bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of Cronobacter sakazakii Strains Isolated from Powdered Milk
Authors: Holý Ondrej , Parra-Flores Julio , Lepuschitz Sarah , Alarcón-Lavín María Paula , Cruz-Córdova Ariadnna , Xicohtencatl-Cortes Juan , Mancilla-Rojano Jetsi , Ruppitsch Werner , Forsythe Stephen
Published: December 2020

Cronobacter spp. are opportunistic pathogens of the Enterobacteriaceae family. The organism causes infections in all age groups, but the most serious cases occur in outbreaks related to neonates with meningitis and necrotizing enterocolitis. The objective was to determine the in silico and in vitro putative virulence factors of six Cronobacter sakazakii strains isolated from powdered milk (PM) in the Czech Republic. Strains were identified by MALDI-TOF MS and whole-genome sequencing (WGS). Virulence and resistance genes were detected with the Ridom SeqSphere+ software task template and the Comprehensive Antibiotic Resistance Database (CARD) platform. Adherence and invasion ability were performed using the mouse neuroblastoma (N1E-115 ATCCCRL-2263) cell line. The CRISPR-Cas system was searched with CRISPRCasFinder. Core genome MLST identified four different sequence types (ST1, ST145, ST245, and ST297) in six isolates. Strains 13755-1B and 1847 were able to adhere in 2.2 and 3.2 × 106 CFU/mL, while 0.00073% invasion frequency was detected only in strain 1847. Both strains 13755-1B and 1847 were positive for three (50.0%) and four virulence genes, respectively. The cpa gene was not detected. Twenty-eight genes were detected by WGS and grouped as flagellar or outer membrane proteins, chemotaxis, hemolysins, and invasion, plasminogen activator, colonization, transcriptional regulator, and survival in macrophages. The colistin-resistance-encoding mcr-9.1 and cephalothin-resis-encoding blaCSA genes and IncFII(pECLA) and IncFIB(pCTU3) plasmids were detected. All strains exhibited CRISPR matrices and four of them two type I-E and I-F matrices. Combined molecular methodologies improve Cronobacter spp. decision-making for health authorities to protect the population.
Boundary Value Problem for Fractional Order Generalized Hilfer-Type Fractional Derivative with Non-Instantaneous Impulses
Authors: Salim Abdelkrim , Benchohra Mouffak , Graef John R. , Lazreg Jamal Eddine
Published: December 2020

This manuscript is devoted to proving some results concerning the existence of solutions to a class of boundary value problems for nonlinear implicit fractional differential equations with non-instantaneous impulses and generalized Hilfer fractional derivatives. The results are based on Banach’s contraction principle and Krasnosel’skii’s fixed point theorem. To illustrate the results, an example is provided.
Using Reciprocal Transplants to Assess Local Adaptation, Genetic Rescue, and Sexual Selection in Newly Established Populations
Authors: Labonne Jacques , Manicki Aurélie , Chevalier Louise , Tétillon Marin , Guéraud François , Hendry Andrew P.
Published: December 2020

Small populations establishing on colonization fronts have to adapt to novel environments with limited genetic variation. The pace at which they can adapt, and the influence of genetic variation on their success, are key questions for understanding intraspecific diversity. To investigate these topics, we performed a reciprocal transplant experiment between two recently founded populations of brown trout in the sub-Antarctic Kerguelen Islands. Using individual tagging and genetic assignment methods, we tracked the fitness of local and foreign individuals, as well as the fitness of their offspring over two generations. In both populations, although not to the same extent, gene flow occurred between local and foreign gene pools. In both cases, however, we failed to detect obvious footprints of local adaptation (which should limit gene flow) and only weak support for genetic rescue (which should enhance gene flow). In the population where gene flow from foreign individuals was low, no clear differences were observed between the fitness of local, foreign, and F1 hybrid individuals. In the population where gene flow was high, foreign individuals were successful due to high mating success rather than high survival, and F1 hybrids had the same fitness as pure local offspring. These results suggest the importance of considering sexual selection, rather than just local adaptation and genetic rescue, when evaluating the determinants of success in small and recently founded populations.
Novel Advances in Modifying BMPR2 Signaling in PAH
Authors: Dannewitz Prosseda Svenja , Ali Md Khadem , Spiekerkoetter Edda
Published: December 2020

Pulmonary Arterial Hypertension (PAH) is a disease of the pulmonary arteries, that is characterized by progressive narrowing of the pulmonary arterial lumen and increased pulmonary vascular resistance, ultimately leading to right ventricular dysfunction, heart failure and premature death. Current treatments mainly target pulmonary vasodilation and leave the progressive vascular remodeling unchecked resulting in persistent high morbidity and mortality in PAH even with treatment. Therefore, novel therapeutic strategies are urgently needed. Loss of function mutations of the Bone Morphogenetic Protein Receptor 2 (BMPR2) are the most common genetic factor in hereditary forms of PAH, suggesting that the BMPR2 pathway is fundamentally important in the pathogenesis. Dysfunctional BMPR2 signaling recapitulates the cellular abnormalities in PAH as well as the pathobiology in experimental pulmonary hypertension (PH). Approaches to restore BMPR2 signaling by increasing the expression of BMPR2 or its downstream signaling targets are currently actively explored as novel ways to prevent and improve experimental PH as well as PAH in patients. Here, we summarize existing as well as novel potential treatment strategies for PAH that activate the BMPR2 receptor pharmaceutically or genetically, increase the receptor availability at the cell surface, or reconstitute downstream BMPR2 signaling.
Combining the Integrated-Change Model with Self-Determination Theory: Application in Physical Activity
Authors: Cheung Kei Long , Eggers Sander Matthijs , de Vries Hein
Published: December 2020

