV-2 with deep-UV LED irradiation.

The spread of novel coronavirus disease 2019 (COVID-19) infections worldwide has raised concerns about the prevention and control of SARS-CoV-2. Devices that rapidly inactivate viruses can reduce the chance of infection through aerosols and contact transmission. This in vitro study demonstrated that irradiation with a deep ultraviolet light-emitting diode (DUV-LED) of 280 ± 5 nm wavelength rapidly inactivates SARS-CoV-2 obtained from a COVID-19 patient. Development of devices equipped with DUV-LED is expected to prevent virus invasion through the air and after touching contaminated objects.

Plasmapheresis for the Treatment of Anti-M Alloimmunization in Pregnancy.

Intrauterine transfusion is the standard antenatal treatment for a fetus with severe anemia. Plasmapheresis is an alternative treatment for cases with a history of severe hemolytic disease of the fetus and newborns at less than 20 weeks of gestation. There is only one previous report of plasmapheresis for the anti-M alloimmunization in pregnancy, and we report here on the successful treatment of plasmapheresis for anti-M alloimmunization. A woman with a history of intrauterine fetal death at 24 weeks of gestation due to severe fetal anemia caused by anti-M alloimmunization received plasmapheresis once or twice a week from 14 weeks of gestation onward. An intrauterine blood transfusion was conducted at 28 weeks, and a cesarean section was performed at 31 weeks. The infant had anemia and jaundice but was discharged at day 46. Plasmapheresis may delay the development of fetal anemia and reduce the risk of early and repeat intrauterine transfusion in cases of anti-M alloimmunization in pregnancy.

Case Report: A Case of Encephalopathy Presenting the Lentiform Fork Sign on MRI in a Diabetic Dialysis Patient.

Basal ganglia lesions showing an expansile high signal intensity on T2-weighted MRI are termed the lentiform fork sign. This specific finding is mainly observed in diabetic patients with uremic encephalopathy with metabolic acidosis, although there are also reports in patients with ketoacidosis, dialysis disequilibrium syndrome, intoxication, and following drug treatment (e.g., metformin). A 57-year-old Japanese man on chronic hemodialysis for 4 years because of diabetic nephropathy was admitted to our hospital for relatively rapid-onset gait disturbance, severe dysarthria, and consciousness disturbance. Brain T2-weighted MRI showed the lentiform fork sign. Hemodialysis was performed the day before admission, and laboratory tests showed mild metabolic (lactic) acidosis, but no uremia. Surprisingly, metformin, which is contraindicated for patients with end-stage kidney disease, had been prescribed for 6 months in his medication record, and his sluggish speaking and dysarthria appeared gradually after metformin treatment was started. Thus, the encephalopathy was considered to be related to metformin treatment. He received hemodialysis treatment for 6 consecutive days, and his consciousness disturbance and dysarthria improved in 1 week. At the 8-month follow-up, the size of the hyperintensity area on MRI had decreased, while the mild gait disturbance remained. Considering the rapid onset of gait and consciousness disturbance immediately before admission, diabetic uremic syndrome may also have occurred with metformin-related encephalopathy, and resulted in the lentiform fork sign, despite the patient showing no evidence of severe uremia on laboratory data.

Characterisation of N-terminal pro-brain natriuretic peptide in dialysis patients and its reduced prognostic significance in the elderly.

Characterisation of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic haemodialysis patients and its prognostic significance in age stratification have not been addressed. A prospective cohort study with cross-sectional analyses at baseline was performed. Outcomes were all-cause mortality, non-malignancy-related mortality, and cardiovascular disease (CVD)-related mortality. NT-proBNP was significantly higher in elderly, female, and low dry weight patients. Study patients were divided into two groups: Group-O (≥75 years) and Group-Y (<75 years). The 7-year follow-up receiver operating curve analysis showed that NT-proBNP significantly predicted all outcomes. All-cause mortality cut-off points were significantly different among the groups (total cohort, 5375 pg/mL; Group-Y, 3682 pg/mL; Group-O, 11750 pg/mL). Cox regression analysis showed risks for all outcomes by tertile NT-proBNP significantly higher in the total cohort and Group-Y as adjusted by potential confounders. For all-cause mortality, hazard ratios and 95% confidence intervals (CI) were T2 1.70 (0.89 to 3.25), p = 0.11, T3 2.95 (1.54 to 5.67), p < 0.01 in Group-Y; and T2 1.00 (0.64 to 1.58), p = 1.00; T3 1.50 (0.94 to 2.40), p = 0.09 in Group-O. In conclusion, NT-proBNP was significantly higher in elderly, female, and low dry weight chronic dialysis patients. NT-proBNP was significantly associated with all outcomes. However, this association was reduced in elderly patients.

Cycloprodigiosin hydrochloride activates the Ras-PI3K-Akt pathway and suppresses protein synthesis inhibition-induced apoptosis in PC12 cells.

Cycloprodigiosin hydrochloride (cPrG-HCl), a member of the prodigiosin family of compounds, has been reported to act as an H(+)/Cl(-) symporter. This compound induces apoptosis in several cancer cells and acts as an antitumor drug in animal models. In this study, we found a novel function of cPrG-HCl; to suppress cell death in PC12 cells, which is caused by protein synthesis inhibitors cycloheximide and actinomycin D. cPrG-HCl activated Akt and suppressed apoptosis, and this was accompanied by inhibition of caspase-3 activity and DNA fragmentation independently of its H(+)/Cl(-) symporter activity. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and dominant-negative Ras attenuated the anti-apoptotic activity of cPrG-HCl, which indicates that cPrG-HCl activated the Ras-PI3K-Akt pathway suppressing apoptosis. On the other hand, serum-deprivation-induced apoptosis was not suppressed by cPrG-HCl.