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Background: The WHO highlight alcohol, tobacco, unhealthy food, and sugar-sweetened beverage (SSB) taxes as one of the most effective policies for preventing and reducing the burden of non-communicable diseases. This umbrella review aimed to identify and summarise evidence from systematic reviews that report the relationship between price and demand or price and disease/death for alcohol, tobacco, unhealthy food, and SSBs. Given the recent recognition as gambling as a public health problem, we also included gambling., Methods: The protocol for this umbrella review was pre-registered (PROSPERO CRD42023447429). Seven electronic databases were searched between 2000-2023. Eligible systematic reviews were those published in any country, including adults or children, and which quantitatively examined the relationship between alcohol, tobacco, gambling, unhealthy food, or SSB price/tax and demand (sales/consumption) or disease/death. Two researchers undertook screening, eligibility, data extraction, and risk of bias assessment using the ROBIS tool., Results: We identified 50 reviews from 5,185 records, of which 31 reported on unhealthy food or SSBs, nine reported on tobacco, nine on alcohol, and one on multiple outcomes (alcohol, tobacco, unhealthy food, and SSBs). We did not identify any reviews on gambling. Higher prices were consistently associated with lower demand, notwithstanding variation in the size of effect across commodities or populations. Reductions in demand were large enough to be considered meaningful for policy., Conclusions: Increases in the price of alcohol, tobacco, unhealthy food, and SSBs are consistently associated with decreases in demand. Moreover, increasing taxes can be expected to increase tax revenue. There may be potential in joining up approaches to taxation across the harm-causing commodities., (© 2024. The Author(s).)

Background: Consumers have difficulty understanding alcoholic units and low risk drinking guidelines (LRDG). Labelling may improve comprehension. The aims of this rapid evidence review were to establish the effectiveness of on-bottle labelling for (i) improving comprehension of health risks; (ii) improving comprehension of unit and/or standard drink information and/or LRDG, and (iii) reducing self-reported intentions to drink/actual drinking., Methods: Electronic database searches were carried out (January 2008-November 2018 inclusive). Papers were included if they were: published in English; from an Organization for Economic Co-operation and Development country; an experimental/quasi-experimental design. Papers were assessed for quality using the Effective Public Health Practice Project Quality Assessment tool. Ten papers were included. Most studies were moderate quality (n = 7)., Results: Five themes emerged: comprehension of health risks; self-reported drinking intentions; comprehension of unit/standard drink information and/or LRDG; outcome expectancies; and label attention. Labelling can improve awareness, particularly of health harms, but is unlikely to change behaviour. Improved comprehension was greatest for labels with unit information and LRDG., Conclusions: Alcohol labelling can be effective in improving people's comprehension of the health risks involved in drinking alcohol enabling them to make informed consumption decisions, and perhaps thereby provide a route to changing behaviour. Thus, effective alcohol labelling is an intervention that can be added to the broader suite of policy options. That being said, the literature reviewed here suggests that the specific format of the label matters, so careful consideration must be given to the design and placement of labels., (© 2023. The Author(s).)

Background: Atrazine is one of the most widespread chlorinated herbicides, leaving large bulks in soils and groundwater. The biodegradation of atrazine by bacteria is well described, but many aspects of the fungal metabolism of this compound remain unclear. Thus, we investigated the toxicity and degradation of atrazine by 13 rainforest basidiomycete strains., Results: In liquid medium, Pluteus cubensis SXS320, Gloelophyllum striatum MCA7, and Agaricales MCA17 removed 30, 37, and 38%, respectively, of initial 25 mg L - 1 of the herbicide within 20 days. Deficiency of nitrogen drove atrazine degradation by Pluteus cubensis SXS320; this strain removed 30% of atrazine within 20 days in a culture medium with 2.5 mM of N, raising three metabolites; in a medium with 25 mM of N, only 21% of initial atrazine were removed after 40 days, and two metabolites appeared in culture extracts. This is the first report of such different outcomes linked to nitrogen availability during the biodegradation of atrazine by basidiomycetes. The herbicide also induced synthesis and secretion of extracellular laccases by Datronia caperata MCA5, Pycnoporus sanguineus MCA16, and Polyporus tenuiculus MCA11. Laccase levels produced by of P. tenuiculus MCA11 were 13.3-fold superior in the contaminated medium than in control; the possible role of this enzyme on atrazine biodegradation was evaluated, considering the strong induction and the removal of 13.9% of the herbicide in vivo. Although 88% of initial laccase activity remained after 6 h, no evidence of in vitro degradation was observed, even though ABTS was present as mediator., Conclusions: This study revealed a high potential for atrazine biodegradation among tropical basidiomycete strains. Further investigations, focusing on less explored ligninolytic enzymes and cell-bound mechanisms, could enlighten key aspects of the atrazine fungal metabolism and the role of the nitrogen in the process.

Background: The World Health Organization (WHO) supports the use of Sugar-Sweetened Beverage Taxes (SSBTs) as a fiscal lever to help reduce sugar consumption and tackle obesity. Obesity is associated with a range of adverse health outcomes. In response to increasing levels of obesity in Ireland, an SSBT was introduced in 2018. Previous research in Ireland has noted that the pass-through rate of the SSBT in retail (off-site consumption) settings was poor. However, to date, no research has examined the SSBT pass-through rate in hospitality (on-site consumption) venues in Ireland. Methods: This research examines the SSBT pass-through rate on Coca-Cola versus diet versions of Coca-Cola in a convenience sample of 100 hospitality venues in two provincial Irish cities. Results: Wilcoxon signed rank test analysis revealed that regular Coca-Cola was significantly more expensive compared to the price charged for diet versions of Coca-Cola. However, in 85.6% of cases the same price was charged for both full-sugar and sugar-free drinks. The mean pass-through rate of the SSBT was 33.8%. Conclusion: The effective functioning of the SSBT is premised on persistent price differences between soft drink prices based on sugar content. However, this is barely evident in the hospitality sector in Ireland. A number of recommendations are suggested, including both increasing the SSBT, and increasing it annually in line with inflation. [ABSTRACT FROM AUTHOR]

Background: Alcohol-related mortality and morbidity increased during the COVID-19 pandemic in England, with people from lower-socioeconomic groups disproportionately affected. The North East and North Cumbria (NENC) region has high levels of deprivation and the highest rates of alcohol-related harm in England. Consequently, there is an urgent need for the implementation of evidence-based preventative approaches such as identifying people at risk of alcohol harm and providing them with appropriate support. Non-alcohol specialist secondary care clinicians could play a key role in delivering these interventions, but current implementation remains limited. In this study we aimed to explore current practices and challenges around identifying, supporting, and signposting patients with Alcohol Use Disorder (AUD) in secondary care hospitals in the NENC through the accounts of staff in the post COVID-19 context. Methods: Semi-structured qualitative interviews were conducted with 30 non-alcohol specialist staff (10 doctors, 20 nurses) in eight secondary care hospitals across the NENC between June and October 2021. Data were analysed inductively and deductively to identify key codes and themes, with Normalisation Process Theory (NPT) then used to structure the findings. Results: Findings were grouped using the NPT domains 'implementation contexts' and 'implementation mechanisms'. The following implementation contexts were identified as key factors limiting the implementation of alcohol prevention work: poverty which has been exacerbated by COVID-19 and the prioritisation of acute presentations (negotiating capacity); structural stigma (strategic intentions); and relational stigma (reframing organisational logics). Implementation mechanisms identified as barriers were: workforce knowledge and skills (cognitive participation); the perception that other departments and roles were better placed to deliver this preventative work than their own (collective action); and the perceived futility and negative feedback cycle (reflexive monitoring). Conclusions: COVID-19, has generated additional challenges to identifying, supporting, and signposting patients with AUD in secondary care hospitals in the NENC. Our interpretation suggests that implementation contexts, in particular structural stigma and growing economic disparity, are the greatest barriers to implementation of evidence-based care in this area. Thus, while some implementation mechanisms can be addressed at a local policy and practice level via improved training and support, system-wide action is needed to enable sustained delivery of preventative alcohol work in these settings. [ABSTRACT FROM AUTHOR]

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future. Summary: MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone. [ABSTRACT FROM AUTHOR]

