Highly porous nature of a primitive asteroid revealed by thermal imaging.

Carbonaceous (C-type) asteroids1 are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites2,3 and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth's atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)4 onboard the spacecraft Hayabusa25, indicating that the asteroid's boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m-2 s-0.5 K-1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites6 and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect7,8. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites6. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity9 of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies10.

Antiproliferative Effect of N-Heterocyclo-Coumarin Derivatives against Multidrug-Resistant Cells.

Chemotherapy refers principally to the use of small molecules to treat cancer, and natural product derivatives have been main sources of clinically using anticancer drugs. While the coumarin skeleton does not inhibit cell growth, its derivatives are often active, and numerous coumarins have been examined for antiproliferative activity against human cancer cell lines. In this study, 16 novel coumarin derivatives (1, 1a-5a, 1b, 2b, 6b, 7b, 8-13) with attached N-heterocycles, including aminopyrrolidine, aminopiperidine, aminoazepane, and indoline, were prepared and ultimately esterified or amidated with alcohols or amines, respectively. All synthesized N-heterocycles containing coumarin derivatives with alcohols, amines, and carboxylic acids were assessed for antiproliferative activity against several human cancer cell lines, containing triple-negative breast cancer (TNBC) as well as a P-glycoprotein (P-gp) overexpressing multidrug-resistant (MDR) KB subline KB-VIN. Five coumarin derivatives (3a-5a, 12, 13) showed no effect (IC50 >40 µM) against all tested cell lines. In contrast, derivative 1a showed broad-spectrum activity against four cell lines, while 1b and 10 were nearly twice as selective for KB-VIN cells as the parent KB. The coumarin derivatives 1a, 1b, and 10 were optimal for antiproliferative activity in this study and could provide a new avenue for overcoming MDR tumors. Derivatives 1a, 1b, and 10 showed MDR cell-selective antiproliferative activity, indicating that N-heterocycle-coumarins exert previously unexplored bioactivity with selective action on MDR cancer cells.

A prospective cohort study on the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam.

Tobacco consumption, as a worldwide problem, is a risk factor for several types of cancer. In Vietnam, tobacco consumption in the form of waterpipe tobacco smoking is common. This prospective cohort study aimed to study the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam. A total of 25,619 eligible participants were followed up between 2008 and 2019. Waterpipe tobacco and cigarette smoking data were collected; semi-quantitative food frequency and lifestyle questionnaires were also utilized. Gastric cancer mortality was determined via medical records available at the state health facilities. A Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). During 314,992.8 person-years of follow-up, 55 men and 25 women deaths due to gastric cancer were identified. With never-smokers as the reference, the risk of gastric cancer mortality was significantly increased in participants who were ever-smoking (HR = 2.43, 95% CI = 1.35-4.36). The positive risk was also observed in men but was not significantly increased in women. By types of tobacco use, exclusive waterpipe smokers showed a significantly increased risk of gastric cancer mortality (HR = 3.22, 95% CI = 1.67-6.21) but that was not significantly increased in exclusive cigarette smokers (HR = 1.90, 95% CI = 0.88-4.07). There was a significant positive association between tobacco smoking and gastric cancer death for indicators of longer smoking duration, higher frequency per day, and cumulative frequency of both waterpipe and cigarette smoking. Waterpipe tobacco smoking would significantly increase the risk of gastric cancer mortality in the Vietnamese population. Further studies are required to understand the waterpipe tobacco smoking-driven gastric cancer burden and promote necessary interventions.

Stability of hen egg-white lysozyme during embryonic development.

It is of interest to determine whether and how egg-white proteins are maintained in fertile eggs. We previously observed that egg-white ovalbumin attained high stability during embryogenesis. Herein, we observed that the total mass of egg white and that of its gross protein content showed a decrease according to the days of incubation. The total bacteriolytic activity also lowered, in accord with previous observations. We purified lysozyme from egg-white samples on several incubation days. These purified lysozyme proteins were observed to have enzymatic and bacteriolytic activities against Micrococcus lysodeikticus as well as growth-inhibition potency against Staphylococcus aureus. As the embryogenesis proceeded, the purified lysozyme showed changes in Km and Vmax, a small decrease in the denaturation temperature, and symptoms of an increase in surface hydrophobicity. These results indicate that the lysozyme protein maintained its enzymatic and antibacterial activities until the late period of incubation while undergoing slight conformational changes.

