bluuebunny/crossref_metadata_2025 huggingface dataset:
Progressive Tricuspid Regurgitation and Elevated Tricuspid Regurgitation Pressure Gradient after Transvenous Permanent Pacemaker Implantation
Authors: Lee Weichieh , Fang Hsiu-Yu , Chen Huang-Chung , Chen Yung-Lung , Tsai Tzu-Hsien , Pan Kuo-Li , Lin Yu-Sheng , Liu Wen-Hao , Chen Mien-Cheng
Published: October 2020

Background The association of post-implant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. This study aimed to explore the clinical outcomes about progressive post-implant TR after permanent pacemaker (PPM) implantation. Methods A total of 1,670 patients who underwent a single ventricular or dual-chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, heart failure (HF), and baseline abnormal TR and TRPG were excluded. Finally, a total of 1,075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and/or TRPG of >30 mmHg after implant. Results 198 (18.4%) patients (group 1) experienced progressive post-implant TR and/or elevated TRPG, whereas 877 patients (group 2) did not have progressive post-implant TR. Group 1 had larger change in post-implant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p < 0.001) than group 2. Group 1 had a higher incidence of HF hospitalization compared to group 2 (13.6% vs. 4.7%; p < 0.001). Pre-implant TRPG (HR: 1.075; 95% confidence interval (CI): 1.032-1.121; p = 0.001) was an independent predictor of progressive post-implant TR. Conclusions After a transvenous ventricular-based PPM implantation, 18.4% of patients experienced progressive post-implant TR and/or elevated TRPG. Higher pre-implant TRPG was an independent predictor of progressive post-implant TR.
Sleep and Its Relation to Health-Related Quality of Life in 3–10-year-old Children 
Authors: Sundell Anna Lena , Angelhoff Charlotte
Published: October 2020

Background: Considering the reports of increasing sleep problems in children, affecting health and well-being in young children and their families, we found it important to gain more knowledge about sleep and its correlation to health-related quality of life (HRQoL) in young, healthy children. The aims with this study were to describe sleep quality, sleep duration, and HRQoL in healthy 3–10-year-old children and to test associations between children’s sleep and HRQoL. Methods: Parents of 160 children (average age: 6.9 years, SD ±2.2) participated in the study. Sleep onset problems (SOP), sleep maintenance problems (SMP), and sleep duration were measured by the Pediatric Insomnia Severity Index (PISI). KIDSCREEN-27 was used to measure HRQoL in five dimensions: physical well-being, psychological well-being, autonomy and parent relation, social support and peers, and school environment. Results: The average score was 2.2 for SOP (SD +/-2.2) and 1.3 for SMP (SD +/-1.6). Few children (2%) were reported to sleep less than eight hours per night. Younger children had statistically significant higher SOP and SMP than older children. Correlations were found between SOP and poor psychological well-being (p < 0.05, ρ = - 0.16), and between SMP and poor physical wellbeing (p < 0.05, ρ = -0.16), psychological well-being (p < 0.05, ρ = - 0.21), poor school environment (p < 0.01, ρ = - 0.29), autonomy and parent relation (p < 0.05, ρ = - 0.16), and poor social support and peers (p < 0.05, ρ = - 0.19).Conclusion: Children’s sleep associates with health-related quality of life and needs to be acknowledged in child health care settings and schools.
Adherence to veterinary recommendations for ectoparasiticides purchased by cat owners in the USA
Authors: Lavan Robert Philip , Armstrong Rob , Normile Dorothy , Vaala Wendy
Published: October 2020

Background: Safe and effective flea and tick treatment options for cats are important in companion animal practice because of feline ectoparasite infestation prevalence and the potential for parasitic disease transmission. Retrospective cat owner purchasing transactions at United States of America (USA) veterinary clinics were obtained for three topical feline flea and tick ectoparasiticides. One medication, fluralaner, had a 12-week redosing interval, while two other medications (fipronil/s-methoprene/pyriproxyfen ;imidacloprid/pyriproxyfen) were approved for monthly redosing. The annual number of doses purchased by cat owners was determined for each of the three medications and then compared between medications. The objective was to evaluate whether 12-week retreatment intervals resulted in a different duration of coverage compared to monthly treatments for ectoparasiticide products. Methods: Study results were obtained by analyzing the transactional records from a commercial database derived from veterinary practice management software. The study database consisted of cat owner purchasing records from January 2017 through June 2019 from 671 veterinary practices representing 41,630 cats.Results: Cat owners purchased an average of 1.5 doses of fluralaner per year which, based on a 12-week redosing interval, provides 4.2 months of treatment coverage. Cat owners who used monthly flea and tick medications respectively purchased 3.6 months (fipronil/s-methoprene/pyriproxyfen combination) and 2.8 months (imidacloprid/pyriproxyfen) annually of each of the two medications. Average yearly cat owner purchases of fluralaner provide a significantly longer duration of coverage than for cat owners purchasing fipronil/s-methoprene/pyriproxyfen (17% more) or imidacloprid/pyriproxyfen (50% more). Conclusions: Cat owners who obtained a flea and tick treatment with a 12-week redosing interval (fluralaner) protected their cats for up to 17% or 50% longer duration each year, respectively, compared to the duration of protection obtained by cat owners who used a medication re-dosed monthly. Cat owners should increase their duration of flea and tick coverage to come closer to achieving veterinary recommendations.
Physician-patient communication in decision-making about Caesarean sections in eight district hospitals in Bangladesh: A mixed-method study
Authors: Doraiswamy Sathyanarayanan , Billah Sk Masum , Karim Farhana , Siraj Md. Shahjahan , Buckingham Alan , Kingdon Carol
Published: October 2020