Background: The use of alcohol-flavored beverages not containing alcohol (hereinafter referred to as non-alcoholic beverages) is recommended to reduce alcohol consumption. However, it is unclear if this reduces excessive drinking. Objective: To verify whether non-alcoholic beverages impact the alcohol consumption of excessive drinkers. Study design: Single-center, open-label, randomized, parallel-group study. Methods: Participants aged 20 years or older who were not diagnosed with alcoholism, who drank at least four times a week, and whose alcohol consumption on those days was at least 40 g in males and 20 g in females, were recruited. Participants were randomized into the intervention or control group by simple randomization using a random number table. In the intervention group, free non-alcoholic beverages were provided once every 4 weeks for 12 weeks (three times in total), and thereafter, the number of alcoholic and non-alcoholic beverages consumed were recorded for up to 20 weeks. The consumption of alcoholic and non-alcoholic beverages was calculated based on a drinking diary submitted with the previous 4 weeks of data. The primary endpoint was the change from baseline in total alcohol consumption during past 4 weeks at week 12. The participants were not blinded to group allocations. Results: Fifty-four participants (43.9%) were allocated to the intervention group and 69 (56.1%) to the control group. None of the participants in the intervention group dropped out, compared to two (1.6%) in the control group. The change in alcohol consumption was − 320.8 g (standard deviation [SD], 283.6) in the intervention group and − 76.9 g (SD, 272.6) in the control group at Week 12, indicating a significant difference (p < 0.001). Even at Week 20 (8 weeks after the completion of the intervention), the change was − 276.9 g (SD, 39.1) in the intervention group, which was significantly greater than − 126.1 g (SD, 41.3) in the control group (p < 0.001). The Spearman rank correlation coefficient between the change in non-alcoholic beverage consumption and alcohol consumption at Week 12 was significantly negative only in the intervention group (ρ = − 0.500, p < 0.001). There were no reports of adverse events during the study. Conclusions: Providing non-alcoholic beverages significantly reduced alcohol consumption, an effect that persisted for 8 weeks after the intervention. Trial registration: UMIN UMIN000047949. Registered 4 June 2022. [ABSTRACT FROM AUTHOR]

Background: Smaller serving sizes of alcoholic drinks could reduce alcohol consumption across populations thereby lowering the risk of many diseases. The effect of modifying the available range of serving sizes of beer and cider in a real-world setting has yet to be studied. The current study assessed the impact on beer and cider sales of adding a serving size of draught beer and cider (2/3 pint) that was between the current smallest (1/2 pint) and largest (1 pint) standard serving sizes. Methods: Twenty-two licensed premises in England consented to taking part in the study. The study used an ABA reversal design, set over three 4-weekly periods, with A representing the non-intervention periods, during which standard serving sizes were served and B the intervention period when a 2/3 pint serving size of draught beer and cider was added to the existing range, along with smaller 1/2 pint and larger 1 pint serving sizes. The primary outcome was the daily volume of beer and cider sold, extracted from sales data. Results: Fourteen premises started the study, of which thirteen completed it. Twelve of those did so per protocol and were included in the primary analysis. After adjusting for pre-specified covariates, the intervention did not have a significant effect on the volume of beer and cider sold per day (3.14 ml; 95%CIs -2.29 to 8.58; p = 0.257). Conclusions: In licensed premises, there was no evidence that adding a smaller serving size for draught beer and cider (2/3 pint) when the smallest (1/2 pint) and largest (1 pint) sizes were still available, affected the volume of beer and cider sold. Studies are warranted to assess the impact of removing the largest serving size. Trial registration: ISRCTN: https://doi.org/10.1186/ISRCTN33169631 (08/09/2021), OSF: https://osf.io/xkgdb/ (08/09/2021). [ABSTRACT FROM AUTHOR]

Background: Integrating evidence-based interventions for people with alcohol use disorder (AUD) into primary healthcare (PHC) can increase access to care and reduce morbidity, mortality, and population burden. However, for the integration to be feasible, acceptable, and sustainable, there is a need to contextualize the approach and involve stakeholders. Therefore, this study aimed to use participatory methods to adapt a model for integrating AUD interventions in Tanzania's PHC system at the community, facility, and organizational levels. Methods: A mixed-methods study was used. Participants include key mental health stakeholders, experts, and PHC providers. We conducted a situational analysis to investigate opportunities and constraints in the existing systems of care, utilizing data available from the routine collection and/or in the public domain, individual semi-structured interviews (n = 11), and focus group discussions (3 groups; total n = 26 participants) and a series of theory of change (ToC) workshops (n = 32). Data from the three methods were triangulated to develop the adapted model for integrating interventions for AUD in PHC. Results: A situational appraisal revealed limited community, facility, and organizational resources and infrastructures for supporting services delivery of integrated AUD interventions. Also, shortage of health workforce, inadequate health management information systems, and limited medical supply and financing. Nevertheless, the theory of change proposed integrated AUD intervention packages and strategies to facilitate integrated care for people with AUD. Additionally, the barriers and facilitators for implementing these integrated AUD interventions and how to overcome them were explored. Conclusions: The adapted model for the integrated AUD intervention in Tanzanian PHC revealed limited resources and system functioning for facilitating integrated AUD services. Nevertheless, it proposes the needed integrated AUD interventions and its barriers, facilitators, and strategies for overcoming them. There is a need to pilot the adapted model to inform plans for more comprehensive implementation or scaling up. [ABSTRACT FROM AUTHOR]

Background: Exposure to alcohol advertising and sponsorship through elite sport is associated with harmful use of alcohol. Owing to strong financial and cultural ties between alcohol and sport in Australia, policy action to restrict alcohol sport sponsorship is unlikely to occur without strong public support for change. This study tested whether exposure to counter-advertising exposing industry marketing of harmful products—a technique shown to be effective in tobacco control—promotes higher support for policy change and less favourable beliefs about the alcohol industry among sport spectators. Methods: A sample of 1,075 Australian adults aged 18–49 years who planned to watch an National Rugby League (NRL) State of Origin series game, featuring prominent alcohol sponsorship, was recruited through an online panel and randomly assigned to one of three conditions: control (neutral advertisement); counter-advertisement exposing alcohol harms; counter-advertisement exposing alcohol sponsorship and harms. Participants completed a pre-test questionnaire and viewed their assigned counter-advertisement multiple times in the 5–7 days before the NRL game. Within four days of watching the game, participants completed post-test measures. Results: Compared to both the control advertisement and the counter-advertisement exposing alcohol harms, participants who viewed the counter-advertisement exposing alcohol sponsorship and harms were significantly more likely to indicate support for each of four policies aimed at restricting sports-related alcohol marketing, including the complete removal of alcohol sponsorship from sport (51% vs. 32% and 37%). They were also significantly less likely to agree with statements such as "alcohol companies should be allowed to sponsor sport since their products are legal" (39% vs. 63% and 60%) and significantly less likely to report liking alcohol companies in general (38% vs. 59% and 54%). There were no significant differences in policy support or industry beliefs between participants who saw the counter-advertisement exposing alcohol harms and those who saw the control advertisement. Conclusion: Counter-advertising employing messages that expose and critique the intent and impact of pervasive alcohol sponsorship in sport has potential to bolster public support for policies targeting alcohol sport sponsorship, diminish beliefs supportive of alcohol industry marketing strategies and enhance negative views of alcohol companies and their marketing practices. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. Methods: Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. Results: HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. Conclusion: Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers. [ABSTRACT FROM AUTHOR]

Background: Exposure to heavy metals in the environment is widespread, while the relationship between combined exposure to heavy metals and dyslipidemia is unclear. Methods: A cross-sectional study was performed, and 3544 participants aged 30 years or older were included in the analyses. Heavy metal concentrations in plasma were based on inductively coupled plasma‒mass spectrometry. The relationship between heavy metals and dyslipidemia was estimated by logistic regression. BKMR was used to evaluate metal mixtures and their potential interactions. Results: In logistic regression analysis, participants in the fourth quartile of Fe and Zn (Fe > 1352.38 µg/L; Zn > 4401.42 µg/L) had a relatively higher risk of dyslipidemia (Fe, OR = 1.13, 95% CI: 0.92,1.38; Zn, OR = 1.30, 95% CI: 1.03,1.64). After sex stratification, females in the third quartile of plasma Zn (1062.05-4401.42 µg/L) had a higher relative risk of dyslipidemia (OR = 1.75, 95% CI: 1.28, 2.38). In BKMR analysis, metal mixtures were negatively associated with dyslipidemia in females when all metal concentrations were above the 50th percentile. In the total population (estimated from 0.030 to 0.031), As was positively associated with dyslipidemia when other metals were controlled at the 25th, 50th, or 75th percentile, respectively, and As was below the 75th percentile. In females (estimated from − 0.037 to -0.031), Zn was negatively associated with dyslipidemia when it was above the 50th percentile. Conclusion: This study indicated that As was positively associated with dyslipidemia and that Zn may be negatively associated with dyslipidemia in females. Combined metal exposure was negatively associated with dyslipidemia in females. Females with low plasma Zn levels are more likely to develop dyslipidemia and should receive more clinical attention in this population. [ABSTRACT FROM AUTHOR]