Changes in cause-specific mortality trends across occupations in working-age Japanese women from 1980 to 2015: a cross-sectional analysis.

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.

Occupation- and industry-specific cancer mortality among Japanese women from 1980 to 2015.

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.

Proactive Engagement of the Expert Meeting in Managing the Early Phase of the COVID-19 Epidemic, Japan, February-June 2020.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Malaria rapid diagnostic test (HRP2/pLDH) positivity, incidence, care accessibility and impact of community WASH Action programme in DR Congo: mixed method study involving 625 households.

BACKGROUND: Malaria is one of the most prevalent and deadliest illnesses in sub-Saharan Africa. Despite recent gains made towards its control, many African countries still have endemic malaria transmission. This study aimed to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory Water, Sanitation and Hygiene (WASH) Action programme. METHODS: Mixed method research was conducted in two semi-rural towns, Mbanza-Ngungu (a WASH action site) and Kasangulu (a WASH control site) in DRC between 1 January 2017 through March 2018, involving 625 households (3,712 household members). Baseline and post-intervention malaria surveys were conducted with the use of World Bank/WHO Malaria Indicator Questionnaire. An action research consisting of a six-month study was carried out which comprised two interventions: a community participatory WASH action programme aiming at eliminating mosquito breeding areas in the residential environment and a community anti-malaria education campaign. The latter was implemented at both study sites. In addition, baseline and post-intervention malaria rapid diagnostic test (RDT) was performed among the respondents. Furthermore, a six-month hospital-based epidemiological study was conducted at selected referral hospitals at each site from 1 January through June 2017 to determine malaria trend. RESULTS: Long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%); 24% of households did not use any measures. Baseline malaria survey showed that 96% of respondents (heads of households) reported at least one episode occurring in the previous six months; of them only 66.5% received malaria care at a health setting. In the Action Research, mean incident household malaria cases decreased significantly at WASH action site (2.3 ± 2.2 cases vs. 1.2 ± 0.7 cases, respectively; p < 0.05), whereas it remained unchanged at the Control site. Similar findings were observed with RDT results. Data collected from referral hospitals showed high malaria incidence rate, 67.4%. Low household income (ORa = 2.37; 95%CI: 1.05-3.12; p < 0.05), proximity to high risk area for malaria (ORa = 5.13; 95%CI: 2-29-8.07; p < 0.001), poor WASH (ORa = 4.10; 95%CI: 2.11-7.08; p < 0.001) were predictors of household malaria. CONCLUSION: This research showed high prevalence of positive malaria RDT among the responders and high household malaria incidence, which were reduced by a 6-month WASH intervention. DRC government should scale up malaria control strategy by integrating efficient indoor and outdoor preventive measures and improve malaria care accessibility.

Factors associated with participation in an ongoing national catch-up campaign against rubella: a cross-sectional internet survey among 1680 adult men in Japan.

BACKGROUND: Since 2019, aiming to eliminate periodic rubella outbreaks, the Japanese government has provided a rubella immunization program targeting men born in fiscal years 1972 to 1978, who lacked the opportunity to be vaccinated against rubella in childhood. This study aimed to explore the factors associated with participation in the rubella vaccination program among the first-year target population in 2019. METHODS: A total of 11,754 adult men in Japan born in fiscal years 1972 to1978 living in seven rubella epidemic areas (Tokyo, Chiba, Kanagawa, Saitama, Aichi, Osaka, and Fukuoka) were selected from a list of a survey agency and invited to complete an Internet questionnaire in March 2020. Recruitment ended when the participants reached 1680 individuals. Multivariable log binomial regression analyses were performed to explore the association between awareness of rubella prevention and rubella antibody testing in fiscal year 2019, adjusting for social characteristics. RESULTS: Of the 1680 men aged 41-47 years who completed the survey, approximately half (51.3%) said that they had received a voucher for the rubella antibody testing and vaccination program. One-quarter (25.9%) of the respondents had used the voucher for rubella antibody testing in 2019, and 6.0% had used the voucher for rubella vaccination in fiscal year 2019. Respondents who understood the government recommendation for rubella antibody testing and vaccination for men of their generation (odds ratio [OR]: 5.50; 95% confidence interval [CI]: 4.01-7.53), those with acquaintances who had undergone rubella testing (OR: 1.39; 95% CI: 1.22-1.59), and those who knew that about their lack of opportunity for rubella vaccination (OR: 1.33; 95% CI: 1.11-1.60) tended to undergo rubella antibody testing. Receiving the most recent seasonal influenza vaccination (OR: 1.26; 95% CI: 1.10-1.43) and being able to confirm a rubella vaccination history (OR: 1.28; 95% CI: 1.13-1.46) were also associated with rubella antibody testing. CONCLUSIONS: The ongoing Japanese test-and-vaccinate rubella program has yet to achieve its participation rate goal for 2019. Further dissemination of the government recommendation to the population is necessary, along with improvements in the accessibility of the rubella vaccination program.

