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Background: The number of women in Japan who continue working after childbirth is on the rise. Over the past few years, Japan's cancer mortality rate has increased. About 50% of all cancer deaths among Japanese women aged 25-64 are caused by lung, gastric, pancreatic and colorectal cancers. This study aims to examine the difference in mortality risk for key cancers among women and explore the effect of the economic crisis in the mid-1990s separately for occupational and industrial categories., Methods: Data from 1980 to 2015 were gathered from the Japanese Population Census and National Vital Statistics conducted in the same year. A Poisson regression analysis was used to estimate mortality risk and mortality trends for lung, gastric, pancreatic and colorectal cancer among Japanese working women aged 25-64 years., Results: Across most industrial and occupational groups, the trends in age-standardised cancer mortality rate for women have declined. Workers in management, security and transportation have a higher cancer mortality risk than sales workers. The risk of death from all four cancers is higher for workers in the mining and electricity industries than for wholesale and retail workers., Conclusion: To improve the health and well-being of employed Japanese women, it is crucial to monitor cancer mortality trends. Using these population-level quantitative risk estimates, industry- and occupation-specific prevention programmes can be developed to target women at higher cancer risk and enable the early detection and treatment of cancer., (© 2022. The Author(s).)

Background: Reducing health inequalities is an important public health challenge. Many studies have examined the widening health gap by occupational class among men, but few among women. We therefore estimated variation in absolute and relative mortality by occupational category across four leading causes of mortality-cancer, ischaemic heart disease, cerebrovascular disease, and suicide-to explore how occupational class is associated with health among working women aged 25-64 in Japan., Methods: We conducted a repeated cross-sectional study using Poisson regression analysis on each five-yearly mortality data from 1980 to 2015, obtained from the National Vital Statistics and the Japanese Population Census., Results: There was a decreasing trend in mortality from all cancers, ischaemic heart disease, cerebrovascular disease, and suicide among women in all occupational groups from 1980 to 2015. Agriculture workers had higher risk of mortality than professional workers for all four causes of death. The absolute difference in mortality rates for all cancers and cerebrovascular disease was higher in 2000-2015 than 1980-1995. The mortality trend among clerks and sales workers decreased after 2000, except for suicide., Conclusions: Mortality rates from all four causes are higher among agriculture workers compared to professional workers, and attention is needed to reduce this mortality gap. Continuous monitoring of ongoing mortality trends is essential to ensure better health and wellbeing in Japan., (© 2022. The Author(s).)