Background: Critically testing and integrating theoretical models can aid health promotion research and intervention planning. This study aimed to critically compare and integrate Self-Determination Theory (SDT) and Integrated-Change Model (ICM) for explaining physical activity behaviour. Methods: A dataset was used with Dutch adults, consisting of information on demographics and socio–cognitive and behavioural determinants. There were three measurements over a period of six months, with the baseline sample consisting of 1867 participants. Confirmatory factor analysis was conducted to assess the reliability of the items and their corresponding scales. To examine cognitive pathways, we applied Structural Equation Modelling (SEM). Results: For SDT, none of the pathways were significant but the model fit was decent (R2 = 0.20; RMSEA = 0.07; CFI = 0.91). For ICM, the model fit was similar (R2 = 0.19; RMSEA = 0.07; CFI = 0.73), with many significant pathways, as stipulated by the theory. The integration of STD and ICM constructs revealed similar explained behavioural variance (R2 = 21%), with no significantly different model fit. Conclusion: The integration of SDT and ICM added no value as a prediction model. However, the integrated model explains the underlying mechanism of STD constructs, as well as the determinants of attitude, social influences, and self-efficacy. In the context of intervention design, ICM or the integrated model seem most useful as it reveals the stages and pathways to behaviour change.
Childhood Adversities and Salivary Cortisol Responses to the Trier Social Stress Test: A Systematic Review of Studies Using the Children Trauma Questionnaire (CTQ)
Authors: Lai Chuk Ling Julian , Lee Daryl Yu Heng , Leung Monique On Yee
Published: December 2020

Alteration in cortisol response to acute social stressors has been hypothesized to mediate childhood adversities (CA) and increased morbidity in adulthood. However, the evidence supporting an association between CA and cortisol response to social stressors is inconclusive. The present review addressed this issue by reviewing the literature on CA and cortisol response to acute social stressors, with a focus on studies with adolescents or adults, using the Childhood Trauma Questionnaire (CTQ) to assess CA, and examining salivary cortisol response to the Trier Social Stress Test (TSST). Systematic searches of relevant articles in PsycINFO, PubMed, Web of Science and ScienceDirect in February and March 2020 identified 12 articles including 1196 participants with mean ages ranging from 15.3 to 52.3 yrs. across studies. CTQ scores were significantly associated with cortisol response in 2 studies. In addition, the physical abuse and emotional neglect subscales were associated with cortisol response respectively in 2 separate studies. The lack of association between CA and cortisol response calls for more longitudinal studies, and the use of formal records of maltreatment or informant reports in future research to complement information collected by retrospective measures. In addition, increased attention to biological mechanisms other than that associated with the regulation of cortisol in explaining the connection between CA and psychiatry morbidity is warranted.
Crop Diversity at the Landscape Level Affects the Composition and Structure of the Vegetation-Dwelling Arthropod Communities in Naked Oat (Avena Chinensis) Fields
Authors: Zhao Huan , Li Jiahuan , Guo Lizhu , Wang Kun
Published: December 2020

The expansion of agriculture and intensive mechanized production have resulted in the loss of habitats and biodiversity, which has led to the loss of ecological services such as the biological control of pests and diseases, and insect-borne pollination. Current studies mainly focus on the impact of small-scale crop diversity (such as intercropping) on ecological service but lack research on the effects of crop diversity at the landscape scale. In this study, vegetation-dwelling arthropods in naked oat (Avena chinensis) fields under different planting patterns were collected at different growth stages by standardized sweep netting sampling, and the differences in arthropod communities and temporal dynamics were analyzed. Taking this information as an example, the effects of crop diversity at the landscape scale caused by different planting patterns on arthropod communities were studied. It was found that herbivores were the most abundant functional group in the arthropod community in naked oat fields, accounting for 70.13% of the total abundance, followed by natural enemies, accounting for 23.45%, and, finally, other insects. The abundance and species richness of natural enemies in naked oat fields under diversified planting pattern were significantly higher than those under intensive planting pattern, while the abundance and species richness of herbivorous pests showed no significant difference between the two planting patterns. Planting patterns significantly affected the composition and structure of arthropod communities in naked oat fields. Significantly higher ratio of natural enemy to pest and more diverse natural enemies under the diversified planting pattern have shown better biological control potential and the significance of biodiversity protection.
The Participation of Senior Citizens in Policy-Making: Patterning Initiatives in Europe
Authors: Falanga Roberto , Cebulla Andreas , Principi Andrea , Socci Marco
Published: December 2020

