AI Analysis of General Medicine in Japan: Present and Future Considerations.

This paper presents an interpretation of artificial intelligence (AI)-generated depictions of the present and future of general medicine in Japan. Using text inputs, the AI tool generated fictitious images based on neural network analyses. We believe that our study makes a significant contribution to the literature because the direction of general medicine in Japan has long been unclear, despite constant discussion. Our AI analysis shows that Japanese medicine is currently plagued by issues with polypharmacy, likely because of the aging patient population. Additionally, the analysis indicated a distressed female physician and evoked a sense of anxiety about the future of female physicians. It discusses whether the ability to encourage the success of female physicians is a turning point for the future of medicine in Japan.

Dental Care to Reduce Aspiration Pneumonia Recurrence: A Prospective Cohort Study.

BACKGROUND: Aspiration pneumonia has a high recurrence rate, and oral care by dentists has been found effective in preventing its onset; however, this has not been evaluated using prospective studies. Therefore, we conducted a prospective study to evaluate the effectiveness of professional oral care by dentists in reducing aspiration pneumonia recurrence in older adult patients. METHODS: In this prospective cohort study, we evaluated a dental oral care intervention, using a historical control group (control group). It was conducted at a single-centre regional core hospital in Japan that serves a large number of patients aged older than 80 years. Patients who were hospitalised for aspiration pneumonia were included in this study. During the study period (1 April 2021 to 31 March 2022), the clinical group received weekly professional cleaning by a dentist and the control group received standard oral care by a nurse as usual from 1 April 2020 to 31 March 2021. The dentist oral care group received weekly professional oral care from a dentist and was followed prospectively for 1 year. A Kaplan-Meier analysis was used to evaluate the timing of recurrent aspiration pneumonia or death. A Cox proportional hazards model was used to obtain a hazard ratio and determine the 95% confidence intervals. RESULTS: There were 91 participants in the clinical group and 94 in the control group. The mean age of participants was 85 years, and 75 (40.5%) were female. The recurrence rate was 27.5% in the clinical group and 44.7% in the control group (P = .005). Professional cleaning by a dentist reduced the risk of recurrence of aspiration pneumonia by approximately 50% (adjusted hazard ratio, 0.465; 95% confidence interval, 0.278-0.78). CONCLUSIONS: Professional cleaning by a dentist was associated with a lower rate of aspiration pneumonia recurrence than nurse-provided conventional oral care.

Dietary Intake in Older Patients with Dementia Prior to and After the Onset of Coronavirus Disease 2019.

This was an observational study of hospitalized patients with dementia who developed COVID-19. The disease course, dietary intake, and disease severity (mild/severe) were evaluated. Twenty-nine patients with a median age of 84 years, with both mild (18) and severe conditions, (11) were evaluated. Mild group had decreased food intake from the day of symptom onset. In the severe group, the decline began the day before symptom onset. On day 30 of the disease, the median food intake of the mild group returned to levels observed prior to symptom onset, in contrast to those in the severe group.

Association between serum uric acid levels and achievement of target blood pressure among Japanese community residents with hypertension.

The authors examined the sex-specific association between serum uric acid (SUA) levels and achievement of target blood pressure among Japanese patients with hypertension. This cross-sectional study was conducted between January 2012 and December 2015 and examined 17 113 eligible participants (6499 men; 10 614 women) with hypertension among 66 874 Japanese community residents who underwent voluntary health checkups. Multivariate analysis was used to estimate the association between high SUA level (≥7.0 mg/dL for men and ≥6.0 mg/dL for women) and "therapeutic failure" in achieving target blood pressure (BP) of 140/90 and 130/80 mmHg in both sexes. Multivariate analysis revealed that high SUA level was significantly associated with failure to achieve the 130/80 mmHg treatment goal among men (AOR = 1.24, 95% CI = 1.03-1.50, p = .03). Among women, high SUA level was significantly associated with failure to achieve both the 130/80 and 140/90 mmHg treatment goals (AOR = 1.33, 95% CI = 1.20-1.47, p < .01 and AOR = 1.17, 95% CI = 1.04-1.32, p < .01, respectively). Each increase in SUA quartile was positively associated with increases in systolic BP (SBP) and diastolic BP (DBP) (p < .01 for trend) in both sexes. SBP and DBP in each quartile (Q2-Q4) were also significantly higher compared with those of Q1 in both sexes (p < .01). Our data confirms the difficulties in maintain goal BP control in those with elevated SUA.