Background: The prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is alarmingly high. Reintroduction of colistin as last resort treatment in the infections caused by drug-resistant Gram-negative bacteria has led to the emergence and spread of colistin resistance. This study was designed to determine the prevalence of drug-resistance among beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae, isolated from the clinical specimens received at a tertiary care centre of Kathmandu, Nepal during the period of March to August, 2019., Methods: A total of 3216 different clinical samples were processed in the Microbiology laboratory of Kathmandu Model Hospital. Gram-negative isolates (E. coli and K. pneumoniae) were processed for antimicrobial susceptibility test (AST) by using modified Kirby-Bauer disc diffusion method. Drug-resistant isolates were further screened for extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), carbapenemase and K. pneumoniae carbapenemase (KPC) production tests. All the suspected enzyme producers were processed for phenotypic confirmatory tests. Colistin resistance was determined by minimum inhibitory concentration (MIC) using agar dilution method. Colistin resistant strains were further screened for plasmid-mediated mcr-1 gene using conventional polymerase chain reaction (PCR)., Results: Among the total samples processed, 16.4% (529/3216) samples had bacterial growth. A total of 583 bacterial isolates were recovered from 529 clinical samples. Among the total isolates, 78.0% (455/583) isolates were Gram-negative bacteria. The most predominant isolate among Gram-negatives was E. coli (66.4%; 302/455) and K. pneumoniae isolates were 9% (41/455). In AST, colistin, polymyxin B and tigecycline were the most effective antibiotics. The overall prevalence of multidrug-resistance (MDR) among both of the isolates was 58.0% (199/343). In the ESBL testing, 41.1% (n = 141) isolates were confirmed as ESBL-producers. The prevalence of ESBL-producing E. coli was 43% (130/302) whereas that of K. pneumoniae was 26.8% (11/41). Similarly, 12.5% (43/343) of the total isolates, 10.9% (33/302) of E. coli and 24.3% of (10/41) K. pneumoniae were resistant to carbapenem. Among 43 carbapenem resistant isolates, 30.2% (13/43) and 60.5% (26/43) were KPC and MBL-producers respectively. KPC-producers isolates of E. coli and K. pneumoniae were 33.3% (11/33) and 20% (2/10) respectively. Similarly, 63.6% (21/33) of the E. coli and 50% (5/10) of the K. pneumoniae were MBL-producers. In MIC assay, 2.2% (4/179) of E. coli and 10% (2/20) of K. pneumoniae isolates were confirmed as colistin resistant (MIC ≥ 4 µg/ml). Overall, the prevalence of colistin resistance was 3.1% (6/199) and acquisition of mcr-1 was 16.6% (3/18) among the E. coli isolates., Conclusion: High prevalence of drug-resistance in our study is indicative of a deteriorating situation of AMR. Moreover, significant prevalence of resistant enzymes in our study reinforces their roles in the emergence of drug resistance. Resistance to last resort drug (colistin) and the isolation of mcr-1 indicate further urgency in infection management. Therefore, extensive surveillance, formulation and implementation of effective policies, augmentation of diagnostic facilities and incorporation of antibiotic stewardship programs can be some remedies to cope with this global crisis.

Background: Dengue is one of the newest emerging diseases in Nepal with increasing burden and geographic spread over the years. The main objective of this study was to explore the epidemiological patterns of dengue since its first outbreak (2006) to 2019 in Nepal., Methods: This study is a retrospective analysis that covers the last 14 years (2006-2019) of reported dengue cases from Epidemiology Diseases Control Division (EDCD), Ministry of Health and Population, Government of Nepal. Reported cases were plotted over time and maps of reported case incidence were generated (from 2016 through 2019). An ecological analysis of environmental predictors of case incidence was conducted using negative binomial regression., Results: While endemic dengue has been reported in Nepal since 2006, the case load has increased over time and in 2019 a total of 17 992 dengue cases were reported from 68 districts (from all seven provinces). Compared to the case incidence in 2016, incidence was approximately five times higher in 2018 [incidence rate ratio (IRR): 4.8; 95% confidence interval (CI) 1.5-15.3] and over 140 times higher in 2019 (IRR: 141.6; 95% CI 45.8-438.4). A one standard deviation increase in elevation was associated with a 90% decrease in reported case incidence (IRR: 0.10; 95% CI 0.01-0.20). However, the association between elevation and reported cases varied across the years. In 2018 there was a cluster of cases reported from high elevation Kaski District of Gandaki Province. Our results suggest that dengue infections are increasing in magnitude and expanding out of the lowland areas to higher elevations over time., Conclusions: There is a high risk of dengue outbreak in the lowland Terai region, with increasing spread towards the mid-mountains and beyond as seen over the last 14 years. Urgent measures are required to increase the availability of diagnostics and resources to mitigate future dengue epidemics.

