Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Effect of habitual exercise on urinary liver-type fatty acid-binding protein levels in middle-aged and older adults.

The purpose of this study was to examine the effect of habitual exercise on urinary liver-type fatty acid-binding protein (L-FABP), which can reflect the degree of various stresses on renal proximal tubule related to the progression of renal disease, in middle-aged and older adults. Cross-sectional and interventional approaches were used to comprehensively achieve this purpose. In the cross-sectional study, we investigated the relationship between physical activity levels and urinary L-FABP levels in 130 middle-aged and older adults. In the interventional study, subjects (n=31) were divided into two groups: exercise (n=19) and control group (n=12), whereby we examined the effects of 12-week aerobic exercise training on urinary L-FABP levels. The cross-sectional study showed that the urinary L-FABP levels were significantly lower in the higher physical activity group than in the lower physical activity group (P<.05). In the interventional study, 12-week aerobic exercise training significantly decreased urinary L-FABP levels (P<.01). Furthermore, the relative changes in urinary L-FABP levels were significantly correlated with the relative changes in physical activity levels and mean arterial pressure after intervention (r=-.374 and r=.530, respectively). Our results revealed that the urinary L-FABP levels were lower in the higher physical activity individuals, and aerobic exercise training decreased urinary L-FABP levels. These results suggest that habitual exercise appears to be associated with a decrease in the degree of several stresses on renal proximal tubule and to be beneficial for kidney health in middle-aged and older adults.

Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19.

OBJECTIVES: Detailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. RESULTS: Of the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5°C) was only observed in 20 (11.6%) individuals. CONCLUSIONS: As much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.

Effects of resistance training on arterial compliance and plasma endothelin-1 levels in healthy men.

Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training.

Background model for the NaI(Tl) crystals in COSINE-100.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2-6) keV energy interval. The dominant contributors in this energy region are found to be 210 Pb and 3 H.

Cloning and sequence analysis of the gene encoding 3-hexulose-6-phosphate synthase from the methylotrophic bacterium, Methylomonas aminofaciens 77a, and its expression in Escherichia coli.

A DNA fragment of 550 bp was specifically amplified by PCR with primers based on the N-terminal sequence of the purified 3-hexulose-6-phosphate synthase from Methylomonas aminofaciens 77a and on that of a lysyl endopeptidase-derived peptide. Using this PCR product as a probe, a gene coding for 3-hexulose-6-phosphate synthase in M. aminofaciens 77a chromosomal DNA was cloned in Escherichia coli JM109. Sequencing analysis revealed that the gene encoding 3-hexulose-6-phosphate synthase contained a 624-bp open reading frame, encoding a protein composed of 208 amino acid residues with a calculated relative molecular mass of 21,224.

Participation of vasoactive intestinal polypeptide (VIP) as a humoral mediator in the erectile response of canine corpus cavernosum penis.

The ability of anti-vasoactive intestinal peptide (anti-VIP) serum to suppress the electrically induced relaxation of the corpus cavernosum was evaluated in vitro to define the role of VIP in penile erection. Strips of canine corpora cavernosa were placed in 5-ml organ chambers containing oxygenated Krebs-Ringer solution. They were stretched and fixed in place at both ends and pretreated with 2 x 10(-7)M noradrenaline (NA). NA was given to produce an optimal state of isometric smooth muscle contraction so that subsequent electrical field stimulation (EFS) could induce a good range of measurable relaxation response. This response was deemed to be an in vitro representation of penile erection. After NA treatment the cavernous tension rose markedly by 2-2.5 g; it then declined by up to 1-1.2 g upon EFS. Anti-VIP serum (1:16) or atropine sulfate (10(-6)M) was added at various time points between NA administration and EFS. When anti-VIP serum was administered, subsequent EFS-induced relaxation was attenuated by 20%-55% compared to the control EFS treatments. The degree of attenuation depended upon the frequency of EFS applied, being 20.6% +/- 4.0% at 20 Hz and 54.7% +/- 6.3% at 2 Hz. Atropine administered additionally following anti-VIP serum produced no further attenuation. However, atropine alone was capable of producing up to 23.7% +/- 3.5% attenuation. When anti-VIP serum was administered following atropine, the degree of attenuation that ensured was the sum of the attenuations produced by each of the two substances independently.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetastatic efficacy of niosomal pentoxifylline and its combination with activated macrophages in murine B16F10 melanoma model.