Factors associated with adults' actions to confirm their own rubella immune status in Japan's drive toward rubella elimination: Cross-sectional online survey of non-healthcare workers in their 20s to 40s.

BACKGROUND: Rubella outbreaks occurred among adults in Japan in 2013-2014 and 2018-2019 due to immunity gaps. In response and aiming at rubella elimination by 2020, the government introduced countermeasures comprising supplementary immunization activities for voluntary testing of adult non-healthcare-related workers and vaccination of susceptible individuals. However, as of October 2020, rubella immunity testing and vaccination rates remained low. This study was conducted to identify factors associated with adults voluntarily confirming their rubella immune status, to help develop effective promotion activities for hard-to-reach and left-behind populations. METHODS: In this cross-sectional study, a general population sample of non-healthcare workers aged 20-49 years in Japan completed an online survey in November 2020. Univariate analysis was performed to examine associations of specific actions taken to confirm rubella immune status with social background characteristics, knowledge of rubella, and attitude to testing and vaccination. Log binomial regression analysis was performed to explore the associations following adjustment for social background characteristics. RESULTS: Among 1,854 respondents (927 men, 927 women), only 23.4% of men and 39.4% of women in their 20s to 40s have taken some action related to rubella prevention. Three major factors were associated with the targeted population having taken voluntary action: (1) knowing about testing for confirmation of immunity status (adjusted odds ratio [AOR] 4.29 men, 2.89 women), the rubella outbreak in 2013 among men in their 20s to 40s (AOR 2.79 men, 1.64 women), and congenital rubella syndrome (AOR 1.89 men, 3.10 women); (2) having acquaintances who were vaccinated against or tested for rubella (AOR 2.98 men, 1.95 women); and (3) having a positive attitude toward influenza vaccination (AOR 2.48 men, 1.83 women). Marriage, desire for pregnancy, and having children were weakly associated with taking action. CONCLUSIONS: Currently, insufficient voluntary action is being taken by high-risk adult populations to close the identified immunity gaps. In this last mile to rubella elimination, our findings and suggested potential interventions via annual health check-ups and occupational health and public health initiatives could prove helpful in developing further countermeasures that actively promote and implement supplementary immunization activities targeting all adult generations.

Environmental Sampling for Severe Acute Respiratory Syndrome Coronavirus 2 During a COVID-19 Outbreak on the Diamond Princess Cruise Ship.

During a COVID-19 outbreak on the Diamond Princess cruise ship we sampled environmental surfaces after passengers and crew vacated cabins. SARS-CoV-2 RNA was detected in 58 of 601 samples (10%) from case cabins 1-17 days after cabins were vacated but not from noncase cabins. There was no difference in detection proportion between cabins of symptomatic (15%, 28/189; cycle quantification [Cq], 29.79-38.86) and asymptomatic cases (21%, 28/131; Cq, 26.21-38.99). No SARS-CoV-2 virus was isolated from any of the samples. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients may be similar and surfaces could be involved in transmission.

Dimensions of women's empowerment on access to skilled delivery services in Nepal.