Worldwide, active aging policy calls for greater participation of senior citizens in the social, economic, and political realms. Despite emerging evidence of initiatives engaging senior citizens in social activities, little is known about the use of participatory approaches in the design and/or implementation of policies that matter to older citizens. This article identifies initiatives facilitating the civic participation of older people in policy-making in European Union member and associate states, drawing on a review of the literature, consultation of national policy experts, and exemplary case studies. Four main patterns of senior civic participation are identified: adopting consultative or co-decisional participatory approaches in policy design or policy implementation. The four are represented to varying degrees at different geographical levels (national, regional, local), with different actor configurations (appointed, elected/nominated, corporate representation), and with varying degree of institutionalization (temporary/permanent). Case studies illustrate approaches taken to enhance the quality and effectiveness of public services for senior citizens. Future research should strengthen this line of enquiry to cast further light on conditions facilitating the civic participation of senior citizens.
Epidemiological Characteristics of Road Traffic Injuries Involving Children in Three Central American Countries, 2012–2015
Authors: Núñez-Samudio Virginia , Mayorga-Marín Francisco , López Castillo Humberto , Landires Iván
Published: December 2020

Although motor vehicle collisions (MVCs) are a worldwide public health concern due to their high injury, mortality, and fatality rates, few studies have addressed the epidemiologic behavior of MVCs in Latin American youth. Thus, this study was aimed at describing and comparing the characteristics of MVCs involving 0 to 14-year-olds in Costa Rica, Guatemala, and Panama. A secondary aim was to estimate the crude MVC-related injury, fatality, and mortality rates and their trends over time. We conducted a descriptive, retrospective study using publicly available data for Costa Rica, Panama, and Guatemala between 2012 and 2015. We examined the reported MVC cases and calculated the crude injury, fatality, and mortality rates and their trends over time (α = 0.05). Publicly available data reported 12,020 MVC-related injuries and 431 MVC-related deaths involving 0 to 14-year-olds. The most frequent mechanisms involved 0 to 14-year-olds as passengers or pedestrians in MVCs (>85% of all cases). The highest crude MVC-related injury and mortality rates were reported for Panama (119.35 and 2.14 per 100,000 population, respectively, in 0 to 14-years-olds), while Guatemala had the highest median MVC-related fatality rate (8.84 per 100,000 events; χ2 [2] = 377.8; p < 0.001) with a statistically significant trend increasing over time (r = 0.947; p = 0.027). Although several factors play a role in the prevention of MVCs among 0 to 14-year-olds, we found that Costa Rica was the only country that implemented a policy on child restraint systems resulting in the lowest rates of MVC-related injury, mortality, and fatality. These results could be used by decision makers from the aforementioned Central American countries to develop adequate policies addressing MVC preventative strategies to protect Central American infants and children.
Boundaries of Belonging: Theorizing Black African Migrant Experiences in Australia
Authors: Gatwiri Kathomi , Anderson Leticia
Published: December 2020

As nationalist ideologies intensify in Australia, so do the experiences of ‘everyday racism’ and exclusion for Black African immigrants. In this article, we utilize critical theories and engage with colonial histories to contextualize Afrodiasporic experiences in Australia, arguing that the conditional acceptance of Black bodies within Australian spaces is contingent upon the status quo of the white hegemony. The tropes and discourses that render the bodies of Black African migrants simultaneously invisible and hyper-visible indicate that immigration is not only a movement of bodies, but also a phenomenon solidly tied to global inequality, power, and the abjection of blackness. Drawing on critical race perspectives and theories of belonging, we highlight through use of literature how Black Africans in Australia are constructed as ‘perpetual strangers’. As moral panics and discourses of hyper-criminality are summoned, the bordering processes are also simultaneously co-opted to reinforce scrutiny and securitization, with significant implications for social cohesion, belonging and public health.
Letter to the Editor—Changes in Muscle Pattern Activity during the Asymmetric Flat Bench Press
Authors: Saeterbakken Atle Hole , Solstad Tom Erik , Shaw Matthew Peter , Andersen Vidar
Published: December 2020

In June 2020, the paper “Changes in Muscle Pattern Activity during the Asymmetric Flat Bench Press” was published in the International Journal of Environmental Research and Public Health [...]
The Impact of Transitions in Caregiving Status on Depressive Symptoms among Older Family Caregivers: Findings from the Korean Longitudinal Study of Aging
Authors: Hurh Kyungduk , Youn Hin Moi , Park Yoon Sik , Park Eun-Cheol , Jang Sung-In
Published: December 2020

This study identifies the effects of transitions in caregiving status on depressive symptoms among middle-aged or older adults who care for family members with limitations in activities of daily living (ADL). Data were collected from the 2006–2018 Korean Longitudinal Study of Aging. A total of 7817 subjects were included. On the basis of their caregiving status transition, participants were categorized into four groups: started caregiving, continued caregiving, stopped caregiving, and noncaregivers. Depressive symptoms were measured using the 10 item Center for Epidemiologic Studies Depression Scale. Analysis using a generalized estimating equation model and subgroup analyses were conducted. Compared to noncaregivers, women who started caregiving showed more depressive symptoms in the following year (β 0.761, p < 0.0001). Regardless of sex, older adults who continued caregiving had more depressive symptoms than noncaregivers did (β 0.616, p < 0.0277 in men, and β 1.091, p < 0.0001 in women). After relinquishing caregiving responsibilities to other caregivers, participants’ depressive symptoms in the following year showed no statistically significant difference from that of noncaregivers. Thus, starting or continuing caregiving was associated with increased depressive symptoms, and those symptoms could be normalized by stopping caregiving. Intervention strategies to reduce family caregivers’ depressive symptoms are needed.
Implementation and Maintenance of a Community-Based Intervention for Refugee Youth Reporting Symptoms of Post-Traumatic Stress: Lessons from Successful Sites
Authors: Lampa Elin , Sarkadi Anna , Warner Georgina
Published: December 2020