Background: The food environment within and surrounding homes influences family dietary habits with socio-economic areas at a nutritional disadvantage. Families' perception of the food environment and how it influences their food decisions is less clear. This rapid review aimed to synthesise qualitative evidence of parental perspectives of the food environment and their influence on food decisions among disadvantaged families. Method: Qualitative and mixed-methods peer-reviewed journal articles published after 2000, that explored the perspectives of low-income parents in relation to their food environment and how this impacted food decisions for families with children aged 2-17 years, were included in this review. Embase, Scopus and PsycINFO were the databases chosen for this review. Search strategies included seven concepts related to family, food, perceptions, influences, environment, socio-economic status and study type. Two independent reviewers screened sixty-four studies. Thematic synthesis was employed. Results: Two thousand one hundred and forty five results were identified through database searching and 1,650 were screened. Fourteen articles that originated from the US, Australia and the UK were included in this review. No articles were excluded following quality appraisal. Child preferences, financial and time constraints, and location and access to food outlets were barriers to accessing healthy food. Parental nutrition education and feeding approaches varied but positive outcomes from interventions to address these behaviours will be short-lived if inequities in health caused by poverty and access to affordable and healthy food are not addressed. The reliance on social support from families or government sources played an important role for families but are likely to be short-term solutions to health and nutritional inequities. Conclusions: This qualitative evidence synthesis provides an insight into the perceptions of low-income parents on the factors influencing food decisions. Findings have implications for public health and the development of effective strategies to improve the dietary habits of children of disadvantaged families. Sustainable changes to dietary habits for families on low-income requires policy responses to low income, food access and to the high cost of healthy foods. [ABSTRACT FROM AUTHOR]

Background: Alcohol use is a leading cause of harm in young people and increases the risk of alcohol dependence in adulthood. Alcohol use is also a key driver of rising health inequalities. Quantifying inequalities in exposure to alcohol outlets within the activity spaces of pre-adolescent children-a vulnerable, formative development stage-may help understand alcohol use in later life.Methods: GPS data were collected from a nationally representative sample of 10-and-11-year-old children (n = 688, 55% female). The proportion of children, and the proportion of each child's GPS, exposed to alcohol outlets was compared across area-level income-deprivation quintiles, along with the relative proportion of exposure occurring within 500 m of each child's home and school.Results: Off-sales alcohol outlets accounted for 47% of children's exposure, which was higher than expected given their availability (31% of alcohol outlets). The proportion of children exposed to alcohol outlets did not differ by area deprivation. However, the proportion of time children were exposed showed stark inequalities. Children living in the most deprived areas were almost five times more likely to be exposed to off-sales alcohol outlets than children in the least deprived areas (OR 4.83, 3.04-7.66; P < 0.001), and almost three times more likely to be exposed to on-sales alcohol outlets (OR 2.86, 1.11-7.43; P = 0.03). Children in deprived areas experienced 31% of their exposure to off-sales outlets within 500 m of their homes compared to 7% for children from less deprived areas. Children from all areas received 22-32% of their exposure within 500 m of schools, but the proportion of this from off-sales outlets increased with area deprivation.Conclusions: Children have little control over what they are exposed to, so policies that reduce inequities in alcohol availability should be prioritised to ensure that all children have the opportunity to lead healthy lives. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulation (OAC) is the mainstay of secondary prevention in ischemic stroke patients with atrial fibrillation (AF). However, in AF patients with large vessel occlusion stroke treated by endovascular therapy (ET) and acute carotid artery stenting (CAS), the optimal antithrombotic medication remains unclear. Methods: This is a subgroup analysis of the German Stroke Registry—Endovascular Treatment (GSR-ET), a prospective multicenter cohort of patients with large vessel occlusion stroke undergoing ET. Patients with AF and CAS during ET were included. We analyzed baseline and periprocedural characteristics, antithrombotic strategies and functional outcome at 90 days. Results: Among 6635 patients in the registry, a total of 82 patients (1.2%, age 77.9 ± 8.0 years, 39% female) with AF and extracranial CAS during ET were included. Antithrombotic medication at admission, during ET, postprocedural and at discharge was highly variable and overall mortality in hospital (21%) and at 90 days (39%) was high. Among discharged patients (n = 65), most frequent antithrombotic regimes were dual antiplatelet therapy (DAPT, 37%), single APT + OAC (25%) and DAPT + OAC (20%). Comparing DAPT to single or dual APT + OAC, clinical characteristics at discharge were similar (median NIHSS 7.5 [interquartile range, 3–10.5] vs 7 [4–11], p = 0.73, mRS 4 [IQR 3–4] vs. 4 [IQR 3–5], p = 0.79), but 90-day mortality was higher without OAC (32 vs 4%, p = 0.02). Conclusions: In AF patients who underwent ET and CAS, 90-day mortality was higher in patients not receiving OAC. Registration: https://www.clinicaltrials.gov; Unique identifier: NCT03356392. [ABSTRACT FROM AUTHOR]

At the onset of the COVID-19 pandemic in early 2020 in South Africa, many safety measures were implemented to protect the lives of the population. Ironically, these same safety measures have negatively impacted on the lives of children and their caregivers resulting in increased mental health problems. This study forms part of the multicountry Co-SPACE (COVID-19: Supporting Parents, Adolescents and Children during Epidemics) study that explores how families are coping during the COVID-19 pandemic, and what caregivers can do to help support their children's mental health. This paper aims to gain a better understanding of the mental health status of families specifically in South Africa in the early onset of the pandemic during restrictive lockdown measures, and identify certain risk factors that might contribute towards deteriorating mental health. Two hundred and fifty-four South African parents and carers of children and adolescents completed an online survey about their child's mental health as well as their own mental health during and post- hard lockdown in South Africa. Data collection took place over the period of the first and second waves of the COVID-19 pandemic in South Africa. Results showed that children experienced significantly higher mental health problems than adolescents (p = 0.016). Younger children were particularly negatively affected by lockdown and had more mental health problems than adolescents (p = 0.023); including emotional problems (p = 0.017), misconduct (p = 0.030), and hyperactivity (p = 0.001). Additionally, the presence of special educational needs/neurodevelopmental disorders (SEN/ND) was associated with more mental health problems (p = 0.001). Surprisingly, single parent households, which is another well-known risk factor showed no differences in mental health problems compared to nuclear families. There was also a reciprocal relationship between parental/carer mental health and child/adolescent mental health, with higher level of endorsement of mental health problems in children by parents/caregivers who themselves associated with higher levels of depression, anxiety and stress (all p's < 0.001). These results highlight the dramatic impact that COVID-19 had on children, adolescents and parents in South Africa early in the pandemic, and emphasises the need for specific support structures to be implemented within the SEN/ND community, as well as for younger children and single parent households. [ABSTRACT FROM AUTHOR]

Background: Gambling is an inherently risky activity. New technologies have led to the development of new, online forms of gambling such as sports betting, with round the clock availability and accessibility. While young men have been identified as a group that may be particularly vulnerable to the harms associated with these new online products, few studies have qualitatively explored young men's perceptions of the risks associated with these products. Using concepts associated with the sociology of risk, this paper sought to explore the range of factors that may influence how 18-24 year old young Australian men conceptualise the risks associated with sports betting.Methods: Using a critical qualitative inquiry approach, in-depth interviews were conducted with sixteen participants in Victoria, Australia, who engaged in sports betting at least monthly. The data interpreted for this study included questions relating to awareness of gambling, the contexts associated with early gambling experiences; the factors that influenced current gambling behaviours, and why they engaged in gambling. A reflexive approach to thematic analysis was used to interpreted themes from the data.Results: Four key themes were constructed from the data relating to the factors that influenced risk perceptions. These included: 1) 'The role of early experiences', including exposure to gambling advertising in sport, and the gambling behaviours of social networks; 2) 'The influence of peer rivalry and competition', in which sports betting was used to form connections within and across peer groups; 3) 'The normalisation of gambling', including the embedding of gambling in everyday activities; and 4) 'The influence of perceptions of knowledge, skill, and control', including the belief that they could engage in responsible behaviours and stop gambling if they needed to.Conclusion: This study indicated that a range of factors may influence how young men conceptualise the risks and benefits associated with sports betting. Current public health strategies for gambling that focus on individual determinants and responsibility paradigms must be broadened to target the social and commercial factors that influence young men's attitudes towards, and engagement in sports betting. [ABSTRACT FROM AUTHOR]

Background: To assess the association of HSD17B13 rs72613567:TA allelic variant with liver disease, we performed the current review and meta-analysis.Methods: Seven studies were identified by a search of CNKI,CBM,MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to November 2021. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The Stata 14.0 software was employed for data analysis.Results: Statistical analysis showed that the HSD17B13 rs72613567:TA allelic variant can decrease the risk of hepatocellular carcinoma(HCC) in nonalcoholic fatty liver disease (NAFLD) patients, alcoholic fatty liver disease (ALD) patients and viral hepatitis patients (TA vs T OR = 0.766, 95% CI = 0.682-0.860, P = 0.000; TATA + TAT vs TT OR = 0.755, 95% CI = 0.645-0.885, P = 0.001) or healthy controls(TA vs T OR = 0.649, 95% CI = 0.431-0.977, P = 0.038). Besides, the HSD17B13 rs72613567:TA allelic variant can also provide protection from nonalcoholic fatty liver disease (NAFLD) not only in entire population (TA vs T OR = 0.669, 95% CI = 0.524-0.856, P = 0.001) but also in healthy people (TA vs T OR = 0.600, 95% CI = 0.464-0.777, P = 0.000). No significant publication bias found in this airticle.Conclusion: The present findings suggest HSD17B13 rs72613567:TA allelic variant can reduce the risk of HCC and NAFLD in the entire population studied. [ABSTRACT FROM AUTHOR]