Achievement of target blood pressure among community residents with hypertension and factors associated with therapeutic failure in the northern territory of Japan.

OBJECTIVE: This study aimed to determine the rate of achieving the target blood pressure (BP) defined by Japanese hypertension management guidelines and to examine factors associated with achieving the target BP. METHODS: This cross-sectional study, which was conducted between January 2012 and December 2015, examined the BP control status and associated factors among 9,016 Japanese community residents with hypertension. Residents were divided into the following six groups: G1, young, middle-aged, and early-phase elderly patients; G2, patients with cerebrovascular disease; G3, patients with coronary artery disease; G4, patients with chronic kidney disease with proteinuria; G5, patients with diabetes; and G6, patients with chronic kidney disease without proteinuria. BP target achievement rates were calculated for each group. A multivariate analysis identified factors associated with "therapeutic failure" of target BP. RESULTS: The target BP was achieved by 52.6% participants in G1, 84.3% in G2, 50.6% in G3, 45.6% in G4, 48.7% in G5, and 75.0% in G6. The body mass index and receiving antilipidemic medication were associated with therapeutic failure. CONCLUSION: This study shows that achievement rates for treatment goals among Japanese patients with hypertension are still low. Body mass index and treatment of dyslipidemia may be associated with the control of BP.

Paragonimus westermani as a cause of Löeffler's syndrome.

In 1936, Löeffler first recognized the association between a distinctive form of severe heart failure and marked eosinophilia. Most cases are caused by either parasitic infections or drugs; however, no cause has been identified in one-third of the patients [1]. This report presents a rare case of Löeffler's syndrome caused by the parasite Paragonimus westermani.

Polymyalgia Rheumatica in a Patient with Pseudogout and Dementia.

BACKGROUND The differential diagnosis of generalized pain includes reactivity associated with bacterial and viral infections, autoimmune rheumatic disease, and orthopedic diseases. Obtaining a detailed medical history and establishing an accurate diagnosis are difficult in elderly patients with dementia. In addition, the differential diagnosis between polymyalgia rheumatica and pseudogout is often difficult. Thus, in our work, we examined the importance of interviewing the family of an elderly patient with dementia. CASE REPORT We report the case of an 88-year-old woman with dementia and a history of recurrent pseudogout who presented with a 12-day history of fever and generalized pain. Physical examination findings revealed warmth and swelling in the shoulder joints and right knee. Blood tests indicated increased inflammatory marker levels. The primary working impression was oligo-articular pseudogout. Based on family interview, the patient was seen to manifest atypical symptoms, including movement difficulty. Joint ultrasound findings showed inflammation of the left long head of the biceps attachment. Further, right knee arthrocentesis detected no calcium pyrophosphate crystals. After obtaining a detailed medical history from the patient's family and conducting other diagnostic tests, the patient was finally diagnosed with polymyalgia rheumatica, rather than oligo-articular pseudogout, with rapid improvement after undergoing low-dose prednisolone treatment. CONCLUSIONS Family interviews can be helpful for obtaining correct diagnosis in elderly patients with dementia.

Pembrolizumab-related systemic myositis involving ocular and hindneck muscles resembling myasthenic gravis: a case report.

