Detection of human coronavirus RNA in surgical smoke generated by surgical devices.

BACKGROUND: Gaseous by-products generated by surgical devices - collectively referred to as 'surgical smoke' - present the hazard of transmitting infective viruses from patients to surgical teams. However, insufficient evidence exists to evaluate and mitigate the risks of SARS-CoV-2 transmission via surgical smoke. AIM: To demonstrate the existence and infectivity of human coronavirus RNA in surgical smoke using a model experiment and to evaluate the possibility of lowering transmission risk by filtration through a surgical mask. METHODS: Pelleted HeLa-ACE2-TMPRSS2 cells infected with human coronavirus were incised by electric scalpel and ultrasonic scalpel, separately. A vacuum system was used to obtain surgical smoke in the form of hydrosol. Reverse transcription-quantitative polymerase chain reaction was used to analyse samples for the presence of viral RNA, and infectivity was determined through plaque assay. Furthermore, a surgical mask was placed centrally in the vacuum line to evaluate its ability to filter viral RNA present in the surgical smoke. FINDINGS: In this model, 1/106 to 1/105 of the viral RNA contained in the incision target was detected in the collected surgical smoke. The virus present in the smoke was unable to induce plaque formation in cultured cells. In addition, filtration of surgical smoke through a surgical mask effectively reduced the amount of viral RNA by at least 99.80%. CONCLUSION: This study demonstrated that surgical smoke may carry human coronavirus, though viral infectivity was considerably reduced. In clinical settings, surgical mask filtration should provide sufficient additional protection against potential coronavirus, including SARS-CoV-2, infection facilitated by surgical smoke.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Four-day continuous gastric pH monitoring following anti-acid secretory drug administration: cross-over test to assess the early effects.

BACKGROUND: There have been few reports that compare the effect of histamine H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) using continuous gastric pH monitoring for a long duration. AIM: To assess the early effects of both drugs on gastric pH using a wireless pH monitoring system. METHODS: The test was conducted by a cross-over test: 10 healthy male volunteers were administered famotidine 20 mg twice a day and lansoprazole 30 mg once a day. Monitoring of gastric pH over four consecutive days was performed using a unique method we have developed that is an elaboration of the Bravo system. RESULTS: The time to reach a pH level of 3 or more with famotidine was significantly shorter than that for lansoprazole. The pH3 holding time ratio of famotidine during the first 4 h of administration was significantly higher than that of lansoprazole. The pH3 holding time ratio on each day from day 1 to day 3 was significantly higher following lansoprazole administration compared with famotidine administration. CONCLUSIONS: Famotidine was shown to act quickly in elevating gastric pH; however, lansoprazole was superior to famotidine in terms of its ability to elevate gastric pH for a long duration.

Colonic transit time and rectoanal videomanometry in Parkinson's disease.

BACKGROUND: Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson's disease (PD). OBJECTIVE: To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD. METHODS: Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (<3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two). RESULTS: In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (p<0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p<0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p<0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p<0.05), evidence of paradoxical sphincter contraction on defecation (PSD). CONCLUSIONS: Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.

Digital subtraction angiogram registration method with local distortion vectors to decrease motion artifact.

We have been investigating registration methods for improving digital subtraction angiography (DSA) images to extract blood vessels by reducing artifacts due to body motion, such as rotation, contraction, and dilation. In this paper, we propose a new and simple DSA registration algorithm with local distortion vectors to reduce artifacts. According to the results, the proposed method works well for vascular system around the nasal cavity and the orbit of the head and neck DSA images, which cannot be observed clearly by conventional methods. Additionally, we have applied the proposed method to abdominal and leg DSA images.

Prenatal radiation-induced limb defects mediated by Trp53-dependent apoptosis in mice.

We reported previously that in utero radiation-induced apoptosis in the predigital regions of embryonic limb buds was responsible for digital defects in mice. To investigate the possible involvement of the Trp53 gene, the present study was conducted using embryonic C57BL/6J mice with different Trp53 status. Susceptibility to radiation-induced apoptosis in the predigital regions and digital defects depended on both Trp53 status and the radiation dose; i.e., Trp53 wild-type (Trp53(+/+)) mice appeared to be the most sensitive, Trp53 heterozygous (Trp53(+/-)) mice were intermediate, and Trp53 knockout (Trp53(-/-)) mice were the most resistant. These results indicate that induction of apoptosis and digital defects by prenatal irradiation in the later period of organogenesis are mediated by the Trp53 gene. These findings suggest that the wild-type Trp53 gene may be an intrinsic genetic susceptibility factor that is responsible for certain congenital defects induced by prenatal irradiation.

