bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of COVID-19-imposed lockdown and online searches for toothache in Iran
Authors: Sofi-Mahmudi Ahmad , Shamsoddin Erfan , Ghasemi Peyman , Mehrabi Bahar Ali , Shaban Azad Mansour , Sadeghi Ghasem
Published: February 2021

Background

Novel coronavirus disease-2019 (COVID-19) has impacted populations in many ways worldwide, including access to oral health services. This study aims to assess the association between lockdown due to COVID-19 and online searches for toothache in Iran using Google Trends (GT).

Methods

We investigated GT online searches for toothache within the past five years. The time frame for data gathering was considered as the initiation and end dates of the national lockdown in Iran. We performed one-way ANOVA statistical test to compare relative search volumes (RSVs) between the year 2020 and 2016–2019 for the whole country. Then we investigated the possible association of RSVs in provinces with dentists’ density, prevalence of current daily smokers, Human Development Index (HDI), Internet access, and fluoride concentration in water using linear regression.

Results

When comparing 2020 with the previous four years, there was a rise of 2020 RSVs versus all previous years combined and each year (P < 0.001 for all of them). In the linear model for the year 2020, HDI (B = − 3.29, 95% CI: (− 5.80, − 0.78), P = 0.012) had a strong negative relationship with provincial RSVs. HDI mostly had strong positive relationship with provincial RSVs in prior years. Fluoride concentration (B = − 0.13, 95% CI: (− 0.24, − 0.03), P = 0.017) and dentists’ density (B = − 0.04, 95% CI: (− 0.25, 0.17), P = 0.669) were also negatively associated with RSVs in 2020. These associations were mostly negative in the previous years as well. Internet access (B = 0.36, 95% CI: (− 0.38, 1.09), P = 0.325) and prevalence of daily smokers (B = 0.33, 95% CI: (0.13, 0.53), P = 0.002) were positively associated with RSVs.

Conclusion

The RSVs for toothache in 2020 have increased due to COVID-19-imposed lockdown compared with the same period in the past four years. This increase was related to socioeconomic factors.
Psychological predictors of intention and avoidance of attending organized mammography screening in Norway: applying the Extended Parallel Process Model
Authors: Ivanova Anna , Kvalem Ingela Lundin
Published: February 2021

Background

Mammography screening is the main method for early detection of breast cancer in Norway. Few studies have focused on psychological determinants of both attendance and non-attendance of publicly available mammography screening programs. The aim of the current study, guided by the Extended Parallel Process Model, was to examine how psychological factors influence defensive avoidance of breast cancer screening and intention to attend mammography.

Methods

Cross-sectional survey data from a community sample of women living in Norway aged ≥ 18 (N = 270), and without a history of breast cancer, was collected from September 2018 to June 2019 and used to investigate the relationships between the Extended Parallel Process Model (EPPM) constructs and two outcomes: defensive avoidance of breast cancer screening and intention to attend mammography within the next two years. After adjusting for confounding factors, the hierarchical multiple linear regression analyses was conducted to assess the ability of the independent variables based on the EPPM to predict the two outcome variables. Significance level was chosen at p < 0.05.

Results

Multivariate analyses showed that defensive avoidance of breast cancer screening was predicted by lower perceived susceptibility to breast cancer (β =  − 0.22, p = 0.001), lower response efficacy of mammography screening (β =  − 0.33, p = 0.001), higher breast cancer fear (β = 0.15, p = 0.014), and checking breasts for lumps (β =  − 0.23, p = 0.001). Intention to attend mammography within the next two years was predicted by higher response efficacy of mammography screening (β = 0.13, p = 0.032), having a lower educational level (β =  − 0.10, p = 0.041), and regular previous mammography attendance compared to never attending (β = 0.49, p = 0.001).

