Nightlife clusters of coronavirus disease in Tokyo between March and April 2020.

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.

Development and validation of the comprehensive assessment scale for chemotherapy-induced peripheral neuropathy in survivors of cancer.

BACKGROUND: Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity. METHODS: We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach's α. RESULTS: Factor analysis showed that the structure consisted of 15 items in four dimensions: "Threatened interference in daily life by negative feelings", "Impaired hand fine motor skills", "Confidence in choice of treatment/management," and "Dysesthesia of the palms and soles." The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity. CONCLUSIONS: The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.

Carrier status of leptospirosis among cattle in Sri Lanka: a zoonotic threat to public health.

Leptospirosis is a zoonotic disease of global importance and one of the notifiable diseases in Sri Lanka. Recent studies on human leptospirosis have suggested that the cattle could be one of the important reservoirs for human infection in the country. However, there is a dearth of local information on bovine leptospirosis, including its implications for human transmission. Thus, this study attempted to determine the carrier status of pathogenic Leptospira spp in cattle in Sri Lanka. A total of 164 cattle kidney samples were collected from the meat inspection hall in Colombo city during routine inspection procedures conducted by the municipal veterinary surgeons. The DNA was extracted and subjected to nested PCR for the detection of leptospiral flaB gene. Amplicons were sequenced, and phylogenic distances were calculated. Of 164 samples, 20 (12.2%) were positive for flaB-PCR. Sequenced amplicons revealed that Leptospira species were deduced to L. borgpetersenii (10/20, 50%), L. kirschneri (7/20, 35%) and L. interrogans (3/20, 15%). The results indicate that a high proportion of the sampled cattle harbour a variety of pathogenic Leptospira spp, which can serve as important reservoirs for human disease.

Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer.

Chitinase 3-like 1 (CHI3L1), one of the mammalian members of the chitinase family, is expressed in several types of human cancer, and elevated serum level of CHI3L1 is suggested to be a biomarker of poor prognosis in advanced cancer patients. However, the overall biological function of CHI3L1 in human cancers still remains unknown. Studies were performed to characterize the role of CHI3L1 in cancer pathophysiology utilizing human colorectal cancer samples and human cell lines. Plasma protein and tissue mRNA expression levels of CHI3L1 in colorectal cancer were strongly upregulated. Immunohistochemical analysis showed that CHI3L1 was expressed in cancer cells, and CHI3L1 expression had a significant association with the number of infiltrated macrophages and microvessel density (MVD). By utilizing transwell migration and tube-formation assays, overexpression of CHI3L1 in SW480 cells (human colon cancer cells) enhanced the migration of THP-1 cells (human macrophage cells) and HUVECs (human endothelial cells), and the tube formation of HUVECs. The knockdown of CHI3L1 by RNA interference or the neutralization of CHI3L1 by anti-CHI3L1 antibody displayed strong suppression of CHI3L1-induced migration and tube formation. Cell proliferation assay showed that CHI3L1 overexpression significantly enhanced the proliferation of SW480 cells. Enzyme-linked immunosorbent assay (ELISA) analysis showed that CHI3L1 increased the secretion of inflammatory chemokines, IL-8 and monocyte chemoattractant protein-1 (MCP-1), from SW480 cells through mitogen-activated protein kinase (MAPK) signaling pathway. Both neutralization of IL-8 or MCP-1 and inhibition or knockdown of MAPK in SW480 cells significantly inhibited CHI3L1-induced migration and tube formation. In a xenograft mouse model, overexpression of CHI3L1 in HCT116 cells (human colon cancer cells) enhanced the tumor growth as well as macrophage infiltration and MVD. In conclusion, CHI3L1 expressed in colon cancer cells promotes cancer cell proliferation, macrophage recruitment and angiogenesis. Thus, the inhibition of CHI3L1 activity may be a novel therapeutic strategy for human colorectal cancer.

Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits.

We have developed an animal model of learning and memory impairment associated with activation of microglia in the mouse brain. Injection of lipopolysaccharide into the CA1 region of the mouse hippocampus resulted in an increased production of inflammatory cytokines, such as interleukin-1ß. Immunostaining for interleukin-1ß revealed an increase in the signal at 6 hr after lipopolysaccharide injection. Immunopositive cells for interleukin-1ß were colocalized with those immunopositive for CD11b. When subacute lipopolysaccharide treatment (20 µg/2 µl/injection, bilaterally for 5 consecutive days) was performed, long-term activation of microglia and learning and memory deficits as evaluated using a step-through passive avoidance test were observed in the wild-type mice. Gene expression of the N-methyl-D-aspartate receptor NR1 and NR2A subunits was also decreased by the lipopolysaccharide treatment. In contrast, activation of microglia and the associated behavioral deficits were not observed in mice lacking interleukin-1α and -1ß following the subacute lipopolysaccharide treatment, together with little change in the gene expression of NR1 and NR2A subunits. However, the subacute lipopolysaccharide treatment produced almost similar changes in those parameters in the tumor necrosis factor-α knockout mice as in the wild-type animals. The injection of interleukin-1ß neutralizing antibody with lipopolysaccharide for 5 consecutive days resulted in the improvement of lipopolysaccharide-induced learning and memory deficits. These findings suggest that the expression of interleukin-1 plays an important role in lipopolysaccharide-induced activation of microglia and the associated functional deficits in learning and memory.

Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness.

BACKGROUND: Bartter syndrome (BS) is a genetic disorder accompanied by hypokalaemic metabolic alkalosis. BS with sensorineural deafness (SND, OMIM602522) is a newly identified phenotype caused by mutations in the BSND gene that encodes barttin, a beta-subunit for chloride channel ClC-Ka and ClC-Kb and classified as type IV BS. Type IV BS features the most severe phenotype entailing life-threatening neonatal volume depletion and chronic renal failure developing during infancy. A recent report described a case of BS with SND from a consanguineous family who showed homozygous mutations in the CLCNKA and CLCNKB genes. This case indicated the possibility of the occurrence of digenic inheritance in BS with SND resulting from double mutations in the CLCNKA and CLCNKB genes. SUBJECT AND RESULTS: The current report concerns a 2-year-old girl from a non-consanguineous family with BS accompanied by SND. In our case, four loss-of-function mutations, consisting of mutations in both parental alleles in both CLCNKA and CLCNKB, were identified. The paternal allele had a nonsense mutation (Q260X) in CLCNKA and a splicing site mutation (IVS17+1 g>a) in CLCNKB. The maternal allele had a large deletion mutation (about 12 kbp) extending from CLCNKA to CLCNKB. Our case provides clear evidence that loss-of-function alleles in both alleles of both CLCNKA and CLCNKB results in a phenotype indistinguishable from that of mutations in BSND (type IV BS). CONCLUSIONS: Recent advances in genetics have resulted in a better understanding of many human inherited diseases, but most of them are monogenic disorders and more complex inheritance patterns remain unresolved. Our case provides clear evidence of digenic inheritance outside the scope of Mendelian inheritance disorders.

Estimating nurses' workload using the Diagnosis Procedure Combination in Japan.

AIM: To examine the methods used to estimate nurse staffing levels in acute care settings with Diagnosis Related Groups, which in Japan are called the Diagnosis Procedure Combination (DPC). METHODS: For estimating staffing requirements, the study used four DPC groups: (1) acute or recurrent myocardial infarction (AMI) with stenting, (2) angina pectoris with coronary artery bypass grafting (CABG), (3) sub-arachnoid haemorrhage (SAH) with clipping surgery, and (4) cerebral infarction with carotid endarterectomy (CEA). Registered nurses with more than 3-year nursing experience in nine university hospitals in the Tokyo metropolitan area completed self-report questionnaires in order to obtain nursing care time and care intensity per each DPC. The concordance rate was measured by Kendall's coefficient of concordance. The relationship between the care time and the care intensity was examined by a time series graph per DPC. Care intensity consisted of professional judgement, mental effort for helping patients, professional skill, physical effort for providing activities of daily living support, and nurse stress, based on the Hsiao and colleagues' model of resource-based relative value scale. RESULTS: Twenty-five nurses in nine university hospitals answered for a hypothetical typical patient with AMI and with CABG, and 28 nurses in nine university hospitals answered for a hypothetical typical patient with SAH and with CEA. Kendall's coefficient of concordance was 0.896 for AMI, 0.855 for CABG, 0.848 for SAH, 0.854 for CEA. The time series data of the care time and the care intensity items showed different patterns for each DPC. CONCLUSION: The DPC for cardiovascular and cerebral surgical procedures can be used for estimating nurses' workload.

Transcriptional expression of survivin and its splice variants in cervical carcinomas.

The objective of this study was to evaluate transcriptional expression of survivin and the two splice variants (survivin-2B and survivin-DeltaEx3) in cervical carcinomas. The gene expression levels of survivin and its splice variants in 11 human cervical carcinoma cell lines and 20 malignant and 12 normal cervical tissue samples were analyzed using quantitative reverse transcription-polymerase chain reaction analysis. Gene expression levels of survivin and survivin-DeltaEx3 in cell lines were higher than those in normal cervical tissues (P= 0.0193 and 0.0489). Transcript levels of survivin and survivin-DeltaEx3 in carcinoma tissues were also higher than those in normal controls (P= 0.0016 and 0.0011). Gene expression levels of survivin and survivin-DeltaEx3 in adenocarcinomas were statistically higher than those in squamous cell carcinomas (P= 0.0260 and 0.0487). There was no significant difference in survivin-2B gene expression between malignant and normal cervical samples or different histologic types. The ratios of survivin-2B/survivin and survivin-DeltaEx3/survivin in carcinoma tissues were higher than those in normal controls (P= 0.0288 and 0.0081). Interestingly, the ratio of survivin-2B/survivin was increased in the patients with higher stages and with pelvic lymph node metastasis (P= 0.0205 and 0.0437), respectively. We conclude that survivin and its splice variants might be involved in the pathogenesis and development of cervical carcinomas.

Activation of the c-myc p1 promoter in Burkitt's lymphoma by the hs3 immunoglobulin heavy-chain gene enhancer.