Background: Caesarean sections (CS) in Bangladesh have risen eight-fold in the last 15 years. Few studies have explored why. Anecdotally, physicians suggest maternal request for CS is a reason. Women and families suggest physicians influence their decision-making. The aim of this research was to understand more about the decision-making process surrounding CS by exploring physician-patient communication leading to informed-consent for the operation. Methods: We conducted a mixed-method study using structured observations with the Option Grid Collaborative’s OPTION5 tool and interviews with physicians and women between July and December 2018. Study participants were recruited from eight district public-sector hospitals. Eligibility criteria for facilities was ≥80 births every month; and for physicians, was that they had performed CSs. Women aged ≥18 years, providing consent, and delivering at a facility were included in the observation component; primigravid women delivering by CS were selected for the in-depth interviews. Quantitative data from observations were analysed using descriptive statistics. Following transcription and translation, a preliminary coding framework was devised for the qualitative data analysis. We combined both inductive and deductive approaches in our thematic analysis. Results: In total, 306 labour situations were observed, and interviews were conducted with 16 physicians and 32 women who delivered by CS (16 emergency CS; 16 elective CS). In 92.5% of observations of physician-patient communication in the context of labour situations, the OPTION5 mean scores were low (5-25 out of 100) for presenting options, patient partnership, describing pros/cons, eliciting patient preferences and integrating patient preferences. Interviews found that non-clinical factors prime both physicians and patients in favour of CS prior to the clinical encounter in which the decision to perform a CS is documented. These interactions were both minimal in content and limited in purpose, with consent being an artefact of a process involving little communication.Conclusions: Insufficient communication between physicians and patients is one of many factors driving increasing rates of caesarean section in Bangladesh. While this single clinical encounter provides an opportunity for practice improvement, interventions are unlikley to impact rates of CS without simultaneoulsy addressing physician, patient and health system contextual factors too.
A Functional Variant of CXCL16 Is Associated with Predisposition to Sepsis and MODS in Trauma Patients
Authors: Sun Jianhui , Zhang Huacai , Liu Di , Cui Li , Wang Qiang , Gan Lebin , Wen Dalin , Wang Jun , Du Juan , Huang Hong , Zhang Anqiang , Deng Jin , Jiang Jianxin , Zeng Ling
Published: October 2020

Background: CXC chemokine famliy genes play an important role in inflammatory and immune diseases. CXCL16 affects the occurrence and development of inflammation through leukocyte chemotaxis, leukocyte adhesion and endotoxin clearance. In this study, we selected a set of tag SNPs in the CXCL16 gene and investigated their clinical relevance to the development of sepsis and multiple organ dysfunction syndrome (MODS) in patients with major trauma in three independent Chinese Han populations. Methods: A total of 1,620 major trauma patients were enrolled in this study. Among these patients, 920 came from Chongqing in western China, 350 came from Zhejiang Province in eastern China, and 350 came from Guizhou Province in southern China. The improved multiplex ligation detection reaction (iMLDR) method was employed in the genotyping and genetic association analyses to determine the associations between CXCL16 haplotypes and sepsis morbidity rate and higher MOD scores in three cohorts. Results: The CXCL16 T123V181 haplotype was determined to be associated with increased risk for sepsis morbidity and higher MOD scores in the three cohorts. In vitro chemotactic experiments demonstrated that the T123V181 protein enhanced the chemotaxis of immunocytes. The adhesion ability of THP-1 cells expressing T123V181 to immunocytes was also stronger than those of cells with the other three haplotypes. T123 and V181 altered the structure of the CXCL16 active center, which resulted in changes in protein function and changes in the adhesion and chemotaxis of CXCL16-expressing immunocytes. These structural changes might be responsible for the increased incidence of sepsis and the higher MODS scores. Conclusions: We demonstrate that genetic variations in the CXCL16 gene regulate the sepsis morbidity rate, and we explore a paradigm for the prewarning diagnosis of sepsis tailored to the genetic information of individual patients. Trial registration: ClinicalTrials.gov, NCT01713205. Registered 18 October 2012, retrospectively registered.
Insulin Increases Central Aortic Stiffness in Response To Hyperglycemia in Healthy Humans: A Randomized Four-Way Crossover Study
Authors: Horton William B , Jahn Linda A , Hartline Lee M , Aylor Kevin W , Barrett Eugene J
Published: October 2020

Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Emerging evidence demonstrates that reversal of the normal lower central to higher peripheral arterial stiffness gradient predicts adverse cardiovascular consequences, including target organ damage. Preferential stiffening of central over peripheral arteries has been reported in type 2 diabetes, though mechanisms for this remain unclear. We tested the effect of acutely increasing plasma glucose, plasma insulin, or both on hemodynamic function, central aortic stiffness (carotid-femoral pulse wave velocity), and peripheral arterial stiffness (augmentation index) in a randomized, four-way, crossover study of 19 healthy young adults. Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.4 m/s; p=0.02), while augmentation index did not change significantly within any intervention (all p>0.05). Heart rate significantly increased only during hyperglycemic-hyperinsulinemia (+3.62 bpm; p=0.02). There was a significant inverse correlation between the changes of central and peripheral arterial stiffness only during hyperglycemic-hyperinsulinemia. We conclude that combined hyperglycemia and hyperinsulinemia acutely increased aortic stiffness, changed the normal central-to-peripheral arterial stiffness gradient, and increased heart rate in healthy humans. (ClinicalTrials.gov number NCT03520569; registered 9 May 2018).
Developmental regulation of Dirofilaria immitis microfilariae and evaluation of ecdysone signaling pathway transcript level using droplet digital polymerase chain reaction
Authors: Kuan Tsai-Chi Shang , Prichard Roger K
Published: October 2020

BackgroundCurrent Dirofilaria immitis prevention relies on macrocyclic lactones but evidence of drug-resistant isolates has called for alternative approaches to disease intervention. As microfilariae are known to be in a state of developmental arrest in their mammalian host and then undergo two molts once inside the arthropod, this study aimed to look at the developmental regulation of D. immitis microfilariae that occurs in their arthropod host using in vitro approaches and to investigate the role of the ecdysone signaling system in this development. MethodsD. immitis microfilariae extracted from dog blood were incubated in various media conditions to identify suitable conditions for in vitro culture and development, and to determine the effects of FBS, mosquito cells, and ecdysteroid on the development of the microfilariae. Transcript level of the ecdysone signaling pathway components were measured with droplet digital PCR. ResultsIn vitro conditions that best promote early development of D. immitis microfilariae to the “late sausage stage” have been identified, although shedding of the cuticle was not observed. FBS showed inhibitory effects on the development and motility of the microfilariae, but media conditioned with Anopheles gambiae cells was favorable to microfilarial growth. Transcript level study using droplet digital PCR also showed that developing microfilariae displayed upregulation of the ecdysone signaling system components, and 20‑hydroxyecdysone increased the proportion of larvae developing to the sausage and late sausage stages in vitro.ConclusionsThe arthropod host environment provides cues required for the rapid development of the D. immitis microfilariae and the ecdysone signaling system may play an important role in filarial nematode developmental transitions. This study contributes to a better understanding the developmental process of D. immitis microfilariae.
HBP1-mediated transcriptional regulation of AFP and its impact on hepatoma
Authors: Cao Zhengyi , Cheng Yuning , Wang Jiyin , Liu Yujuan , Yang Ruixiang , Jiang Wei , Li Hui , Zhang Xiaowei
Published: October 2020

Background: Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. Methods: The expression of transcription factor HBP1 and AFP and clinical significance were father analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1-/- mice.Results: This study demonstrated that the relative expressions of HBP1 and AFP correlated with decreased survival and prognosis in hepatoma patients. HBP1 represses the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promotes malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibits malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuates AFP effect on PTEN, MMP9 and caspase-3, thus inhibits proliferation and migration, and induces apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributes to hepatoma progression in mice. Conclusion: Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the early diagnosis and treatment of hepatoma.
Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients
Authors: Spadaro Savino , Fogagnolo Alberto , Campo Gianluca , Zucchetti Ottavio , Verri Marco , Ottaviani Irene , Tanushree Tunstall , Grasso Salvatore , Scaramuzzo Valentina , Murgolo Francesco , Marangoni Elisabetta , Sega Francesco Vieceli Dalla , Fortini Francesca , Pavasini Rita , Rizzo Paola , Ferrari Roberto , Papi Alberto , Volta Carlo Alberto , Contoli Marco
Published: October 2020

