bluuebunny/crossref_metadata_2025 huggingface dataset:
A qualitative study of old patients’ experiences of the quality of the health services in hospital and 30 days after hospitalization
Authors: Lilleheie Ingvild , Debesay Jonas , Bye Asta , Bergland Astrid
Published: May 2020

Background: The number of people aged 80 years and above is projected to triple over the next 30 years. People in this age group normally have at least two chronic conditions. The impact of multimorbidity is often significantly greater than expected from the sum of the effects of each condition. The World Health Organization has indicated that healthcare systems must prepare for a change in the focus of clinical care for older people. The World Health Organization (WHO) defines healthcare quality as care that is effective, efficient, integrated, patient centered, equitable and safe. The degree to which healthcare quality can be defined as acceptable is determined by services’ ability to meet the needs of users and adapt to patients’ expectations and perceptions.Method: We took a phenomenological perspective to explore older patients’ subjective experiences and conducted semistructured individual interviews. Eighteen patients (aged from 82 to 100 years) were interviewed twice after discharge from hospital. The interview transcriptions were analyzed thematically.Results: The patients found their meetings with the health service to be complex and demanding. They reported attempting to restore a sense of security and meaning in everyday life, balancing their own needs against external requirements. Five overarching themes emerged from the interviews: hospital stay and the person behind the diagnosis, poor communication and coordination, life after discharge, relationship with their next of kin, and organizational and systemic determinants.Conclusion: According to the WHO, to deliver quality healthcare, services must include all six of the dimensions listed above. Our findings show that they do not. Healthcare focused on measurable values and biomedical inquiries. Few opportunities for participation, scant information and suboptimal care coordination left the patients with a feeling of being in limbo, where they struggled to find balance in their everyday life. Further work must be done to ensure that integrated services are provided without a financial burden, centered on the needs and rights of older people.
Skin transcriptome reveals the periodic changes in genes underlying cashmere (ground hair) follicle transition in Cashmere goats
Authors: Yang Feng , Liu Zhihong , Zhao Meng , Mu Qing , Che Tianyu , Xie Yuchun , Ma Lina , Mi Lu , Zhao hong Yan , Li Jinquan
Published: May 2020

Background: Cashmere goats make an outstanding contribution to the livestock textile industry and their cashmere is famous for its slenderness and softness and has been extensively studied. However, there are few reports on the molecular regulatory mechanisms of the secondary hair follicle growth cycle in cashmere goats. In order to explore the regular transition through the follicle cycle and the role of key genes in this cycle, we used a transcriptome sequencing technique to sequence the skin of Inner Mongolian cashmere goats during different months. We analyzed the variation and difference in genes throughout the whole hair follicle cycle. We then verified the regulatory mechanism of the cashmere goat secondary hair follicle growth cycle using fluorescence quantitative PCR. Results: The growth cycle of cashmere hair could be divided into three distinct periods: a growth period (March–September), a regression period (September–December), and a resting period (December–March). The results of differential gene analyses showed that March was the most significant month. Cluster analysis of gene expression throughout the whole growth cycle further supported the key nodes of the three periods of cashmere growth, and the differential gene expression of keratin corresponding to the ground haircashmere growth cycle further supported the results from tissue slices. Quantitative fluorescence analysis showed that KAP3-1, KRTAP 8-1, and KRTAP 24-1 genes had close positive correlation with the cashmere growth cycle, and their regulation was consistent with the growth cycle of cashmere. Conclusion: The growth cycle of cashmere cashmere could be divided into three distinct periods: a growth period (March–September), a regression period (September–December) and a resting period (December–March). March was considered to be the beginning of the cycle. KAP and KRTAP showed close positive correlation with the growth cycle of secondary hair follicle cashmere growth, and their regulation was consistent with the cashmere growth cycle. But hair follicle development-related genes are expressed earlier than cashmere growth, indicating that cycle regulation could alter the temporal growth of cashmere. This study laid a theoretical foundation for the study of the cashmere development cycle and provided evidence for key genes during transition through the cashmere cycle. Our study provides a theoretical basis for cashmere goat breeding.
The effect of information on prostate cancer screening decision process: A discrete choice experiment
Authors: Charvin Maud , Launoy Guy , Berchi Célia
Published: May 2020

