Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Since hand deformities in rheumatoid arthritis (RA) are relatively not very painful, the worsening of the deformities often goes unnoticed and the functional impairment progresses irreversibly. Herein, we report a case of boutonnière deformity of the left middle and ring fingers treated with rehabilitation since an early stage. The patient was a 58-year-old woman who was referred to our hospital due to joint pain in the fingers and feet, following which a diagnosis of RA as made；however, she could not be administered methotrexate due to complications. PIP joint deformity of the left middle and ring fingers developed later. The middle finger was in -50-degree extension and difficult to correct passively, while the ring finger was in -35-degree extension and correctable. Surgery for the left middle finger was proposed based on the diagnosis of boutonnière deformity；however, consent was not obtained. After a steroid injection in the painful middle finger, she was managed using a Capener splint and ROM exercises with finger stretching. The symptoms improved five months following the rehabilitation intervention. Nalebuff et al. classified the severity of the boutonnière deformity based on the limited PIP joint extension and recommended treatment accordingly. In this case, surgical treatment was believed to be required；however, since the patient refused surgery, conservative treatment was chosen. Although the extension was severe, there was little joint destruction, due to which the symptoms improved with early and active intervention. Orthotic treatment and occupational therapy were effective in improving ADL.

Since hand deformities in rheumatoid arthritis (RA) are relatively not very painful, the worsening of the deformities often goes unnoticed and the functional impairment progresses irreversibly. Herein, we report a case of boutonnière deformity of the left middle and ring fingers treated with rehabilitation since an early stage. The patient was a 58-year-old woman who was referred to our hospital due to joint pain in the fingers and feet, following which a diagnosis of RA as made；however, she could not be administered methotrexate due to complications. PIP joint deformity of the left middle and ring fingers developed later. The middle finger was in -50-degree extension and difficult to correct passively, while the ring finger was in -35-degree extension and correctable. Surgery for the left middle finger was proposed based on the diagnosis of boutonnière deformity；however, consent was not obtained. After a steroid injection in the painful middle finger, she was managed using a Capener splint and ROM exercises with finger stretching. The symptoms improved five months following the rehabilitation intervention. Nalebuff et al. classified the severity of the boutonnière deformity based on the limited PIP joint extension and recommended treatment accordingly. In this case, surgical treatment was believed to be required；however, since the patient refused surgery, conservative treatment was chosen. Although the extension was severe, there was little joint destruction, due to which the symptoms improved with early and active intervention. Orthotic treatment and occupational therapy were effective in improving ADL.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC50 values of 12.6, 21.8, and 11.12 μM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 μM with no observed toxicity in Vero cells at 10 μM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

Background: Radiotherapy is often used for treating patients with gastric mucosa-associated lymphoid tissue (MALT) lymphomas who fail to respond to Helicobacter pylori eradication.However, non-gastric intestinal MALT lymphoma is rare, and no standard therapeutic strategies have been established. This study was designed to assess the long-term prognosis of non-gastric intestinal MALT lymphoma treated with radiotherapy and to compare the outcomes with that of post-radiotherapy gastric MALT lymphoma. Methods: The study included 34 patients with stage I EA gastrointestinal MALT lymphoma according to the Ann Arbor classification who underwent definitive radiotherapy. The primary site was the rectum in 3, the duodenum in 1, and the stomach in 30 patients. The radiotherapy dose was 1.5‒2.0 Gy (median, 1.5 Gy) and the total dose was 30‒40 Gy (median, 30 Gy).The clinical target volume (CTV) was defined as the volume of the entire organ with the lymphoma. Adjacent lymph node areas were not routinely included in the CTV. Results: Complete response (CR) was achieved in all patients. There were no local recurrences, and two cases of recurrence were observed at other sites. The 5-year overall survival rates for non-gastric and gastric MALT lymphomas were 100% and 94.7%, respectively, and the 5-year disease-free survival rates were 100% and 95.7%, respectively. None of the patients died of the current illness. Conclusion Radiotherapy for non-gastric intestinal MALT lymphoma is expected to result in good local control and long-term survival, similar to that for gastric MALT lymphoma.