Over the last few years there have been attempts to scale-up Teaching Recovery Techniques (TRT), a community-based group intervention for refugee youth reporting symptoms of post-traumatic stress, across Sweden using the distribution network pathway model. This implementation model allows for quick spread, but only for a low level of control at local sites. This study explores factors and agents that have facilitated the implementation and maintenance of the community-based intervention in successful sites. Seven semi-structured interviews were conducted with personnel from “successful” community sites, defined as having conducted at least two groups and maintaining full delivery. Data were analyzed using content analysis to identify a theme and categories. The main theme “Active networking and collaboration” was key to successful maintenance of community-based delivery. Categories included “Going to where the potential recipients are”, relating to the importance of networks, and “Resource availability and management for maintenance”, relating to the challenges due to the lack of a lead organization supplying necessary funds and support for maintenance. Additionally, “Careful integration of the interpreter” underlined that interpreters were essential co-facilitators of the intervention. Although the interviewed professionals represented successful sites, they remained dependent on informal networks and collaboration for successful maintenance of community-based delivery.
Efficacy of Sea Salt-Based Mouthwash and Xylitol in Improving Oral Hygiene among Adolescent Population: A Pilot Study
Authors: Ballini Andrea , Cantore Stefania , Signorini Luca , Saini Rajiv , Scacco Salvatore , Gnoni Antonio , Inchingolo Alessio Danilo , De Vito Danila , Santacroce Luigi , Inchingolo Francesco , Dipalma Gianna
Published: December 2020

The scientific community has definitely demonstrated the importance of the use of mouthwash in daily oral hygiene. In our pilot study, we tested the effectiveness of a novel mouth rinse containing sea salt, xylitol, and lysozyme. Streptococcus mutans (S. mutans) growth, and plaque index in adolescent patients aged 14–17 years, were observed. The bacterial load was investigated by in vitro microbiological analysis; the plaque index was assessed through the O’Leary’s Plaque Control Record (PCR). The study has shown that the use of a sea salt-based mouthwash in daily oral hygiene reduces the bacterial levels of S. mutans (p < 0.01) linked to the combined action of xylitol and lysozyme, together with the action of sea salt. Our preliminary data confirm and improve the main results reported in the scientific literature on the importance of the use of xylitol, lysozyme, and sea salt in oral health.
“They Were Willing to Work with Me and Not Pressure Me”: A Qualitative Investigation into the Features of Value of a Smoking Cessation in Pregnancy Program for Aboriginal and Torres Strait Islander Women
Authors: Lyall Vivian , Guy Jillian , Egert Sonya , Pokino Leigh-Anne , Rogers Lynne , Askew Deborah
Published: December 2020

With tobacco commonly used for stress relief, smoking cessation during pregnancy can present challenges for women facing stressful circumstances. This can be pronounced for Aboriginal and Torres Strait Islander women who experience disproportionately high smoking rates during pregnancy and also have a greater intersection of stressors from social disadvantage, institutional racism and trauma. To contribute understandings into how women can be best supported at this time, this study identified the features of value of an Aboriginal and Torres Strait Islander pregnancy smoking cessation program that addressed the contexts of women’s lives in culturally affirming and strength-based ways. A narrative methodology using a yarning approach was used to interview 7 pregnant women, 6 significant others, 3 case managers, and 4 healthcare professionals. Data were analyzed using thematic analysis, guided by an Indigenist research practice of deep and reflexive researcher listening. Features of value included: relationship-based care, holistic wraparound care, flexibility, individualized care, and culturally orientated care. Combined, they enabled highly relevant and responsive women-centered, trauma-informed, and harm-reducing smoking cessation support that was well received by participants, who achieved promising smoking changes, including cessation. This approach strongly departs from standard practices and provides a blueprint for meaningful support for pregnant women experiencing vulnerabilities.
Perceived Factors of Stress and Its Outcomes among Hotel Housekeepers in the Balearic Islands: A Qualitative Approach from a Gender Perspective
Authors: Chela-Alvarez Xenia , Bulilete Oana , García-Buades M. Esther , Ferrer-Perez Victoria A. , Llobera-Canaves Joan
Published: December 2020

Tourism is the main economic sector in the Balearic Islands (Spain) and hotel housekeepers (HHs) are a large occupational group, in which stress is becoming a major issue. This study aims at exploring in-depth factors perceived as stressors by HHs and key-informants, and their effects on work-life balance (WLB). A qualitative design with phenomenological approach was used, conducting six focus groups with 34 HHs and 10 individual interviews with key-informants. Results were analyzed adopting the job demands-resources model and a gender perspective. High demands, e.g., work overload, time pressure, physical burden…, lack of enough resources and little control, derived from role conflict, unexpected events…, were the most important factors explaining HHs’ stress. Additionally, this imbalance was perceived as leading to health problems, mainly musculoskeletal disorders. Working schedule was mentioned as a facilitator to WLB, whereas an imbalance between job demands and resources led to work-home conflict, preventing them from enjoying leisure time. Multiple roles at work and at home increased their stress. HHs experienced their job as invisible and unrecognised. Regarding practical implications, our recommendations for hotel organization include reducing workload and increasing resources, which would improve the job demands-resource balance, diminish negative mental and physical outcomes and improve WLB.
Bayesian Spatial Survival Analysis of Duration to Cure among New Smear-Positive Pulmonary Tuberculosis (PTB) Patients in Iran, during 2011–2018
Authors: Nazar Eisa , Baghishani Hossein , Doosti Hassan , Ghavami Vahid , Aryan Ehsan , Nasehi Mahshid , Sharafi Saeid , Esmaily Habibollah , Yazdani Charati Jamshid
Published: December 2020