Background: Prostate cancer screening is controversial because of uncertainty about its benefits and risks. The aim of this survey was to reveal preferences of men concerning prostate cancer screening and to test the effect of an informative video on these preferences. Methods: A stated preferences questionnaire was sent by e-mail to men aged 50-75 with no history of prostate cancer. Half of them were randomly assigned to view an informative video. A discrete choice model was established to reveal men’s preferences for six prostate cancer screening characteristics: mortality by prostate cancer, number of false positive and false negative results, number of overdiagnosis, out-of-pocket costs and recommended frequency. Results: A population-based sample composed by 1024 men representative of the French general population filled in the entire questionnaire. Each attribute gave the expected sign except for overdiagnosis. The video seemed to increase the intention to abstain from prostate cancer screening.Conclusions: The participants attached greater importance to a decrease in the number of false negatives and a reduction in prostate cancer mortality than to other risks such as the number of false positives and overdiagnosis. Further research is needed to help men make an informed choice regarding screening.
Tight versus standard blood pressure control on the incidence of myocardial infarction and stroke: An observational retrospective cohort study in the general ambulatory setting
Authors: Park Bumsoo , Budzynska Katarzyna , Almasri Nada , Islam Sumaiya , Alyas Fanar , Carolan Rachel L. , Abraham Benjamin E. , Castro-Camero Pamela A. , Shreve Maria E. , Rees Della A. , Lamerato Lois
Published: May 2020

Background: The 2017 American College of Cardiology and American Heart Association guideline defined hypertension as blood pressure (BP) ≥ 130/80 mmHg compared to the traditional definition of ≥ 140/90 mmHg. This change raised much controversy. We conducted this study to compare the impact of tight (TBPC) versus standard BP control (SBPC) on the incidence of myocardial infarction (MI) and stroke. Methods: We retrospectively identified all hypertensive patients in an ambulatory setting based on the diagnostic code for 1 year at our institution who were classified by the range of BP across 3 years into 2 groups of TBPC (< 130 mmHg) and SBPC (130-139 mmHg). We compared the incidence of new MI and stroke between the 2 groups across a 2-year follow-up. Multivariate analysis was done to identify independent predictors for the incidence of new MI and stroke.Results: Of 5640 study patients, the TBPC group showed significantly less incidence of stroke compared to the SBPC group (1.5% vs. 2.7%, P < 0.010). No differences were found in MI incidence between the 2 groups (0.6% vs. 0.8%, P = 0.476). Multivariate analysis showed that increased age independently increased the incidence of both MI (OR 1.518, 95% CI 1.038-2.219) and stroke (OR 1.876, 95% CI 1.474-2.387), and TBPC independently decreased the incidence of stroke (OR 0.583, 95% CI 0.374-0.910) but not of MI. Conclusions: Our observational study suggests that TBPC may be beneficial in less stroke incidence compared to SBPC but it didn’t seem to affect the incidence of MI. Our study is limited by its retrospective design with potential confounders.
Metabolic engineering of Escherichia coli for efficient production of L-alanyl-L-glutamine
Authors: Zhu Jiangming , Yang Wei , Wang Bohua , Liu Qun , Zhong Xiaotong , Gao Quanxiu , Liu Jiezheng , Huang Jianzhong , Lin Baixue , Tao Yong
Published: May 2020

Background: L-alanyl-L-glutamine (AQ) is a functional dipeptide with high water solubility, good thermal stability and high bioavailability. It is widely used in clinical treatment, post-operative rehabilitation, sports health care and other fields. AQ is mainly produced via chemical synthesis which is complicated, time-consuming, labor-intensive, and have a low yield accompanied with the generation of by-products. It is therefore highly desirable to develop an efficient biotechnological process for the industrial production of AQ.Results: A metabolically engineered E. coli strain for AQ production was developed by over-expressing L-amino acid α-ligase (BacD) from Bacillus subtilis, and inactivating the peptidases PepA, PepB, PepD, and PepN, as well as the dipeptide transport system Dpp. In order to use the more readily available substrate glutamic acid, a module for glutamine synthesis from glutamic acid was constructed by introducing glutamine synthetase (GlnA). Additionally, we knocked out glsA-glsB to block the first step in glutamine metabolism, and glnE-glnB involved in the ATP-dependent addition of AMP/UMP to a subunit of glutamine synthetase, which resulted in increased glutamine supply. Then the glutamine synthesis module was combined with the AQ synthesis module to develop the engineered strain that uses glutamic acid and alanine for AQ production. The expression of BacD and GlnA was further balanced to improve AQ production. Using the final engineered strain p15/AQ10 as a whole-cell biocatalyst, 71.7 mM AQ was produced with a productivity of 3.98 mM/h and conversion rate of 71.7 %.Conclusion: A metabolically engineered strain for AQ production was successfully developed via inactivation of peptidases, screening of BacD, introduction of glutamine synthesis module, and balancing the glutamine and AQ synthesis modules to improve the yield of AQ. This work provides a microbial cell factory for efficient production of AQ with industrial potential.
Pattern and determinants of antibiotic mal-prescription by family physicians in primary health care facilities of Iran
Authors: Karimi Gholamali , Azizi Hosein , Kabir Kourosh , Farrokhi Babak , Delpisheh Ali , Abbaszadeh Effat , Esmaeili Elham Davtalab
Published: May 2020