Background: There is a continued need for improved enzymes for industry. β-xylosidases are enzymes employed in a variety of industries and although many wild-type and engineered variants have been described, enzymes that are highly tolerant of the products produced by catalysis are not readily available and the fundamental mechanisms of tolerance are not well understood. Results: Screening of a metagenomic library constructed of mDNA isolated from horse manure compost for β-xylosidase activity identified 26 positive hits. The fosmid clones were sequenced and bioinformatic analysis performed to identity putative β-xylosidases. Based on the novelty of its amino acid sequence and potential thermostability one enzyme (XylP81) was selected for expression and further characterization. XylP81 belongs to the family 39 β-xylosidases, a comparatively rarely found and characterized GH family. The enzyme displayed biochemical characteristics (KM—5.3 mM; Vmax—122 U/mg; kcat—107; Topt—50 °C; pHopt—6) comparable to previously characterized glycoside hydrolase family 39 (GH39) β-xylosidases and despite nucleotide identity to thermophilic species, the enzyme displayed only moderate thermostability with a half-life of 32 min at 60 °C. Apart from acting on substrates predicted for β-xylosidase (xylobiose and 4-nitrophenyl-β-D-xylopyranoside) the enzyme also displayed measurable α-L-arabainofuranosidase, β-galactosidase and β-glucosidase activity. A remarkable feature of this enzyme is its ability to tolerate high concentrations of xylose with a Ki of 1.33 M, a feature that is highly desirable for commercial applications. Conclusions: Here we describe a novel β-xylosidase from a poorly studied glycosyl hydrolase family (GH39) which despite having overall kinetic properties similar to other bacterial GH39 β-xylosidases, displays unusually high product tolerance. This trait is shared with only one other member of the GH39 family, the recently described β-xylosidases from Dictyoglomus thermophilum. This feature should allow its use as starting material for engineering of an enzyme that may prove useful to industry and should assist in the fundamental understanding of the mechanism by which glycosyl hydrolases evolve product tolerance. [ABSTRACT FROM AUTHOR]

Background: In association with the novel coronavirus (SARS-CoV-2) disease 2019 (COVID-19) pandemic, many numbers of Ethiopian migrants are returning to their home country, and they are required to stay in mandatory quarantine centers. This results in severe disruptions of life routines, social isolation, and loss of freedom. Studies on psychological distress among Ethiopian migrant returnees in the context of COVID-19 are scarce. This study aimed to investigate the prevalence of psychological distress and associated factors among migrant returnees who were in quarantine during the time of COVID-19. Methods: A cross-sectional study was conducted with 405 migrant returnees recruited from quarantine centers in Addis Ababa. We developed a structured questionnaire to collect data on sociodemographic, migration related, quarantine related and COVID-19 related characteristics of participants. We used the 21 item Depression, Anxiety and Stress Scale to assess psychological distress. Univariate and multivariable negative binomial regression models were fitted to assess the association between exposure variables with depression, anxiety and stress separately. Results: A little more than half of the participants (55%) had depressive symptoms; around half had anxiety symptoms (48.9%) and more than a third (35.6%) experienced symptoms of stress. We found significantly higher prevalence of anxiety (ARR = 0.59; 95% CI = 0.39, 0.91) and depressive symptoms (ARR = 0.56; 95% CI = 0.39, 0.81) among women than men. Fear of discrimination after the quarantine was significantly associated with depressive (ARR = 0.76; 95% CI = 0.63, 0.92) and anxiety symptoms (ARR = 0.77; 95% CI = 0.62, 0.97). Experiencing COVID-19 like symptoms is associated with depressive (ARR = 0.40; 95% CI = 0.25, 0.65), anxiety (ARR = 0.35; 95% CI = 0.20, 0.62) and stress symptoms (ARR = 0.43; 95% CI = 0.28, 0.66). Have no a plan of what to do after the quarantine (ARR = 1.30; 95% CI = 1.09, 1.54) was significantly associated with increasing stress scores. Conclusions: We found a very high prevalence of depressive, anxiety and stress symptoms among Ethiopian migrant returnees who were in quarantine due to the COVID-19 pandemic. Screening, integration of mental health services with other socioeconomic and psychosocial services, and effective and efficient referral may be useful to address the burden of psychological distress in this group. [ABSTRACT FROM AUTHOR]

Background: Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein. Results: In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b. Conclusions: These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Interactions between neurons, astrocytes, and microglia critically influence neuroinflammatory responses to insult in the central nervous system. In vitro astrocyte and microglia cultures are powerful tools to study specific molecular pathways involved in neuroinflammation; however, in order to better understand the influence of cellular crosstalk on neuroinflammation, new multicellular culture models are required.Methods: Primary cortical cells taken from neonatal rats were cultured in a serum-free "tri-culture" medium formulated to support neurons, astrocytes, and microglia, or a "co-culture" medium formulated to support only neurons and astrocytes. Caspase 3/7 activity and morphological changes were used to quantify the response of the two culture types to different neuroinflammatory stimuli mimicking sterile bacterial infection (lipopolysaccharide (LPS) exposure), mechanical injury (scratch), and seizure activity (glutamate-induced excitotoxicity). The secreted cytokine profile of control and LPS-exposed co- and tri-cultures were also compared.Results: The tri-culture maintained a physiologically relevant representation of neurons, astrocytes, and microglia for 14 days in vitro, while the co-cultures maintained a similar population of neurons and astrocytes, but lacked microglia. The continuous presence of microglia did not negatively impact the overall health of the neurons in the tri-culture, which showed reduced caspase 3/7 activity and similar neurite outgrowth as the co-cultures, along with an increase in the microglia-secreted neurotrophic factor IGF-1 and a significantly reduced concentration of CX3CL1 in the conditioned media. LPS-exposed tri-cultures showed significant astrocyte hypertrophy, increase in caspase 3/7 activity, and the secretion of a number of pro-inflammatory cytokines (e.g., TNF, IL-1α, IL-1β, and IL-6), none of which were observed in LPS-exposed co-cultures. Following mechanical trauma, the tri-culture showed increased caspase 3/7 activity, as compared to the co-culture, along with increased astrocyte migration towards the source of injury. Finally, the microglia in the tri-culture played a significant neuroprotective role during glutamate-induced excitotoxicity, with significantly reduced neuron loss and astrocyte hypertrophy in the tri-culture.Conclusions: The tri-culture consisting of neurons, astrocytes, and microglia more faithfully mimics in vivo neuroinflammatory responses than standard mono- and co-cultures. This tri-culture can be a useful tool to study neuroinflammation in vitro with improved accuracy in predicting in vivo neuroinflammatory phenomena. [ABSTRACT FROM AUTHOR]

Background: Increasing the availability of healthier food increases its selection and consumption. However, there is an absence of evidence related to alcohol. This study aimed to estimate the impact of increasing the absolute and relative availability of non-alcoholic compared to alcoholic drinks on selection. We also assessed whether effects were modified by cognitive resource.Methods: UK adult weekly alcohol consumers (n = 808) were recruited to an online experiment with a hypothetical drink selection task. Participants were randomly assigned to one of eight conditions, in a 4 (availability) × 2 (cognitive resource) factorial design. The four availability conditions were: i. Reference 1 (two non-alcoholic, two alcoholic drinks); ii. Reference 2 (four non-alcoholic, four alcoholic drinks); iii. Increased non-alcoholic drinks (six non-alcoholic, two alcoholic drinks); iv. Increased alcoholic drinks (two non-alcoholic, six alcoholic drinks). The two cognitive resource conditions were: a. Low (high time pressure); b. High (low time pressure). Logistic regression was used to assess selection of a non-alcoholic drink.Results: 49% of participants selected a non-alcoholic drink in the Increased non-alcoholic drinks condition, compared to 36% in Reference 1, 39% in Reference 2, and 26% in the Increased alcoholic drinks condition. Non-alcoholic drink selection was similar between Reference 1 and 2 when the total number of drinks increased (absolute availability) but the proportion of non-alcoholic compared to alcoholic drinks (relative availability) was unchanged (OR = 1.15, 95% CI 0.77, 1.73). In contrast, the odds of selecting a non-alcoholic drink were 71% higher when both absolute and relative availability of non-alcoholic compared to alcoholic drinks was increased from Reference 1 to the Increased non-alcoholic drinks condition (OR: 1.71, 95% CI 1.15, 2.54), and 48% higher when increased from Reference 2 to the Increased non-alcoholic drinks condition (OR: 1.48, 95% CI 0.99, 2.19). There was no evidence of an effect of cognitive resource.Conclusions: Greater availability of non-alcoholic drinks, compared to alcoholic drinks, increased their online selection, an effect that may be larger when changing their relative availability, i.e., increasing the proportion of non-alcoholic drinks. Naturalistic studies are needed to determine the impact of availability interventions on reducing alcohol purchasing and consumption. [ABSTRACT FROM AUTHOR]