Conclusions

The study revealed that defensive avoidance of breast cancer screening and intention to attend mammography were not predicted by the same pattern of psychological factors. Our findings suggest future health promotion campaigns need to focus not only on the psychological factors that encourage women’s decision to attend the screening, but also to counter factors that contribute to women’s decision to avoid it.
Breast cancer screening knowledge among Hungarian women: a cross-sectional study
Authors: Reményi Kissné Diána , Gede Noémi , Szakács Zsolt , Kiss István
Published: February 2021

Background

Breast cancer (BC) is the leading malignant tumor among women worldwide. Although attending regular BC screening effectively reduces cancer-related mortality, surveys testify that screening knowledge is critically low among women. We aimed to conduct a comparative cross-sectional survey to assess BC and BC screening-related knowledge in Hungary.

Methods

Women between 25 and 65 years of age without a previous history of malignant tumors were included with non-probability sampling in 2017. Respondents were recruited either from primary care (laywomen) or from the waiting rooms of mammography (screening attendees). A self-completion questionnaire was constructed with questions about BC (risk factors, signs and symptoms, curability, and mortality), BC screening (mammography and breast self-examination), and BC-related information sources to assess knowledge among laywomen and screening attendees. In addition to descriptive statistics, odds ratios with 95% confidence intervals were calculated in univariate analysis and logistic regression was used in multivariate analysis.

Results

Altogether, 480 women completed the questionnaire, of which 429 (227 laywomen and 202 screening attendees) were eligible for inclusion. Laywomen and screening attendees knew the recommended age at first mammography in 35.2% and 86.6%, the recommended frequency of screening in 33.9% and 12.9%, the recommended age at first breast-self examination in 38.8% and 51.2%, had sufficient knowledge of the risk factors of BC in 7.0% and 5.9%, and that of signs and symptoms of BC in 16.7% and 28.9%, respectively. A higher proportion of screening attendees correctly identified the recommended age of first BC screening correctly than that of laywomen (86.6% vs. 35.2%; p < 0.001). The most popular information sources were television among laywomen and general practitioners or specialists among screening attendees. In multivariate analysis, older age, higher education, and place of residency were significant predictors of the right answers.

Conclusions

Although knowledge was insufficient in almost all fields of the questionnaire, the most prominent gap was observed concerning risk factors and signs and symptoms of BC both in laywomen and, unexpectedly, screening attendees. Most laywomen were lacking knowledge of screening protocol. These results urge breast health and BC knowledge interventions in Hungary.
How supervision and educational supports impact medical students’ preparation for future learning of endotracheal intubation skills: a non-inferiority experimental trial
Authors: Manzone Julian C. , Mylopoulos Maria , Ringsted Charlotte , Brydges Ryan
Published: February 2021

Background

Professional education cannot keep pace with the rapid advancements of knowledge in today’s society. But it can develop professionals who can. ‘Preparation for future learning’ (PFL) has been conceptualized as a form of transfer whereby learners use their previous knowledge to learn about and adaptively solve new problems. Improved PFL outcomes have been linked to instructional approaches targeting learning mechanisms similar to those associated with successful self-regulated learning (SRL). We expected training that includes evidence-based SRL-supports would be non-inferior to training with direct supervision using the outcomes of a ‘near transfer’ test, and a PFL assessment of simulated endotracheal intubation skills.

Method

This study took place at the University of Toronto from October 2014 to August 2015. We randomized medical students and residents (n = 54) into three groups: Unsupervised, Supported; Supervised, Supported; and Unsupervised, Unsupported. Two raters scored participants’ test performances using a Global Rating Scale with strong validity evidence. We analyzed participants’ near transfer and PFL outcomes using two separate mixed effects ANCOVAs.

Results

For the Unsupervised, Supported group versus the Supervised, Supported group, we found that the difference in mean scores was 0.20, with a 95% Confidence Interval (CI) of − 0.17 to 0.57, on the near transfer test, and was 0.09, with a 95% CI of − 0.28 to 0.46, on the PFL assessment. Neither mean score nor their 95% CIs exceeded the non-inferiority margin of 0.60 units. Compared to the two Supported groups, the Unsupervised, Unsupported group was non-inferior on the near transfer test (differences in mean scores were 0.02 and − 0.22). On the PFL assessment, however, the differences in mean scores were 0.38 and 0.29, and both 95% CIs crossed the non-inferiority margin.

