Impact of hospital environmental cleaning with a potassium peroxymonosulphate-based environmental disinfectant and antimicrobial stewardship on the reduction of hospital-onset Clostridioides difficile infections.

BACKGROUND: A 1% potassium peroxymonosulphate-based environmental disinfectant (PPED) produces sodium hypochlorite when combined with sodium chloride, which functions as a disinfectant. However, little is known about the impact of hospital cleaning with PPED on hospital-onset Clostridioides difficile infection (HO-CDI). AIM: To reduce HO-CDI, we promoted antimicrobial stewardship and hospital ward cleaning with PPED: this study was conducted to evaluate their impact. METHODS: We began a promotion of post-prescription review with feedback for broad-spectrum antimicrobials and hospital ward cleaning with PPED. We reviewed the ratio of HO-CDI, PPED consumption, and days of therapy (DOT) of broad-spectrum antimicrobials between July 2014 and March 2018, dividing this time into the pre-promotion (July 2014 to June 2015) and post-promotion periods (July 2015 to March 2018). FINDINGS: Using interrupted time series analysis, an immediate significant change in HO-CDI was observed after intervention (P=0.03), although a downward trend was not observed over this period (P=0.19). Trends in PPED consumption significantly changed over this period (P=0.02). DOT of carbapenems decreased immediately after the intervention began (P<0.01). A Poisson regression analysis showed that PPED consumption and DOT of carbapenems were independent factors affecting HO-CDI (P=0.039 and 0.016, respectively). CONCLUSION: We revealed that DOT of carbapenems and use of PPED were associated with the HO-CDI ratio and that both interventions reduced the rate of HO-CDI. This is the first report on the impact of hospital ward cleaning with PPED on the reduction of HO-CDI.

The 'lysine cluster' in the N-terminal region of Na+/K(+)-ATPase alpha-subunit is not involved in ATPase activity.

The alpha-subunit of the Na+/K(+)-ATPases from several animal species have markedly similar amino acid sequences. However, the N-terminal sequences of the alpha-subunit are rather divergent except for lysine-rich sequences, the 'lysine cluster'. Here we report that the alpha-subunit from frog (Rana catesbeiana) has an N-terminal sequence with the 29 amino acid residues shorter than that of the Xenopus alpha-subunit deduced from its cDNA and hence lacks the 'lysine cluster'. Nevertheless, the Rana enzyme still exhibits ATPase activity. The ATP-dependent Na+ transport activity of the Rana enzyme was similar to that of the dog enzyme, which contains the 'lysine cluster'. Moreover, the Torpedo alpha-subunits deprived of the 'lysine cluster' by means of two gene deletions showed the same Na+/K(+)-ATPase activities as that of the wild type when expressed in Xenopus oocytes from their mRNAs. These results strongly suggest that the 'lysine cluster' in the N-terminal region of the alpha-subunit is not involved in the ATPase and ion transport activities. Since an active alpha-subunit was translated in Xenopus oocytes from mRNA lacking the N-terminal region including the 'lysine cluster', these regions were proved not to function as a membrane insertion signal sequence.

The functional roles of disulfide bonds in the beta-subunit of (Na,K)ATPase as studied by site-directed mutagenesis.

The beta-subunit of Torpedo californica (Na,K)ATPase contains seven cysteine residues; one (Cys46) is in the single transmembrane segment and the other six (Cys127, Cys150, Cys160, Cys176, Cys215 and Cys278) are in the extracellular domain and form three highly conserved disulfide bonds. A beta-subunit mutant with replacement of Cys46 by Ser could assemble with the alpha-subunit, and the resulting alpha beta-complex was catalytically active. Mutants in which either the N-terminal side or both Cys residues of the Cys127-Cys150 bond were replaced by Ser could also tightly assemble with the alpha-subunit, but the resulting alpha beta-complex was catalytically inactive. On the other hand, disruption of either the Cys160-Cys176 or Cys215-Cys278 bond by substituting the N-terminal side only or both Cys residues with Ser led to a beta-subunit that could not assemble with the alpha-subunit. We conclude that the structure of the beta-subunit around the Cys160-Cys176 and Cys215-Cys278 loops is indispensable for assembly with the alpha-subunit, whereas the Cys127-Cys150 loop is not essential for assembly but is required for enzyme activity.