The expression of c-myc is deregulated in Burkitt's lymphoma by the translocation t(8;14). Most of the increased c-myc expression is from the P1 promoter, which is normally a minor promoter. How the P1 promoter is activated by the immunoglobulin heavy chain gene enhancers is not understood. We identified a YY1 site in the immunoglobulin heavy-chain gene HS3 enhancer, which increased c-myc P1 promoter activity, and a MARE site, which decreased c-myc P1 activity. Small Maf proteins bound to the MARE site both in vitro and in vivo, recruited histone deacetylase 2, and resulted in deacetylation of histones H3 and H4 at the c-myc promoter region. In contrast, YY1 recruited CBP and increased histone acetylation at the c-myc promoter. Rb interacts with YY1 to prevent DNA binding in normal B cells, but no significant interaction with YY1 was detected in Burkitt's cells, and binding of YY1 to the HS3 enhancer was observed by chromatin immunoprecipitaton. Increased expression of MafK and/or decreased expression of YY1 by silencing RNA downregulated endogenous c-myc mRNA levels and increased the sensitivity of the cells to doxorubicin. Mutation of the major active sites (nuclear factor-kappa B and YY1) in the enhancers prevented c-myc activation.

Fas gene promoter -670 polymorphism in gynecological cancer.

Single-nucleotide polymorphism at -670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas -670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08-6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05-2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter -670 may be associated with the risk of cervical cancer in a Japanese population.

Embolisation of proximal anastomotic pseudoaneurysm developing after surgical repair of abdominal aortic aneurysm with a bifurcated graft with n-butyl cyanoacrylate.

We report a 60-year-old man who after undergoing surgical repair of an abdominal aortic aneurysm with a bifurcated graft subsequently developed a proximal anastomotic pseudoaneurysm, which was successfully treated by embolisation with n-butyl cyanoacrylate.

Stimulation of the nucleus basalis of Meynert increases diameter of the parenchymal blood vessels in the rat cerebral cortex.

To verify the hypothesis that stimulation of the nucleus basalis of Meynert (NBM) induces vasodilation in the cerebral cortical parenchyma, we investigated whether the diameter of parenchymal blood vessels of rat parietal cortex is increased during stimulation of NBM using histological techniques. The parietal cortex was fixed by immersion fixation in situ during focal electrical stimulation of the NBM, which increased cortical blood flow. Cortical tissues were sectioned horizontally to the cortical surface, and the parenchymal blood vessels were morphometrically analyzed using electron microscopy. Mean inner diameter of the parenchymal blood vessels in NBM stimulated rats (5.51+/-0.33 microm) was significantly larger than that in non-stimulated control rats (4.93+/-0.23 microm). The result suggests that functional vasodilation in the cortical parenchyma during NBM stimulation correlates with histologically observed vasodilation in the cortical parenchyma.

Ascending aortic cannulation via left thoracotomy for distal aortic arch aneurysm operation.

We have cannulated the ascending aorta for cardiopulmonary bypass via left thoracotomy in order to avoid conventional retrograde perfusion from the femoral arteries, which is associated with an increased risk of cerebral embolism. We use silk sutures to retract the anterior margin of the opened pericardium from the chest wall, which provides good exposure and easy control of the ascending aorta. Between July 1997 and November 2000, cannulation proved easy to do and reliable in 24 serial patients.

Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis.

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, alpha- and beta-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, alpha- or beta-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, alpha- and beta-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.

Analysis of the gene expression of SPARC and its prognostic value for bladder cancer.

PURPOSE: We analyzed the gene expression of the glycoprotein termed secreted protein, acidic and rich in cysteine (SPARC), also called osteonectin and BM40, in bladder cancer and its relationship with conventional clinical-histopathological manifestations, evaluated its prognostic value for patient outcome and determined the possible mechanism underlying the effect of SPARC on bladder cancer progression. MATERIALS AND METHODS: Tissue samples from 63 patients with bladder cancer were used for analysis. Gene expression levels of SPARC and matrix metalloproteinase-2 were analyzed using reverse transcription-polymerase chain reaction. Correlations of the expression of SPARC with histopathological findings or patient outcome and with matrix metalloproteinase-2 were evaluated. RESULTS: Significantly higher expression of SPARC was observed in grades 3 and 2 than in grade 1 tumors (p <0.001 and <0.05, respectively). Stage T2 or greater invasive tumors expressed a significantly higher level of SPARC than stages T1 or less superficial tumors (p <0.0001). Patients in whom the lesions showed high SPARC expression had a significantly worse prognosis than those with low SPARC expression disease (p <0.0001). Even in those with invasive bladder cancer high SPARC expression was associated with significantly worse survival than low expression (p <0.01). Moreover, gene expression of SPARC significantly correlated with matrix metalloproteinase-2 gene expression (p <0.0001), implying that regulation of matrix metalloproteinase-2 expression may be a possible mechanism underlying the effect of SPARC on bladder cancer progression. CONCLUSIONS: A significant correlation was detected of the gene expression level of SPARC with histological grade, pathological stage and bladder cancer prognosis. SPARC may have an important role in bladder cancer progression and provide some additional information in patients with bladder cancer.