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The Kobe Journal Of Medical Sciences[JOURNAL]

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Effect of Bisphosphonate and Active Vitamin D Analog on Glucocorticoid-induced Osteoporosis in Patients with IgA Nephropathy: A Retrospective Observational Study.

Takiguchi R, Nishi S, Goto S … +1 more , Fujii H

Kobe J Med Sci · 2023 Apr · PMID 37088694

Few studies on glucocorticoid (GC)-induced osteoporosis exist in IgA nephropathy (IgAN). Here we aimed to compare the effects of bisphosphonate (Bis) and active vitamin D analog (Vit. D) in maintaining bone mineral densi... Few studies on glucocorticoid (GC)-induced osteoporosis exist in IgA nephropathy (IgAN). Here we aimed to compare the effects of bisphosphonate (Bis) and active vitamin D analog (Vit. D) in maintaining bone mineral density (BMD) in patients with IgAN. This study is a retrospective observational one. Between April 2007 and December 2014, a total of 127 patients with IgAN received GC treatment at Kobe University Hospital. Among them, we measured the BMD of 48 patients with a mean age of approximately 30 years, before and after GC treatment. The %ΔBMD of the lumber spine increased in the Bis group (1.6% ± 2.3%), but decreased in the Vit. D group (-3.3% ± 3.6%). The %ΔBMD of the two groups differed significantly (p < 0.05). Although the %ΔBMD of the femoral neck showed the same tendency, the difference between two groups was not significant. Bis was significantly superior to Vit. D in maintaining the BMD of lumbar spine bones. Even in young patients with IgAN, Bis is recommended to prevent the reduction of BMD during GC treatment.

Chlorogenic Acid and Caffeine in Coffee Restore Insulin Signaling in Pancreatic Beta Cells.

Ihara Y, Asahara SI, Inoue H … +5 more , Seike M, Ando M, Kabutoya H, Kimura-Koyanagi M, Kido Y

Kobe J Med Sci · 2023 Mar · PMID 37088693

The incidence of type 2 diabetes is reported to be lower in frequent coffee drinkers than in non-coffee drinkers. To elucidate the mechanism by which coffee prevents the onset of type 2 diabetes, we analyzed how caffeine... The incidence of type 2 diabetes is reported to be lower in frequent coffee drinkers than in non-coffee drinkers. To elucidate the mechanism by which coffee prevents the onset of type 2 diabetes, we analyzed how caffeine and chlorogenic acid, which are components of coffee, alter insulin signaling in MIN6 cells, a mouse pancreatic Β cell line. The results showed that caffeine improved insulin signaling under endoplasmic reticulum stress, and chlorogenic acid protected pancreatic Β cells by enhancing the expression of insulin receptor substrate 2 via cAMP response element-binding protein and promoting insulin signaling downstream of insulin receptor substrate 2. In addition, chlorogenic acid was a potent antioxidant for the protection of pancreatic Β cells. Furthermore, in vivo and in vitro analyses revealed that the pancreatic Β cell-protective effect of chlorogenic acid was mediated by the alleviation of endoplasmic reticulum stress. The results suggest that these components of coffee have the potential to reduce the pathogenesis of type 2 diabetes and improve pancreatic Β cell insufficiency.

Successful Management of Refractory Autoimmune Hemolytic Anemia with Cold Agglutinin Disease with Splenectomy: A Case Report with Review of Literature.

Okamoto S, Urade T, Yakushijin K … +11 more , Kido M, Kuramitsu K, Komatsu S, Gon H, Yamashita H, Shirakawa S, Tsugawa D, Terai S, Yanagimoto H, Toyama H, Fukumoto T