Conclusions

Training with SRL-supports was non-inferior to training with a supervisor. Both interventions appeared to impact PFL assessment outcomes positively, yet inconclusively when compared to the Unsupervised and Unsupported group, By contrast, the Unsupervised, Supported group did not score well on the near transfer test. Based on the observed sensitivity of the PFL assessment, we recommend researchers continue to study how such assessments may measure learners’ SRL outcomes  during structured learning experiences.
Assessing communication skills during OSCE: need for integrated psychometric approaches
Authors: Piumatti Giovanni , Cerutti Bernard , Perron Noëlle Junod
Published: February 2021

Background

Physicians’ communication skills (CS) are known to significantly affect the quality of health care. Communication skills training programs are part of most undergraduate medical curricula and are usually assessed in Objective Structured Clinical Examinations (OSCE) throughout the curriculum. The adoption of reliable measurement instruments is thus essential to evaluate such skills.

Methods

Using Exploratory Factor Analysis (EFA), Multi-Group Confirmatory Factor Analysis (MGCFA) and Item Response Theory analysis (IRT) the current retrospective study tested the factorial validity and reliability of a four-item global rating scale developed by Hodges and McIlroy to measure CS among 296 third- and fourth-year medical students at the Faculty of Medicine in Geneva, Switzerland, during OSCEs.

Results

EFA results at each station showed good reliability scores. However, measurement invariance assessments through MGCFA across different stations (i.e., same students undergoing six or three stations) and across different groups of stations (i.e., different students undergoing groups of six or three stations) were not satisfactory, failing to meet the minimum requirements to establish measurement invariance and thus possibly affecting reliable comparisons between students’ communication scores across stations. IRT revealed that the four communication items provided overlapping information focusing especially on high levels of the communication spectrum.

Conclusions

Using this four-item set in its current form it may be difficult to adequately differentiate between students who are poor in CS from those who perform better. Future directions in best-practices to assess CS among medical students in the context of OSCE may thus focus on (1) training examiners so to obtain scores that are more coherent across stations; and (2) evaluating items in terms of their ability to cover a wider spectrum of medical students’ CS. In this respect, IRT can prove to be very useful for the continuous evaluation of CS measurement instruments in performance-based assessments.
Oral cancer patient’s profile and time to treatment initiation in the public health system in Rio de Janeiro, Brazil
Authors: da Conceição Manoela Garcia Dias , Emmerick Isabel Cristina Martins , Figueiró Ana Claudia , Luiza Vera Lucia
Published: February 2021

Background

This paper aims to describe the profile of oral cancer (OC) patients, their risk classification and identify the time between screening and treatment initiation in Rio de Janeiro Municipality.

Method

Data were obtained from the healthcare Regulation System (SISREG) regarding the period January 2013 to September 2015. Descriptive, bivariate and multivariate analysis were performed identifying the factors associates with a diagnosis of OC as well as the time to treatment initiation (TTI) differences between groups.

Results

From 3,862 individuals with a potential OC lesion, 6.9 % had OC diagnosis. OC patients were 62.3 y.o. (mean), 64.7 % male, 36.1 % were white and 62.5 % of the records received a red/yellow estimated risk classification. Being older, male, white and receiving a high-risk classification was associated with having an OC diagnosis. OC TTI was in average 59.1 days and median of 50 days significantly higher than non-OC individuals (p = 0.007). TTI was higher for individuals older than 60 years old, male, and white individuals and for risk classification red and yellow, nevertheless while in average none of these differences were statistically significant, the median of individuals classified as low risk was significantly (p = 0.044) lower than those with high risk.

Conclusions

Time to treatment initiation (TTI) was higher for OC patients related to non OC. Despite OC confirmed was associated with risk at screening classified as urgent or emergent, a high percentage of OC patients had their risk classified for elective care when specialized care was requested.
Clinical diagnosis in paediatric patients at urban primary health care facilities in southern Malawi: a longitudinal observational study
Authors: Gondwe Mtisunge Joshua , Henrion Marc Y. R. , O’Byrne Thomasena , Masesa Clemens , Lufesi Norman , Dube Queen , Majamanda Maureen D. , Makwero Martha , Lalloo David G. , Desmond Nicola
Published: February 2021

Background

Despite health centres being the first point of contact of care, there are challenges faced in providing care to patients at this level. In Malawi, service provision barriers reported at this level included long waiting times, high numbers of patients and erratic consultation systems which lead to mis-diagnosis and delayed referrals. Proper case management at this level of care is critical to prevent severe disease and deaths in children. We aimed to adopt Emergency, Triage, Assessment and Treatment algorithm (ETAT) to improve ability to identify severe illness in children at primary health centre (PHC) through comparison with secondary level diagnoses.