Background: Mal-prescription of antibiotics is a major and ongoing global public health problem both in developing and developed countries. Family physicians are the most important and dominant health services providers in Iran their prescription pattern is poorly understood. This study aimed to assess the pattern and factors affecting antibiotic prescribing by family physicians in primary health care (PHC). Methods: In this descriptive-analytical study, 1068 prescriptions of family physicians in PHC were assessed in Alborz province health facilities. Prescriptions were selected by simple random sampling. The mal-prescribing was assessed based on four criteria including dose per consumption, dose per day, correct duration of therapy and possible interaction with other drugs. Logistic regression was used to estimate the odds ratio and 95% confidence interval for the association between antibiotic prescription and the affecting factors. Results: The average number of antibiotics was found 1.27 per prescription and 56.8% of the prescriptions had at least one antibiotic. There was a statistically significant relationship between age, gender, type of health insurance, work experience of physician, seasons of the year and receiving antibiotics (P<0.05). In 59.31% of antibiotic prescriptions at least one of the scientific criteria was not satisfied. Conclusion: The number of prescribed antibiotics and the mal-prescription percentage were high among family physicians. Strong political commitment and altering physicians' training curricula especially promoting a preventive approach and developing a registration system for identifying adverse drug reactions, antibiotic use patterns and control of mal-prescription are imperative at the grass-root level.
Caregiver Burden is Reduced by Personalized Social Support for Non-Dependent Old Persons: a Longitudinal Study of 876 Old Persons and Their Caregivers
Authors: Arlotto Sylvie , Gentile Stéphanie , Durand Anne Claire , Bonin-Guillaume Sylvie
Published: May 2020

Background . Informal care provided by family caregivers to old persons is associated with a high risk of burden and poor health status. This study aimed to analyze the impact of Personalized Social Support (PSS) for non-dependent old persons living in the community on caregiver burden, satisfaction, and frailty. Methods . This non-interventional longitudinal study was performed in the southeast of France: old persons asking for PSS (>70 years of age, with no disability and no severe chronic disease, living at home) and their caregivers were included with a 6-month follow-up. Eligible dyads were visited at home by social workers. Caregiver burden was assessed with Mini-Zarit and frailty status with FiND (Frail Non-Disabled). Results . 876 dyads were eligible for PSS. Old persons were 82.2 ± 5.8 years old and 77.6% were women. Most caregivers were women (64.5%). Most caregivers were the children of the old person (61%), the rest were mostly spouses. Nearly 64% of old persons were frail and 38% were highly dependent. Follow-up was conducted for 686 dyads (78.3%). Of these, only 569 had PSS. The PSS was mainly for housework and meal preparation. At the time of follow-up, 53% of the caregivers for whom the old person had PSS had less difficulty helping their old person. Two-thirds (61.5%) of caregivers were fully satisfied with the PSS. Whether or not they had received the PSS, 73% of caregivers had reduced burden at 6 months, only 6% still had a high burden, 17% were less frail, and 18% felt healthier than at the time of inclusion. Conclusions . Our study highlights that non-dependent old person’s caregivers also experience burden. Implementing social support for activities of daily living had a major impact on their burden but not on their level of frailty. This means that the determinants of caregiver frailty are more complex and further studies are needed.
Application of the matched nested case-control design to the secondary analysis of trial data
Authors: Partlett Christopher , Hall Nigel J , Leaf Alison , Juszczak Edmund , Linsell Louise
Published: May 2020