BACKGROUND: Pembrolizumab is an immune-checkpoints inhibitor that enhances the immune response against cancer cells and therefore is useful for the treatment of several carcinomas. However, pembrolizumab sometimes perturbs the immune system resulting in various autoimmune neurological complications. In this situation, autoimmune myositis due to pembrolizumab is a rare but not-negligible complication. Here, we report two cases of autoimmune myositis due to pembrolizumab, with systemic myositis involving levator palpebrae superioris, extraocular and hindneck muscles. CASE PRESENTATION: Case 1 was a 78-year-old man with advanced urinary cancer referred to the neurological ward presenting with bilateral ptosis, restriction of eye movements, dropped head and weakness in the lower extremities after pembrolizumab administration. His blood examination showed elevated serum levels of creatine kinase with positive anti-PM-Scl 75 and anti-signal recognition particle antibodies. Needle electromyography and MRI suggested systemic inflammatory myopathy. There were no findings to indicate myocardial involvement on electrocardiogram or echocardiogram. Administration of intravenous methylprednisolone following plasma exchange ameliorated creatine kinase levels and inhibited the progression of clinical symptoms. Case 2 was a 72-year-old female with lung cancer and multiple metastasis, including lymph nodes and brain. She presented with back pain, right-sided ptosis, weakness of her neck extensors and flexors and elevated serum creatine kinase after receiving pembrolizumab. Although myositis specific autoantibodies were negative, needle electromyography and MRI suggested systemic inflammatory myopathy and muscle biopsy indicated necrotizing myopathy. There were no signs indicating heart dysfunction and her electrocardiogram was normal. Clinical symptoms and serum creatine kinase levels were ameliorated after the administration of intravenous methylprednisolone. CONCLUSIONS: Both cases showed atypical extensive inflammatory myositis including levator palpebrae superioris, extraocular and hindneck muscles, resembling myasthenia gravis (MG), but they did not have MG-related antibodies. Edrophonium test was negative and showed no daily fluctuation. Two previously reported cases also presented with systemic necrotizing systemic myositis involving extraocular and facial muscles caused by pembrolizumab. Idiopathic inflammatory myositis evolving levator palpebrae superioris and ocular muscles is quite rare; however, myositis due to immune-checkpoint inhibitors may preferentially involve these muscles. This case report will alert physicians to the possibility of systemic inflammatory myopathy evolving levator palpebrae superioris, extraocular and hindneck muscles mimicking MG due to pembrolizumab.

The Interrelationship between Abscisic Acid and Reactive Oxygen Species Plays a Key Role in Barley Seed Dormancy and Germination.

Seed dormancy is one of the adaptive responses in the plant life cycle and an important agronomic trait. Reactive oxygen species (ROS) release seed dormancy and promote seed germination in several cereal crops; however, the key regulatory mechanism of ROS-mediated seed dormancy and germination remains controversial. Here, we focused on the relationship between hydrogen peroxide (a ROS) and abscisic acid (ABA) in dormant and non-dormant barley seeds. The hydrogen peroxide (H2O2) level produced in barley seed embryos after imbibition was higher in non-dormant seeds than in dormant seeds. H2O2 regulated the ABA content in the embryos through ABA-8'-hydroxylase, an ABA catabolic enzyme. Moreover, compared with non-dormant seeds, in dormant seeds the activity of NADPH oxidase, which produces ROS, was lower, whereas the activity of catalase, which is a H2O2 scavenging enzyme, was higher, as was the expression of HvCAT2. Furthermore, precocious germination of isolated immature embryos was suppressed by the transient introduction of HvCAT2 driven by the maize (Zea mays) ubiquitin promoter. HvCAT2 expression was regulated through an ABA-responsive transcription factor (HvABI5) induced by ABA. These results suggest that the changing of balance between ABA and ROS is active in barley seed embryos after imbibition and regulates barley seed dormancy and germination.

Role of reactive oxygen species produced by NADPH oxidase in gibberellin biosynthesis during barley seed germination.