The aims of the present study were a) to enhance the effectiveness of antimetastatic agent, Pentoxifylline (PTX) by encapsulation in niosomes and b) to investigate the anticancer activity by combination therapy involving activated macrophages and PTX solution/PTX niosomes. Niosomes were prepared by lipid film hydration method. Particle size distribution revealed bimodal distribution with median vesicle size of 462 nm. The entrapment efficacy of PTX niosomes was found to be 9.64%. A cumulative release of 82.43% from niosomal suspension was observed at the end of 21 hours. Intravenous administration of niosomal PTX (6 mg/kg and 10 mg/kg) resulted in significant reduction in lung nodules in an experimental metastatic B16F10 model suggesting accumulation of PTX in a distant target organ-lung. Light microscopic observations of histologic sections showed a decrease in number of tumor islands in the lung. Macrophages activated by intraperitoneal injection of Iscove's Modified Dulbecco's Medium (IMDM) containing 20% fetal calf serum (FCS) followed by in vitro incubation with muramyl dipeptide (MDP) were more effective in controlling tumor spread than those activated by FCS alone. Combination therapy of activated macrophages and PTX solution/niosomal PTX showed no additive or synergistic effect in controlling tumor spread. Carbon clearance studies revealed that PTX inhibits the phagocytic ability of activated macrophages, thereby resulting in the failure of combination therapy.

Use of a 64 channel computerized cardiac mapping system in arrhythmia surgery.

A multipoint and computerized intraoperative mapping system has been known to be of value in improving the results of surgery for cardiac arrhythmia. It shows great potential as a new tool in the surgical intervention of the more common and lethal types of supraventricular tachyarrhythmias such as atrial flutter and atrial fibrillation. In addition, it also enhances the ability of the investigators to map and ablate the sometimes fleeting automatic atrial tachycardia. The authors developed a 64 channel computerized cardiac mapping system using a microcomputer (Macintosh IIx) and this has been used for basic research in cardiac electrophysiology as well as in arrhythmia surgery. In this system, bipolar electrograms are obtained from 64 different cardiac sites simultaneously at a sampling rate of 1 Ksample/sec and with a continuous and total data storage of up to 30 seconds. When the reference electrode is selected, delay time from the reference point is displayed on a two dimensional diagram of the heart. This system was used in one patient who underwent a surgical ablation of a ventricular tachycardia in whom we observed a ventricular activation sequence involving a variety of rhythms over several minutes. The system design permits easy expansion to a simultaneous sampling from 256 sites. This 64-channel mapping appeared to have the potential to be of great help in our understanding of cardiac arrhythmia as well as in its diagnosis and surgical treatment.

Prevalence of antibodies to PPD and lipoarabinomannan of Mycobacterium tuberculosis among patients with an indication of fine needle aspiration biopsy.

Recent increase in the incidence of lung cancer often makes it difficult to differentiate between lung cancer and tuberculosis (TB), due to their radiologic similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not high enough. As a rapid screening test for tuberculosis, we evaluated serological tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens. A total of 95 patients with indication of FNAB cytology from initial CT findings were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the lung cancer patients also had TB, indicating much higher prevalence of TB in thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast, only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was therefore significantly greater than that amongst the healthy controls (p<0.001, chi-square test). However, no significant difference in the prevalence of anti-LAM antibodies was found between study subjects and controls. This study demonstrates that thoracic tumor patients have significantly elevated antibodies to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should be cautiously interpreted. A longitudinal investigation on seropositive thoracic tumor patients is required to determine the role of the serological test for TB in lung cancer patients.

Digestibility and dry matter intake of diets containing alfalfa and kenaf.