Methods

We implemented ETAT mobile Health (mHealth) at eight urban PHCs in Blantyre, Malawi between April 2017 and September 2018. Health workers and support staff were trained in mHealth ETAT. Stabilisation rooms were established and equipped with emergency equipment. All PHCs used an electronic tracking system to triage and track sick children on referral to secondary care, facilitated by a unique barcode. Support staff at PHC triaged sick children using ETAT Emergency (E), Priority (P) and Queue (Q) symptoms and clinician gave clinical diagnosis. The secondary level diagnosis was considered as a gold standard. We used statistical computing software R (v3.5.1) and used exact 95% binomial confidence intervals when estimating diagnosis agreement proportions.

Results

Eight-five percentage of all cases where assigned to E (9.0%) and P (75.5%) groups. Pneumonia was the most common PHC level diagnosis across all three triage groups (E, P, Q). The PHC level diagnosis of trauma was the most commonly confirmed diagnosis at secondary level facility (85.0%), while a PHC diagnosis of pneumonia was least likely to be confirmed at secondary level (39.6%). The secondary level diagnosis least likely to have been identified at PHC level was bronchiolitis 3 (5.2%). The majority of bronchiolitis cases (n = 50; (86.2%) were classified as pneumonia at the PHC level facility.

Conclusions

Implementing a sustainable and consistent ETAT approach with stabilisation and treatment capacity at PHC level reinforce staff capacity to diagnose and has the potential to reduce other health system costs through fewer, timely and appropriate referrals.
Development of a novel nannochloropsis strain with enhanced violaxanthin yield for large‐scale production
Authors: Park Su-Bin , Yun Jin-Ho , Ryu Ae Jin , Yun Joohyun , Kim Ji Won , Lee Sujin , Choi Saehae , Cho Dae-Hyun , Choi Dong-Yun , Lee Yong Jae , Kim Hee-Sik
Published: February 2021

Background

Nannochloropsis is a marine microalga that has been extensively studied. The major carotenoid produced by this group of microalgae is violaxanthin, which exhibits anti-inflammatory, anti-photoaging, and antiproliferative activities. Therefore, it has a wide range of potential applications. However, large-scale production of this pigment has not been much studied, thereby limiting its industrial application.

Results

To develop a novel strain producing high amount of violaxanthin, various Nannochloropsis species were isolated from seawater samples and their violaxanthin production potential were compared. Of the strains tested, N. oceanica WS-1 exhibited the highest violaxanthin productivity; to further enhance the violaxanthin yield of WS-1, we performed gamma-ray-mediated random mutagenesis followed by colorimetric screening. As a result, Mutant M1 was selected because of its significant higher violaxanthin content and biomass productivity than WS-1 (5.21 ± 0.33 mg g− 1 and 0.2101 g L− 1 d− 1, respectively). Subsequently, we employed a 10 L-scale bioreactor to confirm the large-scale production potential of M1, and the results indicated a 43.54 % increase in violaxanthin production compared with WS-1. In addition, comparative transcriptomic analysis performed under normal light condition identified possible mechanisms associated with remediating photo-inhibitory damage and other key responses in M1, which seemed to at least partially explain enhanced violaxanthin content and delayed growth.

Conclusions

Nannochloropsis oceanica mutant (M1) with enhanced violaxanthin content was developed and its physiological characteristics were investigated. In addition, enhanced production of violaxanthin was demonstrated in the large-scale cultivation. Key transcriptomic responses that are seemingly associated with different physiological responses of M1 were elucidated under normal light condition, the details of which would guide ongoing efforts to further maximize the industrial potential of violaxanthin producing strains.
Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma
Authors: Zhao JiangSheng , Chen GuoFeng , Li Jingqi , Liu Shiqi , Jin Quan , Zhang ZhengWei , Qi Fuzhen , Zhang JianHuai , Xu JianBo
Published: February 2021

Background

PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC.