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and pulmonary TB is the most prevalent form of the disease worldwide. One of the most concrete actions to ensure an effective TB control program is monitoring TB treatment outcomes, particularly duration to cure; but, there is no strong evidence in this respect. Thus, the primary aim of this study was to examine the possible spatial variations of duration to cure and its associated factors in Iran using the Bayesian spatial survival model. All new smear-positive PTB patients have diagnosed from March 2011 to March 2018 were included in the study. Out of 34,744 patients, 27,752 (79.90%) patients cured and 6992 (20.10%) cases were censored. For inferential purposes, the Markov chain Monte Carlo algorithms are applied in a Bayesian framework. According to the Bayesian estimates of the regression parameters in the proposed model, a Bayesian spatial log-logistic model, the variables gender (male vs. female, TR = 1.09), altitude (>750 m vs. ≤750 m, TR = 1.05), bacilli density in initial smear (3+ and 2+ vs. 1–9 Basil & 1+, TR = 1.09 and TR = 1.02, respectively), delayed diagnosis (>3 months vs. <1 month, TR = 1.02), nationality (Iranian vs. other, TR = 1.02), and location (urban vs. rural, TR = 1.02) had a significant influence on prolonging the duration to cure. Indeed, pretreatment weight (TR = 0.99) was substantially associated with shorter duration to cure. In summary, the spatial log-logistic model with convolution prior represented a better performance to analyze the duration to cure of PTB patients. Also, our results provide valuable information on critical determinants of duration to cure. Prolonged duration to cure was observed in provinces with low TB incidence and high average altitude as well. Accordingly, it is essential to pay a special attention to such provinces and monitor them carefully to reduce the duration to cure while maintaining a focus on high-risk provinces in terms of TB prevalence.
Frequency of Occupational Bloodborne Infections and Sharps Injuries among Polish Paramedics from Selected Ambulance Stations
Authors: Ganczak Maria , Topczewska Katarzyna , Biesiada Daniel , Korzeń Marcin
Published: December 2020

To evaluate the prevalence of bloodborne infections (BBIs) and assess the incidence and selected risk factors for sharps injuries (SIs), a cross-sectional serosurvey was performed between December 2018 and October 2019 among 286 paramedics (76.5% males; mean age, 37 years) from 17 randomly selected ambulance stations in the West Pomeranian region of Poland. An ELISA system was used to detect anti-HBc, anti-HCV, and anti-HIV. HBV vaccination uptake was 95.6%; 7.3% (95% CI: 4.6–11.0%) paramedics were anti-HBc positive, and anti-HCV/anti-HIV seropositivity was not reported. Almost one-fourth of paramedics reported having had ≥1 SI during the preceding year (Me = 6.0, range 1–100). Most recent exposures primarily took place during an emergency procedure (76.7%), in an ambulance (45.2%), caused by hollow-bore needles (73.8%), and were not reported (50.0%). Additionally, 52.2% of paramedics reported needle recapping, and 52.6% did not use safety engineered devices (SEDs) at work. Mean knowledge score was low (2.6 ± 1.7); 3.4% had never participated in infection-control (IC) training, and those not trained were more likely to suffer a SI (odds ratio (OR) 4.64; p = 0.03). Due to frequent SIs, of which half are unreported, paramedics remain at risk of acquiring occupational BBIs. SI risk could be reduced by providing training on IC procedures, ensuring better compliance with safe work practices, and supplying more SEDs.
Geospatial and Temporal Associations between Increases in Opioid Deaths, Socioeconomics, and Rates of Sexually Transmitted Infections in the Northeast United States 2012–2017
Authors: Drewes Matthew R. , Jones Jamison , Christiansen Emily Nelson , Wilson Jordan P. , Allen Brian , Sloan Chantel D.
Published: December 2020

With the introduction of fentanyl to illegal markets in 2013 and an overall rise in rates of synthetic opioid use, opioid-related deaths have increased significantly. A similar trend has been observed for sexually transmitted infections, homicides, and poor mental health outcomes. In this paper, we explore the spatiotemporal relationship between opioid death rates and sexually transmitted infection (STI) rates in counties from the Northeast region of the United States between the years 2012–2017. We hypothesized that rates for gonorrhea, chlamydia, and human immunodeficiency virus (HIV) would all be positively associated with opioid death rates and that there would be a similar association between the STI rates and later time periods relative to earlier time periods. A negative binomial mixed-effects regression model was employed to assess these associations. Contrary to the study hypothesis, opioid death rates were not found to be significantly associated with the STI rates after accounting for other demographic and socioeconomic variables, with the exception of opioid deaths and gonorrhea in urban counties. Additionally, the regression demonstrated a significant association between infection rate and time period beyond the included socioeconomic variables and opioid deaths. Overall, this study indicates that declining sexual health outcomes may parallel rising opioid death, though both trends may be explained by similar underlying factors related to time period.
Ammonium Accumulation Caused by Reduced Tonoplast V-ATPase Activity in Arabidopsis thaliana
Authors: Liang Guihong , Song Haixing , Xiao Yan , Zhang Zhenhua
Published: December 2020