Background A nested case-control study is an efficient design that can be embedded within an existing cohort study or randomised trial. It has a number of advantages compared to the conventional case-control design, and has the potential to answer important research questions using untapped prospectively collected data. Methods We demonstrate the utility of the matched nested case-control design by applying it to a secondary analysis of the Abnormal Doppler Enteral Prescription Trial. We investigated the role of milk feed type and changes in milk feed type in the development of necrotising enterocolitis in a group of 398 high risk growth-restricted preterm infants. Results Using matching, we were able to generate a comparable sample of controls selected from the same population as the cases. In contrast to the standard case-control design, exposure status was ascertained prior to the outcome event occurring and the comparison between the cases and matched controls could be made at the point at which the event occurred. This enabled us to reliably investigate the temporal relationship between feed type and necrotising enterocolitis. Conclusions A matched nested case-control study can be used to identify credible associations in a secondary analysis of clinical trial data where the exposure of interest was not randomised, and has several advantages over a standard case-control design. This method offers the potential to make reliable inferences in scenarios where it would be unethical or impractical to perform a randomised clinical trial.
The association between physical fitness and mental health in Norwegian adolescents
Authors: Åvitsland Andreas , Leibinger Eva , Haugen Tommy , Lerum Øystein , Solberg Runar Barstad , Kolle Elin , Dyrstad Sindre Mikal
Published: May 2020

Background: Studies indicate that health-related components of physical fitness are associated with mental health outcomes. However, research is scarce concerning this relationship in young adolescents in general and non-existent in Norwegian populations specifically. The aim of the study was to examine whether body composition, muscular strength and cardiorespiratory fitness were associated with self-reported mental health in Norwegian adolescents. Methods: Adolescents from four regions of Norway (n = 1486; mean age = 13.9; girls = 50.6%) participated. Self-reported mental health (psychological difficulties) was measured by completing the Strengths and Difficulties Questionnaire. Cardiorespiratory fitness was assessed with an intermittent running test; muscular strength was assessed by measuring handgrip strength, standing broad jump and sit-ups; and body composition was assessed by calculating body mass index from weight and height. Linear mixed effects models were conducted to assess the associations between the health-related components of physical fitness and psychological difficulties. School clusters were included as random effects and all models were controlled for sex, socioeconomic status and birthplace (domestic or foreign). Results: Body composition was not associated with psychological difficulties. Muscular strength was independently associated with psychological difficulties, but when all independent variables were entered in the fully adjusted model, only cardiorespiratory fitness was associated with psychological difficulties. Conclusions: There was a small but significant inverse association between cardiorespiratory fitness and levels of psychological difficulties in Norwegian adolescents. The results suggest that muscular strength is not associated with psychological difficulties in adolescents, when controlling for cardiorespiratory fitness. Future research should focus on the prospective association between physical fitness components and mental health outcomes in adolescents.
Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of neutrophils
Authors: Mei Hongxia , Tao Ying , Zhang Tianhao , Qi Feng
Published: May 2020

Background: Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of neutrophils that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the neutrophil function in a rat model of lipopolysaccharide (LPS)-induced ALI.Results: Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with neutrophil deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced neutrophils via the up-regulation of the ability of neutrophils to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the neutrophil respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated neutrophils, alleviating the damage of neutrophils to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of neutrophils. Conclusion: Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of neutrophils. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.
In silico pathway analysis based on Chromosomal Instability in Breast Cancer Patients
Authors: KOUR AKEEN , Sambyal Vasudha , Guleria Kamlesh , Singh Neeti Rajan , Uppal Manjit Singh , Manjari Mridu , Sudan Meena
Published: May 2020

Background: Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability. Results: Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 hours Peripheral lymphocyte culturing and GTG-banding. Karyotypic analyses found more frequent chromosomal aberrations (structural and numerical) on chromosome 1, 2, 3, 4, 5, 8, 9, 17 and X. The data of genes harbored by chromosomal regions showing increased aberration frequency was retrieved from online databases. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription. Conclusion: The chromosomal instability analysis in a non-target in cancer patients thus can be used to identify genes and decipher the pathway involved in tumorigenesis. The bioinformatics approach can help in identifying aberrant genes in transcription pathways and their relation with breast cancer progression.
Health-related quality of life in adult Mediterranean women with polycystic ovary syndrome attending to a tertiary hospital: a case-control study.
Authors: Sánchez-Ferrer María L , Adoamnei Evdochia , Prieto-Sánchez María T , Mendiola Jaime , Corbalán-Biyang Shiana , Moñino-García Miriam , Palomar-Rodríguez Joaquín A , Torres-Cantero Alberto M
Published: May 2020