NADPH oxidase catalyzes the production of the superoxide anion (O2(-)), a reactive oxygen species (ROS), and regulates the germination of barley (Hordeum vulgare L.). Diphenyleneiodonium (DPI) chloride, an NADPH oxidase inhibitor, delayed barley germination, and exogenous H2O2 (an ROS) partially rescued it. Six enzymes, ent-copalyl diphosphate synthase (CPS), ent-kaurene synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA20-oxidase (GA20ox) and GA3-oxidase (GA3ox), catalyze the transformation of trans-geranylgeranyl diphosphate to active gibberellin, which promotes germination. Exogenous H2O2 promoted the expressions of HvKAO1 and HvGA3ox1 in barley embryos. These results suggest that ROS produced by NADPH oxidase are involved in gibberellin biosynthesis through the regulation of HvKAO1 and HvGA3ox1.

A Role for Reactive Oxygen Species Produced by NADPH Oxidases in the Embryo and Aleurone Cells in Barley Seed Germination.

Reactive oxygen species (ROS) promote the germination of several seeds, and antioxidants suppress it. However, questions remain regarding the role and production mechanism of ROS in seed germination. Here, we focused on NADPH oxidases, which produce ROS. After imbibition, NADPH oxidase mRNAs were expressed in the embryo and in aleurone cells of barley seed; these expression sites were consistent with the sites of ROS production in the seed after imbibition. To clarify the role of NADPH oxidases in barley seed germination, we examined gibberellic acid (GA) / abscisic acid (ABA) metabolism and signaling in barley seeds treated with diphenylene iodonium chloride (DPI), an NADPH oxidase inhibitor. DPI significantly suppressed germination, and suppressed GA biosynthesis and ABA catabolism in embryos. GA, but not ABA, induced NADPH oxidase activity in aleurone cells. Additionally, DPI suppressed the early induction of α-amylase by GA in aleurone cells. These results suggest that ROS produced by NADPH oxidases promote GA biosynthesis in embryos, that GA induces and activates NADPH oxidases in aleurone cells, and that ROS produced by NADPH oxidases induce α-amylase in aleurone cells. We conclude that the ROS generated by NADPH oxidases regulate barley seed germination through GA / ABA metabolism and signaling in embryo and aleurone cells.

A case of Trousseau syndrome caused by pulmonary adenocarcinoma that was controlled for one year and 10 months with thrombosis treatment using an EGFR tyrosine kinase inhibitor and chemotherapy.

A 47-year-old female with no history of previous illnesses developed cerebral infarction and was diagnosed with lung cancer, specifically EGFR mutation-positive adenocarcinoma, and Trousseau syndrome. The patient's response to anticoagulant therapy with non-fractionated heparin was very poor; however we were able to control the thrombosis with chemotherapy. She survived for one year and 10 months following treatment with gefitinib, CBDCA + PEM and erlotinib, without recurrence of thrombosis. Trousseau syndrome carries a poor prognosis and controlling thrombosis is difficult. In this case, the administration of anticancer therapy allowed use to control the patient's thrombosis. Therefore, this case highlights the importance of treating cancer in patients with Trousseau syndrome. In addition, the FDP and D-dimer levels changed in parallel with changes in the CEA level, which suggests that the activity of cancer is related to an internal thrombotic tendency. Hence, changes in the FDP and D-dimer values are associated with the efficacy of treatment with EGFR tyrosine kinase inhibitors and chemotherapy and may function as markers of recurrence.

Programmed cell death in barley aleurone cells is not directly stimulated by reactive oxygen species produced in response to gibberellin.

