[Two cases of cerebral amyloid angiopathy in which white matter lesions appearing after brain biopsy got improvement without immunotherapy].

The first case was a 75-year-old woman with intermittent sensory impairment of the left hand. FLAIR of the head MRI revealed hyperintensity along the pia mater in the right parieto-temporal lobe with few microbleeds. Our second case was a 78-year-old man who presented with motor aphasia. His MRI showed swollen cortex on FLAIR and cortical hemosiderosis on T2* weighted imaging of the right cerebral hemisphere. Pathological findings indicated the first case as cerebral amyloid angiopathy (CAA)-related inflammation and the second case as CAA. Additionally, after brain biopsy, widespread white matter lesions were detected in the area surrounding the biopsy site. However, both patients showed improvement without immunotherapy. Therefore, it is important to consider whether immunotherapy is required when white matter lesions appear in the area surrounding the biopsy site.

[A case of multiple small cerebral infarcts in the cerebellum and bilateral cerebrum, diagnosed with amyloid angiopathy by brain biopsy].

An 82-year-old woman had been suffering from progressive forgetfulness and abnormal speech and behavior for One month. Findings of the MRI of the head indicated scattered small cerebral infarcts in the cerebellum and in bilateral cerebral cortex/subcortical white matter. After admission, she experienced a subcortical hemorrhage, and the percentage of small cerebral infarcts increased over time. Based on the suspicion of central primary vasculitis or malignant lymphoma, we performed a brain biopsy targeting the right temporal lobe hemorrhage site, and the patient was diagnosed with cerebral amyloid angiopathy (CAA). We conclude that CAA can cause multiple small progressive cerebral infarcts.

Happiness Detected by the Emotion Cognition System Is Associated with Burnout in an Information Technology Products and Services Trading Company.

(1) Background: Although many previous studies have found an association between burnout and emotions, none have examined the association between emotions detected by an emotion cognition system and burnout. The purpose of this study is to examine the relationship between the emotions detected by the emotion cognition system and burnout among workers. We hypothesized that burnout survivors are less likely to express their emotions as facial expressions. (2) Methods: One hundred and forty-one workers at an Information Technology (IT) products and services trading company were asked to take facial images for three months when they started and left work and responded to a burnout questionnaire once a month. Microsoft Azure was used to detect their emotions. (3) Results: Hierarchical multiple regression analyses revealed that happiness in Period 1 was significantly and negatively associated with burnout at Time 2. This association was also observed after the various covariates were included. However, burnout at Time 3 was not significantly related to any emotions in Period 1. (4) Conclusions: Happiness, as detected by the emotion cognition system, was associated with burnout immediately afterward.

[Primary central nervous system post-transplant lymphoproliferative disorder with few specific abnormal findings observed on MRI and in the cerebrospinal fluid].

A 60-year-old woman, who had a kidney transplant 16 years ago, was admitted to our hospital owing to cognitive decline and gait disturbances. She developed ataxia, consciousness disturbances, and myoclonus, and died two years after the onset of symptoms. No specific findings were observed on MRI or in the cerebrospinal fluid and blood analyses. The patient was diagnosed with post-transplant lymphoproliferative disorder (PTLD) based on the results of the autopsy. Pathological findings revealed proliferating monoclonal B cells in the perivascular space that was confined to the central nervous system. PTLD is a serious complication of transplantation. Furthermore, PTLD of the central nervous system usually presents as nodular lesions on MRI. When neurological symptoms appear after transplantation, it is necessary to consider PTLD as a differential diagnosis even if abnormal findings cannot be pointed out on MRI.

Effect of Jersey cow defatted dry milk on salivary volume and composition in elderly persons†:†a pilot study.

The administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK), and His59-Lys60 (HK) from ß-lactoglobulin C variant, which is specific to Jersey cow milk, has been shown to prevent and/or restore the age-dependent atrophy and functional decline of salivary glands by affecting gene expression in elderly rats. In this study, we investigated the effect of Jersey cow defatted milk on salivary volume and composition in elderly persons. Participants (aged 85 to 98, n = 8) were administered defatted dry milk from Jersey cows twice a day for 4 weeks. Before and after 4 weeks from the start of drinking, saliva was collected and weighed. Salivary cystatin S and amylase levels were analyzed by Western blotting. To assess the effect of Jersey cow defatted milk on taste perception, questionnaires were used. Salivary volume after oral administration of 40 g of Jersey cow defatted dry milk daily for 4 weeks was 1.8 times higher than that before administration. Salivary cystatin S and amylase levels significantly increased after administration of Jersey cow defatted dry milk. Moreover, all participants who had taste impairment reported improved taste perception after administration. The administration of Jersey cow defatted dry milk increased salivary volume and changed the composition of saliva in elderly persons. Furthermore, it improved taste perception. J. Med. Invest. 68 : 280-285, August, 2021.

[A case of central nervous system primary lymphomatoid granulomatosis with multiple vascular lesions in the spinal cord and brain].

A 71-year-old man was hospitalized because of low back pain and weakness in both lower limbs. He presented with fever and stiff neck, and his cerebrospinal fluid sample contained blood. MRI revealed intramedullary and epidural hemorrhages in the spinal cord. Microhemorrhages occurred frequently in the central nervous system over a short period. A brain biopsy was performed. The diagnosis was primary lymphomatoid granulomatosis (LYG) of the central nervous system (grade 2). As a result of lymphocytic infiltration to the vascular walls in LYG, hemorrhages occurred in multiple sites in the central nervous system. The biopsy of samples from the sites of microhemorrhages proved useful for diagnosis even in the absence of mass lesions.

Comparison of the intraocular pressure following an intravitreal triamcinolone acetonide injection for diabetic macula oedema in vitrectomised and non-vitrectomised eyes.

PURPOSE: To compare the intraocular pressure (IOP) after an intravitreal triamcinolone acetonide (IVTA) between vitrectomised and non-vitrectomised eyes in patients with diabetes and diabetic macular oedema (DME). DESIGN: Retrospective comparative study. METHODS: Medical records of 157 patients (157 eyes) with type 2 diabetes who received IVTA for DME were reviewed, and the best-corrected visual acuity, IOP and optical central retinal thickness (CRT) were compared preoperatively, at 1, 4, 12 and 24 weeks after IVTA between the vitrectomised and non-vitrectomised groups. RESULTS: IOP significantly increased at 1 (p<0.0001), 4 (p<0.0001), 8 (p<0.0001), 12 (p=0.0019), 16 (p=0.0006) and 20 weeks (p=0.0191) in the non-vitrectomised group, whereas a significant increase was only observed at 1 (p=0.0003) and 4 weeks (p=0.0006) in the vitrectomised group. ΔIOP, IOP changes from baseline, in the non-vitrectomised group was significantly higher than that in the vitrectomised group at 4 (p=0.0014), 8 (p=0.0081), 12 (p=0.0032) and 16 weeks (p=0.0038). No significant difference was observed in logMAR and CRT at any time point after IVTA between the two groups. CONCLUSIONS: After an initial IVTA, increased IOP and ΔIOP from the baseline IOP were significantly more frequently observed in the non-vitrectomised than that in the vitrectomised group. IVTA is a safer and more effective treatment option for DME in vitrectomised than that in non-vitrectomised eyes.

Pharmacological monitoring of antiepileptic drugs in epilepsy patients on haemodialysis.