Background: Biofilms, as a kind of fixed-cell community, can greatly improve industrial fermentation efficiency in immobilized fermentation, but the regulation process is still unclear, which restricts their application. Ca2+ was reported to be a key factor affecting biofilm formation. However, the effect of Ca2+ on biofilm structure and microbiology was yet only studied in bacteria. How Ca2+-mediated calcineurin signaling pathway (CSP) alters biofilm formation in bacteria and fungi has rarely been reported. On this basis, we investigated the regulation of CSP on the formation of biofilm in Aspergillus niger. Results: Deletion of the key genes MidA, CchA, CrzA or CnaA in the CSP lowered the Ca2+ concentration in the mycelium to a different extent, inhibited the formation of A. niger biofilm, reduced the hydrophobicity and adhesion of spores, destroyed the cell wall integrity of hyphae, and reduced the flocculation ability of hyphae. qRT-PCR results showed that the expression of spore hydrophobic protein RodA, galactosaminogalactan (GAG) biosynthesis genes (uge3, uge5, agd3, gtb3), and α-1,3-glucan biosynthesis genes (ags1, ags3) in the ∆MidA, ∆CchA, ∆CrzA, ∆CnaA strains were significantly down-regulated compared with those of the wild type (WT). In addition, the transcription levels of the chitin synthesis gene (chsB, chsD) and β-1,3-glucan synthesis gene (FksA) were consistent with the change in chitin and β-1,3-glucan contents in mutant strains. Conclusion: These results indicated that CSP affected the hydrophobicity and adhesion of spores, the integrity of mycelial cell walls and flocculation by affecting Ca2+ levels in mycelium, which in turn affected biofilm formation. This work provides a possible explanation for how CSP changes the formation of A. niger biofilm, and reveals a pathway for controlling biofilm formation in industrial immobilized fermentation. [ABSTRACT FROM AUTHOR]

Background: Midkine (MK) is a multifunctional cytokine found upregulated in the brain in the presence of different disorders characterized by neuroinflammation, including neurodegenerative disorders and ischemia. The neuroinflammatory response to traumatic brain injury (TBI) represents a key secondary injury factor that can result in further neuronal injury. In the present study, we investigated the role of endogenous MK in secondary injury, including neuroinflammation, immune response, and neuronal apoptosis activity, after TBI.Methods: Wild type (Mdk+/+) and MK gene deficient (Mdk-/-) mice were subjected to fluid percussion injury for TBI models and compared at 3, 7, and 14 days after TBI, in terms of the following: brain tissue loss, neurological deficits, microglia response, astrocytosis, expression of proinflammatory M1 and anti-inflammatory M2 microglia/macrophage phenotype markers, and apoptotic activity.Results: As opposed to Mdk+/+ mice, Mdk-/- mice reported a significantly reduced area of brain tissue loss and an improvement in their neurological deficits. The ratios of the Iba1-immunoreactive microglia/macrophages in the perilesional site were significantly decreased in Mdk-/- than in the Mdk+/+ mice at 3 days after TBI. However, the ratios of the glial fibrillary acidic protein immunoreactive area were similar between the two groups. The M1 phenotype marker (CD16/32) immunoreactive areas were significantly reduced in Mdk-/- than in the Mdk+/+ mice. Likewise, the mRNA levels of the M1 phenotype markers (TNF-α, CD11b) were significantly decreased in Mdk-/- mice than in Mdk+/+ mice. Furthermore, flow cytometry analysis identified the M2 markers, i.e., CD163+ macrophages cells and arginase-1+ microglia cells, to be significantly higher in Mdk-/- than in Mdk+/+ mice. Finally, the ratios of apoptotic neurons were significantly decreased in the area surrounding the lesion in Mdk-/- than in Mdk+/+ mice following TBI.Conclusion: Our findings suggest that MK-deficiency reduced tissue infiltration of microglia/macrophages and altered their polarization status thereby reducing neuroinflammation, neuronal apoptosis, and tissue loss and improving neurological outcomes after TBI. Therefore, targeting MK to modulate neuroinflammation may represent a potential therapeutic strategy for TBI management. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the influence of inter-domain interactions on the substrate affinity and hydrolysis product specificity of xylanase. Methods: Genes encoding a GH10 endo-xylanase from Streptomyces chartreusis L1105 xynA and its truncated derivative were cloned and expressed in Escherichia coli. The catalytic activities of the enzyme (xynA) and the derivative xynADCBM, lacking the carbohydrate binding module (CBM), were assessed to evaluate the role of CBM in xynA. Results: Recombinant xynA (44 kDa) was found to be optimally active on beechwood xylan at 65 °C with pH 7.7, while xynADCBM (34 kDa) exhibited optimal activity at 65 °C with pH 7.2. Additionally, xynA and xynADCBM were found to be highly thermostable at 40–60 °C, each retaining 80% of their original activity after 30 min. The xynADCBM without the CBM domain was highly efficient at hydrolyzing xylan to produce xylobiose (over 67%), which may be because the CBM domain facilitates substrate binding with xylanase. Meanwhile, the xylan hydrolysis efficiency of xynADCBM was higher than that of xynA. Conclusion: These findings showed that the CBM domain with non-catalytic activity has no significant effect on the characteristics of the enzyme at optimum pH and pH tolerance. It has also been suggested that the derivative xynADCBM without CBM components can promote hydrolysis of xylan to yield xylooligosaccharides, which has great potential economic benefits. [ABSTRACT FROM AUTHOR]

Researchers have expressed increasing interest in the xylanolytic enzymes used in hemicellulose hydrolysis that convert wood and agricultural residues to second-generation biofuels. In our study, 32 isolates showed clear hydrolysis zones on agar plates containing xylan after Congo red staining. Among these isolates, strain LY-62 exhibited the highest β-xylosidase activity (1.29 ± 0.05 U/mL). According to the phylogenetic analysis of the 16S rDNA, strain LY-62 belongs to the Enterobacter genus. Using a combination of electron microscopy, Gram-staining, and conventional physiological and biochemical examinations, the strain LY-62 was identified as Enterobacter ludwigii. The β-xylosidase gene from Enterobacter ludwigii LY-62 was cloned, and the full-length protein was expressed in Escherichia coli as an N-terminal or C-terminal His-tagged fusions protein. Optimal β-xylosidase activity was achieved at pH 7.0 and 40 °C. The Michaelis constant KM values for His-Xyl62 and Xyl62-His were 1.55 and 2.8 mmol/L, respectively. The kcat values for His-Xyl62 and Xyl62-His were 8.51 and 6.94 s−1, respectively. The catalytic efficiencies of His-Xyl62 and Xyl62-His were 5.49 and 2.48 s−1 × mM−1, respectively. Thus, Xyl62 is a functional β-xylosidase, and our study represents the first report of a β-xylosidase from Enterobacter ludwigii. [ABSTRACT FROM AUTHOR]

Background: Accurate data to measure population cigarette consumption are vital for surveillance and for evaluating the impact of tobacco control policies. This study uses cigarette retail sales data to provide novel insights into trends and patterns in cigarette consumption in Great Britain.Methods: Cigarette sales estimates derived from electronic sales from most large grocery stores and a weighted representative sample of smaller convenience stores were obtained from Nielsen. Data on the number of cigarette sticks sold per calendar month and per week were obtained for Scotland and England/Wales (combined) for the period January 2008 to December 2015. Cigarette consumption per adult smoker per month was calculated using survey-based smoking prevalence estimates and mid-year population estimates.Results: Population cigarette consumption in Great Britain declined between 2008 and 2013. Cigarette sales have since stabilised at around 400 cigarettes per adult smoker per month. Cigarettes sold in 14- to 19-packs have substituted a sharp decline in 20-packs and now account for over half of all cigarettes sold in Great Britain. Cigarette consumption has been consistently higher in Scotland than England/Wales. This is due to higher sales of 20-packs in Scotland between 2008 and 2013, which has been substituted by higher sales of 14- to 19-packs in recent years.Conclusions: Cigarette retail sales data provide unique insights into levels and patterns of cigarette consumption and should be used for monitoring and evaluating tobacco control policy in Great Britain. [ABSTRACT FROM AUTHOR]