Plant vacuoles are unique compartments that play a critical role in plant growth and development. The vacuolar H+-ATPase (V-ATPase), together with the vacuolar H+-pyrophosphatase (V-PPase), generates the proton motive force that regulates multiple cell functions and impacts all aspects of plant life. We investigated the effect of V-ATPase activity in the vacuole on plant growth and development. We used an Arabidopsisthaliana (L.) Heynh. double mutant, vha-a2 vha-a3, which lacks two tonoplast-localized isoforms of the membrane-integral V-ATPase subunit VHA-a. The mutant is viable but exhibits impaired growth and leaf chlorosis. Nitrate assimilation led to excessive ammonium accumulation in the shoot and lower nitrogen uptake, which exacerbated growth retardation of vha-a2 vha-a3. Ion homeostasis was disturbed in plants with missing VHA-a2 and VHA-a3 genes, which might be related to limited growth. The reduced growth and excessive ammonium accumulation of the double mutant was alleviated by potassium supplementation. Our results demonstrate that plants lacking the two tonoplast-localized subunits of V-ATPase can be viable, although with defective growth caused by multiple factors, which can be alleviated by adding potassium. This study provided a new insight into the relationship between V-ATPase, growth, and ammonium accumulation, and revealed the role of potassium in mitigating ammonium toxicity.
Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss
Authors: Fok Christine , Bogosanovic Milan , Pandya Madhavi , Telang Ravindra , Thorne Peter R. , Vlajkovic Srdjan M.
Published: December 2020

We and others have previously identified signalling pathways associated with the adenosine A1 receptor (A1R) as important regulators of cellular responses to injury in the cochlea. We have shown that the “post-exposure” treatment with adenosine A1R agonists confers partial protection against acoustic trauma and other forms of sensorineural hearing loss (SNHL). The aim of this study was to determine if increasing A1R responsiveness to endogenous adenosine would have the same otoprotective effect. This was achieved by pharmacological targeting of the Regulator of G protein Signalling 4 (RGS4). RGS proteins inhibit signal transduction pathways initiated by G protein-coupled receptors (GPCR) by enhancing GPCR deactivation and receptor desensitisation. A molecular complex between RGS4 and neurabin, an intracellular scaffolding protein expressed in neural and cochlear tissues, is the key negative regulator of A1R activity in the brain. In this study, Wistar rats (6–8 weeks) were exposed to traumatic noise (110 dBSPL, 8–16 kHz) for 2 h and a small molecule RGS4 inhibitor CCG-4986 was delivered intratympanically in a Poloxamer-407 gel formulation for sustained drug release 24 or 48 h after noise exposure. Intratympanic administration of CCG-4986 48 h after noise exposure attenuated noise-induced permanent auditory threshold shifts by up to 19 dB, whilst the earlier drug administration (24 h) led to even better preservation of auditory thresholds (up to 32 dB). Significant improvement of auditory thresholds and suprathreshold responses was linked to improved survival of sensorineural tissues and afferent synapses in the cochlea. Our studies thus demonstrate that intratympanic administration of CCG-4986 can rescue cochlear injury and hearing loss induced by acoustic overexposure. This research represents a novel paradigm for the treatment of various forms of SNHL based on regulation of GPCR.
Thapsigargin—From Traditional Medicine to Anticancer Drug
Authors: Jaskulska Agata , Janecka Anna Ewa , Gach-Janczak Katarzyna
Published: December 2020

A sesquiterpene lactone, thapsigargin, is a phytochemical found in the roots and fruits of Mediterranean plants from Thapsia L. species that have been used for centuries in folk medicine to treat rheumatic pain, lung diseases, and female infertility. More recently thapsigargin was found to be a potent cytotoxin that induces apoptosis by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump, which is necessary for cellular viability. This biological activity encouraged studies on the use of thapsigargin as a novel antineoplastic agent, which were, however, hampered due to high toxicity of this compound to normal cells. In this review, we summarized the recent knowledge on the biological activity and molecular mechanisms of thapsigargin action and advances in the synthesis of less-toxic thapsigargin derivatives that are being developed as novel anticancer drugs.
Effect of Amyloid-β Monomers on Lipid Membrane Mechanical Parameters–Potential Implications for Mechanically Driven Neurodegeneration in Alzheimer’s Disease
Authors: Drabik Dominik , Chodaczek Grzegorz , Kraszewski Sebastian
Published: December 2020