BACKGROUND: We hypothesized that ketamine, when administered as the anesthetic induction agent, may prevent cardiovascular depression during high-dose remifentanil administration, unlike propofol. To test our hypothesis, we retrospectively compared the hemodynamic effects of ketamine, during high-dose remifentanil administration, with those of propofol. METHODS: Thirty-eight patients who underwent oral surgery at the Nagasaki University Hospital between April 2014 and June 2015 were included in this study. Anesthesia was induced by the following procedure: First, high-dose remifentanil (0.3-0.5 µg/kg/min) was administered 2-3 min before anesthesia induction; next, the anesthetic induction agent, either propofol (Group P) or ketamine (Group K), was administered. Mean arterial pressure (MAP) and the heart rate were recorded by the automated anesthesia recording system at four time points: immediately before the administration of high-dose remifentanil (T1); immediately before the administration of propofol or ketamine (T2); 2.5 min (T3), and 5 min (T4) after the administration of the anesthetic induction agent. RESULTS: In Group P, the MAP at T3 (75.7 ± 15.5 mmHg, P = 0.0015) and T4 (68.3 ± 12.5 mmHg, P < 0.001) were significantly lower than those at T1 (94.0 ± 12.4 mmHg). However, the MAP values in the K group were very similar (P = 0.133) at all time points. The heart rates in both Groups P (P = 0.254) and K (P = 0.859) remained unchanged over time. CONCLUSIONS: We showed that ketamine, when administered as the anesthetic induction agent during high-dose remifentanil administration, prevents cardiovascular depression.
Anesthesia ; Arterial Pressure ; Depression ; Heart Rate ; Hemodynamics* ; Humans ; Ketamine* ; Propofol* ; Retrospective Studies* ; Surgery, Oral

BACKGROUND: We hypothesized that ketamine, when administered as the anesthetic induction agent, may prevent cardiovascular depression during high-dose remifentanil administration, unlike propofol. To test our hypothesis, we retrospectively compared the hemodynamic effects of ketamine, during high-dose remifentanil administration, with those of propofol. METHODS: Thirty-eight patients who underwent oral surgery at the Nagasaki University Hospital between April 2014 and June 2015 were included in this study. Anesthesia was induced by the following procedure: First, high-dose remifentanil (0.3-0.5 µg/kg/min) was administered 2-3 min before anesthesia induction; next, the anesthetic induction agent, either propofol (Group P) or ketamine (Group K), was administered. Mean arterial pressure (MAP) and the heart rate were recorded by the automated anesthesia recording system at four time points: immediately before the administration of high-dose remifentanil (T1); immediately before the administration of propofol or ketamine (T2); 2.5 min (T3), and 5 min (T4) after the administration of the anesthetic induction agent. RESULTS: In Group P, the MAP at T3 (75.7 ± 15.5 mmHg, P = 0.0015) and T4 (68.3 ± 12.5 mmHg, P < 0.001) were significantly lower than those at T1 (94.0 ± 12.4 mmHg). However, the MAP values in the K group were very similar (P = 0.133) at all time points. The heart rates in both Groups P (P = 0.254) and K (P = 0.859) remained unchanged over time. CONCLUSIONS: We showed that ketamine, when administered as the anesthetic induction agent during high-dose remifentanil administration, prevents cardiovascular depression.
Anesthesia ; Arterial Pressure ; Depression ; Heart Rate ; Hemodynamics* ; Humans ; Ketamine* ; Propofol* ; Retrospective Studies* ; Surgery, Oral

Introduction : One of the key challenges in promotion of medical and nursing care collaboration in long term care is the difficulty in understanding the current state of acceptance of clients with high medical acuity by local long term care service providers. This study therefore aimed to clarify the current state and issues regarding such clients.
Methods : Information was obtained via face to face interviews at 102 facilities out of 105 located in Area B in Prefecture A.
Results : (1) Most of the facilities, except Long-Term Care Health Facilities, do not have night shift nurses, making it difficult for them to accept anyone who needs a medical procedure, such as tube feedings or sputum suctioning.
(2) The number of the facilities accepting elderly clients who require sputum suctioning decreased after the current regulations came into force, due to lack of human resources to provide the time off for training of the staff, and concern regarding costs of training and equipment given the current provider business environment.
(3) Lack of understanding by physicians appears to be the largest challenge with regards to end-of-life care, and is a larger factor than lack of understanding and experience of the facilities.
Conclusion : Collaboration between medical and nursing care needs to be further enhanced based on clear understanding of roles and reality of the facilities.