Adaptive response in embryogenesis. III. Relationship to radiation-induced apoptosis and Trp53 gene status.

We reported previously that a radiation-induced adaptive response existed in the late period of embryogenesis, and that radiation-induced apoptosis in the predigital regions was responsible for digital defects in embryonic ICR mice. To investigate the possible involvement of the Trp53 gene and radiation-induced apoptosis in radiation-induced adaptive responses in embryogenesis, the present study was conducted using Trp53 wild-type (Trp53(+/+)) and Trp53 heterozygous (Trp53(+/-)) embryonic mice of the C57BL/6 strain. The existence of a radioadaptive response in the Trp53(+/+) embryonic mice was demonstrated by irradiating the embryos with 5 or 30 cGy on embryonic day 11 prior to a challenging irradiation at 3 Gy on embryonic day 12. The two conditioning doses at 5 and 30 cGy significantly suppressed the induction of apoptosis by the challenging dose in the predigital regions of limb buds in the Trp53(+/+) embryonic mice, while no such effect was found in the Trp53(+/-) embryonic mice. These findings indicate that induction of a radioadaptive response in embryogenesis is related to Trp53 gene status and the occurrence of radiation-induced apoptosis.

Quantitative analysis of bowel gas using plain abdominal radiograph in patients with irritable bowel syndrome.

OBJECTIVE: Ideally, the diagnosis of irritable bowel syndrome (IBS) would be achieved using a minimal number of procedures. It is presumed that bowel gas is related to IBS, and it is easily visualized by plain abdominal radiograph. In the present study, to clarify the relationship between IBS and the quantity of bowel gas, the measured bowel gas volume using plain abdominal radiographs was compared with the pathology of IBS. METHODS: Plain abdominal radiographs were digitized and transmitted to a computer (computed radiography) in 30 IBS patients and 30 normal controls. The quantity of bowel gas, determined as the pixel value on images and standardized by physique, was defined as the gas volume score (GVS). Using the mean +/- 2SD of GVS in the control group as the normal score, IBS patients were divided into three groups: high, normal, and low. To examine the sequential reproducibility of a similar quantity of bowel gas, a second plain abdominal radiography was performed about 2 months later, and the GVS were compared. The colonic transit time was determined using radiopaque markers. RESULTS: There was a strong correlation between the quantities of bowel gas measured by two independent gastroenterologists. The mean GVS of IBS patients was significantly higher than that in the control group (p < 0.001). The sequential reproducibility was recognized in all 10 IBS patients. There was no significance between colonic transit time and GVS, nor between symptoms and GVS. CONCLUSIONS: Abdominal gas was analyzed objectively by using GVS, and GVS was considered to represent a useful tool for the diagnosis of IBS.

UVC-induced apoptosis in human epithelial tumor A431 cells: sequence of apoptotic changes and involvement of caspase (-8 and -3) cascade.

Human epidermoid tumor A431 cells underwent apoptosis following exposure to ultraviolet C (UVC). The apoptosis was of the interphase death type, and mostly occurred within one cell cycle, independent of the cell-cycle phases. We further examined the detailed sequential order of apoptotic changes in cells after UVC exposure and the involvement of caspases using six caspase inhibitors. The loss of mitochondrial transmembrane potential (delta psi m) appeared in the earliest phase; subsequently, the chromatin condensation and DNA-fragmentation occurred. Cell shrinkage and loss of the plasma-membrane integrity, judged by propidium iodide (PI) staining, were observed in the later phase. A broad-spectrum caspase inhibitor, z-VAD-fmk, completely prevented all apoptotic changes, except for the depletion of delta psi m. Both Ac-DEVD-CHO and Ac-IETD-CHO, inhibitors of caspase -3 and -8, respectively, effectively inhibited typical chromatin condensation to almost the same extent. However, the nuclei still showed partial condensation. A caspase -9 inhibitor, Ac-LEHD-CHO, did not prevent chromatin condensation, though it partially inhibited cell-size reduction and PI-stainability. None of the caspase inhibitors could inhibit the delta psi m reduction. These results strongly suggest that the collapse of delta psi m is not a part of the central apoptotic machinery, and that caspase cascade(s), especially caspase-8 to -3, play an important role in UVC-induced apoptosis in A431.

Adaptive response in embryogenesis: II. Retardation of postnatal development of prenatally irradiated mice.