Background: Polycystic ovary syndrome (PCOS) is a chronic condition with symptoms affecting many women at reproductive age and evaluating their health-related quality of Life (HRQoL) is an important issue. Moreover, differences in the HRQoL between women with different PCOS phenotypes have never been analyzed. Therefore, the aim of our study was to compare the HRQoL between women with PCOS -and its phenotypes- and controls attending to a tertiary hospital. Methods: A group of 117 women with PCOS and 153 controls were studied between 2014 and 2016. Controls were women without PCOS attending the gynecological outpatient clinic for routine examinations. Cases were women attending the same setting and diagnosed with PCOS. PCOS diagnose was performed following the Rotterdam Criteria and women were further classified by anovulatory or ovulatory phenotypic subtype. Women underwent physical and gynecological exams and completed health questionnaires including the Short Form-12v2. Eight scales and two component summary scores [Physical (PCS) and Mental (MCS), respectively] were calculated. Bivariate and multivariate analyses were performed to assess differences in HRQoL between women with PCOS and controls. Results: All women with PCOS and anovulatory PCOS presented lower score in PCS compared to controls [mean (95%CI): 53.7 (52.5-54.9) and 52.9 (51.5-54.4) vs. 55.8 (54.8-56.8); p-values<0.01], as well as lower scores for five out of the eight scales (p-values < 0.05) after adjusting by age, body mass index, infertility, educational level and current occupation. No significant differences were observed for the MCS between women with or without PCOS or its phenotypic subtypes. Conclusions: HRQoL was significantly decreased in adult women with PCOS and its anovulatory phenotype compared to controls attending the outpatient clinic of a tertiary hospital. These results may have implications for the clinical practice and suggest the need for specific interventions in women with PCOS.
The efficacy of the novel zinc-containing desensitizer CAREDYNE Shield on dentin hypersensitivity: a study protocol for a pilot randomized controlled trial
Authors: Matsuura Takashi , Mae Megumi , Ohira Masayuki , Yamashita Yasunori , Nakazono Ayako , Sugimoto Kouji , Yanagiguchi Kajiro , Yamada Shizuka
Published: May 2020

Background: Dentin hypersensitivity (DH) is a condition characterized by short and sharp pain which will arise in response to tactile, chemical, thermal, evaporative or osmotic stimuli. The painful symptoms cause discomfort in patients and reduce their quality of life. Recently, the novel zinc-containing desensitizer CAREDYNE Shield has been developed as a new type of desensitizer that acts by inducing chemical occlusion of dentinal tubules, and releasing zinc ion for root caries prevention. However, the clinical effectiveness of CAREDYNE Shield on DH remains unclear. Therefore, the aim of this study is to evaluate the effectiveness of CAREDYNE Shield on DH by comparing with that of another desensitizer Nanoseal commonly used in Japan.Methods/Design: This study protocol is a two-arm parallel pilot randomized controlled trial. Forty DH patients will be randomly allocated to two groups. Participants in the intervention group will be treated with CAREDYNE Shield, while those in the control group will be treated with Nanoseal. The primary outcome is the reduction of pain intensity in response to air stimuli measured with a five-points verbal response scale from baseline to four weeks after the intervention, and Fisher's exact test will be used for analyses.Discussion: CAREDYNE Shield can be casually applied to subgingival areas and proximal surfaces because it reacts with only tooth substance. Furthermore, zinc has been reported to reduce the demineralization of enamel and dentin and inhibit biofilm formation, plaque growth and dentin collagen degradation. Therefore, CAREDYNE Shield may be expected to be a useful novel desensitizer that acts not only as a desensitizer but also as a root caries inhibitor.Trial registration:UMIN Clinical Trials Registry (UMIN-CTR), UMIN000038072. Registered on 21st September 2019.Trial statusThis study (protocol version number: version 1.4.0; approved on 22 October 2019) is ongoing. The recruitment of participants began in December 2019 and will be continued until November 2020 (1).
Compared to plasma, bronchial washing fluid shows higher diagnostic yields for detecting EGFR-TKI sensitizing mutations by ddPCR in lung cancer
Authors: Lee Sang Hoon , Kim Eun Young , Kim Taehee , Chang Yoon Soo
Published: May 2020

Background: The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference. Methods: Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR). Results: The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822–0.969] for BWF and 0.686 (95% CI: 0.592–0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I–IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients. Conclusions: The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.
Cervical and oral human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil
Authors: Suehiro Tamy Taianne , Damke Gabrielle Marconi Zago Ferreira , Damke Edilson , Ramos Paloma Luana Rodrigues de Azevedo , Silva Marcela de Andrade Pereira , Pelloso Sandra Marisa , Huh Warner K , Franco Ricardo Argemiro Fonseca , Silva Vânia Ramos Sela da , Scarinci Isabel Cristina , Consolaro Marcia Edilaine Lopes
Published: May 2020

Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil.Material and methods: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12.Results: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall (P = 0.03) and in cervical mucosa (P = 0.01). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa.Conclusion: Our data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.
Canadian after-school care providers’ perceived role promoting healthy lifestyles: A focused ethnography
Authors: Elias Pierrette H. , Montemurro Genevieve , Sulz Lauren , Torrance Brian , Storey Kate Elizabeth
Published: May 2020

BACKGROUND: After-school care programs have garnered interest in recent years as the hours of 3:00–6:00p.m. are an opportune time for children to engage in healthy behaviours, specifically healthy eating and physical activity. Care providers are major influencers within the after-school care setting, impacting health promoting opportunities for children. However, little is known regarding the role care providers play in health promotion interventions in this setting, specifically those using comprehensive approaches. The purpose of this research was to explore care providers’ role and experience promoting healthy eating and physical activity through the after-school care health promotion intervention School’s Out…Let’s Move (SOLMo). SOLMo was guided by the evidence-based comprehensive school health framework, and included a focus on healthy eating and physical activity. METHODS: This research was guided by the qualitative method focused ethnography. Semi-structured interviews with care providers (n=13) taking part in SOLMo were conducted. Participant observation was included as part of data generation to further understand care provider roles. RESULTS: Overall, care providers were supportive of promoting health behaviours in the after-school setting. Through latent content analysis, five themes emerged related to care providers’ role and experience promoting healthy eating and physical activity through SOLMo: 1) enhanced awareness; 2) improved programming; 3) strong relationships; 4) collaborative approach; and 5) role tension. CONCLUSIONS: As major influencers, care providers play a crucial role, and these results will contribute to implementation strategies used to promote healthy lifestyle behaviours for children.
Study of hospitalization and mortality in Korean diabetic patients using the diabetes complications severity index
Authors: Yoo Hyunju , Choo Eunjung , Lee Sukhyang
Published: May 2020

Background The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase from 7.7% in 2017 to 8.4% in 2045 worldwide. Diabetes complications contribute to morbidity and mortality. To evaluate whether the diabetes complications severity index (DCSI) was associated with increased risks of mortality and hospitalization. Methods A retrospective cohort study was conducted using the National Health Insurance Database (NHID) sample cohort of 1,102,047 patients (2002–2015) in Korea. Diabetes complications were evaluated at 2 years after the initial diagnosis and during the subsequent follow up period. The type and severity of complications were evaluated on the basis of the International Classification of Disease ninth (ICD-9) codes used in DCSI with 7 categories and 55 subcategories of complications. The Cox proportional hazard and Poisson regression models were used to evaluate the mortality and hospitalization rates. The incidence and relative risk of diabetes complications as well as the risk of mortality and hospitalization were the main outcome measures. Results A total of 27,871 patients were finally included and grouped by the number of diabetic complications, when 490 patients (5.37%) died without complications, 659 (7.31%) died with one complication and 1,153 (11.85 %) died with two or more complications. The risks of mortality and hospitalization were related with DCSI linear [hazard ratio 1.13 (95% CI 1.11–1.16), relative risk 1.04 (95% CI 1.03–1.06)]. Conclusions Patients with higher incidence and severity of diabetes complications have increased risks of mortality and hospitalization.
EZH2 inhibitors-mediated epigenetic reactivation of FOSB inhibits triple-negative breast cancer progress
Authors: Zhang Ruishan , Li Xiang , Liu Zhuangkai , Wang Yuying , Zhang Hao , Xu Hong
Published: May 2020