Methods

PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing.

Results

PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2.

Conclusions

This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.
Malaria in migrant agricultural workers in western Ethiopia: entomological assessment of malaria transmission risk
Authors: Dugassa Sisay , Murphy Mathew , Chibsa Sheleme , Tadesse Yehualashet , Yohannes Gedeon , Lorenz Lena M. , Solomon Hiwot , Yewhalaw Delenasaw , Irish Seth R.
Published: February 2021

Background

Ethiopia has made great strides in malaria control over the last two decades. However, this progress has not been uniform and one concern has been reported high rates of malaria transmission in large agricultural development areas in western Ethiopia. Improved vector control is one way this transmission might be addressed, but little is known about malaria vectors in this part of the country.

Methods

To better understand the vector species involved in malaria transmission and their behaviour, human landing collections were conducted in Dangur woreda, Benishangul-Gumuz, between July and December 2017. This period encompasses the months with the highest rain and the peak mosquito population. Mosquitoes were identified to species and tested for the presence of Plasmodium sporozoites.

Results

The predominant species of the Anopheles collected was Anopheles arabiensis (1,733; i.e. 61.3 % of the entire Anopheles), which was also the only species identified with sporozoites (Plasmodium falciparum and Plasmodium vivax). Anopheles arabiensis was collected as early in the evening as 18:00 h-19:00 h, and host-seeking continued until 5:00 h-6:00 h. Nearly equal numbers were collected indoors and outdoors. The calculated entomological inoculation rate for An. arabiensis for the study period was 1.41 infectious bites per month. More An. arabiensis were collected inside and outside worker’s shelters than in fields where workers were working at night.

Conclusions

Anopheles arabiensis is likely to be the primary vector of malaria in the agricultural development areas studied. High rates of human biting took place inside and outdoor near workers’ residential housing. Improved and targeted vector control in this area might considerably reduce malaria transmission.
Parasite genetic diversity reflects continued residual malaria transmission in Vhembe District, a hotspot in the Limpopo Province of South Africa
Authors: Gwarinda Hazel B. , Tessema Sofonias K. , Raman Jaishree , Greenhouse Bryan , Birkholtz Lyn-Marié
Published: February 2021

Background

South Africa aims to eliminate malaria transmission by 2023. However, despite sustained vector control efforts and case management interventions, the Vhembe District remains a malaria transmission hotspot. To better understand Plasmodium falciparum transmission dynamics in the area, this study characterized the genetic diversity of parasites circulating within the Vhembe District.

Methods

A total of 1153 falciparum-positive rapid diagnostic tests (RDTs) were randomly collected from seven clinics within the district, over three consecutive years (2016, 2017 and 2018) during the wet and dry malaria transmission seasons. Using 26 neutral microsatellite markers, differences in genetic diversity were described using a multiparameter scale of multiplicity of infection (MOI), inbreeding metric (Fws), number of unique alleles (A), expected heterozygosity (He), multilocus linkage disequilibrium (LD) and genetic differentiation, and were associated with temporal and geospatial variances.

Results

A total of 747 (65%) samples were successfully genotyped. Moderate to high genetic diversity (mean He = 0.74 ± 0.03) was observed in the parasite population. This was ascribed to high allelic richness (mean A = 12.2 ± 1.2). The majority of samples (99%) had unique multi-locus genotypes, indicating high genetic diversity in the sample set. Complex infections were observed in 66% of samples (mean MOI = 2.13 ± 0.04), with 33% of infections showing high within-host diversity as described by the Fws metric. Low, but significant LD (standardised index of association, ISA = 0.08, P < 0.001) was observed that indicates recombination of distinct clones. Limited impact of temporal (FST range − 0.00005 to 0.0003) and spatial (FST = − 0.028 to 0.023) variation on genetic diversity existed during the sampling timeframe and study sites respectively.