Kobe J Med Sci · 2023 Jan · PMID 36647084

BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by agglutination of red blood cells at temperatures below the normal core body temperature. In patients with CAD, splenectomy... BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by agglutination of red blood cells at temperatures below the normal core body temperature. In patients with CAD, splenectomy is not indicated because of its low therapeutic effect on hemolytic anemia induced by extravascular hemolysis. Herein, we report a case of refractory hemolytic anemia with CAD successfully managed with splenectomy. CLINICAL CASE: A 60-year-old man visited a municipal hospital with the chief complaint of fatigue. He was found to have hemolytic anemia and icterus with increased cold agglutination and was diagnosed with CAD. Malignant lymphoma was suspected as the underlying disease; however, no clear underlying disease was identified. Hemolytic anemia progressed during the subsequent winter seasons, and he was treated with temperature control, warming, and weekly blood transfusions. However, despite the blood transfusions, his hemoglobin level did not improve during the summer 2 years after diagnosis, and his previously observed splenomegaly had progressed. He was referred to our department, and a splenectomy was performed to diagnose any occult malignant lymphoma and improve the refractory hemolytic anemia. Because histopathological examination revealed no evidence of malignant lymphoma, a diagnosis of primary CAD was made. The hemolytic anemia improved, and no blood transfusion was required after splenectomy. CONCLUSIONS: Splenectomy significantly improved the patient's refractory hemolytic anemia due to primary CAD. Thus, it may be an effective treatment option in such cases, although further cases and studies are required to evaluate the effects of splenectomy.

Increase in the Number and Duration of Sleep Episodes During Class After Reopening of Schools Following Closure due to COVID-19.

Kimura S, Takaoka Y, Sugano A

Kobe J Med Sci · 2022 Dec · PMID 36647083

Sleep is important for the well-being of school-aged children. Almost all schools in Hyogo prefecture in Japan were closed from April 7 to May 31, 2020, owing to the coronavirus disease 2019 pandemic. The pandemic restri... Sleep is important for the well-being of school-aged children. Almost all schools in Hyogo prefecture in Japan were closed from April 7 to May 31, 2020, owing to the coronavirus disease 2019 pandemic. The pandemic restrictions resulted in the disruption of the sleep routines of children. The number of children who experienced sleepiness in class after school closure increased. The number of children who visited our hospital 1 year before and after the closure was 208 (11.73 ± 3.24 years of age) and 155 (11.45 ± 3.30 years), respectively. The number of chief complaints of sleep-related symptoms at the first visits showed no significant difference between the two time periods. The percentage of patients who slept during class increased (but not significantly) after the school closure. However, the mean number and duration of sleep episodes during class significantly increased from 0.31 ± 0.76 to 1.04 ± 1.14 episodes/day and from 15.8 ± 38.6 to 45.7 ± 46.9 min/day (each P < 0.001) before and after school closure, respectively. The total number of patients in our hospital with the primary central disorders of hypersomnolence, i.e., narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome, and the number of patients with insufficient sleep syndrome after the school closure significantly increased compared with those before closure (P = 0.034 and 0.048, respectively). School closure was associated with an increased incidence of sleeping during class; therefore, maintaining a stable daily routine for children with sleep disorders could have an alleviating effect.

Longitudinal Changes and Features of Sleep Patterns of Mothers with Preterm Infants during the Early Postpartum Period.

Toda Miyano M, Yasuda H, Takada S

Kobe J Med Sci · 2022 Dec · PMID 36647082

This study comprised 13 mothers of preterm infants and 21 mothers of term infants. Sleep assessment was conducted using an actigraph for three consecutive days. The participants were asked to record their sleep behaviors... This study comprised 13 mothers of preterm infants and 21 mothers of term infants. Sleep assessment was conducted using an actigraph for three consecutive days. The participants were asked to record their sleep behaviors and activities over these 3 days, and complete two questionnaires (Edinburgh Postnatal Depression Scale [EPDS] and Pittsburgh Sleep Quality Index [PSQI]). As compared to the mothers of term infants, the sleep efficiency in the preterm mothers was significantly lower than that in the term mothers. The total sleep time was shorter and nighttime awakenings were more frequent in the preterm mothers at 2 weeks after childbirth, but without a significant difference. We analyzed the changes in the sleep data of the mothers of preterm infants longitudinally, including sleep behaviors and the EPDS and PSQI scores. The total sleep time at 1 month postpartum was shorter than that at other periods, and significantly shorter than that at 2 weeks and 6 months postpartum. Our results suggested that sleep problems tended to last longer in mothers of preterm infants than in mothers of term infants, as the problems occurred twice, immediately after childbirth and immediately after discharge.

Accuracy of a Professional Continuous Glucose Monitoring Device in Individuals with Type 2 Diabetes Mellitus.