BackgroundEvaluation of biomarkers in the context of ARDS is used to detect the presence of endothelial and/or alveolar epithelial injuries. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aim of this study was to evaluate whether the trends in plasma concentration of the biomarkers mentioned above were different in survivors and non-survivors of COVID-19-related ARDS. Furthermore, we compared the expression of biomarkers of vascular and endothelial injury in patients with COVID-19-related ARDS and classical ARDS. MethodsThis prospective study was performed in two COVID-19 dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 10 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7±2 days (T2) and 14±2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS.ResultsIn COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p=0.04 and p=0.03, respectively) whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS, than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19 related ARDS (all p<0.001).ConclusionsCOVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways.Trial registration: NCT04343053 Date of registration: April 13, 2020
Verification of the Efficacy of New Diagnostic Criteria for Retropharyngeal Nodes in a Cohort of Nasopharyngeal Carcinoma Patients
Authors: Tu Dom-Gene , Chen Hsuan-Yu , Yao Wei-Jen , Hung Yu-Sheng , Chang Yu-Kang , Chang Chih-Han , Wang Yu Wen
Published: October 2020

Background: A multistage approach to diagnose lateral retropharyngeal nodes (LRPNs) of nasopharyngeal carcinoma (NPC) had been proposed and warranted for validation. Methods: From 2012 to 2017, we collected NPC cases with LRPNs before radiotherapy-based treatments. The responsive nodes or those that progressed during follow-up were positive. The proposed criteria for the multistage approach delimited LRPNs with a minimal axial diameter (MIAD) ≥ 6.1 mm were positive and if the mean standard uptake value ≥ 2.6, or if the maximal coronal diameter ≥ 25 mm and maximal axial diameter ≥ 8 mm with nodes MIAD < 6.1 mm were also positive. The outcomes were compared with the MIAD cutoff value ≥ 6 mm (traditional method). Chi-squared test was used to compare two areas under the curve (AUC) of receiver operating characteristic curves. Results: A total of 67 eligible NPC cases and 155 LRPNs (72 positive and 83 negative) were analyzed. The accuracy, specificity, and sensitivity of the traditional method were 0.91, 0.93, and 0.89, respectively. The values for the multistage approach all reached 0.94. The AUC was significantly greater for the multistage approach compared with that for the traditional method (p = 0.023). Conclusion: The results of LRPN data in this cohort of patients support the advantage of the multistage approach.
Stopping-power ratio of mouthpiece materials for charged-particle therapy in head and neck cancer
Authors: Ikawa Hiroaki , Inaniwa Taku , Koto Masashi , Bhattacharyya Tapesh , Kaneko Takashi , Takiyama Hirotoshi , Shinoto Makoto , Yamada Shigeru , Tsuji Hiroshi
Published: October 2020

Background: In charged-particle therapy treatment planning, CT numbers of a patient’s body are converted into stopping power ratios (SPRs) using a CT-number-to-SPR conversion table constructed for standard human tissues. Since artificial devices used in treatments of head and neck cancer, such as mouthpieces, do not fit into the CT-number-to-SPR conversion table, they may deteriorate treatment accuracy. In this study, the SPRs of five mouthpiece materials were measured, and the error in predicted SPRs based on the conversion table was investigated.Methods: SPRs of five mouthpiece materials were predicted from their CT numbers using a calibrated conversion table. Independently, the SPRs of the materials were measured by the Bragg-peak shift of a carbon-ion beam passing through the materials. The errors in SPR of the materials were determined as the difference between the predicted and measured SPRs.Results: The SPRs (error) of the ethylene-vinyl acetate copolymers (EVAs), Nipoflex 710TM and BioplastTM, were 0.997 (0.023) and 0.982 (0.007), respectively. The SPRs (error) of the vinyl silicon impression material (Exafine putty typeTM), the light curable resin (Clear Photoreactive Resin for Formlabs 3D printersTM), and the bis-acrylic resin (TempsmartTM) were 1.517 (0.134), 1.161 (0.068), and 1.26 (0.101), respectively. Conclusions: The EVA BioplastTM had the minimum SPR error among the five tested materials, indicating the highest human-tissue equivalency. If other artificial materials such as Exafine putty typeTM are used as mouthpieces, it is recommended that their SPRs be overwritten by the correct values in treatment planning processes.
Heat Killed Salmonella typhimurium protects intestine against radiation injury through Wnt signaling pathway
Authors: Chen Yuanyuan , Cao Kun , Hu Xuguang , Liu Tingting , Li Bailong , Cui Jianguo , Cai Jian ming , Gao Fu , Yang Yanyong
Published: October 2020