Alzheimer’s disease (AD) is a neurodegenerative disease that results in memory loss and the impairment of cognitive skills. Several mechanisms of AD’s pathogenesis were proposed, such as the progressive accumulation of amyloid-β (Aβ) and τ pathology. Nevertheless, the exact neurodegenerative mechanism of the Aβ remains complex and not fully understood. This paper proposes an alternative hypothesis of the mechanism based on maintaining the neuron membrane’s mechanical balance. The incorporation of Aβ decreases the lipid membrane’s elastic properties, which eventually leads to the impairment of membrane clustering, disruption of mechanical wave propagation, and change in gamma oscillations. The first two disrupt the neuron’s ability to function correctly while the last one decreases sensory encoding and perception enabling. To begin discussing this mechanical-balance hypothesis, we measured the effect of two selected peptides, Aβ-40 and Aβ-42, as well as their fluorescently labeled modification, on membrane mechanical properties. The decrease of bending rigidity, consistent for all investigated peptides, was observed using molecular dynamic studies and experimental flicker-noise techniques. Additionally, wave propagation was investigated with molecular dynamic studies in membranes with and without incorporated neurodegenerative peptides. A change in membrane behavior was observed in the membrane system with incorporated Aβ.
CB2 Receptor in Microglia: The Guardian of Self-Control
Authors: Komorowska-Müller Joanna Agnieszka , Schmöle Anne-Caroline
Published: December 2020

Microglia are key to maintaining the homeostasis of the brain. These immune cells of the brain can be our biggest ally in fighting infections, but can worsen pathology or hinder recovery when uncontrolled. Thus, understanding how microglia contribute to neuroinflammatory processes and how their activity can be controlled is of great importance. It is known that activation of endocannabinoid system, and especially the cannabinoid type 2 receptor (CB2R), decreases inflammation. Alongside its non-psychoactive effect, it makes the CB2R receptor a perfect target for treating diseases accompanied by neuroinflammation including neurodegenerative diseases. However, the exact mechanisms by which CB2R regulates microglial activity are not yet understood. Here, we review the current knowledge on the roles of microglial CB2R from in vitro and in vivo studies. We look into CB2R function under physiological and pathological conditions and focus on four different disease models representing chronic and acute inflammation. We highlight open questions and controversies and provide an update on the latest discoveries that were enabled by the development of novel technologies. Also, we discuss the recent findings on the role of microglia CB2R in cognition and its role in neuron–microglia communication.
FOXE1 Gene Dosage Affects Thyroid Cancer Histology and Differentiation In Vivo
Authors: Credendino Sara C. , Moccia Carmen , Amendola Elena , D’Avino Giuliana , Di Guida Luigi , Clery Eduardo , Greco Adelaide , Bellevicine Claudio , Brunetti Arturo , De Felice Mario , De Vita Gabriella
Published: December 2020

The transcription factor Forkhead box E1 (FOXE1) is a key player in thyroid development and function and has been identified by genome-wide association studies as a susceptibility gene for papillary thyroid cancer. Several cancer-associated polymorphisms fall into gene regulatory regions and are likely to affect FOXE1 expression levels. However, the possibility that changes in FOXE1 expression modulate thyroid cancer development has not been investigated. Here, we describe the effects of FOXE1 gene dosage reduction on cancer phenotype in vivo. Mice heterozygous for FOXE1 null allele (FOXE1+/−) were crossed with a BRAFV600E-inducible cancer model to develop thyroid cancer in either a FOXE1+/+ or FOXE1+/− genetic background. In FOXE1+/+ mice, cancer histological features are quite similar to that of human high-grade papillary thyroid carcinomas, while cancers developed with reduced FOXE1 gene dosage maintain morphological features resembling less malignant thyroid cancers, showing reduced proliferation index and increased apoptosis as well. Such cancers, however, appear severely undifferentiated, indicating that FOXE1 levels affect thyroid differentiation during neoplastic transformation. These results show that FOXE1 dosage exerts pleiotropic effects on thyroid cancer phenotype by affecting histology and regulating key markers of tumor differentiation and progression, thus suggesting the possibility that FOXE1 could behave as lineage-specific oncogene in follicular cell-derived thyroid cancer.
Extracellular Matrix Composition Modulates the Responsiveness of Differentiated and Stem Pancreatic Cancer Cells to Lipophilic Derivate of Gemcitabine
Authors: Forciniti Stefania , Dalla Pozza Elisa , Greco Maria Raffaella , Amaral Carvalho Tiago Miguel , Rolando Barbara , Ambrosini Giulia , Carmona-Carmona Cristian Andres , Pacchiana Raffaella , Di Molfetta Daria , Donadelli Massimo , Arpicco Silvia , Palmieri Marta , Reshkin Stephan Joel , Dando Ilaria , Cardone Rosa Angela
Published: December 2020

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Gemcitabine (GEM) is used as the gold standard drug in PDAC treatment. However, due to its poor efficacy, it remains urgent to identify novel strategies to overcome resistance issues. In this context, an intense stroma reaction and the presence of cancer stem cells (CSCs) have been shown to influence PDAC aggressiveness, metastatic potential, and chemoresistance. Methods: We used three-dimensional (3D) organotypic cultures grown on an extracellular matrix composed of Matrigel or collagen I to test the effect of the new potential therapeutic prodrug 4-(N)-stearoyl-GEM, called C18GEM. We analyzed C18GEM cytotoxic activity, intracellular uptake, apoptosis, necrosis, and autophagy induction in both Panc1 cell line (P) and their derived CSCs. Results: PDAC CSCs show higher sensitivity to C18GEM treatment when cultured in both two-dimensional (2D) and 3D conditions, especially on collagen I, in comparison to GEM. The intracellular uptake mechanisms of C18GEM are mainly due to membrane nucleoside transporters’ expression and fatty acid translocase CD36 in Panc1 P cells and to clathrin-mediated endocytosis and CD36 in Panc1 CSCs. Furthermore, C18GEM induces an increase in cell death compared to GEM in both cell lines grown on 2D and 3D cultures. Finally, C18GEM stimulated protective autophagy in Panc1 P and CSCs cultured on 3D conditions. Conclusion: We propose C18GEM together with autophagy inhibitors as a valid alternative therapeutic approach in PDAC treatment.
CD85k Contributes to Regulatory T Cell Function in Chronic Viral Infections
Authors: Estrada Brull Anna , Rost Felix , Oderbolz Josua , Kirchner Florian R. , Leibundgut-Landmann Salomé , Oxenius Annette , Joller Nicole
Published: December 2020