Nakagawa Y, Hirota Y, Yamamoto A … +6 more , Takayoshi T, Takeuchi T, Hamaguchi T, Matsuoka A, Sakaguchi K, Ogawa W

Kobe J Med Sci · 2022 Oct · PMID 36647081

Among continuous glucose monitoring (CGM) devices, which continuously measure glucose concentration in subcutaneous interstitial fluid for comprehensive monitoring of blood glucose profile, only FreeStyle Libre Pro® (Abb... Among continuous glucose monitoring (CGM) devices, which continuously measure glucose concentration in subcutaneous interstitial fluid for comprehensive monitoring of blood glucose profile, only FreeStyle Libre Pro® (Abbott Diabetes Care) is currently available in Japan as a professional system. FreeStyle Libre Pro® is easy to use because it does not require calibration by self-monitoring of blood glucose (SMBG), but information on its accuracy has been insufficient. To evaluate the measurement accuracy of FreeStyle Libre Pro®, we have now compared blood glucose levels determined by this device with those measured by SMBG in 40 individuals with type 2 diabetes mellitus. The mean absolute relative difference (MARD) for FreeStyle Libre Pro® measurements compared with SMBG measurements was calculated as an index of CGM accuracy. Overall blood glucose values measured by SMBG were 167.0 ± 60.1 mg/dL, and those determined by FreeStyle Libre Pro® were 155.0 ± 60.7 mg/dL, with this difference being statistically significant. The MARD for FreeStyle Libre Pro® relative to SMBG was 12.7 ± 9.3%. It was substantially higher in 2 of the 40 patients, at 49.2% and 47.5%, than in the other 38 individuals. MARD values did not differ significantly between before and 2 h after meals. However, the MARD was significantly higher for SMBG values of <100 mg/dL than for those of ≥250 mg/dL. Our results thus indicate that the measurement accuracy of FreeStyle Libre Pro® is relatively good, but that some cases in which values determined by the device deviate from SMBG values require caution in interpretation.

A Case with Iron Deficiency Anemia Developed Aplastic Crisis.

Iketani K, Minamikawa S, Sakata M … +2 more , Ishida Y, Nakagishi Y

Kobe J Med Sci · 2022 Jul · PMID 36647080

A toddler with an unbalanced diet and gastrointestinal bleeding by juvenile polyp developed an aplastic crisis due to the human parvovirus B19 (HPVB19). Although he exhibited microcytic anemia without iron deficiency in... A toddler with an unbalanced diet and gastrointestinal bleeding by juvenile polyp developed an aplastic crisis due to the human parvovirus B19 (HPVB19). Although he exhibited microcytic anemia without iron deficiency in the acute phase of HPVB19 infection, he presented with iron deficiency anemia (IDA) in the chronic phase. IDA results in erythroblast hyperplasia and shortened red blood cell lifespan as like congenital hemolytic diseases, which may lead to an aplastic crisis during HPVB19 infection. It should be noted that iron deficiency is often masked, and microcytic anemia may be a clue for IDA.

Behavioral Therapy for Children with Avoidant/Restrictive Food Intake Disorder Dependent on Tube or Oral Enteral Nutrient Formula: A Feasibility Study.

Tomioka K, Nishiyama M, Tokumoto S … +3 more , Yamaguchi H, Nozu K, Nagase H

Kobe J Med Sci · 2022 Mar · PMID 35368003

In children with eating disorders, nutritional status and growth may depend on enteral nutrient formula. Ultimately, its goal is to introduce or reintroduce oral feeding. Japanese research on the treatment of tube or ora... In children with eating disorders, nutritional status and growth may depend on enteral nutrient formula. Ultimately, its goal is to introduce or reintroduce oral feeding. Japanese research on the treatment of tube or oral formula-dependent children is scarce. This study determined the feasibility of behavioral therapy for children with avoidant/restrictive food intake disorder and dependency on the tube or oral enteral nutrient formula in Japan. Medical records of children diagnosed with this disorder, dependent on the tube or oral enteral nutrient formula and who had received behavioral therapy intervention to withdraw from the formula were retrospectively investigated. We collected their characteristics at first visit and the caloric percentage from oral food intake six months after starting the treatment. In total, four patients (age range: 2-5 years) participated in this study. The feeding routes employed before the intervention were a nasogastric tube for one patient, a gastrostomy bottom for the other patient, and oral formula for the remaining patients (i.e., two children). At the sixth month of the behavioral treatment, none of the patients needed the formula, and the caloric percentage of required nutrition from oral food intake was 100%. Our data demonstrate that this behavioral therapy is feasible for children with avoidant/restrictive food intake disorder dependent on the tube or oral formula in Japan.