Background: Harm reduction refers to interventions aimed at reducing the negative effects of health behaviors without necessarily extinguishing the problematic health behaviors completely. The vast majority of the harm reduction literature focuses on the harms of drug use and on specific harm reduction strategies, such as syringe exchange, rather than on the harm reduction philosophy as a whole. Given that a harm reduction approach can address other risk behaviors that often occur alongside drug use and that harm reduction principles have been applied to harms such as sex work, eating disorders, and tobacco use, a natural evolution of the harm reduction philosophy is to extend it to other health risk behaviors and to a broader healthcare audience. Methods: Building on the extant literature, we used data from in-depth qualitative interviews with 23 patients and 17 staff members from an HIV clinic in the USA to describe harm reduction principles for use in healthcare settings. Results: We defined six principles of harm reduction and generalized them for use in healthcare settings with patients beyond those who use illicit substances. The principles include humanism, pragmatism, individualism, autonomy, incrementalism, and accountability without termination. For each of these principles, we present a definition, a description of how healthcare providers can deliver interventions informed by the principle, and examples of how each principle may be applied in the healthcare setting. Conclusion: This paper is one of the firsts to provide a comprehensive set of principles for universal harm reduction as a conceptual approach for healthcare provision. Applying harm reduction principles in healthcare settings may improve clinical care outcomes given that the quality of the provider-patient relationship is known to impact health outcomes and treatment adherence. Harm reduction can be a universal precaution applied to all individuals regardless of their disclosure of negative health behaviors, given that health behaviors are not binary or linear but operate along a continuum based on a variety of individual and social determinants. [ABSTRACT FROM AUTHOR]

Background: The fungal cell wall forms a compact network whose integrity is essential for cell morphology and viability. Thus, fungal cells have evolved mechanisms to elicit adequate adaptive responses when cell wall integrity (CWI) is compromised. Functional genomic approaches provide a unique opportunity to globally characterize these adaptive mechanisms. To provide a global perspective on these CWI regulatory mechanisms, we developed chemical-genomic profiling of haploid mutant budding yeast cells to systematically identify in parallel those genes required to cope with stresses interfering the cell wall by different modes of action: β-1,3 glucanase and chitinase activities (zymolyase), inhibition of β-1,3 glucan synthase (caspofungin) and binding to chitin (Congo red). Results: Measurement of the relative fitness of the whole collection of 4786 haploid budding yeast knock-out mutants identified 222 mutants hypersensitive to caspofungin, 154 mutants hypersensitive to zymolyase, and 446 mutants hypersensitive to Congo red. Functional profiling uncovered both common and specific requirements to cope with different cell wall damages. We identified a cluster of 43 genes highly important for the integrity of the cell wall as the common "signature of cell wall maintenance (CWM)". This cluster was enriched in genes related to vesicular trafficking and transport, cell wall remodeling and morphogenesis, transcription and chromatin remodeling, signal transduction and RNA metabolism. Although the CWI pathway is the main MAPK pathway regulating cell wall integrity, the collaboration with other signal transduction pathways like the HOG pathway and the invasive growth pathway is also required to cope with the cell wall damage depending on the nature of the stress. Finally, 25 mutant strains showed enhanced caspofungin resistance, including 13 that had not been previously identified. Only three of them, wsc1Δ, elo2Δ and elo3Δ, showed a significant decrease in β-1,3-glucan synthase activity. Conclusions: This work provides a global perspective about the mechanisms involved in cell wall stress adaptive responses and the cellular functions required for cell wall integrity. The results may be useful to uncover new potential antifungal targets and develop efficient antifungal strategies by combination of two drugs, one targeting the cell wall and the other interfering with the adaptive mechanisms. [ABSTRACT FROM AUTHOR]

Background: Wound healing is an intricate process whereby the skin repairs itself after injury. The epithelial-mesenchymal transition (EMT) is associated with wound healing and tissue regeneration. Naphthochalcone derivatives have various pharmaceutical properties. We investigated the effect of a novel naphthochalcone derivative, 2-(5-(2,4,6-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol (TDPN), on dermal wound healing in vivo and the migration of keratinocytes in vitro. Result: We investigated the effect of TDPN on signaling pathway and epithelial-mesenchymal transition through protein and transcriptional expression. The TDPN treatment accelerated dermal closure about 3 days and remodeling of dermis. We found that treatment with TDPN induced the migration of keratinocytes but not cytotoxicity. TDPN induced the phosphorylation of ERK and AKT. TDPN-treated cells showed loss of adherence protein and showed induction of the transcriptional factor Slug, mesenchymal marker, and fibronectin. Moreover, TDPN treatment induced the expression of matrix metalloproteinase-1 (MMP-1), which degrades specific components of the extracellular matrix, thereby providing new substrates that facilitate migration and invasion. MMP expression is considered to be one of the major attributes acquired by cells after EMT. Conclusion: We propose that a novel naphthochalcone derivative TDPN is capable of promoting keratinocyte migration via the induction of EMT resulting acceleration of wound closure and matrix remodeling. [ABSTRACT FROM AUTHOR]

Background: In the pathogen P. aeruginosa, the formation of virulence factors is regulated via Quorum sensing signaling pathways. Due to the increasing number of strains that are resistant to antibiotics, there is a high interest to develop novel antiinfectives. In the combat of resistant bacteria, selective blockade of the bacterial cell-to-cell communication (Quorum sensing) has gained special interest as anti-virulence strategy. Here, we modeled the las, rhl, and pqs Quorum sensing systems by a multi-level logical approach to analyze how enzyme inhibitors and receptor antagonists effect the formation of autoinducers and virulence factors. Results: Our rule-based simulations fulfill the behavior expected from literature considering the external level of autoinducers. In the presence of PqsBCD inhibitors, the external HHQ and PQS levels are indeed clearly reduced. The magnitude of this effect strongly depends on the inhibition level. However, it seems that the pyocyanin pathway is incomplete. Conclusions: To match experimental observations we suggest a modified network topology in which PqsE and PqsR acts as receptors and an autoinducer as ligand that up-regulate pyocyanin in a concerted manner. While the PQS biosynthesis is more appropriate as target to inhibit the HHQ and PQS formation, blocking the receptor PqsR that regulates the biosynthesis reduces the pyocyanin level stronger. [ABSTRACT FROM AUTHOR]

Background We sought to define the sensitivity and specificity of intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in depicting ex vivo small intestinal total ischemia during GItract surgery. We hypothesized that IL as opposed to IP microdialysis detects small intestinal ischemia with higher sensitivity and specificity. Methods IL and IP microdialysate lactate, pyruvate, glucose and glycerol were analysed from small intestine of pancreaticoduodenectomy patients before and after occluding the mesenteric vasculature and routine resection of a segment of small intestine. Ex vivo time sequences of microdialysate metabolites were described and ROC analyses after 0-30, 31-60, 61-90 and 91-120 minutes after the onset ischemia were calculated. Results IL lactate to pyruvate ratio (L/P ratio) indicated ischemia after 31-60 minutes with 0.954 ROC AUC (threshold: 109) in contrast to IP L/P (ROC AUC of 0.938 after 61-90 minutes, threshold: 18). At 31-60 minutes IL glycerol concentration indicated ischemia with 0.903 ROC AUCs (thresholds: 69 μmol/l). IP glycerol was only moderately indicative for ischemia after 91-120 minutes with 0,791 ROC AUCs (threshold 122 μmol/l). After 31-60 minutes IL and IP lactate to glucose ratios (L/G ratio) indicated ischemia with 0.956 and 0,942 ROC AUCs (thresholds: 48,9 and 0.95), respectively. Conclusions The results support the hypothesis that intraluminal application of microdialysis and metabolic parameters from the small intestinal lumen indicate onset of ischemia earlier than intraperioneal microdialysis with higher sensitivity and specificity. [ABSTRACT FROM AUTHOR]

The article reports on the study conducted to determine the mechanism of MUC1 cytoplasmic dimers in Src recruitment and ICAM-1 binding induced cell invasion. It states that chemical crosslinker is used in the study for the detection of dimers and non-reducing SDS-PAGE investigate the nature of MUC1 dimers. Results conclude that dimers are necessary for Src recruitment and are not linked with ICAM-1 binding.