MeOTf-mediated alkynylation of selenoamides leading to beta-methylselenenyl alpha,beta-unsaturated ketones and their characterization.

[reaction: see text] beta-Methylselenenyl alpha,beta-unsaturated ketones were effectively synthesized by treating selenoamides with methyl triflate, followed by reaction with lithium acetylides. The reaction proceeded with high stereoselectivity to give exclusively Z-isomers. (77)Se NMR studies and X-ray molecular structure analysis of beta-methylselenenyl alpha,beta-unsaturated ketones suggested that the products show 1,5-nonbonding interaction between the selenium atom and carbonyl oxygen atom.

High-dose cytosine arabinoside as consolidation chemotherapy for acute nonlymphocytic leukemia in remission.

A controlled study was conducted to evaluate the efficacy of high-dose cytosine arabinoside (Ara-C) in consolidation therapy of acute nonlymphocytic leukemia in remission. Twenty-seven patients with acute nonlymphocytic leukemia during their first complete remission were divided into two groups. The high-dose Ara-C group (15 patients) received two courses of high-dose Ara-C and daunorubicin, i.e., 3 g/m2 of Ara-C IV over 1 h every 12 h eight times followed by 25 mg/m2 per day daunorubicin IV bolus for 2 days, and no maintenance chemotherapy. The control group (12 patients) received the conventional consolidation therapy (usually 7 days administration of 200 mg/m2 of behenoyl-arabino-furanosylcytosine and 2 to 3 days administration of 25 mg/m2 of daunorubicin) repeated every 3 to 4 months for more than 2 years. There were no significant differences in the duration of remission and survival between the two groups. It is suggested that high-dose Ara-C consolidation is worth employing in the treatment of acute nonlymphocytic leukemia because of its convenience for patients.

Adrenomedullin-sensitive receptors are preferentially expressed in cultured rat mesangial cells.

By using cultured rat mesangial cells, we compared the effects on cyclic nucleotide levels of adrenomedullin with those of the structurally related peptides, calcitonin gene-related peptide (CGRP) and amylin. Adrenomedullin potently increased cAMP levels 7-fold in a time- and concentration-dependent manner. Its EC50 was 3 x 10(-9) M. CGRP was less potent (2-fold) with an EC50 of 10(-7) M, and amylin had no effect on cAMP levels. All three peptides failed to increase cGMP levels. Treatment of cells with near maximal concentrations of adrenomedullin (10(-7) M) and CGRP (10(-6) M) had no additive effect on cAMP levels. Human adrenomedullin-(22-52)-NH2, a putative adrenomedullin receptor antagonist, inhibited the production of cAMP elicited by adrenomedullin (IC50: 7 x 10(-8) M) and CGRP (IC50: 5 x 10(-8) M). Human CGRP-(8-37), a CGRP receptor antagonist, conversely, reduced the cAMP elevation caused by these peptides with a lower potency (IC50: 10(-6) M for both peptides). This demonstrated that human adrenomedullin-(22-52)-NH2 was a more effective antagonist for adrenomedullin- and CGRP-specific receptors than human CGRP-(8-37). Results suggest that receptors sensitive to adrenomedullin are preferentially expressed in cultured rat mesangial cells. Immunohistochemical study showed almost no immunoreactive adrenomedullin and CGRP, if any, in the cells. Adrenomedullin may regulate mesangial function as either a paracrine or circulating hormone via a cAMP- but not a cGMP-dependent mechanism.

Adrenomedullin increases cyclic AMP more potently than CGRP and amylin in rat renal tubular basolateral membranes.

In rat renal tubular basolateral membranes, the potency to increase cAMP of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, was compared with those of calcitonin gene-related peptide (CGRP) and amylin. Although all three peptides raised cAMP in a time- and concentration-dependent manner with a 4-fold increase at 10(-6)-10(-5) M, the EC50 value (10(-9) M) of AM was 100-fold smaller than those of CGRP and amylin. CGRP[8-37], an antagonist for CGRP receptors, attenuated cAMP elevation induced by these peptides with the essentially similar concentration-inhibition curves. These results suggest that the receptors for AM, CGRP and amylin share a common structural homology, and that the receptors sensitive to AM are preferentially expressed in renal tubular basolateral membranes.

Recovery of pancreatic beta-cell function in hemochromatosis: combined treatment with recombinant human erythropoietin and phlebotomy.