Purpose: Gastrointestinal (GI) toxicity caused by ionizing radiation (IR) appears to be a limited factor in radiotherapy and a great threat for soldiers on nuclear-related military missions. However, there are currently no approved medical strategies to effectively prevent or mitigate the damage on intestine induced by IR. The present study aimed to elucidate the protective activity of Heat Killed Salmonella typhimurium (HKST) on intestine against ionizing radiation exposure. Materials and Methods: Mouse intestinal crypts and intestinal organoids were isolated from C57BL/6J mice. Mice and HIEC cells were exposed to 60Co γ‐radiation. The dosage was set as following: whole body radiation of 8 Gy; mouse intestinal organoids were irradiated with 0 Gy, 4 Gy, and 6 Gy of γ-rays at dose rate of 1 Gy/min. Cells or mice were pretreated with Heat Killed Salmonella typhimurium (HKST) (107 cells/mice) at 12 hours prior to irradiation.Results: By culturing mouse intestinal organoids and employing whole body irradiation of mice, we found that the radiation-induced damage on intestine was dramatically mitigated by pretreating with HSKT in vitro and in vivo, in which the structure of intestinal organoids and small intestine of the HKST-treated group was more integrated than of the radiation damage group, and HKST pretreatment remarkably promoted the proliferation of intestinal cells post IR exposure (Figure 1 and 2). Further study showed that the radio-protective effects of HKST was involved in DNA damage response (DDR) signaling. Moreover, the stimulation of DDR signaling by HKST upon radiation damage was mediated by Wnt signaling, in which the inhibition of Wnt signaling diminished the radio-protective effects of HKST. Conclusion: Our study demonstrated that Heat Killed Salmonella typhimurium (HKST) could significantly alleviate the damage on intestine induced by IR, and the radio-protective effect of HKST was depended on DDR mediated by Wnt signaling pathway. These findings demonstrated that HKST is a potential bacterium using for the prevention of IR-induced GI toxicity in clinical practice.
Protocol for Systematic Review on Inequity in Child Health Care Service Utilization in Low and Middle-income Countries
Authors: Demessie Hailu Fekadu , Hailemariam Damen Hailemariam , Kloos Helmut Kloos , Adugna Aynalem Adugna , Mekonnen Wubegzier Mekonnen
Published: October 2020

Background: One challenge to achieving Millennium Development Goals was inequitable access to quality health services. In order to achieve the Sustainable Development Goals, interventions need to reach underserved populations, it appears that the maternal, newborn and child health goals (MDG 4 and 5) will not be universally achieved. There was early recognition that it could be possible to achieve the health goals while decreasing health inequity, because most of the gains might go to the better-off rather than to the very poor.Methodology/Design: The current protocol adopts a strategy informed by the guidelines of The Cochrane Handbook for Systematic Reviews. Our systematic review will identify studies in English, provided inclusion of an English abstract - from 2010 onwards till 2020, by searching MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and the gray literature. Study selection criteria include research setting, study design, reported outcomes and determinants of interest. Our primary outcome is inequity in utilization of child health care services, and determinants of concern are: 1) socioeconomic status (for example, income, education); 2) geographic determinants (for example, distance to a health center, rural versus urban residence); and 3) demographic determinants (for example, age, ethnicity, religion, and marital status). Screening, data abstraction, and scientific quality assessment will be conducted independently by two reviewers using standardized forms. Where feasible, study results will be combined through meta-analyses to obtain a pooled measure of association between utilization of child health care services and key determinants. Results will be stratified by income levels (World Bank classification) geographical residence and demographical determinants.Discussion: Our review will inform policy-making with the aim of decreasing inequities in utilization of child health care services. This research will provide evidence on unmet needs for child health care services in LMICs, knowledge gaps and recommendations to health policy planners. Our research will help promote universal coverage of quality child health care services as an integral part of the continuum of maternal and child health care. This protocol will be registered with the Prospero database.
Antimicrobial-associated Organ Injury Among Older Adults: A Systematic Review and Meta-analyses Protocol
Authors: Chinzowu Tichawona , Roy Sandipan , Nishtala Prasad S
Published: October 2020