Conclusions

Consistent with the Vhembe District’s classification as a ‘high’ transmission setting within South Africa, P. falciparum diversity in the area was moderate to high and complex. This study showed that genetic diversity within the parasite population reflects the continued residual transmission observed in the Vhembe District. This data can be used as a reference point for the assessment of the effectiveness of on-going interventions over time, the identification of imported cases and/or outbreaks, as well as monitoring for the potential spread of anti-malarial drug resistance.
Correlation between antimicrobial resistance and biofilm formation capability among Klebsiella pneumoniae strains isolated from hospitalized patients in Iran
Authors: Shadkam Shadi , Goli Hamid Reza , Mirzaei Bahman , Gholami Mehrdad , Ahanjan Mohammad
Published: February 2021

Background

Klebsiella pneumoniae is a common cause of nosocomial infections. Antibiotic resistance and ability to form biofilm, as two key virulence factors of K. pneumoniae, are involved in the persistence of infections. The purpose of this study was to investigate the correlation between antimicrobial resistance and biofilm formation capability among K. pneumoniae strains isolated from hospitalized patients in Iran.

Methods

Over a 10-month period, a total of 100 non-duplicate K. pneumoniae strains were collected. Antibiotic susceptibility was determined by Kirby–Bauer disk diffusion method according to CLSI. Biofilm production was assessed by tissue culture plate method. Finally, polymerase chain reaction was conducted to detect four families of carbapenemase: blaIMP, blaVIM, blaNDM, blaOXA−48; biofilm formation associated genes: treC, wza, luxS; and K. pneumoniae confirming gene: rpoB.

Results

Most of the isolates were resistant to trimethoprim-sulfamethoxazole (52 %), cefotaxime (51 %), cefepime (43 %), and ceftriaxone (43 %). Among all the 100 isolates, 67 were multidrug-resistant (MDR), and 11 were extensively drug-resistant (XDR). The prevalence of the blaVIM, blaIMP, blaNDM, and blaOXA−48 genes were 7 , 11 , 5 , and 28 %, respectively. The results of biofilm formation in the tissue culture plate assay indicated that 75 (75 %) strains could produce biofilm and only 25 (25 %) isolates were not able to form biofilm. Among these isolates, 25 % formed fully established biofilms, 19 % were categorized as moderately biofilm-producing, 31 % formed weak biofilms, and 25 % were non-biofilm-producers. The antimicrobial resistance among biofilm former strains was found to be significantly higher than that of non-biofilm former strains (p < 0.05). Molecular distribution of biofilm formation genes revealed that 98 , 96 , and 34 % of the isolates carried luxS, treC, and wza genes, respectively.

Conclusions

The rise of antibiotic resistance among biofilm-producer strains demonstrates a serious concern about limited treatment options in the hospital settings. All of the data suggest that fundamental actions and introduction of novel strategies for controlling of K. pneumoniae biofilm-related infections is essential.
mRNA vaccine: a potential therapeutic strategy
Authors: Wang Yang , Zhang Ziqi , Luo Jingwen , Han Xuejiao , Wei Yuquan , Wei Xiawei
Published: February 2021

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.
Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia
Authors: Cruz-Bautista Ivette , Huerta-Chagoya Alicia , Moreno-Macías Hortensia , Rodríguez-Guillén Rosario , Ordóñez-Sánchez María Luisa , Segura-Kato Yayoi , Mehta Roopa , Almeda-Valdés Paloma , Gómez-Munguía Lizeth , Ruiz-De Chávez Ximena , Rosas-Flota Ximena , Andrade-Amado Arali , Bernal-Barroeta Bárbara , López-Carrasco María Guadalupe , Guillén-Pineda Luz Elizabeth , López-Estrada Angelina , Elías-López Daniel , Martagón-Rosado Alexandro J. , Gómez-Velasco Donají , Lam-Chung Cesar Ernesto , Bello-Chavolla Omar Yaxmehen , Del Razo-Olvera Fabiola , Cetina-Pérez Lucely D. , Acosta-Rodríguez José Luis , Tusié-Luna María Teresa , Aguilar-Salinas Carlos A.
Published: February 2021

Background

Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease.

Methods

This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups.

Results

Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG.