A patient with diabetes mellitus caused by secondary hemochromatosis was treated using recombinant human erythropoietin and phlebotomy. A total of 12 g of iron had been infused in the patient because of iron deficiency anemia. Blood glucose level was 17.3 mmol/L, and hemoglobin A1c level was 9.0% at admission. He was treated using phlebotomy (400 mL per week), along with subcutaneous injection of 3,000 U of recombinant human erythropoietin three times a week. After approximately 100 days, a total of 5,500 mL of blood (2.75 g iron) could be removed. Serum ferritin level decreased from 10,000 micrograms/L to 4,807 micrograms/L. Fasting and maximum serum C-peptide immunoreactivity values during 100-g oral glucose tolerance tests were improved from 0.14 nmol/L to 0.42 nmol/L and from 1.84 nmol/L to 2.61 nmol/L, respectively. This case suggests that pancreatic beta-cell recovers in diabetes caused by hemochromatosis by reducing iron overload during a short period.

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. I. Microbial deepoxidation and subsequent isomerization of deltamycins A1, A2, A3, A4 (carbomycin A) and X.

Carbomycin A (deltamycin A4) was deepoxidized to carbomycin A P1 by Streptomyces halstedii subsp. deltae (a deltamycins producer), favorably under anaerobic conditions. Carbomycin A P1 was spontaneously converted to geometric isomers designated carbomycins A P2 and A P3. This type of deepoxidation and subsequent isomerization was not limited to carbomycin A, but generally occurrable in other 16-membered epoxyenone macrolide compounds. Many bacteria and actinomycetes were also found to have an ability to deepoxidize deltamycins reductively. The chemical structures of carbomycins A P1, A P2 and A P3 were elucidated as shown in Fig. 3.

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. III. In vitro and in vivo evaluation of deepoxidation products of carbomycin A, deltamycin A1, 4"-phenylacetyldeltamycin, angolamycin and rosamicin.

Deepoxidation products P1, P2 and P3 of carbomycin A, deltamycin A1 and 4"-phenylacetyldeltamycin showed high in vitro antibacterial and antimycoplasmal activities which were comparable to those of the respective parent compounds. By contrast, the in vitro antimicrobial potencies of angolamycin P1 and rosamicin P1 were about ten-fold lower than those of the parent macrolides. In mice, the increase in the plasma levels of the epoxyenone macrolides due to deepoxidation was highly significant with the P1, P2 and P3 derivatives of carbomycin A and 4"-phenylacetyldeltamycin, whereas angolamycin P1 gave a moderately-improved plasma level compared with angolamycin.

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. II. Chemical deepoxidation by dissolving metal reduction.

16-Membered epoxyenone macrolide antibiotics were reductively deepoxidized with dissolving metals such as zinc. Angolamycin and rosamicin which have a methyl substituent at C-12 in the epoxyenone structure were deepoxidized, but not isomerized further to the geometric isomers P2 and P3.

Chemical modification of deltamycins. I. 4''-O-acyl analogs of deltamycins.

Using 4''-O-deacyldeltamycin as a starting material, various 4''-O-acyl derivatives were chemically synthesized by the following scheme: 2'-O-acetylation leads to 4''-O-acylation leads to 2'-O-deacetylation. 4''-O-Deacyldeltamycin is produced during the fermentation of deltamycin producing organisms or can be prepared by the biological deacylation of the deltamycins. 4''-O-Phenylacetyl-4''-O-deacyldeltamycin (PAD) showed good activity against various bacteria and mycoplasma. Among para-substituted PAD derivatives, NPAD (p-nitrophenylacetyl-) and SPAD (p-methylsulfonylphenylacetyl-) showed increased potency as compared to PAD against certain bacteria. The PAD was evaluated by in vivo experiments for plasma levels in mice and dogs and curative activity on the infected mice with Staphylococcus aureus Smith by subcutaneous or oral administration.

Effects of bicarbonate ingestion on the respiratory compensation threshold and maximal exercise performance.