Background: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for risk of organ injury following antimicrobial exposure among older adults. This protocol will outline how we will conduct a systematic review and meta-analyses to examine the relationship between antimicrobial exposure and organ injury in older adults. Methodology: We will search for Psych INFO, PubMed, and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles will be screened for inclusion into or exclusion from the study by two reviewers. Title and abstract screening will be done first, followed by full-text screening. The Newcastle-Ottawa scale will be used to assess the risk of bias for cohort and case-control studies, and the Cochrane collaboration's tool will be used to assess the risk of bias for randomised control trials. We will explore the potential sources of heterogeneity and bias using funnel and forest plots of the included studies. Discussion and registration: In this protocol, systematic review methods to identify relevant literature on antimicrobial exposure and associated organ injury have been described. The findings from the review are intended to increase our understanding of the different types of antimicrobials associated with organ injury among older adults, therefore has the potential for improving the prescribing practice for this vulnerable population. This protocol is registered in the PROSPERO database (registration number CRD42020152621).
Guidelines on the Diagnosis, Clinical Assessments, Treatment and Management for CLN2 Disease Patients
Authors: Mole Sara , Schulz Angela , Badoe Eben , Berkovic Samuel , Reyes Emily de Los , Dulz Simon , Gissen Paul , Gilbert Norberto , Lourenco Charles , Mink Jonathan , Murphy Noreen , Nickel Miriam , Olaya Joffre , Scarpa Maurizio , Scheffer Ingrid , Simonati Alessandro , Specchio Nicola , Von Lobbecke Ina , Wang Raymond , Williams Ruth
Published: October 2020

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2), or Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL), is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition. Methods: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria.Results: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality). Conclusion: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease. This addresses the clinical need to complement other information available.
Identification of novel salivary candidate protein biomarkers for tuberculosis diagnosis
Authors: Mutavhatsindi Hygon , Calder Bridget , McAnda Shirley , Malherbe Stephanus T. , Stanley Kim , Kidd Martin , Walzl Gerhard , Chegou Novel N
Published: October 2020

Background: The diagnosis of TB remains one of the major challenges in the control of the disease, due to limitations in the currently available diagnostic tests. There is an urgent need for new, accurate, rapid, and affordable diagnostic tests. The aim of the present study was to use mass spectrometry to identify new candidate TB diagnostic protein biomarkers in saliva obtained from individuals with TB, and patients with other respiratory diseases (ORD).Methods: Saliva samples were collected from 22 individuals who self-presented with symptoms requiring investigation for TB as part of a larger TB biomarker project. Eleven of the participants were finally diagnosed with TB using routine clinical, radiological and laboratory tests and 11 with ORD. Salivary proteins were concentrated and purified, followed by tryptic digestion. Peptides were analyzed using a QExactive Orbitrap MS coupled to a Dionex liquid chromatography system. Raw files were processed using MaxQuant software against the database of human proteins. Identified proteins were subjected to gene ontology and ingenuity pathway analysis for functional enrichment analysis.Results: We identified 1176 protein groups across all samples, of which 46 (3.91%) were contaminants, 12 (1.02%) were reverse hits and 170 (14.46%) were single-peptide protein groups. After removal of the contaminants, reverse hits and protein groups represented by single peptides, 26 of the remaining 948 proteins significantly discriminated individuals with TB from those with ORD after Benjamini Hochberg correction, with five of these proteins diagnosing TB with AUC ³ 0.80. A 5-protein biosignature comprising of P01011, Q8NCW5, P28072, A0A2Q2TTZ9 and Q99574 diagnosed TB with an AUC of 1.00 (95% CI, 1.00-1.00), sensitivity of 100% (95% CI, 76.2-100%) and specificity of 90.9% (95% CI, 58.7-99.8%) after leave-one-out cross validation. Conclusions: We identified novel salivary protein biomarkers and biosignatures with strong potential as TB diagnostic candidates. Our results are preliminary and require validation in larger studies.
Sero-prevalence and risk factors of human brucellosis among febrile patients visited health institutes at Awra and Gulina district, Afar Region, Ethiopia
Authors: Zerfu Biruk , Mehari Sintayehu , Desta Kassu
Published: October 2020

Background: Brucellosis is an important neglected bacterial zoonotic disease that affects animals and humans for decades. The aim of this study was to determine the sero-prevalence and risk factors of human brucellosis among febrile patients visited health institutes at Awra and Gulina district of Afar region Ethiopia.Methods: A purposive cross-sectional study was conducted among 444 febrile patients visiting two health institutes in Awra and Gulina district of Afar region from February to May 2019. A 3-5ml blood samples were collected, thick and thin blood films were examined microscopically for malaria; serum was separated and tested antibody of Brucella using Rose Bengal Plate Test (RBPT) and positives ones were further subjected to ELISA. Data were entered using EpiData3.1 and analyses were performed using StataSE 14.Results: A total of 444 febrile individuals (59.5% female) of age ranging from 2-83 years (mean= 26.1, SD = ±11.8) participated in this study. The overall sero-prevalence of brucellosis was 31.5 % and 15.8% by RBPT and ELISA, respectively and 4.3% of the patients were positive for P. falciparum. Being male (AOR=2.41, 95%CI: 1.36 – 4.26, p < 0.002), drinking raw milk (AOR=15.42, 95%CI: 5.17 - 45.95, p < 0.001) and touching aborted fetus/discharges without protectives (AOR= 3.70, 95%CI: 1.61 - 8.50, p = 0.02) were independently associated with brucellosis among febrile patients.Conclusion: Human brucellosis is highly prevalent in pastoralist patients presenting with fever in this study area. Consumption of raw milk and contamination with aborted or discharge of animals are major risk factors. Hence, brucellosis should be considered as an important public health problem in this study area.
Impact of sugar beet pulp and wheat bran on serum biochemical profile, inflammatory responses and gut microbiota in sows during late gestation and lactation
Authors: Shang Qinghui , Liu Sujie , Liu Hansuo , Mahfuz Shad , Piao Xiangshu
Published: October 2020