To retrospectively evaluate the pharmacological profiles of antiepileptic drugs (AEDs) in epilepsy patients during haemodialysis using therapeutic drug monitoring data. The serum concentration of AEDs was collected before and after haemodialysis, and the clearance rate and concentration-to-dose ratio were calculated as pharmacological parameters. Thirty-six patients were enrolled in the study (25 males, 11 females; age: 65.3 ± 14.8 years). In 24 of the 36 patients, epilepsy was associated with cerebrovascular disorders, and diabetes was the most common reason for haemodialysis in 16 patients. With regards to seizure type, focal aware seizures were less frequent than focal impaired awareness seizures and focal-to-bilateral tonic-clonic seizures. Interictal EEG showed intermittent rhythmic slow waves and intermittent slow waves more often than spikes or sharp waves. Levetiracetam was the most commonly used AED and led to the highest percentage of responders (80%; 16/20 patients). However, the clearance rate of levetiracetam during dialysis was highest among the antiepileptic drugs used, requiring supplementary doses after haemodialysis in all 20 patients. Valproic acid was not effective for focal epilepsy for patients on haemodialysis, and non-responders to phenytoin had low serum concentration of phenytoin both before and after haemodialysis. The pre-haemodialysis concentration of levetiracetam tended to be higher than the reference range, suggesting a potential risk of overdosing before haemodialysis. The pre- and post-haemodialysis concentrations of valproic acid tended to be lower than the reference range, suggesting a potential risk of underdosing. The concentration-to-dose ratios for levetiracetam, valproic acid, phenytoin, and carbamazepine were significantly lower after than before haemodialysis. The majority of patients with epilepsy on haemodialysis had cerebrovascular diseases, and therapeutic drug monitoring for levetiracetam, valproic acid, and phenytoin, before and after haemodialysis, is needed to ensure proper dosing.

Real-world evidence of the safety and efficacy profile of suvorexant in elderly patients with insomnia: a sub-analysis of the post-marketing drug-use results survey in Japan.

Objective: Global Phase III trials of suvorexant showed no obvious differences in the safety and efficacy profile of suvorexant between elderly and non-elderly patients. However, the clinical profile of suvorexant in elderly patients with comorbidities in a real-world setting was not evaluated. To further understand the safety and efficacy profile of suvorexant in elderly patients with insomnia in a daily clinical practice setting, we conducted a sub-group analysis of the post-marketing drug-use results survey.Methods: Patients with insomnia who were treated with suvorexant for the first time were divided into three groups: group-1 (<65 years, N = 1490), group-2 (≥65 years and <75 years, N = 730), and group-3 (≥75 years, N = 1028).Results: The incidence of overall adverse drug reactions (ADRs) were 11.28% (N = 168), 8.63% (N = 63), and 8.17% (N = 84) in group-1, -2, and -3, respectively. The ADRs most commonly observed in this survey were somnolence, insomnia, and dizziness, with no new safety concerns or differences in safety issues found. The numbers of patients in group-1, -2, and -3 who visited internal medicine departments were: 690 patients (46.3%), 521 patients (71.4%), and 793 patients (77.1%), respectively. The percentage of patients who were deemed to have "improved", based on the patient's self-assessment and their physician's assessment, was 70-75% of patients in all groups.Conclusion: These results reveal the safety and efficacy profile of suvorexant in elderly patients who often have various and multiple comorbidities and were treated in a daily clinical practice setting.

[The application and usefulness of virtual reality aimed at encouraging an understanding of and reducing and eliminating prejudice towards dementia patients among local residents].