We previously reported that a priming dose of 0.3 Gy on gestation day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations caused by exposure to 5 Gy X rays on gestation day 12 in ICR mice. In the present study, postnatal development of the live offspring was investigated using a set of developmental and behavioral parameters. The offspring of the mice irradiated with 0.3 Gy generally showed a delay in the appearance of most of the physiological markers, impaired acquisition of neonatal reflexes, and alteration of adult behavior. However, an increase in body weight in the females was observed 4 weeks postnatally. In the offspring primed with 0.3 Gy followed by a challenging dose of 5 Gy prenatally, a high postnatal mortality was found, and all the survivors had various radiation-induced detrimental effects. The results indicated that the priming dose was advantageous to survival itself, but was disadvantageous to the health of survivor. The results also suggested that studying the whole animal can show the extent of the effects of radiation, i.e. quality of life, in a way that cellular or molecular studies cannot.

Induction of apoptosis by beta radiation from tritium compounds in mouse embryonic brain cells.

Induction of apoptosis by tritium exposure was investigated in both cultured embryonic mid brain cells and brain sections of embryos and of newborns in mice. In the cultures of mid brain cells, addition of methyl-3H-thymidine (3H-TdR) (21 kBq mL(-1)) and tritiated water (5.616 MBq mL(-1)) induced late appearances and low percentages of apoptosis when compared to x-irradiation at the ID50 dose, the inhibitory dose that reduced cellular differentiation by 50% of the control. A significant increase in p53 protein was detected about 2 h before the marked appearance of apoptosis. The pregnant mice were given an intraperitoneal injection of tritiated water at the concentration of 481.8 kBq g(-1) of body weight on gestation day 12.5, by which treatment behavioral changes in the offspring occurred. Increased apoptotic cells were observed in the neural tube of embryos from 1 d after the injection to 1 wk postnatal age. Apoptosis induced by x-rays appeared 2 h after irradiation, with a peak at 4 h. Increase of apoptotic cells was also found in the brain cortexes of newborns. The percentage of apoptosis in the brain was higher in the prenatal tritiated water exposed mice than in the prenatal x-irradiated mice. Possible mechanisms on apoptosis and its relation to the higher relative biological effectiveness value of tritium beta-rays are discussed.

Radiation-induced apoptosis and limb teratogenesis in embryonic mice.

In utero irradiation of the fetus during the period of organogenesis induces a dramatic increase in malformation. However, the mechanisms underlying the teratogenesis remain to be elucidated. In the present study, the correlation between radiation-induced apoptosis and limb malformation was examined in mice. The mice were exposed to X rays in utero on day 11 of gestation during the period of organogenesis of limb buds. A marked increase in the number of apoptotic cells in the predigital regions in the forelimb buds was detected 4 h after irradiation. The preinterdigital regions of the forelimb buds did not show such an increase at the same time. Aphlangy and ectrodactyly were the main types of anomalies observed on day 19 in the limbs of the fetuses irradiated with 5 Gy. The increases in prenatal death and teratogenesis in limb digits in living fetuses were dependent on dose. The possible mechanisms involved are discussed.

Trimethoprim resistance and susceptibility genes in Staphylococcus epidermidis.

Genes encoding trimethoprim (TMP)-resistant and -susceptible dihydrofolate reductases (DHFR) in Staphylococcus epidermidis isolated in Saitama Prefecture were compared with the TMP-resistant DHFR gene of S. aureus, dfrA. The nucleotide sequences of TMPr and TMPs genes in five S. epidermidis isolates tested could be divided into three types: type 1, identical with the TMPr gene dfrA that had been found in S. aureus; type 3, identical with the TMPs gene dfrC in S. epidermidis; and type 2, having only two nucleotide substitutions to dfrC with no amino acid change. TMPr isolates carried either one of the type 2 or type 3 sequences in addition to the type 1 sequence. A Southern hybridization analysis revealed that, in TMPr S. epidermidis, the type 1 sequence was located on a 5.5 kb EcoRI-EcoRV restriction fragment together with the sequence for the gentamicin (GM)-resistant gene, while the type 2 or type 3 sequence was located on the 1.0 kb EcoRI-EcoRV fragment. No plasmid-carrying dfrA-homologous sequence was detected in the S. epidermidis isolates we tested. These results suggest that the TMPr and GMr genes are closely linked and located on the chromosome in S. epidermidis isolated in Japan.

Non-fluorescent chromosome painting using the peroxidase/diaminobenzidine (DAB) reaction.