Influence of Peripheral Arterial Disease on Wound Healing in Heel Pressure Ulcers.

Nishio Y, Tsuji Y, Kitano I … +1 more , Terashi H

Kobe J Med Sci · 2022 Feb · PMID 35368002

BACKGROUND: There are cases of heel pressure ulcer with peripheral arterial disease (PAD). The influence of ischemia on wound healing was investigated. METHODS: We retrospectively studied 253 patients with heel ulcers tr... BACKGROUND: There are cases of heel pressure ulcer with peripheral arterial disease (PAD). The influence of ischemia on wound healing was investigated. METHODS: We retrospectively studied 253 patients with heel ulcers treated between January 2003 and March 2018. The patients were classified into PAD and non-PAD groups. The wound healing rate, wound healing time and the factors that influenced wound healing were examined. RESULTS: There were 186 patients with PAD (73.5%). There were 41 (22.0%) and 35 (52.2%) wound healing cases with PAD and non-PAD, respectively (P < 0.001). In the non-PAD group, the deeper the ulcer, the lower the wound healing rate. However, in the PAD group, the increase in blood flow owing to revascularization affected the wound healing rate. The wound healing rate in the endovascular therapy (EVT) and bypass groups were 26.7% and 65.0%, respectively (P = 0.003). The wound healing time was 128 (interquartile range [IQR] 88-196) and 79 (IQR 35.5-187) days, with PAD and non-PAD, respectively (P = 0.0268). The wound healing time in the PAD group was 128 (IQR 93-174.5) days with bypass and 155.5 (IQR 86-237.5) days with EVT (P = 0.459). CONCLUSIONS: Heel pressure ulcers with PAD are difficult to treat. The wound healing rate was lower in the PAD than in the non-PAD group and the wound healing time also tended to be long. Successful revascularization is important for wound healing and bypass surgery had a shorter wound healing time and a higher wound healing rate than EVT.

ROS1-Rearranged Lung Cancer Successfully Resected after Response to Crizotinib: A Case Report.

Shimizu N, Tanaka Y, Tachihara M … +1 more , Maniwa Y

Kobe J Med Sci · 2022 Feb · PMID 35368001

The usefulness of molecularly targeted therapy as a preoperative therapy for the c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer has not been established. We present the case of ROS1- rearranged l... The usefulness of molecularly targeted therapy as a preoperative therapy for the c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer has not been established. We present the case of ROS1- rearranged lung cancer successfully resected after response to crizotinib. The patient was a 71-year-old woman with prolonged cough. She was diagnosed with ROS1-rearranged lung adenocarcinoma (cT4N2M0, stage IIIB). After eight weeks of crizotinib treatment, right upper lobectomy with chest wall resection, angioplasty, and bronchoplasty were performed. The postoperative course was good, and the patient survived for 41 months after the surgery without recurrence. Surgical resection after molecularly targeted therapy for ROS1-positive lung cancer may lead to good local control.

Correlation Between Changes in Syphilis Treatment and Jarisch-Herxheimer Reaction.

Yang YM, Shigemura K, Onishi R … +5 more , Maeda K, Sung SY, Chen KC, Arakawa S, Fujisawa M