BACKGROUND: Each day, approximately 810 women die during pregnancy and childbirth and 94% of the deaths take place in low and middle income countries. Only 45% of the births in South Asia are attended by skilled professionals, which is lower than that in other Asian regions. Antenatal and postnatal care received from skilled providers can help prevent maternal and neonatal mortality by identifying pregnancy-related complications. Women's empowerment is considered to be a significant determinant of maternal health care outcomes; however, studies on the contextual influences of different dimensions of empowerment in Nepal are relatively limited. Therefore, this study analyzed nationwide survey data to examine the influence of women's economic empowerment, sociocultural empowerment, familial/interpersonal empowerment and media and information technology empowerment on accessing skilled delivery services among the married women in Nepal. METHODS: This study examined the influence of women's empowerment on skilled delivery services among married women (n = 4400) aged 15-49 years using data from the 2016 Nepal Demographic and Health Survey. Descriptive analysis and binary logistic regression analysis were employed to analyze the data. RESULTS: Significant associations were found between women's media and information technology empowerment, economic empowerment and sociocultural empowerment and access to skilled birth attendants. Specifically, the education of women, their occupation, owning a bank account, media exposure, and internet use were significantly associated with the use of skilled birth attendants. CONCLUSION: Focusing on women's access to media and information technology, economic enhancement and education may increase the use of skilled birth attendants in Nepal.

Mortality by occupation and industry among Japanese men in the 2015 fiscal year.

BACKGROUND: Although previous studies have underscored some unique inequalities in occupational mortality in Japan, many of these trends have been dramatically altered during recent decades. We analyzed mortality data by occupation and industry in Japan, to determine whether differences remained by the mid-2010s for men in working-age population. METHODS: We calculated age-standardized all-cause and cause-specific mortality, according to occupation and industry, among men aged 25-64 years in the 2015 fiscal year (1 April 2015 to 31 March 2016). Occupational and industry-specific categories were defined using the Japan Standard Occupational Classification and Japan Standard Industrial Classification, respectively. Age-standardized mortality rates were computed using 5-year age intervals. Mortality rate ratios adjusted for age and 95% confidence intervals (CIs) were estimated using Poisson regression. Cause-specific deaths were classified into four broad groups (cancers [C00-D48], cardiovascular diseases [I00-I99], external causes [V01-Y98], and all other diseases) based on the International Statistical Classification of Diseases 10th Revision (ICD-10). RESULTS: Clear mortality differences were identified by both occupation and industry among Japanese males. All-cause mortality ranged from 53.7 (clerical workers) to 240.3 (service workers) per 100,000 population for occupation and from 54.3 (workers in education) to 1169.4 (workers in mining) for industry. In relative terms, service workers and agriculture, forestry, and fishing workers had 2.89 and 2.50 times higher all-cause mortality than sales workers. Administrative and managerial workers displayed higher mortality risk (1.86; 95% CI 1.76-1.97) than sales workers. Similar patterns of broad cause-specific mortality inequality were identified in terms of both absolute and relative measures, and all broad cause-specific deaths contributed to the differences in mortality by occupation and industry. CONCLUSIONS: Substantial differences in mortality among Japanese male workers, according to occupation and industry, were still present in 2015.

Environmental and sociodemographic factors associated with household malaria burden in the Congo.

BACKGROUND: Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). METHODS: This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The 'malaria indicator questionnaire' (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. RESULTS: There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p < 0.01). In addition, 96.7% of households were affected by malaria (at least one malaria case), and malaria frequency per household was relatively high (mean: 4.5 ± 3.1 cases reported) in the last 12 months. The mean individual malaria care expenditure was relatively high (101.6 ± 10.6 USD) in the previous 12 months; however, the majority of households (74.5%) earned less than 50 USD monthly. In addition, of the responders who suffered from malaria, 24.1% did not have access to malaria care at a health setting. Furthermore, a multivariate analysis with adjustment for age, education level and occupation showed that household size (OR = 1.43 ± 0.13; 95% CI 1.18-1.73; p < 0.001), inappropriate water source (OR = 2.41 ± 0.18; 95% CI 1.17-2.96; p < 0.05) absence of periodic water, sanitation and hygiene (WASH) intervention in residential area (OR = 1.63 ± 1.15; 95% CI 1.10-2.54; p < 0.05), and rural residence (OR = 4.52 ± 2.47; 95% CI 1.54-13.21; p < 0.01) were associated with household malaria. CONCLUSION: This study showed that household size, income, WASH status and rural site were malaria-associated factors. Scaling up malaria prevention through improving WASH status in the residential environment may contribute to reducing the disease burden.

Serologic testing of randomly selected children after hepatitis B vaccination: a cross-sectional population-based study in Lao People's Democratic Republic.