The cereal aleurone layer is a secretory tissue that produces enzymes to hydrolyze the starchy endosperm during germination. We recently demonstrated that reactive oxygen species (ROS), produced in response to gibberellins (GA), promoted GAMyb expression, which induces α-amylase expression in barley aleurone cells. On the other hand, ROS levels increase during programmed cell death (PCD) in barley aleurone cells, and GAMyb is involved in PCD of these cells. In this study, we investigated whether the ROS produced in response to GA regulate PCD directly by using mutants of Slender1 (SLN1), a DELLA protein that negatively regulates GA signaling. The wild-type, the sln1c mutant (which exhibits gibberellin-type signaling even in the absence of GA), and the Sln1d mutant (which is gibberellin-insensitive with respect to α-amylase production) all produced ROS in response to GA, suggesting that ROS production in aleurone cells in response to GA is independent of GA signaling through this DELLA protein. Exogenous GA promoted PCD in the wild-type. PCD in sln1c was induced even without exogenous GA (and so without induction of ROS), whereas PCD in Sln1d was not induced in the presence of exogenous GA, even though the ROS content increased significantly in response to GA. These results suggest that PCD in barley aleurone cells is not directly stimulated by ROS produced in response to GA but is regulated by GA signaling through DELLA protein.

Reactive oxygen species are involved in gibberellin/abscisic acid signaling in barley aleurone cells.

Reactive oxygen species (ROS) act as signal molecules for a variety of processes in plants. However, many questions about the roles of ROS in plants remain to be clarified. Here, we report the role of ROS in gibberellin (GA) and abscisic acid (ABA) signaling in barley (Hordeum vulgare) aleurone cells. The production of hydrogen peroxide (H2O2), a type of ROS, was induced by GA in aleurone cells but suppressed by ABA. Furthermore, exogenous H2O2 appeared to promote the induction of α-amylases by GA. In contrast, antioxidants suppressed the induction of α-amylases. Therefore, H2O2 seems to function in GA and ABA signaling, and in regulation of α-amylase production, in aleurone cells. To identify the target of H2O2 in GA and ABA signaling, we analyzed the interrelationships between H2O2 and DELLA proteins Slender1 (SLN1), GA-regulated Myb transcription factor (GAmyb), and ABA-responsive protein kinase (PKABA) and their roles in GA and ABA signaling in aleurone cells. In the presence of GA, exogenous H2O2 had little effect on the degradation of SLN1, the primary transcriptional repressor mediating GA signaling, but it promoted the production of the mRNA encoding GAMyb, which acts downstream of SLN1 and involves induction of α-amylase mRNA. Additionally, H2O2 suppressed the production of PKABA mRNA, which is induced by ABA:PKABA represses the production of GAMyb mRNA. From these observations, we concluded that H2O2 released the repression of GAMyb mRNA by PKABA and consequently promoted the production of α-amylase mRNA, thus suggesting that the H2O2 generated by GA in aleurone cells is a signal molecule that antagonizes ABA signaling.

Pioglitazone, a peroxisome proliferator-activated receptor gamma ligand, suppresses bleomycin-induced acute lung injury and fibrosis.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands have been shown to possess potent anti-inflammatory actions. Idiopathic interstitial pneumonia is defined as a specific form of chronic fibrosing lung disease characterized by progressive fibrosis which leads to deterioration and destruction of the lungs. OBJECTIVE: To investigate whether the PPARgamma ligand pioglitazone (PGZ) inhibited bleomycin (BLM)-induced acute lung injury and subsequent fibrosis. METHODS: BLM was administered intratracheally to Wistar rats which were then treated with PGZ. Rat alveolar macrophages were stimulated with BLM for 6 h with or without PGZ pretreatment for 18 h. MRC-5 cells (human lung fibroblasts) were treated with PGZ for 18 h. After the treatment, the cells were stimulated with transforming growth factor- beta (TGF-beta) for 6 h. RESULTS: PGZ inhibited BLM-induced acute lung injury and subsequent lung fibrosis when it was administered from day -7. PGZ treatment suppressed the accumulation of inflammatory cells in lungs and the concentration of tumor necrosis factor-alpha (TNF-alpha) in bronchoalveolar lavage fluid on day 3. PGZ also inhibited BLM-induced TNF-alpha production in alveolar macrophages. Furthermore, PGZ inhibited fibrotic changes and an increase in hydroxyproline content in lungs after instillation of BLM, even when PGZ was administered in the period from day 7 to day 28. Northern blot analyses revealed that PGZ inhibited TGF-beta-induced procollagen I and connective tissue growth factor (CTGF) expression in MRC-5 cells. CONCLUSION: These results suggest that activation of PPARgamma ameliorates BLM-induced acute inflammatory responses and fibrotic changes at least partly through suppression of TNF-alpha, procollagen I and CTGF expression. Beneficial effects of this PPARgamma ligand on inflammatory and fibrotic processes open new perspectives for a potential role of PPARgamma as a molecular target in fibroproliferative lung diseases.