Background: Cesarean section (CS) is a major component of emergency obstetric care. There has been a substantial rise in the rate of CS in private institutions in Nepal which might reflect the successful implementation of delivery schemes introduced by the government extended to the private organizations alternatively, it may also reflect the need for more public health care facilities to provide maternal and child health care services. Hence, the objective of this study was to examine the trends in institutional-based CS rates in Nepal along with its correlates over time., Methods: We used the National Demographic and Health Survey (NDHS) data collected every 5 years, from 1996 to 2016. The trend in CS rates based on five waves of NDHS data along with its correlates were examined using multivariable logistic regression models after adjusting for socio-demographics and pregnancy-related variables., Results: We included 20,824 reproductive-aged women who had a history of delivery within the past 5 years. The population-based CS rate increased from 0.9% in 1996 [95% CI: (0.6-1.2) %] to 10.2% in 2016 [95% CI: (8.9-11.6) %, p < 0.01] whereas the institutional-based CS rate increased from 10.4% in 1996 [95% CI: (8.3-12.9) %] to 16.4% in 2016 [95% CI: (14.5-18.5) %, p < 0.01]. Private institutions had a nearly 3-fold increase in CS rate (8.9% in 1996 [95% CI: (4.8-16.0) %] vs. 26.3% in 2016[95% CI: (21.9-31.3) %]. This was also evident in the trend analysis where the odds of having CS was 3.58 times higher [95% CI: (1.83-7.00), p < 0.01] in 2016 than in 1996 in the private sectors, while there was no evidence of an increase in public hospitals (10.9% in 1996 to 12.9% in 2016; p for trend > 0.05). Education of women, residence, wealth index, parity and place of delivery were significantly associated with the CS rate., Conclusion: Nepal has observed a substantial increase in cesarean delivery over the 20 years, which might indicate a successful implementation of the safe motherhood program in addressing the Millennium Development Goals and Universal Health Care agenda on maternal and child health. However, the Nepal government should examine existing disparities in accessibility of emergency obstetric care services, such as differences in CS between public and private sectors, and promote equity in maternal and child health care services accessibility and utilization.

Background: Plasmid-mediated resistance to the last-resort drugs: carbapenems and colistin is an emerging public health threat. The studies on the prevalence and co-expression of resistant genes among livestock and human pathogens are rare in Nepal. This is the first study in Nepal exploring the prevalence and co-existence of colistin resistance gene, mcr -1 along with carbapenemase resistance gene, OXA -48 in Escherichia coli isolated from poultry and clinical specimens., Methods: A total of 240 rectal swabs from chickens of five different poultry farms of Kathmandu valley and 705 mid-stream urine samples from human subjects attending Kantipur Hospital, Kathmandu were collected between August, 2018 and March, 2019. Rectal swabs and urine specimens were cultured. E. coli isolated from the specimens were screened for antimicrobial susceptibility testing (AST) using disk diffusion method'. Minimum inhibitory concentration (MIC) of colistin was determined by agar dilution method using 0.5 µg/ml to 32 µg/ml. The E. coli isolates were first screened for mcr - 1 followed by screening for OXA - 48 genes using conventional Polymerase chain reaction (PCR)., Results: Of the total samples analyzed, E. coli was isolated from 31.7% (76/240) of poultry and 7.9% (56/705) of clinical specimens. In AST, 80% (61/76) of E. coli from poultry and 79% (44/56) from clinical specimens were MDR. The phenotypic prevalence of colistin resistance in poultry specimens were 31.6% (24/76) and clinical specimens were 21.4% (12/56). In PCR assay, 27.6% (21/76) of poultry and 19.6% (11/56) of clinical isolates had colistin resistant mcr - 1 gene. MICs value of E. coli isolates ranged from 4 to 32 (µg/ml) in both clinical and poultry isolates. Prevalence of co-existing carbapenem resistance gene, OXA -48, among colistin resistant mcr -1 positive isolates was 38% (8/21) in poultry specimens and 18.2% (2/11) in clinical specimens., Conclusions: The high prevalence of colistin and carbapenem resistant genes, and their co-existence in plasmid DNA of E. coli isolates in this study suggests the possible spread to other animal, human and environmental pathogens. Molecular methods in addition to the conventional diagnostics in laboratories can help in early diagnosis, effective management and control of their potential transmission., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide despite the development of various therapeutic strategies. A better understanding of the mechanisms responsible for HCC initiation and progression is essential for the development of more effective therapies. The cancer stem cell (CSC) model has provided new insights into the development and progression of HCC. CSCs are specialized tumor cells that are capable of self-renewal and have long-term repopulation potential. As they are important mediators of tumor proliferation, invasion, metastasis, therapy resistance, and cancer relapse, the selective targeting of this crucial population of cells has the potential to improve HCC patient outcomes and survival. In recent years, the role of epithelial-to-mesenchymal transition (EMT) in the advancement of HCC has gained increasing attention. This multi-step reprograming process resulting in a phenotype switch from an epithelial to a mesenchymal cellular state has been closely associated with the acquisition of stem cell-like attributes in tumors. Moreover, CSC mediates tumor metastasis by maintaining plasticity to transition between epithelial or mesenchymal states. Therefore, understanding the molecular mechanisms of the reprograming switches that determine the progression through EMT and generation of CSC is essential for developing clinically relevant drug targets. This review provides an overview of the proposed roles of CSC in HCC and discusses recent results supporting the emerging role of EMT in facilitating hepatic CSC plasticity. In particular, we discuss how these important new insights may facilitate rational development of combining CSC- and EMT-targeted therapies in the future.