PURPOSE: To develop and validate non-fluorescent chromosome painting for bright-field microscopy using the peroxidase/diaminobenzidine (DAB) reaction. MATERIALS AND METHODS: Peripheral blood lymphocytes were taken from patients with uterine cancer who had received heavy-ion radiation therapy. Chromosome slides were treated with RNase and pepsin, denatured mildly, hybridized with a biotinylated DNA probe specific for whole-chromosome 4 and stained using the peroxidase/DAB reaction with an avidin-biotin amplification. The slides were analysed under a bright-field microscope and an atomic force microscope. The detection rate of chromosome aberrations by DAB painting was compared with that obtained by dual analysis of Giemsa staining and FISH painting. RESULTS: When chromosomes 4 were painted, 11.5% of unstable aberrations were detected by DAB painting, while 10.8% of them were found by dual analysis of Giemsa staining and FISH painting. CONCLUSION: A DAB painting method that can effectively detect rearranged aberrations was established. It has advantages over FISH painting: the preparations can be analysed by bright-field microscope, can be preserved permanently and are suitable for analysis by an automated system.

Adaptive response in embryogenesis: I. Dose and timing of radiation for reduction of prenatal death and congenital malformation during the late period of organogenesis.

An adaptive response was demonstrated during embryogenesis in mice. Whole-body irradiation at a dose of 0-50 cGy was given to condition pregnant ICR mice on day 9 to day 11 of gestation. Then their whole bodies were exposed to a challenging dose of 5 Gy on the next day. The numbers of living fetuses, prenatal deaths and living fetuses with external gross malformations were determined on day 19. A conditioning dose of 30 cGy on day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations induced by a 5-Gy dose on day 12. This indicates the existence of a critical dose and timing for administering a conditioning dose for radioadaptation during the late period of organogenesis in mice. The possible mechanisms involved are discussed.

Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice and dogs.

The pharmacokinetics of troglitazone (CAS 97322-87-7, CS-045), a new oral antidiabetic drug for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), were investigated in rats, mice and dogs following oral and intravenous administration of 14C-labeled troglitazone at doses of 5 mg/kg. The absorption rates, calculated from the AUC ratios of total radioactivity after oral and intravenous administration, or from the biliary excretion rate after intraduodenal administration in rats were both as high as 75%. High uptake by the liver, one of the pharmacological target organs, was demonstrated in both rats and mice. Furthermore, in the KK mouse, an obese NIDDM model animal, the radioactivity was incorporated selectively as troglitazone itself to muscle, the peripheral target organ. Troglitazone reversibly bound to serum albumin with a high ratio (> 99%). Troglitazone was mostly metabolized to the conjugates: sulfate (M 1) and glucuronide (M 2). The oxidized metabolite, a quinone-type metabolite (M 3), was found to be further metabolized to the sulfate (U 2). The biliary excretion rates of these conjugates were high in each animal, and the occurrence of enterohepatic circulation of the conjugates was also suggested. Sex differences in pharmacokinetics were observed in rats; i.e. females showed a higher plasma concentration of troglitazone, and a lower concentration of M 1, than males, and they excreted the sex-related metabolite, a hydroxylated M 1 (U 1), in the bile.

A study of learning splice sites of DNA sequence by neural networks.

To predict of splice sites in DNA sequence, we developed a neural network system with back propagation. This system has a flexible network definition language which can describe any network structure. Three types of neural network were defined using the system for the prediction of splice sites. The neural networks are trained by the arrangements of bases around the splice sites of DNA sequences. The results of simulation showed the excellent ability of the neural networks to predict splice sites by applying and testing the arrangements of DNA sequences. This system also were used to predict the effects of point mutations on the splicing of the IX factor gene which may cause hereditary disease.

A quantitative color recognition measurement system using multimedia computer environment.

We developed a quantitative measurement system that tests the degree of dysgnosia resulting from Obsessive-Compulsive Disorder (OCD). The system outputs a stimulation word that had been set in advance using the voice output facility of the personal computer, then displays a color chart and waits for input from the subject. When the subject touches the CRT screen or clicks the mouse, the system records the response time and coordinates of input position. There were 30 stimulation words in the system. After 30 measurements of response time and input coordinates, the system outputs a results file that includes each response time and input coordinates. This test is easier and simpler than other psychological tests such as MMPI. The influence of the examiner can be reduced to the minimum with this system because it is a computer-based automatic measurement system. To use the computer system, an examiner can easily standardize the environment of the illumination, etc. Moreover, the system can save labor in testing, and can manage large amounts of data easily using the file management facility.