Two experiments were conducted to determine the dietary value of pellets containing kenaf (Hibiscus cannabinus cv. 'Everglade 41') hay. Averaged across both experiments, kenaf pellets contained 82.6% kenaf hay, 16.6% liquid molasses, and 0.8% mineral oil. The chemical composition of the kenaf pellet was 12.6% crude protein (CP), 41.2% neutral detergent fiber (NDF), and 14.4% acid detergent fiber (ADF). In Exp. 1 (digestion and N balance trial), 18 lambs (body weight [BW] = 36.4 kg) were blocked by BW. Lambs were randomly assigned within a block to Diet 1 (59.5% corn and 40.5% alfalfa pellet), Diet 2 (59.7% corn, 28.4% alfalfa pellets, and 11.9% kenaf pellets), or Diet 3 (59.6% corn, 16.5% alfalfa pellets, and 23.9% kenaf pellets). Diets were formulated so that CP was the first-limiting nutrient. Each diet was limit-fed at 2.4% of BW. Replacing alfalfa pellets with kenaf pellets tended to decrease (P = 0.10) CP and ADF intakes, but increased (P = 0.01) DM digestibility. Diet had no effect (P = 0.33) on N balance. In Exp. 2 (dry matter [DM] intake trial), 32 lambs (BW = 30.4 kg) were blocked by gender and BW. Within a block, lambs were randomly assigned to one of four diets in a 2 x 2 factorial arrangement. Main effects were hay (bermudagrass or fescue) and supplemental protein source (kenaf or alfalfa pellets). Lambs were housed in individual pens with ad libitum access to the assigned hay. Supplemental protein was fed (185 g of DM) once daily. Hay intake was measured weekly for 8 wk. Lambs consumed more (P = 0.002) fescue than bermudagrass hay (743 vs 621 g/ d). Lambs fed fescue hay gained weight more rapidly (P = 0.001) than lambs fed bermudagrass hay (120 vs 72 g/d). Hay intake and ADG were similar (P = 0.90) for lambs fed alfalfa or kenaf pellets. Kenaf hay mixed with molasses and mineral oil can be formed into a pellet. In the diets used in this experiments, kenaf pellets can replace alfalfa pellets in diets fed to lambs without altering forage intake, gain, or N retention.

[A case of ureteral disruption caused by a traffic accident].

Disruption of the ureter is very rarely caused by a blunt trauma, only 12 cases having been reported in Japan. A 20-year-old male suffered from a blunt abdominal trauma in a traffic accident. Although his urinalysis showed no abnormalities, a dull pain in the left flank region persisted for over a week after the injury. Under the suspicion of renal or ureteral injury, an excretory urogram (DIP) was conducted. The form of renal pelvis and calyces was almost normal on both sides, while extravasation of contrast medium was recognized around the lower pole of the left kidney. The retrograde pyelogram of the left side revealed that catheterization was possible up to 30 cm from the ureteral orifice, but the injected medium leaked into the retroperitoneal space making it impossible to visualize the left renal pelvis and calyces. An operation was performed under the diagnosis of left ureteral injury on the 19th day after trauma. The left ureter was completely disrupted 2 cm distally from the ureteropelvic junction. An end to end anastomosis of the ureter was done with 6-0 Dexon sutures. The DIP taken on the 25th day after the operation showed slight dilatation of the left pelvis and calyces. However, the renogram conducted 6 months after the operation demonstrated a normal pattern on both sides.

[Transference of antibiotics into prostatic tissues: sampling method by transurethral resection for the measurement of the concentration of antibiotics in prostatic tissue].

The transeference of two antibiotics, i.e. cefmetazole (CMZ) and fosfomycin (FOM), into prostatic tissues was examined. Prostatic tissue samples were obtained from patients with benign prostatic hyperplasia while undergoing open prostatectomy or transurethral resection of the prostate (TUR-P). 2 g of CMZ or 4 g of FOM was intravenously administered within about 10 minutes starting 1 hour before the removal or resection of the prostate, and blood samples were collected at the end of the administration and during surgery. In TUR-P, resected prostatic tissues were washed with the TUR perfusate and the antibiotic in the tissue was presumed to be released into the perfusate. The following preliminary experiments were, therefore, carried out. The removed prostate was divided into three segments, i.e. urethral region, central region and capsular region, and the CMZ or FOM level in each tissue was measured. The remaining tissues were cut into small pieces for immersion in the TUR perfusate for 10-90 minutes. The tissue fragments were removed every 10 minutes to measure the tissue concentration of CMZ or FOM. The concentration of CMZ or FOM in the prostatic tissues did not vary among the three regions, however it markedly decreased with increase in the period of immersion. This suggested that the concentration of these agents into the prostatic tissues was represented by the concentration in the tissues near the urethra obtained immediately after the start of TUR-P.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical value of testicular lymphangiography in diagnosis of retroperitoneal metastases].