Six males performed cycle ergometer exercise on two occasions in random order. Each exercise was preceded by a 2-h period in which matched capsules were administered orally, containing either starch (C) or NaHCO3 (E) in a dose of a 0.2 g.kg-1 body wt; pre-exercise blood pH and [HCO3-] were 7.34 +/- 0.01 and 23.7 +/- 0.5 mM (mean +/- S.E.) for the C study, and 7.41 +/- 0.01 and 28.6 +/- 1.3 mM for the E study (p less than 0.001 and p less than 0.01, respectively). Exercise was continuous and maintained for 10 min at 40% of maximal oxygen uptake (40% VO2max), followed by 15 min at 12 W above the respiratory compensation threshold ([+RCT]) which was determined by the increase of the ventilatory equivalent for carbon dioxide (VE.VCO2(-1)), and for as long as possible at 95% VO2max. Endurance time at 95% VO2max was significantly longer in E than in C (2.98 +/- 0.64 min vs. 2.00 +/- 0.44 min, p less than 0.05). The rate of increase in arterialized venous lactate (LA) was higher in E than in C from rest to exercise at [+RCT], while there was no significant difference in the hydrogen ions ([H+]). Consequently, [H+].LA-1 (nM.mM-1) was significantly lower in E than in C. The change of VE.VCO2(-1) was shifted downward in E compared to C during exercise with the lowest value being observed at the same exercise stage. These results suggest that the respiratory responses to exercise are not affected by the higher level of [HCO3-] induced by NaHCO3 ingestion, and appear to reflect the net change of plasma [HCO3-] or [H+]. Also, induced metabolic acidosis has little effect on [H+] appearance in blood.

Three-dimensional analysis of condylar hyperplasia with computed tomography.

Three-dimensional surface reconstruction imaging from CT scans was used to study the deformity of the mandible in six patients with mandibular asymmetry. High-resolution axial CT scans of the mandible were obtained using Somatom-DR3 (Siemens). COSMOZONE-2SA (Nikon) with PC-9801VX21 (NEC) was used to reconstruct the three-dimensional images. The six patients were divided into two groups. One group was classified as unilateral hybrid forms and the other group was classified hemimandibular elongation on the diagnostic criteria of Obwegeser and Makek (1986). In the three-dimensional surface reconstruction, exact location and the degree of the deformity in the region from the ascending ramus to the condylar head and the lingual aspect from the ascending ramus to the mandibular body were accurately represented. In addition, the three-dimensional images could be easily rotated arbitrarily, precise evaluation could be done at every part of the mandible. On diagnosis, the mandibular morphology classified into the unilateral hybrid forms was presumed to vary from case to case even in the same classification.

Hair-discoloration of Japanese elite swimmers.

To understand hair-discoloration in relation to swimming, we examined sixty-seven elite swimmers of the Japan National Swimming Team and fifty-four, age-matched subjects as controls. The incidence of hair discoloration (61%) in the swimmers' group was significantly higher than that in controls (0%) (p<0.0001). Interestingly, surface damage of the nail plates coexisted in the swimmers with the scalp-hair discoloration. The hairs picked from the eight swimmers and two age-matched individuals as controls were examined by electron microscope (EM) and EM X-ray microanalyzer. The swimmers' discolored, golden hair revealed complete disappearance of hair cuticle both by scanning EM (SEM) and transmission EM (TEM). The quantity of melanosomes in the cortex decreased, and their diameter was smaller than that of controls. In addition, irregularly shaped melanosomes with variable electron density and less electron-dense melanosomes with white haloes were frequently observed in the swimmers' golden hair. The X-ray elemental spectrograph by SEM revealed that the content of sulfur in all the swimmers' discoloured hair was lower than that in the normal controls and that the content of chlorine in the male swimmers' discoloured hair was higher than that in the female swimmers and the normal controls. The X-ray elemental microanalysis by TEM focused on melanosomes in the cortex of the cross section and detected elemental chlorine in all swimmers' golden hairs. It did not detect any element in the control hairs. The 14C-tyrosine uptake test of hairbulbs found no significant difference between the swimmers and the normal controls. These findings suggest that hair discoloration was mainly due to cuticle damage by friction with water. Hypochlorous acid in the swimming pool water can penetrate to the hair cortex through the cuticle. It can oxidize and degenerate melanosomes there.

Characteristics of stress fractures in young athletes under 20 years.