Background: The border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. For two decades, it has been hypothesized that transcription factors such as Distal-less (Dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. In particular, it has been suggested that Dll is a determinant for eyespot size. However, functional evidence for this hypothesis has remained incomplete, due to technical difficulties., Results: Here, we show that ectopically expressed Dll induces ectopic elemental color patterns in the adult wings of the blue pansy butterfly, Junonia orithya (Lepidoptera, Nymphalidae). Using baculovirus-mediated gene transfer, we misexpressed Dll protein fused with green fluorescent protein (GFP) in pupal wings, resulting in ectopic color patterns, but not the formation of intact eyespots. Induced changes included clusters of black and orange scales (a basic feature of eyespot patterns), black and gray scales, and inhibition of cover scale development. In contrast, ectopic expression of GFP alone did not induce any color pattern changes using the same baculovirus-mediated gene transfer system., Conclusions: These results suggest that Dll plays an instructive role in the development of color pattern elements in butterfly wings, although Dll alone may not be sufficient to induce a complete eyespot. This study thus experimentally supports the hypothesis of Dll function in eyespot development.

Background: Candidate genes for color pattern formation in butterfly wings have been known based on gene expression patterns since the 1990s, but their functions remain elusive due to a lack of a functional assay. Several methods of transferring and expressing a foreign gene in butterfly wings have been reported, but they have suffered from low success rates or low expression levels. Here, we developed a simple, practical method to efficiently deliver and express a foreign gene using baculovirus-mediated gene transfer in butterfly wings in vivo., Results: A recombinant baculovirus containing a gene for green fluorescent protein (GFP) was injected into pupae of the blue pansy butterfly Junonia orithya (Nymphalidae). GFP fluorescence was detected in the pupal wings and other body parts of the injected individuals three to five days post-injection at various degrees of fluorescence. We obtained a high GFP expression rate at relatively high virus titers, but it was associated with pupal death before color pattern formation in wings. To reduce the high mortality rate caused by the baculovirus treatment, we administered an anti-gp64 antibody, which was raised against baculovirus coat protein gp64, to infected pupae after the baculovirus injection. This treatment greatly reduced the mortality rate of the infected pupae. GFP fluorescence was observed in pupal and adult wings and other body parts of the antibody-treated individuals at various degrees of fluorescence. Importantly, we obtained completely developed wings with a normal color pattern, in which fluorescent signals originated directly from scales or the basal membrane after the removal of scales. GFP fluorescence in wing tissues spatially coincided with anti-GFP antibody staining, confirming that the fluorescent signals originated from the expressed GFP molecules., Conclusions: Our baculovirus-mediated gene transfer system with an anti-gp64 antibody is reasonably efficient, and it can be an invaluable tool to transfer, express, and functionally examine foreign genes in butterfly wings and also in other non-model insect systems.