Background: Sows are frequently subjected to various stresses during late gestation and lactation, which trigger inflammatory response and metabolic disorders. Dietary fiber can influence animal health by modulating gut microbiota and their by-products, with the effects depending upon the source of the dietary fiber. This study aimed to evaluate the impacts of different fiber sources on body condition, serum biochemical parameters, inflammatory responses and fecal microbiota in sows from late gestation to lactation.Methods: Forty-five multiparous sows (Yorkshire × Landrace; 3-6 parity) were assigned to 1 of 3 dietary treatments from d 85 of gestation to the end of lactation (d 21 post-farrowing): a control diet (CON, a corn-soybean meal diet), a sugar beet pulp diet (SBP, 20% SBP during gestation and 10% SBP during lactation), and a wheat bran diet (WB, 30% WB during gestation and 15% WB during lactation).Results: Compared with CON, supplementation of SBP decreased (P < 0.05) lactation BW loss, reduced (P < 0.05) serum concentration of total cholesterol, non-esterified fatty acids, interleukin-6 and tumor necrosis factor-α, and increased (P < 0.05) fecal water content on d 110 of gestation and d 21 of lactation, while supplementation of WB reduced (P < 0.05) serum concentration of total cholesterol on d 110 of gestation, increased (P < 0.05) fecal water content and decreased (P < 0.05) serum interleukin-6 concentration on d 110 of gestation and d 21 of lactation. In addition, sows fed SBP had lower (P < 0.01) abundance of Clostridium_sensu_stricto_1 and Terrisporobacter than those fed CON, but had greater (P < 0.05) abundance of Christensenellaceae_R-7_group and Ruminococcaceae_UCG-002 than those fed the other two diets on d 110 of gestation. On d 21 of lactation, supplementation of SBP decreased (P < 0.05) the abundance of Firmicutes and Lactobacillus, but enriched (P < 0.05) the abundance of Christensenellaceae_R-7_group, Prevotellaceae_NK3B31_group, Ruminococcaceae_UCG-002, Prevotellaceae_UCG_001 and unclassified_f__Lachnospiraceae compared with WB. Compared with CON, sows fed SBP had greater (P < 0.05) fecal concentrations of acetate, butyrate and total SCFAs during gestation and lactation, while sows fed WB only had greater (P < 0.05) fecal concentration of butyrate during lactation.Conclusions: Supplementation of dietary fiber during late gestation and lactation could improve sow metabolism and gut health, and SBP was more effective than WB.
Mediators of Sexual Distress in Women with Dyspareunia: A Population-based Cross-sectional Study
Authors: Alizadeh Ameneh , Farnam Farnaz
Published: October 2020

Background: Dyspareunia (recently been named as GPPPD), is considered as one of the negative factors affecting couple’s sexual health. The present paper explores the characteristics of pain in dyspareunia cases and also determine protective factors cause fewer sexual distress among sufferers. Methods: A population-based cross-sectional study conducted in 2017, on 590 married women aging 18 -70 years, in 30 health center via cluster-quota sampling method. Demographic data, sexual distress and Binik’s GPPPD Questionnaire were utilized as study tools. Results: Although 33% of the women report dyspareunia, based on standard criteria the prevalence of severe and moderate dyspareunia were dropped to 10.5% and 25.8%, respectively that among them the most common location, time and type of pain were in vaginal entrance, at the beginning of intercourse and with burning nature, respectively. Dyspareunia had a significant negative impact not only on women’s ability to have intercourse (P=.004) but also on their sexual desire (P=.038). Interestingly, 5.4% of the women did not report any distress despite having severe dyspareunia. In comparison with those patients with distress, the latter group had higher sexual satisfaction, more positive body image and self-confidence, as well as more intimacy in relationship (P=.000). Notably, 19% of the participants experienced significant sexual distress, although in 8.5% of them dyspareunia was not confirmed. Conclusion: Promote personal characteristics such as positive self-confidence and body image and interpersonal factors like sexual satisfaction and intimacy, can be effective in the management of dyspareunia via decrease sexual distress.
Co-transfer of plasmid-mediated blaAmpC and fluoroquinolone resistance genes in Klebsiella pneumoniae isolates causing nosocomial urinary tract infection
Authors: Xiong Yilin , Zhang Cong , Gao Wenting , Ma Yong , Zhang Qingqing , Han Yuqiao , Jiang Shiyu , Zhao Zinan , Wang Jia , Chen Yang
Published: October 2020