Kobe J Med Sci · 2022 Jan · PMID 35368000

The number of syphilis patients has significantly increased recently in Japan and worldwide. Previous reports, even in large institutions, may not accurately reflect the current situation in urological clinics. We theref... The number of syphilis patients has significantly increased recently in Japan and worldwide. Previous reports, even in large institutions, may not accurately reflect the current situation in urological clinics. We therefore collected data from 11 urological clinics in Hyogo Prefecture, Japan over a 2-year period subdivided into 1) August 2016 to July 2017 and 2) August 2017 to July 2018 to compare changes in syphilis consults. We analyzed the patient data including a rapid plasma reagin test (RPR), Treponema pallidum (TP) antibody, clinical stage, therapy, and presence of Jarisch-Herxheimer reaction. In total, 45 patients presented for a first consultation, 22 in the first year and 23 in the second year. Almost all patients were male. Initial consolidation and hard chancre were the major symptoms. RPR values and TP antibody values did not change. The treatment period with amoxicillin was significantly longer in the first year (p = 0.006). A Jarisch-Herxheimer reaction was seen in 13.6% in the first year and 60.9% in the second year (p = 0.001). The duration of antibiotic treatments was more likely to be based on the guidelines for antibiotic use in the second year, but Jarisch-Herxheimer reactions increased. Further follow-up including recurrent patients is necessary to draw definitive conclusions.

Offering Neurofeedback as an Intervention for Children with Attention Deficit/Hyperactivity Disorder in Indonesia: A Feasibility Study.

Subandriyo APEP, Jongsma MLA, Wijaya DA … +6 more , Trisnadewi BAP, Paravoti A, Novihartanti BL, Widyorini E, Sulastri A, Breteler MHM

Kobe J Med Sci · 2021 Dec · PMID 35367999

BACKGROUND: EEG Neurofeedback training is an accepted non-pharmacological therapy for attention deficit/ hyperactivity disorder (ADHD). Although stimulant medication is known to decrease ADHD symptoms, possible adverse ef... BACKGROUND: EEG Neurofeedback training is an accepted non-pharmacological therapy for attention deficit/ hyperactivity disorder (ADHD). Although stimulant medication is known to decrease ADHD symptoms, possible adverse effects, concerns about prolonged drug use on neural development, and problems related to the compliance with the medications are often reported. In Indonesia, research on the feasibility of EEG Neurofeedback to treat ADHD is still lacking. The current study aimed to investigate whether setting up an EEG neurofeedback training program for children with ADHD would be feasible in Indonesia. METHODS: Nine children (aged 6-12 years) participated in the study. ADHD was diagnosed using the Vanderbilt ADHD Diagnostic Rating Scale (VADRS). Children received twenty-five sessions of sensorimotor rhythm (SMR) neurofeedback training twice a week. Each session consisted of a 3-minute baseline, followed by 5*3 minutes of training. IQ scores and VADRS scores were collected at baseline, after completion of the intervention, and at 3 months follow-up, while school reports were provided by the schools. The EEG spectral content was determined for all 25 training sessions. In addition, a Go/No-Go Task, was administered at the first 5 training sessions, and at session 10, 15, 20 and 25. RESULTS AND CONCLUSION: An overview of all the collected data is provided descriptively, given the small group size. One child dropped-out during the training because of parental request, but the remaining eight children completed the full intervention program. Descriptive data suggested improvement with respect to both the ADHD symptomatology and performance IQ. These findings are in line with previous studies. Although a control arm was not included, we propose that the abovementioned SMR neurofeedback protocol may still be offered as a suitable non-pharmacological intervention for children with ADHD in Indonesia and deserves further research.

An Investigation on the Consciousness of Patients and Pharmacists Regarding Inhaler Education.

Nakajima T, Nagano T, Hojo D … +1 more , Nishimura Y

Kobe J Med Sci · 2021 Dec · PMID 35367998

Few studies have focused on the awareness of inhaler education in patients and pharmacists who have crucial roles in inhaler education. The aim of this study was to investigate the difference in awareness of inhaler educ... Few studies have focused on the awareness of inhaler education in patients and pharmacists who have crucial roles in inhaler education. The aim of this study was to investigate the difference in awareness of inhaler education between patients and pharmacists. We conducted questionnaire-based surveys involving 270 patients with asthma and chronic obstructive pulmonary disease and 139 pharmacists of 13 pharmacies belonging to the same chain dispensing pharmacy in Hyogo prefecture of Japan in July 2011. We obtained valid responses from 230 patients (85.2%) and 139 pharmacists (100%). Although 75% of pharmacists provided inhaler education about the importance of continuation, only 16% of patients felt that they had learned the importance of continuation. Similarly, 95% of pharmacists provided inhaler education about the importance of gargling, however, only 57% of patients felt that they had learned the importance of gargling. This survey clarified the difference in awareness between pharmacists and patients on inhaler education. It proved to be difficult to educate patients on the importance of compliance and gargling.