Background: Immobilized recombinant perlecan domain I (PlnDI) binds and modulates the activity of heparinbinding growth factors, in vitro. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF165) enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, in vitro. Results: In solution, PlnDI binds VEGF165 in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF165 mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF165 alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF165 reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951), and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF165 but not VEGF121 significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2. Conclusions: Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF165 can enhance VEGFR-2 signaling and angiogenic events, in vitro. We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, in vivo. [ABSTRACT FROM AUTHOR]

Background: Seasonal weight loss (SWL) is a very important limitation to the production of ruminants in the Mediterranean and Tropical regions. In these areas, long dry seasons lead to poor pastures with low nutritional value. During the dry season, ruminants, particularly those raised in extensive production systems, lose around 30% of their body weight. Seasonal weight loss has important consequences on animal productive performance and health. In this study, RNA sequencing was used to characterize feed restriction effects in dairy goat of 2 breeds with different SWL tolerance: Majorera (tolerant) and Palmera (susceptible). Nine Majorera and ten Palmera goats were randomly distributed in a control and a restricted group: Majorera Control (adequately fed; MC; n = 4), Palmera Control (adequately fed; PC; n = 6), Majorera Restricted (feed restricted; ME; n = 5) and Palmera Restricted (feed restricted; PE; n = 4). On day 22 of the trial, mammary gland biopsies were collected for transcriptomics analysis. Results: From these samples, 24,260 unique transcripts were identified. From those, 82 transcripts were differentially expressed between MC and ME, 99 between PC and PE, twelve between both control groups and twenty-nine between both restricted groups. Conclusions: Feed restriction affected several biochemical pathways in both breeds such as: carbohydrate and lipid transport; intracellular trafficking, RNA processing and signal transduction. This research also highlights the importance or involvement of the genes in tolerance (ENPP1, S-LZ, MT2A and GPNB) and susceptibility (GPD1, CTPS1, ELOVL6 and NR4A1) to SWL with respectively higher expression in the Majorera restriced group and the Palmera restricted group in comparison to the control groups. In addition, results from the study may be extrapolated to other dairy ruminant species. [ABSTRACT FROM AUTHOR]

Background: Alcohol guidelines enable individuals to make informed choices about drinking and assist healthcare practitioners to identify and treat at-risk drinkers. The UK Low Risk Drinking Guidelines were revised in 2016 and the weekly guideline for men was reduced from 21 to 14 units per week. This study sought to retrospectively establish 1) the number of additional at-risk male drinkers in England, 2) which demographic characteristics were associated with being an at-risk drinker under the previous versus new guidelines.Methods: Average weekly alcohol consumption for men aged 16+ from the cross-sectional nationally representative Health Survey for England were used to 1) calculate annual population prevalence estimates for newly defined at-risk (> 14 to ≤21 units/week) male drinkers from 2011 to 2015 (N = 3487-3790), and 2) conduct logistic regression analyses for at-risk vs low risk male drinkers under the previous (> 21 vs ≤21 units/week) and new (> 14 vs ≤14 units/week) guidelines to assess characteristics associated with being at-risk drinkers under each guideline using 2015 data (N = 2982).Results: Population prevalence estimates of newly defined at-risk drinkers ranged from 10.2% (2014 = 2,182,401 men)-11.2% (2011 = 2,322,896 men). Under the new guidelines, men aged 55-74 (OR = 1.63,95% CI = 1.25-2.12); men in managerial/professional occupations (OR = 1.64,95% CI = 1.34-2.00); current smokers (OR = 2.26,95% CI = 1.73-2.94), ex-regular smokers (OR = 2.01,95% CI = 1.63-2.47) and ex-occasional smokers (OR = 1.85,95% CI = 1.25-2.74); men from the North East (OR = 2.08,95% CI = 1.38-3.13) and North West (OR = 1.91,95% CI = 1.41-2.60) of England all had greater odds, and non-white men had reduced odds (OR = 0.53,95% CI = 0.34-0.80) of being at-risk drinkers, as they had under the previous guidelines. Under the new guidelines only: a higher percentage of at-risk drinkers aged 16-34 (32% vs 19%) attenuated the odds of men aged 35-54 being at-risk (OR = 1.18,95% CI = 0.92-1.51); a higher percentage of married at-risk drinkers (37% vs 24%) attenuated the odds of single men being at-risk (OR = 1.28,95% CI = 0.99-1.67); men from the West Midlands (OR = 1.68,95% CI = 1.17-2.42) and London (OR = 1.53,95% CI = 1.03-2.28) had greater odds of being at-risk drinkers.Conclusions: The change to the Low Risk Drinking Guidelines would have resulted in more than 2 million additional male at-risk drinkers in England. Most groups with greater odds of being at-risk drinkers under the new guidelines were those already known to be drinking the most, strengthening the case for targeted screening and education. Additionally, under the new guidelines, a marked proportion of 16-35 year olds and married men were at-risk and men in the West Midlands and London had greater odds of being at-risk drinkers. These groups may benefit from specific education around the new Low Risk Drinking Guidelines. [ABSTRACT FROM AUTHOR]

Background: A key component of 'obesogenic environments' is the ready availability of convenient, calorie-dense foods, in the form of hyper-palatable and relatively inexpensive ultra-processed products. Compelling evidence indicates that the regular consumption of soft drinks, specifically carbonated and non-carbonated sugar-sweetened beverages (SSBs), has a significant impact on the prevalence of overweight and obesity. However, to implement country-level effective prevention programmes we need to supplement this evidence with quantitative knowledge of the relationships between overweight/obesity and the main determinants of SSB consumption, notably SSB prices and consumers' disposable income.Method: Affordability considers the simultaneous effects of both price and disposable income on the buying decision. The purpose of this study was to investigate the effect of SSB affordability on the consumers' purchasing behaviour and weight-related health outcomes. Our study was divided into three parts. First, we computed SSB consumption and affordability for approximately 150 countries worldwide. Second, we estimated a demand function for SSBs to assess the impact of affordability on consumption at the country level. Third, we used a multivariate regression model and country data on the prevalence of overweight and obesity to test the role of SSB affordability in the current obesity epidemic.Results: The analysis reveals that SSB affordability: 1) showed both a large variability across countries and a clear tendency to increase substantially with the level of economic development; 2) played a key role in determining cross-country differences in the amount of soft drink consumed per capita; and 3) was significantly associated with the prevalence rates of both overweight and obesity. Specifically, we show that a 10 % increase in SSB affordability was associated, on average, with approximately 0.4 more overweight/obese adults per 100 inhabitants.Conclusions: By controlling for the main possible confounding factors, our results clearly indicate that affordability is a major driver of purchasing behaviours and is significantly associated with the prevalence rates of both overweight and obesity. We thus suggest a fiscal approach to curb SSB consumption based on the effectiveness of 'soda taxes' to affect the long-term dynamic of SSB affordability. [ABSTRACT FROM AUTHOR]

Background: In contrast to our knowledge about the number of cancers attributed to smoking, the number of cancers attributed to alcohol is poorly understood by the public. We estimate the increase in absolute risk of cancer (number of cases per 1000) attributed to moderate levels of alcohol, and compare these to the absolute risk of cancer attributed to low levels of smoking, creating a 'cigarette-equivalent of population cancer harm'.Methods: Alcohol and tobacco attributable fractions were subtracted from lifetime general population risks of developing alcohol- and smoking-related cancers, to estimate the lifetime cancer risk in alcohol-abstaining non-smokers. This was multiplied by the relative risk of drinking ten units of alcohol or smoking ten cigarettes per week, and increasing levels of consumption.Results: One bottle of wine per week is associated with an increased absolute lifetime cancer risk for non-smokers of 1.0% (men) and 1.4% (women). The overall absolute increase in cancer risk for one bottle of wine per week equals that of five (men) or ten cigarettes per week (women). Gender differences result from levels of moderate drinking leading to a 0.8% absolute risk of breast cancer in female non-smokers.Conclusions: One bottle of wine per week is associated with an increased absolute lifetime risk of alcohol-related cancers in women, driven by breast cancer, equivalent to the increased absolute cancer risk associated with ten cigarettes per week. These findings can help communicate that moderate levels of drinking are an important public health risk for women. The risks for men, equivalent to five cigarettes per week, are also of note. [ABSTRACT FROM AUTHOR]

Background: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF.Methods: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis.Results: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency.Conclusions: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain. [ABSTRACT FROM AUTHOR]

Background: Public health in England has opportunities to reduce alcohol-related harms via shaping the availability and accessibility of alcohol through the licensing function in local government. While the constraints of licensing legislation have been recognised, what is currently little understood are the day-to-day realities of how public health practitioners enact the licensing role, and how they can influence the local alcohol environment.Methods: To address this, a mixed-methods study was conducted across 24 local authorities in Greater London between 2016 and 17. Data collection involved ethnographic observation of public health practitioners' alcohol licensing work (in eight local authorities); a survey of public health practitioners (n = 18); interviews with licensing stakeholders (n = 10); and analysis of public health licensing data from five local authorities. Fieldnotes and interview transcripts were analysed thematically, and quantitative data were analysed using descriptive statistics.Results: Results indicated that some public health teams struggle to justify the resources required to engage with licensing processes when they perceive little capacity to influence licensing decisions. Other public health teams consider the licensing role as important for shaping the local alcohol environment, and also as a strategic approach for positioning public health within the council. Practitioners use different processes to assess the potential risks of licence applications but also the potential strengths of their objections, to determine when and how actions should be taken. Identifying the direct influence of public health on individual licences is challenging, but the study revealed how practitioners did achieve some level of impact, for example through negotiation with applicants.Conclusions: This study shows public health impact following alcohol licensing work is difficult to measure in terms of reducing alcohol-related harms, which poses challenges for justifying this work amid resource constraints. However, there is potential added value of the licensing role in strategic positioning of public health in local government to influence broader determinants of health. [ABSTRACT FROM AUTHOR]