Testicular lymphangiography was performed before retroperitoneal lymph node dissection in 20 patients with testicular tumor. The clinical value of testicular lymphangiography in the diagnosis of retroperitoneal metastases was evaluated retrospectively in comparison with the findings obtained by retroperitoneal lymph node dissection. In 12 patients who had no metastasis in the primary lymph nodes of the testis, testicular lymphangiography showed the lymph vessels to be diverged into 2 to 6 vessels (mean: 3.5) at the level between L2 and L4, and 4 to 10 lymph nodes (mean: 6.2) at the level between L1 and L4 were filled with contrast medium. On the other hand, in 8 patients who had metastases in the primary lymph nodes, several abnormal findings were observed in both lymph vessels and nodes, i.e., discontinuity, extravasation of contrast medium, dilatation, displacement and reflux to the distal side in the lymph vessels, and decrease in number (less than 2), non-visualization, filling defect, displacement and contrastfilling in the contralateral side in lymph nodes. Three to 5 of these abnormal findings were usually found in each case. The extravasation of contrast medium was not a finding specific to cases with lymph node metastases, because it was also found in a few cases without metastases. Testicular lymphangiography is a valuable method to detect primary lymph node metastases from testicular tumor. However, the combination of testicular and foot lymphangiography is imperative to demonstrate wide spread lymph node involvement in the retroperitoneum.

[A case of renal liposarcoma].

A-48-year-old male was admitted to our hospital with a right renal tumor. He received radical nephrectomy immediately. Histological examination of surgical specimen revealed renal liposarcoma, which consisted of mixed type of pleomorphic and well differentiated subtypes. Multiple tumorous lesions were scattered in the renal parenchyma. He has been alive without disease for 2 years and 7 months after surgery. Only 23 cases of renal liposarcoma have been reported in Japan.

[A case of occult testicular tumor].

A 43-year-old male presented with a left supraclavicular mass as well as an upper abdominal mass. Biopsy of the supraclavicular mass revealed seminoma with components of both embryonal carcinoma and choriocarcinoma. Right orchiectomy was performed because physical examination showed that the left testis was normal but the right testis was slightly atrophic. The primary tumor which was approximately 1 cm in diameter was found in the right testis and histological examination revealed seminoma. When germ cell tumor is found in a region other than the gonads, either primary extragonadal germ cell tumor or occult testicular tumor is considered. To differentiate between the two, it is imperative to make careful histological exploration of the testes.

[Analysis of brain CT in 120 patients with human cysticercosis].

A study on brain CT was made in 120 patients of human cysticercosis, which is a rare disease in Japan and clinical symptoms and laboratory data for the diagnosis were also discussed. From the point of therapeutic view, we proposed a new differentiation on brain CT of human cysticercosis, which is divided into two groups according to the alive or dead parasite. Furthermore, we proposed a new type named multiple large and small cysts type on brain CT. The idea of diagnostic standard was made integrating brain CT image, clinical symptoms and laboratory data.

ASXL1 and DNMT3A mutation in a cytogenetically normal B3 thymoma.

The molecular drivers of thymoma are poorly understood. Outside of the identification of rarely occurring epidermal growth factor receptor and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog mutations via candidate gene sequencing, mutations in common cancer genes have yet to be observed. Only a single thymoma genome sequence has been previously reported, with no mutations in known cancer genes identified. Thus, we attempted to identify somatic driver mutations in a cytogenetically normal thymoma. A stage IVB type B3 thymoma from a 47-year-old male of Asian descent with no history of myasthenia gravis or other autoimmune condition was genomically evaluated. Exome sequencing and low-pass whole-genome sequencing was performed to identify somatic point mutations, copy number changes and structural variants. Mutations in known tumor suppressors DNMT3A (p.G728D) and ASXL1 (p.E657fs), consistent with mutations of known consequence in acute myeloid leukemia, were identified. Contrary to a previous report, this finding suggests the genetic etiology of thymomas may not be fundamentally distinct from other tumor types. Rather, these findings suggest that further sequencing of cytogenetically normal thymoma samples should reveal the specific molecular drivers of thymoma.