BACKGROUND: With the popularization of organized sports among adolescents and children, the clinical cases of stress fractures in young athletes have increased. This study was carried out to investigate the characteristics of stress fractures in young athletes. METHODS: During the 18-month period between January 1996 and June 1997, new clinical cases of stress fracture due to sports activities were collected from 39 hospitals in Japan. RESULTS: We analyzed 222 stress fractures in 208 athletes under 20 years of age (108 males: 14.4+/-2.2 years, 100 females: 15.2+/-1.5 years). Among these cases, the peak age of occurrence was 16. The most common sport causing stress fracture was basketball. The tibia was the most common location. About 70% of the patients participated in the respective sport for 6 or 7 days per week. High school students trained significantly more often than the primary and junior high school students (p<0.0001). There was a statistically significant difference in the return time to the sport between the cases who visited a hospital within 3 weeks and those who waited for more than 3 weeks after the onset of symptoms (return time, 10.4 vs 18.4 wks). Several cases visited a hospital beyond 8 weeks after the onset of symptoms regardless of the continuous pain of stress fracture, and their recovery was prolonged. CONCLUSIONS: It is important to educate young athletes that continuous pain lasting over 3 weeks is a warning signal to the body, and that early diagnosis leads to early recovery.

Characteristics of leg extensor muscle in a world champion masters jumper. A case study.

To examine the characteristics of a world champion masters jumper (aged 71 yr), a study was undertaken which included a muscle biopsy and measurement of mechanical force production. Comparisons were made to biopsy data obtained from the literature and to force data on 7 active males (63-81 yrs). Cross-sectional areas of vastus lateralis muscle of the jumper's dominant thigh were 3.43 (type I), 3.32 (type IIA) and 2.34 (type IIB) microns 2 X 10(3). This is smaller than what is reported from sedentary young and old. The torque-time curve of maximal isometric knee extension indicates that the jumper had the highest value per body weight from the onset to the peak (3.48 Nm/kg; 58.2% higher than age-matched controls). These results suggest that the daily training of the jumper has a specific effect on the rate of force production despite his relatively small muscle fiber areas.

Efficacy of aquatic exercises for patients with low-back pain.

We have studied 35 patients (25 female and 10 male) with low-back pain who were managed with aquatic exercises after an appropriate period of treatment for their condition in the medical institution. The exercises employed consisted of strengthening exercises for the abdominal, gluteal, and leg muscles, stretching of the back, hip, hamstrings, and calf muscles, walking in water, and swimming. All the patients had been participating in the exercise program for more than 6 months. The frequency of performing exercises was once a week for 7 patients, twice a week for 19, and 3 or more times a week for the remaining patients. The method used in this study was a survey questionnaire which was composed of questions about the patient's physical and psychological condition. Those patients who had performed exercises twice or more in a week showed a more significant improvement in the physical score than those who performed exercises only once a week. More than 90% of the patients felt they had improved after 6 months of participation in the program. The improvement in physical score was independent of the initial ability in swimming. The results obtained suggested that exercises in water may be one of the most useful modes of exercise for a patient with low-back pain.

Reduction and inactivation of the sarcoplasmic Ca(2+)-ATPase by 2-mercaptoethanol--contrast to the (Na+,K+) ATPase.

The sarcoplasmic Ca(2+)-ATPase was reduced with 300 mM 2-mercaptoethanol at elevated temperatures (40-45 degrees C) with a concomitant loss of ATPase activity. The reduction and inactivation of the Ca(2+)-ATPase proceeded rapidly in the absence of Ca2+. The Ca(2+)-ATPase was also inactivated with 2-mercaptoethanol in the presence of diluted SDS (0.4 mg/ml) even at 20 degrees C. In contrast to the (Na+, K+) ATPase, the inactivated Ca(2+)-ATPase in the presence of diluted SDS was sedimented by the centrifugation at 100,000 x g for 30 min.

Aerobic Dance Injuries Among Instructors and Students.

In brief: Aerobic dancing is a popular fitness activity in Japan, primarily among young women. To identify and characterize the injuries associated with aerobic dance, 161 instructors and 800 students from 13 Japanese fitness facilities were surveyed. Results showed an injury rate of 72.4% for instructors and 22.8% for students. The lower leg and foot were the most common injury sites for instructors and students, respectively. Though these results seem to indicate that aerobic dance is hazardous, the number of injuries per 100 hours of participation was only 0.17 for instructors and 0.15 for students. Most aerobic dance injuries seem to be caused by overuse; thus, moderating the frequency and duration of participation and individualizing programs could reduce the number of injuries that occur.