BACKGROUND: Population immunity against hepatitis B virus (HBV) in Lao People's Demographic Republic (PDR) has not been examined since the national HBV vaccination program was started in 2002. Vaccine has been observed to be frozen at times during cold-chain transport in vaccination programs in Lao PDR and other developing countries, which will inactivate the vaccine. Therefore, this study used post-vaccination serologic testing to evaluate the effects of HBV immunization in Lao PDR. METHODS: A cross-sectional serologic study was conducted among children (age range, 5-9 years) and mothers (15-45 years) who were randomly selected using probability-proportional-to-size sampling from central Lao PDR. Blood samples were collected as dried blood spots (DBS) and analyzed using chemiluminescent microparticle immunoassay to detect anti-hepatitis B surface (HBs) titers. We also evaluated the correlation between anti-HBs levels measured in DBS and serum among healthy healthcare workers in Vientiane. RESULTS: Anti-HBs titers from DBS were strongly correlated with serum levels (correlation coefficient = 0.999) in all 12 healthcare workers evaluated. A linear regression model showed that 10 mIU/mL of serum anti-HBs was equivalent to 3.45 mIU/mL (95% CI: 3.06-3.85) of DBS. Among 911 mother-child pairs tested, 171 children had documentation of vaccination. Of the 147 children who had received ≥3 doses of the hepatitis B vaccine, 1 (0.7%) was positive for anti-HBs. The remaining 24 children received the hepatitis B vaccine only twice, once or no dose. CONCLUSIONS: The results showed extremely low positivity for anti-HBs among vaccinated children in central Lao PDR. Therefore, post-vaccination serologic testing is important to evaluate population immunity against HBV infection. DBS testing is a potential low-cost tool to evaluating the effectiveness of HBV vaccination programs.

Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins.

Selective macroautophagy (autophagy) of ubiquitinated protein is implicated as a compensatory mechanism of the ubiquitin-proteasome system. p62/SQSTM1 is a key molecule managing autophagic clearance of polyubiquitinated proteins. However, little is known about mechanisms controlling autophagic degradation of polyubiquitinated proteins. Here, we show that the specific phosphorylation of p62 at serine 403 (S403) in its ubiquitin-associated (UBA) domain increases the affinity between UBA and polyubiquitin chain, resulting in efficiently targeting polyubiquitinated proteins in "sequestosomes" and stabilizing sequestosome structure as a cargo of ubiquitinated proteins for autophagosome entry. Casein kinase 2 (CK2) phosphorylates S403 of p62 directly. Furthermore, CK2 overexpression or phosphatase inhibition reduces the formation of inclusion bodies of the polyglutamine-expanded huntingtin exon1 fragment in a p62-dependent manner. We propose that phosphorylation of p62 at S403 regulates autophagic clearance of ubiquitinated proteins and protein aggregates that are poorly degraded by proteasomes.

Cytotoxic Effects of Diterpenoid Alkaloids Against Human Cancer Cells.

Diterpenoid alkaloids are isolated from plants of the genera Aconitum, Delphinium, and Garrya (Ranunculaceae) and classified according to their chemical structures as C18-, C19- or C20-diterpenoid alkaloids. The extreme toxicity of certain compounds, e.g., aconitine, has prompted a thorough investigation of how structural features affect their bioactivities. Therefore, natural diterpenoid alkaloids and semi-synthetic alkaloid derivatives were evaluated for cytotoxic effects against human tumor cells [A549 (lung carcinoma), DU145 (prostate carcinoma), MDA-MB-231 (triple-negative breast cancer), MCF-7 (estrogen receptor-positive, HER2-negative breast cancer), KB (identical to cervical carcinoma HeLa derived AV-3 cell line), and multidrug-resistant (MDR) subline KB-VIN]. Among the tested alkaloids, C19-diterpenoid (e.g., lipojesaconitine, delcosine and delpheline derivatives) and C20-diterpenoid (e.g., kobusine and pseudokobusine derivatives) alkaloids exhibited significant cytotoxic activity and, thus, provide promising new leads for further development as antitumor agents. Notably, several diterpenoid alkaloids were more potent against MDR subline KB-VIN cells than the parental drug-sensitive KB cells.

Reduction in the IL-6 level at 24 h after admission to the intensive care unit is a survival predictor for Vietnamese patients with sepsis and septic shock: a prospective study.