Conclusions

The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.
Tailored liposomal nanotraps for the treatment of Streptococcal infections
Authors: Besançon Hervé , Babiychuk Viktoriia , Larpin Yu , Köffel René , Schittny Dominik , Brockhus Lara , Hathaway Lucy J. , Sendi Parham , Draeger Annette , Babiychuk Eduard
Published: February 2021

Background

Streptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins.

Results

In this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis-pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens.

Conclusions

Unravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.
Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice
Authors: Liao Chia-Chih , Yu Huang-Ping , Yang Shih-Chun , Alalaiwe Ahmed , Dai You-Shan , Liu Fu-Chao , Fang Jia-You
Published: February 2021

Background

Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury.

Results

The mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%.

Conclusions

The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.
Quantitative proteomic profiling of Cervicovaginal fluid from pregnant women with term and preterm birth
Authors: Kim Young Eun , Kim Kwonseong , Oh Han Bin , Lee Sung Ki , Kang Dukjin
Published: February 2021

Background

Preterm birth (PTB) is one of major causes of perinatal mortality and neonatal morbidity, but knowledge of its complex etiology is still limited. Here we present cervicovaginal fluid (CVF) protein profiles of pregnant women who subsequently delivered at spontaneous preterm or term, aiming to identify differentially expressed CVF proteins in PTB and term birth.

Methods

The CVF proteome of women who sequentially delivered at preterm and term was analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS). We compared the CVF proteome of PTB (n = 5) and control subjects (term birth, n = 7) using pooled control CVF (term birth, n = 20) as spike-in standard.

Results

We identified 1294 CVF proteins, of which 605 were newly identified proteins. Of 990 proteins quantified in both PTB and term birth, 52 proteins were significantly up/down-regulated in PTB compared to term birth. The differentially expressed proteins were functionally associated to immune response, endopeptidase inhibitors and structural constituent of cytoskeleton. Finally, we confirm the down-regulation of SERPINB7 (a serine-type protease inhibitor) in PTB compared to control by Western blot.

Conclusions

Taken together, our study provide quantitative CVF proteome profiles of pregnant women who ultimately delivered at preterm and term. These promising results could help to improve the understanding of PTB etiology and to discover biomarkers for asymptomatic PTB.
Governing heatwaves in Europe: comparing health policy and practices to better understand roles, responsibilities and collaboration
Authors: Vanderplanken Kirsten , van den Hazel Peter , Marx Michael , Shams Ahmad Zia , Guha-Sapir Debarati , van Loenhout Joris Adriaan Frank
Published: February 2021

Background

The expectation that climate change will further exacerbate extreme weather events such as heatwaves is of primary concern to policymakers and scientists. Effective governance is fundamental to preparedness for and response to such threats. This paper explores the governance structures of European heat health action plans and provides insights into key stakeholders, roles, responsibilities and collaboration.

Methods

This was a two-phase qualitative study, in which we complemented a desk review of 15 European national heat health action plans (NHHAPs) with, after obtaining informed consent, 68 interviews in nine countries with key informants involved in the development, implementation and/or evaluation of these NHHAPs. A thematic analysis was used to analyze the NHHAPs inductively. This analysis focused on three themes: identifying key stakeholders, defining and assigning roles and collaboration among stakeholders. The iteratively created codebook was then applied to the analysis of the key informant interviews. All analyses were done using NVivo 10 qualitative analysis software.

Results

The majority of the NHHAPs have governance as one of their main objectives, to support the coordination of actions and collaboration among involved stakeholders. There are, however, significant differences between plan and practice. On the basis of the available data, we have little insight into the process of stakeholder identification, but we do find that most countries involve the same types of stakeholders. Roles are mainly defined and assigned in relation to the alert levels of the warning system, causing other role aspects and other roles to be vague and ambiguous. Collaboration is key to many NHHAP elements and is mainly experienced positively, though improvements and new collaborations are considered.