Background: Effective interventions are required to reduce alcohol consumption and its associated harms at the population level. Reducing the alcohol content of beverages has the potential to reduce alcohol consumption through non-conscious processes. Before implementing a randomised controlled trial (RCT) to assess the effect of alcohol strength on alcohol consumption, its feasibility needs to be established. This study aims to pilot a RCT and obtain data to estimate key parameters required when designing a RCT. These key parameters include the direction and size of the intervention effect, the efficacy and efficiency of the study processes and the rates of licenced premises recruitment, participant recruitment and attrition. Methods: A double-blind randomised controlled cross-over pilot trial comparing the number of units of reduced strength lager consumed and the number of units of regular strength lager consumed in a single drinking occasion within licenced premises in the UK. Descriptive statistics will report the efficacy and efficiency of the study processes and the rates of licenced premises recruitment, participant recruitment and attrition. Mean and 95% confidence intervals will be used to compare the consumption of alcohol and the duration of participation in study sessions, between the intervention arm and the control arm. The mean and standard deviation of UK units of alcohol consumed will be used to calculate a sample size for a definitive RCT. Discussion: This is the first naturalistic experimental study to assess the effect of alcohol strength on alcohol consumption in a single drinking occasion within licenced premises. Results from this pilot study will establish the feasibility of, and inform key data parameters for, a larger scale study. Trial registration: The trial is registered in the American Economic Association (AEA) Randomised Controlled Trial (RCT) Registry as of 16 June 2017. The unique identifying number is AEARCTR-0002266. [ABSTRACT FROM AUTHOR]

Background: Outbreaks of mass psychogenic illness (MPI), which are a constellation of physical signs and symptoms suggestive of organic illness with no identifiable causes. MPI has been documented in numerous cultural, ethnic, and religious groups throughout the world. The aims of this study were to document the nature and impacts of the illness, to assess interventions, and to come up with recommendations and management formulations for dealing with such kinds of outbreaks in the future. Methods: Community based cross-sectional study was conducted in June, 2015 in Derashe Woreda, Segen Area People Zone of the Southern Nations Nationalities and People's Region. Women with complaints of breast cancer but with no objective findings were the subjects of the study. Ninety-seven women were investigated using a semi-structured questionnaire for quantitative study. Two focus group discussions with seven affected and seven non-affected women and four key informant interviews were conducted using guiding questionnaires. Quantitative data was analyzed using SPSS version 20 software packages while qualitative data was analyzed manually going through thematic areas. Result: The ages of the ninety-seven study participants ranged from 17 to 56 years, with a mean (SD) of 32.8 (8.7) years. Onset of illness was dated back to the year 2012 following the death of a 43 year old socially active woman with complications of breast cancer. Following her death many women started to report multiple vague physical complaints similar to those of the deceased woman. Even though the responses from the study participants did not specifically point to a single possible cause and means of transmission, high numbers of women believed the source of their illness could be punishment from God while some said that the cause of their suffering could be environmental pollution. Since the illness was taken to be contagious, affected women faced stigma and discrimination. Moreover, school activities and social gatherings were limited significantly. Conclusion: Unrealistic and exaggerated rumors and inadequate explanations about the nature and spread of the illness were the main contributing factors for the spread and prolongation of the outbreak. An organized intervention, clear and adequate explanations about the nature and transmission of the illness can contain MPI within a short period of time. [ABSTRACT FROM AUTHOR]

Background: Globally, alcohol is causally related to 2.5 million deaths per year and 12.5% of these are due to cancer. Previous research has indicated that public awareness of alcohol as a risk factor for cancer is low and this may contribute to a lack of public support for alcohol policies. The aim of this study was to investigate the relationship between awareness of the alcohol-cancer link and support for a range of alcohol policies in an English sample and policy context.Methods: A cross-sectional survey of 2100 adult residents in England was conducted in which respondents answered questions regarding awareness of the link between alcohol and cancer and support for 21 policy proposals. Principal component analysis (PCA) was used to reduce the 21 policy proposals down to a set of underlying factors. Multiple regression analyses were conducted to estimate the relationship between awareness of the alcohol-cancer link and each of these policy factors.Results: Thirteen per cent of the sample were aware of the alcohol-cancer link unprompted, a further 34% were aware when prompted and 53% were not aware of the link. PCA reduced the policy items to four policy factors, which were named price and availability, marketing and information, harm reduction and drink driving. Awareness of the alcohol-cancer link unprompted was associated with increased support for each of four underlying policy factors: price and availability (Beta: 0.06, 95% CI: 0.01, 0.10), marketing and information (Beta: 0.05, 95% CI: 0.00, 0.09), harm reduction (Beta: 0.09, 95% CI: 0.05, 0.14), and drink driving (Beta: 0.16, 95% CI: 0.11, 0.20).Conclusions: Support for alcohol policies is greater among individuals who are aware of the link between alcohol and cancer. At the same time, a large proportion of people are unaware of the alcohol-cancer link and so increasing awareness may be an effective approach to increasing support for alcohol policies. [ABSTRACT FROM AUTHOR]

Background: β-D-xylosidase is a vital exoglycosidase with the ability to hydrolyze xylooligosaccharides to xylose and to biotransform some saponins by cleaving outer β-xylose. β-D-xylosidase is widely used as one of the xylanolytic enzymes in a diverse range of applications, such as fuel, food and the pharmaceutical industry; therefore, more and more studies have focused on the thermostable and xylose-tolerant β-D-xylosidases. Results: A thermostable β-xylosidase gene (xln-DT) of 1509 bp was cloned from Dictyoglomus thermophilum and expressed in E.coli BL21. According to the amino acid and phylogeny analyses, the β-xylosidase Xln-DT is a novel β-xylosidase of the GH family 39. The recombinant β-xylosidase was purified, showing unique bands on SDS-PAGE, and had a protein molecular weight of 58.7 kDa. The β-xylosidase Xln-DT showed an optimal activity at pH 6.0 and 75 °C, with p-nitrophenyl-β-D-xylopyranoside (pNPX) as a substrate. Xln-DT displayed stability over a pH range of 4.0-7.5 for 24 h and displayed thermotolerance below 85 °C. The values of the kinetic parameters Km and Vmax for pNPX were 1.66 mM and 78.46 U/mg, respectively. In particular, Xln-DT displayed high tolerance to xylose, with 60% activity in the presence of 3 M xylose. Xln-DT showed significant effects on the hydrolyzation of xylobiose. After 3 h, all the xylobiose tested was degraded into xylose. Moreover, β-xylosidase Xln-DT had a high selectivity for cleaving the outer xylose moieties of natural saponins, such as notoginsenoside R1 and astragaloside IV, which produced the ginsenoside Rg1 with stronger anti-fatigue activity and produced cycloastragenol with stronger anti-aging activity, respectively. Conclusion: This study provides a novel GH 39 β-xylosidase displaying extraordinary properties of highly catalytic activity at temperatures above 75 °C, remarkable hydrolyzing activity of xylooligosaccharides and rare saponins producing ability in the pharmaceutical and commercial industries. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopment is a complex process involving both genetic and environmental factors. Prenatal exposure to lead (Pb) has been associated with lower performance on neurodevelopmental tests. Adverse neurodevelopmental outcomes are more frequent and/or more severe when toxic exposures interact with genetic susceptibility. Methods: To explore possible loci associated with increased susceptibility to prenatal Pb exposure, we performed a genome-wide gene-environment interaction study (GWIS) in young children from Mexico (n = 390) and Bangladesh (n = 497). Prenatal Pb exposure was estimated by cord blood Pb concentration. Neurodevelopment was assessed using the Bayley Scales of Infant Development. Results: We identified a locus on chromosome 8, containing UNC5D, and demonstrated evidence of its genome-wide significance with mental composite scores (rs9642758, p meta = 4.35 × 10−6). Within this locus, the joint effects of two independent single nucleotide polymorphisms (SNPs, rs9642758 and rs10503970) had a p-value of 4.38 × 10−9 for mental composite scores. Correlating GWIS results with in vitro transcriptomic profiles identified one common gene, SLC1A5, which is involved in synaptic function, neuronal development, and excitotoxicity. Further analysis revealed interconnected interactions that formed a large network of 52 genes enriched with oxidative stress genes and neurodevelopmental genes. Conclusions: Our findings suggest that certain genetic polymorphisms within/near genes relevant to neurodevelopment might modify the toxic effects of Pb exposure via oxidative stress. Electronic supplementary material The online version of this article (doi:10.1186/s12940-017-0288-3) contains supplementary material, which is available to authorized users.