Synbiotics Improved Stool Form via Changes in the Microbiota and Short-Chain Fatty Acids in Hemodialysis Patients.

Miyoshi M, Kadoguchi H, Usami M … +1 more , Hori Y

Kobe J Med Sci · 2021 Dec · PMID 35367997

Hemodialysis patients often develop constipation. We analyzed the advantage of synbiotics over prebiotics based on the stool form due to the intestinal environment in hemodialysis patients. Patients received either synbi... Hemodialysis patients often develop constipation. We analyzed the advantage of synbiotics over prebiotics based on the stool form due to the intestinal environment in hemodialysis patients. Patients received either synbiotics or prebiotics for four weeks. The synbiotics group was treated with partially hydrolyzed guar gum containing Bifidobacterium longum BB536, while the prebiotics group was treated with the same fiber alone. The defecation status was assessed using the Bristol Stool Form Scale and abdominal bloating was evaluated using a visual analog scale. The fecal microbiota, measured by a terminal restriction fragment length polymorphism analysis, and the fecal short-chain fatty acid concentrations, measured by gas chromatography, were compared between the two groups. Synbiotics ingestion improved the individual stool form and abdominal bloating, and increased Bifidobacterium, which produces short-chain fatty acid, 13.9-fold after ingestion. In particular, acetic acid increased 2.5-fold in the synbiotics group. On the other hand, butyric acid increased 3.0-fold in the prebiotics group. Synbiotics improved the stool form in hemodialysis patients due to the composition of the intestinal microbiota and short-chain fatty acid concentrations.

A Preliminary Investigation on the Antiviral Activities of the Philippine Marshmint (Mentha arvensis) Leaf Extracts against Dengue Virus Serotype 2 In Vitro.

Victoriano-Belvis AFB, Lao RG, Morato MKT … +4 more , Repotente ECT, Saclauso SA, Inovejas SAB, Matias RR

Kobe J Med Sci · 2021 Dec · PMID 35367996

In this study, we investigated the antiviral activity of lyophilized crude leaf extracts of the Philippine marshmint (Mentha arvensis L., commonly called yerba buena) against DENV-2 in vitro. The plant specimen was authe... In this study, we investigated the antiviral activity of lyophilized crude leaf extracts of the Philippine marshmint (Mentha arvensis L., commonly called yerba buena) against DENV-2 in vitro. The plant specimen was authenticated by DNA barcoding analysis using standard primers for amplification of rbcL, matK, ITS1, ITS2 and trnH-psbA. Aqueous, methanol and ethanol leaf extracts were prepared, and lyophilized prior to testing for its cytotoxicity and antiviral activities. All extracts presented cytotoxic activities against Vero cells in a dose-dependent manner. Half maximal cytotoxicity concentration (CC50) was calculated at 2,889.60 µg/mL for the aqueous extract, 1,928.62 µg/mL for the methanol extract, and 3,380.30 µg/mL for the ethanol extract. Antiviral activities assessed by plaque reduction assay revealed reduced DENV-2 viral infectivity, with the ethanol extract observed to have the strongest activity decreasing plaque numbers by 62% relative to the control. The methanol extract was observed to be most effective when added before infection causing 72% reduction in plaque numbers, whereas none of the extracts inhibited plaque formation by more than 40% when added after infection. DENV-2 NS1 antigen production was significantly reduced by the methanol extract, while viral RNA levels were also decreased as determined by real time RT-PCR. Phytochemical analysis revealed the presence of flavonoids, phenolics, tannins, proteins, reducing sugars and saponins. Our preliminary results are promising, however, it should be interpreted with caution as further studies are needed to establish its potential therapeutic application against dengue infection.

High-Velocity Nasal Insufflation Increases Nasopharyngeal Pressure with Flow-Dependent Manner Compared with High Flow Nasal Cannula in Adult Volunteers - A Single-Center Prospective Observational Study.