Conclusions

Our findings show a need for a more deliberate and structured approach to governance in the context of NHHAPs. A cross-sectoral approach to the identification of key stakeholders can facilitate a broader preparedness and response to heatwaves. Roles and responsibilities of stakeholders should be defined and assigned more clearly to avoid confusion and to improve effective implementation. To this extent, we identify and describe seven key roles and potential stakeholders to which these roles are usually assigned. Finally, also collaboration among stakeholders can benefit from a cross-sectoral approach, but also formal structures can be beneficial.
Demographic forecasting of population aging in Greece and Cyprus: one big challenge for the Mediterranean health and social system long-term sustainability
Authors: Lamnisos Demetris , Giannakou Konstantinos , Jakovljevic Mihajlo (Michael)
Published: February 2021

Background

With an increasing aging population and a lower ratio between the active and the dependent population, population aging is considered a global social and health challenge, associated with increased demand in health care needs and social pension. This study projects the Greek and Cypriot population to guide future planning of social and health policies and services.

Methods

The total population by sex and age groups, Total Fertility Rate (TFR), life-expectancies at birth and Potential Support Ratio PSR (persons aged 20–64 years per person 65+ years) are projected probabilistically by the year 2100 using Bayesian hierarchical models and United Nations’ population data for Greece and Cyprus from the period of 1950 to 2015.

Results

The TFR is projected to be around 1.5 children per woman in 2050 and around 1.75 in 2100 for both countries, with all values of prediction intervals being around or below the Replacement level fertility. PSR is expected to decrease remarkably and be 2.5 in 2050 and 1.6 in 2100 for Cyprus while for Greece it will be around 1.5 for both years 2050 and 2100. Life-expectancy is expected to increase to 84 years for men and 87 years for women in 2050 and 90 years for men and 94 years for women in 2100 for both countries. The share of the population aged 65 years and over is projected to increase in both countries and be the one third of the population by 2100.

Conclusions

Greece and Cyprus will acquire the characteristics of an aging population, putting a significance pressure on the social and health systems of both countries. Both countries should reform their social and health policy agenda to confront population aging and its consequence. They should adopt fertility incentives and family policies to increase fertility and migrants’ inclusiveness policies to improve the demographic structure and the economic activity. The national health systems should promote prevention strategies at the primary health sector and promote healthy aging while health research policy should aim to promote research in innovative technologies and digital health to create assistive technology for self-care and greater independence of older people.
The added value of using the HEPA PAT for physical activity policy monitoring: a four-country comparison
Authors:   the PEN Consortium, Gelius Peter , Messing Sven , Forberger Sarah , Lakerveld Jeroen , Mansergh Fiona , Wendel-Vos Wanda , Zukowska Joanna , Woods Catherine
Published: February 2021

Background

Public policy is increasingly recognized as an important component of physical activity promotion. This paper reports on the current status of physical activity policy development and implementation in four European countries based on the Health-Enhancing Physical Activity Policy Audit Tool (HEPA PAT) developed by WHO. It compares the findings to previous studies and discusses the general utility of this tool and its unique features in relation to other instruments.

Methods

The study was conducted as part of the Policy Evaluation Network (www.jpi-pen.eu) in Germany, Ireland, the Netherlands and Poland. Data collection built upon information obtained via the EU Physical Activity Monitoring Framework survey, additional desk research and expert opinion. Data analysis employed Howlett’s policy cycle framework to map and compare national physical activity policies in the four countries.

Results

In all countries under study, policy agenda-setting is influenced by prevalence data from national health monitoring systems, and the sport and/or health sector takes the lead in policy formulation. Key policy documents were located mainly in the health sector but also in sport, urban design and transport. Physical activity programmes implemented to meet policy objectives usually cover a broad range of target groups, but currently only a small selection of major policies are evaluated for effectiveness. National experts made several suggestions to other countries wishing to establish physical activity policies, e.g. regarding cross-sectoral support and coordination, comprehensive national action plans, and monitoring/surveillance.

Conclusions

This study provides a detailed overview of physical activity policies in the four countries. Results show that national governments are already very active in the field but that there is room for improvement in a number of areas, e.g. regarding the contribution of sectors beyond sport and health. Using the HEPA PAT simultaneously in four countries also showed that procedures and timelines have to be adapted to national contexts. Overall, the instrument can make an important contribution to understanding and informing physical activity policy, especially when used as an add-on to regular monitoring tools like the EU HEPA Monitoring Framework.