The sudden development of cyanotic lesions on the foot and toes may be a result of atheroembolic disease referred to as “blue toe syndrome”. During the last 7 years, 10 patients, consisting of 7 men and 3 women, were treated for ischemia of the toes of varied severity. The patients' ages ranged from 58 to 85 years (mean 73 years). Five patients had lesions on both legs and 5 on one leg. Contrast-enhanced abdominal CT scan revealed atherosclerotic changes of the abdominal aorta concomitant with intramural thrombus in every examined case. Four patients were treated medically and 4 underwent surgery consisting of replacement of the abdominal aorta in 3 and minor amputation of the toes in the other case. Two other patients developed acute renal failure within two months after the diagnosis of blue toe syndrome and succumbed to either heart failure or bleeding peptic ulcer. Contrast-enhanced CT scan is important for the diagnosis of blue toe syndrome. Though the prognosis of patients with blue toe syndrome is good in most cases, multiple microembolization to the viscera may cause renal failure and the prognosis of those patients is less favorable. Surgical intervention should be considered if the blue toe syndrome patient has an abdominal aortic aneurysm or history of multiple embolic episodes.

A 13-year-old girl with congenital mitral incompetence had undergone valvoplasty using the De Vega technique at age 5. The patient was referred by the pediatric department due to recurrence of mitral incompetence. Transesophageal echocardiography indicated regurgitation from A2 and P3, mild mitral leaflet tethering and left ventricular dilatation. Intraoperative findings showed valvular agenesis of the posterior leaflet around P3. No leaflet prolapse was observed at A2, but leaflet P2 had fallen to the left ventricular side compared with leaflet A2, thereby inducing regurgitation due to coaptation gap. In a procedure similar to folding plasty, leaflet P3 was folded down and sutured to the annulus extending up to the posteromedial commissure. This technique not only controlled regurgitation at P3 but also improved the coaptation between A2 and P2. Annuloplasty was conducted using a 28-mm Physio-ring. Folding plasty may be an effective surgical option for patients with congenital mitral incompetence because a broad valve orifice area can be maintained because there is no need for annular plication.

Prompt and accurate diagnosis of malarial patients is a crucial factor in controlling the morbidity and mortality of the disease. Effective treatment decisions require a correct diagnosis among mixed-species malarial patients. Differential diagnosis is particularly important in cases of Plasmodium vivax, a species that shares endemicity with P. falciparum in most endemic areas. Moreover, it is difficult to identify P. knowlesi on the basis of morphology alone, and rapid diagnostic tests are still not available for this malaria species. Therefore, the development of diagnostic tests applicable to the field is urgently needed. 1-Cys peroxiredoxin (1-Cys-Prx) in P. falciparum is abundantly expressed in the mature asexual stages, making it a promising candidate as a diagnostic antigen. In this study, we produced five monoclonal antibodies (mAbs) against P. falciparum 1-Cys-Prx (Pf1-Cys-Prx) by immunizing BALB/c mice with recombinant Pf1-Cys-Prx and subsequent hybridoma production. Cross reactivity of established mAbs with the orthologous molecule of Pf1-Cys-Prx in P. vivax (Pv1-Cys-Prx) and P. knowlesi (Pk1-Cys-Prx) was examined. Western blot analyses showed that three mAbs reacted with Pv1-Cys-Prx and Pk1-Cys-Prx but two mAbs did not. These results indicate that the two mAbs were effective in differentiating P. falciparum from P. vivax and P. knowlesi and could be used in differential diagnosis as well as comparative molecular studies of human Plasmodium species.

The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic β-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on “gene-environment interactions” in the development of a reduced pancreatic β-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic β-cells, ultimately resulting in the development of pancreatic β-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic β-cell failure as revealed by previous reports and data from experiments.

Objectives: First steps to promote the proper use of medicines in remote islands and rural areas are as follows: (1) recognition of the profession of “pharmacist” from secondary-remote-island residents who do not have a pharmacy or drugstore or the opportunity for pharmacist contact and (2) an understanding by remote-island residents of the advantages of having a “family pharmacist.”
Methods: Repeated “medicine information and consultation sessions” for secondary-remote-island residents of Japan’s Nagasaki Prefecture were held.  Residents were then surveyed for changes in awareness of or demand for pharmacists and the nature of such changes.
Results: Before the information sessions, 29.7% of residents did not recognize the profession of pharmacy, but the extent of their recognition increased after information sessions were concluded.  They were asked “Who explains medicines in a way that is easy to understand ?”; more than half responded “doctors” before the information session, but after information sessions were concluded, those who said “pharmacists” increased.
Conclusion: Conducting “medicine information and consultation sessions” for residents of secondary-remote islands and rural areas enabled them to understand the profession of pharmacy.  The initiatives in the present study are first steps toward promoting proper use of medicines by residents of remote islands and rural areas who use “family pharmacies/pharmacists.”

BACKGROUND: Although non-thyroidal illness syndrome (NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine (fT3) levels in trauma patients requiring massive transfusion have not been reported. METHODS: A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions (>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of fT3, free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation. RESULTS: Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial fT3 levels in group M (1.95±0.37 pg/mL) were significantly lower than those in group C (2.49±0.72 pg/mL;P<0.01) and remained low until 1 week after admission. Initial inter-group fT4 and TSH levels were not significantly different. TSH levels at 1 week (1.99±1.64 μIU/mL) were higher than at admission (1.48±0.5 μIU/mL) in group C (P<0.05). CONCLUSION: Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.

No abstract available.
Arthritis, Psoriatic* ; Macrophages* ; Scleroderma, Systemic*

A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 µM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 µM). Peptide #2 inhibited the SARSCoV-2 pseudovirus assay at IC50=1.49 µM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.