AIM: To demonstrate the usefulness of a virtual reality device that authentically portrays the emotions of dementia patients and their families (VR Dementia Experience) for encouraging an understanding of and reducing and eliminating prejudice towards dementia patients among local residents. METHOD: In Prefecture T, Town N, 85 residents of Neighborhood A were chosen as the intervention group, and 95 residents of Neighborhood B were chosen as the non-intervention group. The VR Dementia Experience was provided only to the residents of Neighborhood A. Residents of both neighborhoods completed a 35-item questionnaire regarding their degree of understanding and prejudice towards dementia patients before and after the intervention. RESULTS: Seventy-seven residents of Neighborhood A and 82 residents of Neighborhood B were analyzed. Their gender, age, and pre-intervention test baseline values were equivalent in the degree of understanding and prejudice. Significant increases were observed in 9 of 35 items for Neighborhood A residents (7 understanding-related, 2 prejudice-related) and 2 items for Neighborhood B residents (1 understanding-related, 1 prejudice-related). To ascertain the usefulness of the VR Dementia Experience, we compared the number of items with a significant increase: 9/35 (25.7%) in Neighborhood A and 2/35 (5.7%) in Neighborhood B. An effect (≥ 20%) was observed among the residents of Neighborhood A. Furthermore, after exposure to the VR Dementia Experience, the connection between understanding, prejudice, and dementia was strengthened among the residents of Neighborhood A compared to the residents of Neighborhood B. CONCLUSION: The VR Dementia Experience is a useful tool for encouraging an understanding of and reducing and eliminating prejudice towards dementia patients among local residents. However, to encourage the widespread usage of the technology, we should compare results with other public awareness campaigns as well as make improvements to the device and its VR content.

Evaluation of Bioequivalence Between the New Procaterol Hydrochloride Hydrate Dry Powder Inhaler and the Approved Dry Powder Inhaler in Patients With Asthma in a Randomized, Double-Blind, Double-Dummy, Crossover Comparison Study: A Phase 3 Study.

Procaterol hydrochloride hydrate (procaterol) is a ß2 -adrenergic receptor agonist that induces a strong bronchodilatory effect. The procaterol dry powder inhaler (DPI) has been frequently used in patients with bronchial asthma or chronic obstructive pulmonary disease. We evaluated the bioequivalence and safety between the new procaterol DPI (new DPI) and the approved procaterol DPI (approved DPI). This study was a randomized, double-blind, double-dummy, crossover comparison to evaluate the pharmacodynamic equivalence of the new DPI and the approved DPI in patients with bronchial asthma. Primary efficacy variables were area under the concentration-time curve (AUC) forced expiratory volume in the first second (FEV1 )/h and maximum FEV1 during the 480-minute measurement period. Patients were divided into 2 groups, New-DPI-First (n = 8) and Approved-DPI-First (n = 8), according to the investigational medical product that was administered first. Patients inhaled 20 µg of procaterol in each period. FEV1 was measured by a spirometer at predose and at 15, 30, 60, 90, 120, 180, 240, 360, and 480 minutes after each investigational medical product administration. Equivalence was evaluated by confirming that the 2-sided 90%CIs for the difference between the new and the approved DPI in means of AUC (FEV1 )/h and maximum FEV1 were within the acceptance criteria of -0.15 to 0.15 L. The difference in means of AUC (FEV1 )/h and maximum FEV1 was 0.041 L and 0.033 L, respectively, and the 90%CI was 0.004 to 0.078 L and -0.008 to 0.074 L, respectively. These CIs were both within the acceptance criteria. The new DPI was assessed as being bioequivalent to the approved DPI.

[Symmetrical lesions of the cerebral peduncles and internal capsules on MRI in a patient with extranodal NK/T cell lymphoma].

A 72-year-old man was admitted to our hospital because of subacute progressive consciousness disturbance. FLAIR images showed diffuse high intensity areas in the bilateral thalamus, basal ganglia, and white matter. Chest CT revealed a mass in the right lung. The patient was diagnosed with extranodal natural killer/T cell lymphoma (ENKL) according to the results of a biopsy of the right pulmonary mass. The FLAIR images showed diffuse white matter lesions, without a mass such as lymphomatosis cerebri. On diffusion-weighted images, symmetrical high-intensity lesions of the cerebral peduncle and the internal capsule suggested high-density lymphoma cells around neurons. ENKL of the central nervous system and lung is a very rare neoplasm, and this case showed characteristic images.

An Autopsy Case of Intimal Sarcoma of the Abdominal Aorta with Bone Metastasis and Lymph Node Metastasis: A Case Report and Review of the Japanese Literature.