BACKGROUND: Sepsis and septic shock are common problems in intensive care units (ICUs). The mortality of patients with sepsis or septic shock is high. We investigated if reduction in the serum concentration of the cytokines tumor necrosis factor α, interleukin (IL)-6 and IL-10, and the rate of change in the IL-6 level at 24 h after ICU admission were survival predictors for patients with sepsis and septic shock in a Vietnamese population. METHODS: This was a prospective study conducted at an ICU in Cho Ray Hospital, Vietnam, from October 2014 to October 2016. Patients diagnosed with sepsis or septic shock using validated international guidelines were enrolled. Plasma samples were collected upon (T0) and 24 h after (T24) ICU admission for measurement of cytokine concentrations. Blood tests were done to detect organ dysfunction. The duration of ICU stays, hospital stay, APACHE II and SOFA scores, and the in-hospital mortality were compared between survival and non-survival groups. Univariate logistic regression and multivariate analysis were done to determine the association between survival and IL-6 reduction at 24 h after ICU admission. RESULTS: A total of 123 patients were enrolled. The concentration (in pg/mL) of IL-6 at To was 413.3 in survivors and 530.0 in non- survivors. At T24, the IL-6 level was 65.4 for survivors and 286.9 for non-survivors. The survival rate was 39.0%. At T24, the concentrations of IL-6 and the reduction in IL-6 level were predictors of survival in patients with sepsis and septic shock. We found a significant association between IL-6 reduction and survival at ≥86% with Odds Ratio (OR) 5.67, 95% Confidence Interval (CI); 1.27-25.3, compared with an increase in the IL-6 rate of change. CONCLUSIONS: Our findings suggested that a reduction in the IL-6 level of ≥86% at 24 h from ICU admission is a survival predictor for patients with sepsis and septic shock in our population.

Flavor characteristics and antioxidant capacities of hihatsumodoki (Piper retrofractum Vahl) fresh fruit at three edible maturity stages.

To determine the effect of maturity stage on the food attributes of hihatsumodoki (Piper retrofractum Vahl) fresh fruit, the flavor characteristics and antioxidant capacities were investigated at green (GM), orange (OM), and red maturity (RM) stages. Total organic acids, total free amino acids (FAA), and piperine decreased with increasing fruit maturation, reaching minima at the RM stage. Conversely, total sugars and the FAA that contribute to both umami and sweetness were the highest RM stage. Principal component analysis revealed that the volatile composition of the fruit at the GM stage was clearly different from that at the other stages. The DPPH radical scavenging activity and total phenolic content, as measures of antioxidant capacity, decreased with increasing fruit maturation from GM to RM, which was consistent with the changes in piperine content. Therefore, the maturity stage has a significant influence on the flavor and antioxidant characteristics of hihatsumodoki fresh fruit.

Co-worker perceptions of return-to-work opportunities for Japanese cancer survivors.

PURPOSE: This study examined workplace factors and perceptions of Return-to-Work (RTW) opportunities for colleagues with cancer-related symptoms and/or treatment side effects in Japan. METHODS: We conducted an online, cross-sectional survey of 3710 employed Japanese individuals of working age. Colleagues' perceptions of RTW opportunities for cancer survivors were examined (using a Japanese questionnaire), along with workplace factors such as job demand, job control and workplace social support (using the Brief Job Stress Questionnaire). Associations between workplace factors and RTW opportunities were evaluated using multiple logistic regression analysis, with participants stratified in tertiles (low, middle and high) according to their levels of workplace social support and job control. RESULTS: Colleagues' perceptions of inadequate RTW opportunities were associated with low workplace social support (middle tertile: Odds Ratio [OR] 1.22, 95% Confidence Interval [CI]: 1.08-1.36; low tertile: OR 1.43, 95%CI: 1.30-1.57; p for trend <0.01); low levels of job control (middle tertile: OR 1.27, 95%CI: 1.06-1.50; low tertile: OR 1.91, 95%CI: 1.64-2.21; p for trend <0.01); and no prior experience working with a cancer survivor (OR 2.08, 95%CI: 1.83-2.31). CONCLUSIONS: This study suggests that workplace factors and prior experience of working with a cancer survivor may affect a colleagues' perception of RTW opportunities in Japanese workplaces. Consideration of workplace social factors (workplace support and job control), as well as increased openness and awareness of the particular needs of cancer survivors, is therefore essential to facilitate successful RTW in Japan, as elsewhere.Copyright © 2016 John Wiley & Sons, Ltd.