Background: Klebsiella pneumoniae is a pathogen that frequently causes nosocomial urinary tract infection (UTI), and the prevalence of plasmid-mediated resistance determinants among clinical isolates of K. pneumoniae leads to the appearance of resistance to antibiotics. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in acquired AmpC (ac-AmpC) β‑lactamase‑producing K. pneumoniae isolates from patients with nosocomial UTI and to characterize the transmissibility of plasmids co-harbouring blaAmpC and PMQR genes.Methods: From January 2017 to June 2018, we collected 46 AmpC-producing K. pneumoniae isolates causing nosocomial UTI from a tertiary care hospital in China. β-lactamase, PMQR and virulence genes were detected by PCR and sequencing. Clonal relatedness was assessed using ERIC-PCR and multilocus sequence typing (MLST). Plasmids carrying multiple blaAmpC and PMQR genes were characterized by PCR-based replicon typing (PBRT) and S1-PFGE. Conjugation and electroporation experiments were carried out to assess resistance transfer mediated by plasmids. Overlapping PCR was used to map the genetic context of the blaAmpC genes. Results: In the studied isolates, non-susceptibility of third-generation cephalosporin and fluoroquinolone was very high (>80%). blaCMY-2, blaDHA-1, and quinolone resistance gene (qnr) were detected in 11, 41 and 33 isolates, respectively. Among the isolates, 6 strains co-harboured multiple AmpC and qnrB genes. The blaAmpC and qnrB genes from these six isolates were co-transferrable to recipients via conjugation or electroporation, with IncFIA, IncFIB and IncA/C being the dominant replicons (sizes from ~78 to 217 kb). Forty-six isolates were categorized into 25 ERIC types, and the 6 isolates harbouring multiple blaAmpC and qnrB genes belonged to ST1/STnew1. The conserved genetic structures in blaCMY-2 and blaDHA-1 were identical to those described in the pNF4656 and pSAL-1 plasmids, respectively.Conclusion: This work reports that qnrB is highly prevalent in AmpC-producing K. pneumoniae isolates and illustrates the emergence of plasmids co-harbouring multiple acquired blaAmpC and qnrB genes in K. pneumoniae causing UTI in China. We determined that the IncFIA, IncFIB and IncA/C plasmids carrying blaAmpC with qnrB resistance genes and several mobile genetic elements mediate the local prevalence in K. pneumoniae UTI. The genetic context of blaAmpC was highly conserved.
Investigation of the occupational exposure to blood-borne pathogens of staff at a third-class specialist hospital in 2015-2018: A retrospective study
Authors: Ji Yuanyi , Huang Junbo , Jiang Guoguo , Liu Qiaolan , Xiao Dalei , Deng Jianjun
Published: October 2020

Background To understand the current situation of occupational exposure to blood-borne pathogens in a women's and children's hospital and analyze the causes to provide a scientific basis for improving occupational exposure prevention and control measures.Methods We analyzed occupational exposure to blood-borne pathogens in a third-class women's and children's hospital from 2015 to 2018, considering the workers’ occupational categories and length of service; the sites, types, and causes of exposure; and the pathogens of the source patients.Results From 2015 to 2018, there were 146 cases of occupational exposure to blood-borne pathogens, mainly from sharp-instrument injuries (82.2%). Trainees represented the highest proportion of occupational exposure (30.1%), followed by nurses (29.5%). Occupational exposure among staff with less than one year of service accounted for 43.2% of cases. Fisher's exact test showed that different occupational groups had different types of occupational exposure, and nurses had the highest proportion of blood and body fluid exposure (P = 0.008). Different occupational groups faced exposure to different types of pathogens: medical staff were more likely than workmen to be exposed to hepatitis B, while workmen were more likely than medical staff to be exposed to unknown pathogens; these differences were statistically significant (P<0.001). Health records were established for all cases of occupational exposure to blood-borne pathogens, and no staff members contracted a blood-borne disease due to occupational exposure.Conclusions In order to reduce occupational exposure, regular training in occupational protection for junior medical staff and workers should be strengthened, the monitoring and protection system of occupational exposure to blood-borne pathogens improved, standard prevention measures strengthened, operations standardized, safe injection equipment provided, and comprehensive measures taken.