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that lacks expression of estrogen receptor (ER) and progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) gene. Chemotherapy remains the standard of care for TNBC treatment, but considerable patients are very resistant to chemotherapy. Mutations or aberrant upregulation of EZH2 occur frequently, and EZH2 inhibitor (EZH2i) showed some preclinic antitumor effects in TNBC.METHODS: RNA-seq data of 3 TNBC cell lines either treated with 2 μM GSK343, or stably transduced with shEHZ2, compared to untreated controls (GSE112378) were analyzed by Limma R package. The Kaplan Meier plotter (KM plotter) database was used to assess the relevance of FOSB mRNA expression to relapse-free survival (RFS) in TNBC. Cell number counting and colony formation assays were used to detect the biological effect of FOSB on the growth of TNBC cells in vitro. The effect of FOSB on TNBC tumor growth in vivo was investigated in a mice tumor xenograft model. Luciferase reporter and chromatin immunoprecipitation (Chip) assays were used to determine the regulatory roles of C/EBPβ on FOSB expression. RESULTS: We found that FOSB, a member of the activator protein-1 complex, was a direct downstream target of EZH2. FOSB was significantly decreased in TNBC samples and associated with better relapse-free survival (RFS). EZH2-mediated histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation, at the FOSB promoter inhibited it expression. Depletion of FOSB in TNBC cells promoted cell proliferation in vitro and tumor growth in vitro by inactivating the p53 pathway and conferred resistant to EZH2 inhibitor (EZH2i). Mechanistically, EZH2i promotes the shift from H3K27me3 to H3K27ac at the FOSB promoter, and recruits the transcription factor C/EBPβ to activate FOSB gene transcription.CONCLUSION: Together, our results suggest that EZH2-mediated epigenetic inactivation of FOSB promotes TNBC expression and demonstrate that reactivation of FOSB expression by C/EBPβ underlies the anti-TNBC action of EZH2is.
High-yield production of L-serine through a novel identified exporter combined with synthetic pathway in Corynebacterium glutamicum
Authors: Zhang Xiaomei , Gao Yujie , Chen Ziwei , Xu Guoqiang , Zhang Xiaojuan , Li Hui , Shi Jinsong , Koffas Mattheos , Xu Zhenghong
Published: May 2020

Background: L-Serine has wide and increasing applications in industries with fast-growing market demand. Although strategies for achieving and improving L-serine production in Corynebacterium glutamicum (C. glutamicum) have focused on inhibiting its degradation and enhancing its biosynthetic pathway, L-serine yield has remained relatively low. Exporters play an essential role in the fermentative production of amino acids. To achieve higher L-serine yield, L-serine export from the cell should be improved. In C. glutamicum, ThrE, which can export L-threonine and L-serine, is the only identified L-serine exporter so far.Results: In this study, a novel L-serine exporter NCgl0580 was identified and characterized in C. glutamicum ΔSSAAI (SSAAI), and named as SerE (encoded by serE). Deletion of serE in SSAAI led to a 56.5% decrease in L-serine titer, whereas overexpression of serE compensated for the lack of serE with respect to L-serine titer. A fusion protein with SerE and enhanced green fluorescent protein (EGFP) was constructed to confirm that SerE localized at the plasma membrane. The function of SerE was studied by peptide feeding approaches, and the results showed that SerE is a novel exporter for L-serine and L-threonine in C. glutamicum. Subsequently, the interaction of a known L-serine exporter ThrE and SerE was studied, and the results suggested that SerE is more important than ThrE in L-serine export in SSAAI. In addition, probe plasmid and electrophoretic mobility shift assays (EMSA) revealed NCgl0581 as the transcriptional regulator of SerE. Comparative transcriptomics between SSAAI and the NCgl0581 deletion strain showed that NCgl0581 is a positive regulator of NCgl0580. Finally, by overexpressing the novel exporter SerE, combined with L-serine synthetic pathway key enzyme serAΔ197, serC, and serB, the resulting strain presented an L-serine titer of 43.9 g/L with a yield of 0.44 g/g sucrose, which is the highest L-serine titer and yield reported so far in C. glutamicum. Conclusions: This study provides a novel target for L-serine and L-threonine export engineering as well as a new global transcriptional regulator NCgl0581 in C. glutamicum.
Mini-midvastus versus medial parapatellar approach in total knee arthroplasty: Difference in patient-reported outcomes measured with the Forgotten Joint Score
Authors: Lin Wei , Niu Jinghui , Dai Yike , Yang Guangmin , Li Ming , Wang Fei
Published: May 2020

Background: Low knee awareness after minimally invasive total knee arthroplasty (TKA) has become the ultimate target of a natural-feeling knee that meets patient expectations. The objective of this research was to compare the clinical outcomes of TKA via the mini-midvastus (MMV) approach or the medial parapatellar (MPP) approach, and to evaluate which approach can lead to a better quality of life after surgery. Methods: From January 2015 to December 2016, a retrospective cohort study was conducted in 330 patients who underwent TKA via a mini-midvastus (MMV) approach. During this period, we also selected 330 patients who underwent TKA via a medial parapatellar (MPP) approach (MPP group) for comparison. Clinical results were assessed with the visual analog scale score for pain, range of motion, and the Knee Society Score. The Forgotten Joint Score was used to analyze the ability to forget the joint. Results: There were significant differences with regard to visual analog scale score, range of motion, and the Knee Society Score until 6 months after surgery between the MMV and MPP groups ( p < 0.05), but the differences were not significant at 12 months, 24 months, and 36 months after surgery. However, there were significant differences in the Forgotten Joint Score between the groups during the follow-up period ( p < 0.05). Conclusion: When forgetting the artificial joint after TKA is the ultimate target, better quality of life can be acquired by performing TKA via the MMV approach. In addition, compared with the MPP approach, the MMV approach can offer less pain and a faster recovery.
A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients – Design of the Urodiag® PCR Kit for surveillance of patients with non-muscle-invasive bladder cancer (NMIBC)
Authors: ROPERCH Jean-Pierre , HENNION Claude
Published: May 2020