Miyazaki Y, Inoue S, Hirose H … +2 more , Kooguchi K, Kotani J

Kobe J Med Sci · 2021 Dec · PMID 35367995

BACKGROUND: High flow nasal cannula (HFNC) can produce positive airway pressure, and the pressure increases in proportion to the gas flow. Recently, high-velocity nasal insufflation (HiVNI) was developed as a new system... BACKGROUND: High flow nasal cannula (HFNC) can produce positive airway pressure, and the pressure increases in proportion to the gas flow. Recently, high-velocity nasal insufflation (HiVNI) was developed as a new system of HFNC. However, it is still unclear whether HiVNI can increase the airway pressure. The purpose of our study was to evaluate whether the HiVNI can increase the airway pressure compared to HFNC, under various gas flows. METHODS: This single-center prospective observational study recorded nasopharyngeal pressures in fifteen healthy volunteers who received both normal HFNC and HiVNI. After a 10 Fr catheter was inserted via the nose, the catheter was connected to the manometer and high flow oxygen therapy was performed using both systems. The measurements were carried out at flows of 20, 30, and 40 L/min, and the pressures were recorded at 50 Hz. The measurements were repeated with the mouth in the open and closed positions for each high-flow system. RESULTS: With the mouth open, the mean nasopharyngeal pressure was low in both systems, and the difference between the two systems was not significant. However, with the mouth closed, a significantly higher nasopharyngeal pressure was recorded with the HiVNI system compared to the HFNC system at all flows (P < .01). Furthermore, the difference between HiVNI and HFNC at each flow became significantly greater with the increase of flow (P < .01). CONCLUSION: In healthy volunteers, HiVNI can produce higher nasopharyngeal pressure than normal HFNC in a flow-dependent manner.

Endothelial Cell Senescence Exacerbates Pulmonary Fibrosis Potentially Through Accelerated Endothelial to Mesenchymal Transition.

Ramadhiani R, Ikeda K, Hirata KI … +1 more , Emoto N

Kobe J Med Sci · 2021 Nov · PMID 35367994

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease characterized by progressive lung fibrosis and obliteration of normal alveolar structures. Myofibroblasts play a central role in the progression of IPF by... Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease characterized by progressive lung fibrosis and obliteration of normal alveolar structures. Myofibroblasts play a central role in the progression of IPF by producing excess amount of extracellular matrix, and these myofibroblasts show heterogenous origins including resident fibroblasts, epithelial cells via epithelial to mesenchymal transition (EMT) and endothelial cell (EC) via endothelial to mesenchymal transition (EndMT). Although lung aging has been considered as essential mechanisms through abnormal activation of epithelial cells and fibroblasts, little is known about a role of EC senescence in the pathogenesis of IPF. Here, we reveal a detrimental role of EC senescence in IPF by utilizing unique EC-specific progeroid mice. EC-specific progeroid mice showed deteriorated pulmonary fibrosis in association with an accelerated EndMT in the lungs after intratracheal bleomycin instillation. We further confirmed that premature senescent ECs were susceptible to EndMT in vitro. Because senescent cells affect nearby cells through senescence-associated secretory phenotype (SASP), we assessed a potential role of the EC-SASP in EMT and myofibroblastic transition of resident fibroblasts. EC-SASP enhanced the myofibroblastic transition in resident fibroblasts, while no effect was detected on EMT. Our data revealed a previously unknown role of EC senescence in the progression of IPF, and thus rejuvenating ECs and/or inhibiting EC-SASP is an attracting therapeutic strategy for the treatment of IPF.

Hydration Status of Junior Tennis Players and the Difference after a Lecture on Its Practice.

Yoshikawa R, Nakatani T, Furukawa T … +2 more , Kanzaki N, Kuroda R

Kobe J Med Sci · 2021 Nov · PMID 35367993

Dehydration reduces exercise performance and causes heat-related illness. However, the fact that dehydration is a serious sports injury is often forgotten, especially among junior tennis players, who engage in tennis mat... Dehydration reduces exercise performance and causes heat-related illness. However, the fact that dehydration is a serious sports injury is often forgotten, especially among junior tennis players, who engage in tennis matches alone without receiving advice from others. Our objective was to investigate the hydration status of junior tennis players and the difference after attending a lecture on the importance of hydration. In total, 157 junior tennis players attending a training camp participated in this study. The duration of the camp was two days, and a lecture was organized on the first night to educate the players about hydration using a body mass scale. Body mass (BM) was measured immediately before and after practice on the first and second day. The water loss rate (WLR) was calculated by dividing the loss in BM during practice by the BM before practice. In total, 34.4% of players had attended a lecture on hydration in the past. These players had a lower WLR than those who had not, but the difference was not significant. The WLR was significantly lower after attending our lecture than that before. This study suggests that a lecture on hydration could immediately improve the hydration status of the junior tennis players; however, this effect may not be lasting. They may need help from their coaches and parents to implement what they have learned in lecture.