Regulatory T cells (Tregs) prevent excessive immune responses and limit immune pathology upon infections. To fulfill this role in different immune environments elicited by different types of pathogens, Tregs undergo functional specialization into distinct subsets. During acute type 1 immune responses, type 1 Tregs are induced and recruited to the site of ongoing Th1 responses to efficiently control Th1 responses. However, whether a similar specialization process also takes place following chronic infections is still unknown. In this study, we investigated Treg specialization in persistent viral infections using lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV) infection as models for chronic and latent infections, respectively. We identify CD85k as a Th1-specific co-inhibitory receptor with sustained expression in persistent viral infections and show that recombinant CD85k inhibits LCMV-specific effector T cells. Furthermore, expression of the CD85k ligand ALCAM is induced on LCMV-specific and exhausted T cells during chronic LCMV infection. Finally, we demonstrate that type 1 Tregs arising during chronic LCMV infection suppress Th1 effector cells in an ALCAM-dependent manner. These results extend the current knowledge of Treg specialization from acute to persistent viral infections and reveal an important functional role of CD85k in Treg-mediated suppression of type 1 immunity.
Valorization of Gleditsia triacanthos Invasive Plant Cellulose Microfibers and Phenolic Compounds for Obtaining Multi-Functional Wound Dressings with Antimicrobial and Antioxidant Properties
Authors: Marinas Ioana Cristina , Oprea Eliza , Geana Elisabeta-Irina , Tutunaru Oana , Pircalabioru Gratiela Gradisteanu , Zgura Irina , Chifiriuc Mariana Carmen
Published: December 2020

Gleditsia triacanthos is an aggressive invasive species in Eastern Europe, producing a significant number of pods that could represent an inexhaustible resource of raw material for various applications. The aim of this study was to extract cellulose from the Gleditsia triacanthos pods, characterize it by spectrophotometric and UHPLC–DAD-ESI/MS analysis, and use it to fabricate a wound dressing that is multi-functionalized with phenolic compounds extracted from the leaves of the same species. The obtained cellulose microfibers (CM) were functionalized, lyophilized, and characterized by ATR-FTIR and SEM. The water absorption and retention capacity as well as the controlled release of phenolic compounds with antioxidant properties evaluated in temporal dynamics were also determined. The antimicrobial activity against reference and clinical multi-drug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Candida albicans, and Candida parapsilosis strains occurred immediately after the contact with the tested materials and was maintained for 24 h for all tested microbial strains. In conclusion, the multi-functionalized cellulose microfibers (MFCM) obtained from the reproductive organs of an invasive species can represent a promising alternative for the development of functional wound dressings with antioxidant and antimicrobial activity, as well as being a scalable example for designing cost-effective, circular bio-economy approaches to combat the accelerated spread of invasive species.
The Bark Beetle Dendroctonus rhizophagus (Curculionidae: Scolytinae) Has Digestive Capacity to Degrade Complex Substrates: Functional Characterization and Heterologous Expression of an α-Amylase
Authors: Soto-Robles L. Viridiana , López María Fernanda , Torres-Banda Verónica , Cano-Ramírez Claudia , Obregón-Molina Gabriel , Zúñiga Gerardo
Published: December 2020

Dendroctonus-bark beetles are natural agents contributing to vital processes in coniferous forests, such as regeneration, succession, and material recycling, as they colonize and kill damaged, stressed, or old pine trees. These beetles spend most of their life cycle under stem and roots bark where they breed, develop, and feed on phloem. This tissue is rich in essential nutrients and complex molecules such as starch, cellulose, hemicellulose, and lignin, which apparently are not available for these beetles. We evaluated the digestive capacity of Dendroctonus rhizophagus to hydrolyze starch. Our aim was to identify α-amylases and characterize them both molecularly and biochemically. The findings showed that D. rhizophagus has an α-amylase gene (AmyDr) with a single isoform, and ORF of 1452 bp encoding a 483-amino acid protein (53.15 kDa) with a predicted signal peptide of 16 amino acids. AmyDr has a mutation in the chlorine-binding site, present in other phytophagous insects and in a marine bacterium. Docking analysis showed that AmyDr presents a higher binding affinity to amylopectin compared to amylose, and an affinity binding equally stable to calcium, chlorine, and nitrate ions. AmyDr native protein showed amylolytic activity in the head-pronotum and gut, and its recombinant protein, a polypeptide of ~53 kDa, showed conformational stability, and its activity is maintained both in the presence and absence of chlorine and nitrate ions. The AmyDr gene showed a differential expression significantly higher in the gut than the head-pronotum, indicating that starch hydrolysis occurs mainly in the midgut. An overview of the AmyDr gene expression suggests that the amylolytic activity is regulated through the developmental stages of this bark beetle and associated with starch availability in the host tree.