Background We have recently developed a highly accurate urine-based test, named Urodiag®, associating FGFR3 mutation and DNA methylation assays for recurrence surveillance in patients with low-, intermediate-, and high-risk NMIBC. Previously, the detection of four FGFR3 mutations (G372C, R248C, S249C and Y375C) required amplification steps and PCR products were analyzed by capillary electrophoresis (Allele Specific-PCR, AS-PCR), which was expensive and time-consuming. Here, we present the development a novel ultra-sensitive multiplex PCR assay as called “Mutated Allele Specific Oligonucleotide-PCR (MASO-PCR)”, generating a cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in voided urine.Methods Comparative clinical performances of MASO-PCR and AS-PCR technologies were performed from 263 urine DNA samples (87 FGFR3 mutated and 176 FGFR3 wild-type). In the development of Urodiag® PCR Kit, we studied the stability and reproducibility of each all-in-one PCR master mix (single reaction mixture including all the necessary PCR components) for MASO-PCR and QM-MSPCR (Quantitative Multiplex Methylation-Specific PCR to co-amplify SEPTIN9, HS3ST2 and SLIT2 methylated genes) assays.Results Complete concordance (100%) was observed between the MASO-PCR and AS-PCR results. Each PCR master mix displayed excellent reproducibility and stability after 12 months of storage at -20°C, with intra-assay standard deviations lower than 0.3 Ct and coefficient of variations (CV) lower than 1%. The limit of detection (LoD) of MASO-PCR was 5% mutant detection in a 95% of wild-type background. The limit of quantification (LoQ) of QM-MSPCR was 10 pg of bisulfite-converted DNA. Conclusions We developed and clinically validated the MASO-PCR assay, generating cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in urine. We also designed the Urodiag® PCR Kit, which includes the MASO-PCR and QM-MSPCR assays. Adapted to routine clinical laboratory (simplicity, accuracy), the kit will be a great help to urologists for recurrence surveillance in patients at low-, intermediate- and high-risk NMIBC. Reducing the number of unnecessary cystoscopies, it will have extremely beneficial effects for patients (painless) and for the healthcare systems (low cost).
Diffusion Tensor Imaging and Electrophysiology as Robust Assays to Evaluate the Severity of Acute Spinal Cord Injury in Rats
Authors: Chen Beike , Tan Qiang , Zhao Weikang , Yang Qiming , Zhang Hongyan , Gao Fabao , Liu Xin , Feng Hua , Jiang Dianming
Published: May 2020

Background: Diffusion tensor imaging (DTI) is an effective method to identify subtle changes to normal‐appearing white matter (WM). Here we analyzed the DTI data with other examinations, including motor evoked potentials (MEPs), histopathological images, and behavioral results, to reflect the lesion development in different degrees of spinal cord injury (SCI) in acute and subacute stages.Method: Except for 2 Sprague -Dawley rats which died from the anesthesia accident, the rest 42 female rats were randomized into 3 groups: control group (n=6), moderate group (n=18), and severe group (n=18). Moderate (a 50-g aneurysm clip with 0.4-mm thickness spacer) or severe (a 50-g aneurysm clip with no spacer) contusion SCI at T8 vertebrae was induced. Then the electrophysiological assessments via MEPs, behavioral deterioration via the Basso, Beattie, and Bresnaha (BBB) scores, DTI data, and histopathology examination were analyzed. Results: In this study, we found that the damage of WM myelin, MEPs amplitude, BBB scores and the decreases in the values of fractional anisotropy (FA) and axial diffusivity (AD) were more obvious in the severe injury group than those of the moderate group. Additionally, the FA and AD values could identify the extent of SCI in subacute and early acute SCI respectively, which was reﬂected in a robust correlations with MEPs and BBB scores. While the values of radial diffusivity (RD) showed no significant changes. Conclusions: Our data confirmed that DTI was a valuable in ex vivo imaging tool to identify damaged white matter tracts after graded SCI in rat, which may provide useful information for the early identification of the severity of SCI.