[Case of HLA-DR8 positive sarcoidosis following polymyositis and Sjögren's syndrome].

A 69-year-old woman had been found to have idiopathic interstitial pneumonia (fibrotic NSIP) in 1997. Proximal muscle weakness appeared in April 2005. Chest CT revealed hilar and mediastinal lymphadenopathy. Polymyositis and Sjögren's syndrome were subsequently diagnosed. We assumed that the interstitial pneumonia had preceded polymyositis and Sjögren's syndrome. A muscle biopsy and transbronchial needle aspiration biopsy demonstrated noncaseating epithelioid cell granulomas. A diagnosis of sarcoidosis complicated with polymyositis and Sjögren's syndrome was made from these findings. Moreover, her HLA genotype contained DR8. HLA-DR8 is considered to be associated with polymyositis, Sjögren's syndrome, and sarcoidosis in Japanese patients. This case suggests the possibility that there are common immunological and genetical pathogenetic mechanisms in autoimmune diseases and sarcoidosis.

[Case of allergic bronchopulmonary aspergillosis successfully treated with itraconazole].

A 58-year-old woman had a productive cough but not from bronchial asthma. A chest radiograph revealed infiltrative shadows in right middlelung field on September, 2004. Aspergillus fumigatus was detected in a sputum culture. She was treated with oral itraconazole. After the treatment, infiltrative shadows on her chest radiograph disappeared. On October 2005, her peripheral blood showed eosinophilla, a high serum level of total immunoglobulin E (IgE), and a chest radiograph revealed new infiltrative shadows in both lung fields. A chest computed tomography revealed multiple nodular shadows and central bronchiectasis. We detected a mucoid plug which showed a large number of eosinophils pathologically by bronchoscopy. Aspergillus niger was detected in a bronchial lavage fluid. We therefore made a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The decreases of peripheral blood eosinophils and a serum IgE level were recognized and multiple nodular shadows disappeared by reinstitution of itraconazole. However, a chest computed tomography revealed new infiltrative shadows. Therefore, we treated her with the concomitant administration of oral itraconazole and inhaled corticosteroid. All laboratory data and image findings were improved. It is critical to consider the both aspects of allergy and infection in the treatment for ABPA.

[A case of miliary tuberculosis showing acute respiratory failure during pregnancy].

A 36-year-old Philippine woman had had fever and general fatigue from September, 2006 (11th week of pregnancy). She was admitted with high fever, general fatigue and dyspnea on October 16, 2006 (13th week of pregnancy). A chest radiograph on admission showed bilateral miliary shadows and ground glass shadows. She already had severe hypoxia on admission. As acid-fast bacilli were positive in urine (Gaffky 8) and sputum (Gaffky 1), we diagnosed as miliary tuberculosis and pulmonary tuberculosis complicated with acute respiratory distress syndrome (ARDS). We treated her with antituberculosis chemotherapy, corticosteroid, sivelestat sodium hydrate, direct hemoperfusion using a polymyxin B immobilized column, and mechanical ventilation, but she died due to respiratory failure. We emphasize that in this case pregnancy has the risk of to causing disease progression of miliary tuberculosis and we should treat immediately and intensively for miliary tuberculosis complicated with ARDS.