Glycogen Storage Disease Type Ia Screening Using Dried Blood Spots on Filter Paper: Application of COP-PCR for Detection of the c.648G>T G6PC Gene Mutation.

Wijaya YOS, Niba ETE, Yabushita R … +3 more , Bouike Y, Nishio H, Awano H

Kobe J Med Sci · 2021 Nov · PMID 34795158

Glycogen storage disease type Ia (GSDIa, OMIM #232200) is an autosomal recessive metabolic disease characterized by impaired glucose homeostasis and has a long-term complication of hepatocellular adenoma/carcinoma. GSDIa... Glycogen storage disease type Ia (GSDIa, OMIM #232200) is an autosomal recessive metabolic disease characterized by impaired glucose homeostasis and has a long-term complication of hepatocellular adenoma/carcinoma. GSDIa is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). Recent studies have suggested that early treatment by gene replacement therapy may be a good solution to correct the glucose metabolism and prevent serious late complications. Early treatment of the disease needs an early disease detection system. Thus, we aimed to develop a screening system for GSDIa using dried blood spots (DBS) to detect the c.648G>T mutation in G6PC, which is a frequent mutation in the East Asian population. In this study, a total of 51 DBS samples (50 healthy controls and one patient with c.648G>T) were tested by modified competitive oligonucleotide priming PCR (mCOP-PCR). In control DBS samples, the c.648G allele was amplified at lower Cq (quantification cycle) values (<11), while the c.648T allele was amplified at higher Cq values (>14). In the patient DBS sample, the c.648T allele was amplified at a lower Cq value (<11), and the c.648G allele was amplified at a higher Cq value (>14). Based on these findings, we concluded that our mCOP-PCR system clearly differentiated the wild-type and mutant alleles, and may be applicable for screening for GSDIa with the c.648G>T mutation in G6PC.

Protective Effects of Endothelin-2 Expressed in Epithelial Cells on Bleomycin-Induced Pulmonary Fibrosis in Mice.

Soraya AI, Suzuki Y, Morimoto M … +4 more , Ko CJ, Ikeda K, Hirata KI, Emoto N

Kobe J Med Sci · 2021 Nov · PMID 34795157

Initially, endothelin (ET)-2 was described as an endothelium-derived vasoconstrictor. However, accumulating evidence suggests the involvement of ET-2 in non-cardiovascular physiology and disease pathophysiology. The defi... Initially, endothelin (ET)-2 was described as an endothelium-derived vasoconstrictor. However, accumulating evidence suggests the involvement of ET-2 in non-cardiovascular physiology and disease pathophysiology. The deficiency of ET-2 in mice can be lethal, and such mice exhibit a distinct developmental abnormality in the lungs. Nonetheless, the definite role of ET-2 in the lungs remains unclear. The ET-2 isoform, ET-1, promotes pulmonary fibrosis in mice. Although endothelin receptor antagonists (ERAs) show improvements in bleomycin-induced pulmonary fibrosis in mouse models, clinical trials examining ERAs for pulmonary fibrosis treatment have been unsuccessful, even showing harmful effects in patients. We hypothesized that ET-2, which activates the same receptor as ET-1, plays a distinct role in pulmonary fibrosis. In this study, we showed that ET-2 is expressed in the lung epithelium, and ET-2 deletion in epithelial cells of mice results in the exacerbation of bleomycin-induced pulmonary fibrosis. ET-2 knockdown in lung epithelial cell lines resulted in increased apoptosis mediated via oxidative stress induction. In contrast to the effects of ET-1, which induced fibroblast activation, ET-2 hampered fibroblast activation in primary mouse lung fibroblast cells by inhibiting the TGF-β-SMAD2/3 pathway. Our results demonstrated the divergent roles of ET-1 and ET-2 in pulmonary fibrosis pathophysiology and suggested that ET-2, expressed in epithelial cells, exerts protective effects against the development of pulmonary fibrosis in mice.
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