A 73-year-old man complained of sternoclavicular joint pain; blood tests revealed elevated C-reactive protein. The patient developed delirium; magnetic resonance imaging showed metastatic bone tumors. He died two weeks after admission. Autopsy revealed abdominal aortic intimal sarcoma with metastasis to the peritracheal lymph nodes and sternum. Peripheral arterial embolism and bone metastasis are common symptoms of aortic intimal sarcoma, which implies a place for aortic intimal sarcoma in differential diagnoses of embolism or bone tumors of unknown origin.

Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis.

Raynaud's phenomenon is frequently observed in systemic sclerosis (SSc) patients, and cold- or stress-induced norepinephrine (NE) has been speculated to be associated with vasoconstriction. Objective was to elucidate the role of NE in fibrosis in SSc. IL-6 is a potent stimulator of collagen production in fibroblasts. NE enhanced IL-6 production and proliferation more significantly in SSc fibroblasts than in normal fibroblasts. Furthermore, the production of IL-6 and phosphorylation of p38 in SSc fibroblasts was enhanced by adrenergic receptor (AR)ß agonist, isoproterenol, but not ARα agonist, oxymetazoline. ARß blocker, propranolol, inhibited NE-induced IL-6 production and phosphorylation of p38 in SSc fibroblasts. NE-induced IL-6 was significantly inhibited by p38 inhibitor, SB203580, suggesting that NE-induced phosphorylation of p38 via ARß enhances IL-6 production in SSc fibroblasts. NE-induced phosphorylation of ERK1/2 via ARα inhibited IL-6 production in SSc fibroblasts. Combined treatment with NE and endothelin-1 resulted in an additive increase in IL-6 production in SSc fibroblasts. NE-induced IL-6/IL-6 receptor trans-signaling increased the production of collagen type I in SSc fibroblasts, and both propranolol and SB203580 inhibited NE-induced collagen production. These results suggest that cold exposure and/or emotional stress-induced NE might contribute to the skin fibrosis via potentiation of IL-6 production from fibroblasts in SSc.

Factors associated with regular dental visits among hemodialysis patients.

AIM: To investigate awareness and attitudes about preventive dental visits among dialysis patients; to clarify the barriers to visiting the dentist. METHODS: Subjects included 141 dentate outpatients receiving hemodialysis treatment at two facilities, one with a dental department and the other without a dental department. We used a structured questionnaire to interview participants about their awareness of oral health management issues for dialysis patients, perceived oral symptoms and attitudes about dental visits. Bivariate analysis using the χ(2) test was conducted to determine associations between study variables and regular dental check-ups. Binominal logistic regression analysis was used to determine factors associated with regular dental check-ups. RESULTS: There were no significant differences in patient demographics between the two participating facilities, including attitudes about dental visits. Therefore, we included all patients in the following analyses. Few patients (4.3%) had been referred to a dentist by a medical doctor or nurse. Although 80.9% of subjects had a primary dentist, only 34.0% of subjects received regular dental check-ups. The most common reasons cited for not seeking dental care were that visits are burdensome and a lack of perceived need. Patients with gum swelling or bleeding were much more likely to be in the group of those not receiving routine dental check-ups (χ(2) test, P < 0.01). Logistic regression analysis demonstrated that receiving dental check-ups was associated with awareness that oral health management is more important for dialysis patients than for others and with having a primary dentist (P < 0.05). CONCLUSION: Dialysis patients should be educated about the importance of preventive dental care. Medical providers are expected to participate in promoting dental visits among dialysis patients.

Increased susceptibility to oxidative stress- and ultraviolet A-induced apoptosis in fibroblasts in atypical progeroid syndrome/atypical Werner syndrome with LMNA mutation.

Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a disorder of premature ageing caused by mutation of the lamin A gene, the same causal gene involved in Hutchinson-Gilford syndrome (HGS). We previously reported the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). Recently, it has been reported that UVA induced abnormal truncated form of lamin A, called progerin, as well as HGS-like abnormal nuclear structures in normal human fibroblasts, being more frequent in the elderly, suggesting that lamin A may be involved in the regulation of photoageing. The objective of this study was to elucidate the sensitivity to cell damage induced by oxidative stress or UVA in fibroblasts from APS/AWS patient. Using immunofluorescence staining and flow cytometry analysis, the amount of early apoptotic cells and degree of intra-cellular reactive oxygen species (ROS) generation were higher in H2 02 - or UVA-treated APS/AWS fibroblasts than in normal fibroblasts, suggesting that repeated UV exposure may induce premature ageing of the skin in APS/AWS patients and that protecting against sunlight is possibly important for delaying the emergence of APS/AWS symptoms. In addition, we demonstrated that H2 O2 -, or UVA-induced apoptosis and necrosis in normal and APS/AWS fibroblasts were enhanced by farnesyltransferase inhibitor (FTI) treatment, indicating that FTI might not be useful for treating our APS/AWS patient.

Quantitative comparison of cancer and normal cell adhesion using organosilane monolayer templates: an experimental study on the anti-adhesion effect of green-tea catechins.

The main constituent of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG), is known to have cancer-specific chemopreventive effects. In the present work, we investigated how EGCG suppresses cell adhesion by comparing the adhesion of human pancreatic cancer cells (AsPC-1 and BxPC-3) and their counterpart, normal human embryonic pancreas-derived cells (1C3D3), in catechin-containing media using organosilane monolayer templates (OMTs). The purpose of this work is (1) to evaluate the quantitativeness in the measurement of cell adhesion with the OMT and (2) to show how green-tea catechins suppress cell adhesion in a cancer-specific manner. For the first purpose, the adhesion of cancer and normal cells was compared using the OMT. The cell adhesion in different type of catechins such as EGCG, (-)-Epicatechin-3-O-gallate (ECG) and (-)-Epicatechin (EC) was also evaluated. The measurements revealed that the anti-adhesion effect of green-tea catechins is cancer-specific, and the order is EGCG≫ECG>EC. The results agree well with the data reported to date, showing the quantitativeness of the new method. For the second purpose, the contact area of cells on the OMT was measured by reflection interference contrast microscopy. The cell-OMT contact area of cancer cells decreases with increasing EGCG concentration, whereas that of normal cells remains constant. The results reveal a twofold action of EGCG on cancer cell adhesion-suppressing cell attachment to a candidate adhesion site and decreasing the contact area of the cells-and validates the use of OMT as a tool for screening cancer cell adhesion.

MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell-Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages.

Secretion of the powerful angiogenic factor MFG-E8 by pericytes can bypass the therapeutic effects of anti-VEGF therapy, but the mechanisms by which MFG-E8 acts are not fully understood. In this study, we investigated how this factor acts to promote the growth of melanomas that express it. We found that mouse bone marrow-derived mesenchymal stromal cells (MSC) expressed a substantial amount of MFG-E8. To assess its expression from this cell type, we implanted melanoma cells and MSC derived from wild type (WT) or MFG-E8 deficient [knockout (KO)] into mice and monitored tumor growth. Tumor growth and M2 macrophages were each attenuated in subjects coimplanted with KO-MSC compared with WT-MSC. In both xenograft tumors and clinical specimens of melanoma, we found that MFG-E8 expression was heightened near blood vessels where MSC could be found. Through in vitro assays, we confirmed that WT-MSC-conditioned medium was more potent at inducing M2 macrophage polarization, compared with KO-MSC-conditioned medium. VEGF and ET-1 expression in KO-MSC was significantly lower than in WT-MSC, correlating in vivo with reduced tumor growth and numbers of pericytes and M2 macrophages within tumors. Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283-92. ©2016 AACR.

Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia-reperfusion injury.

Ischaemia-reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. However, there is no evidence-based treatment for early-stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31(+) vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68(+) macrophages and the level of transforming growth factor-beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress-induced tissue damage. Topical steroids might not be recommended for the treatment of acute-phase decubitus ulcers.