bluuebunny/crossref_metadata_2025 huggingface dataset:
Anteroposterior lumbar spine X-ray of L5 lamina for screening of possibility of lower lumbar disc herniation in young adults
Authors: Jin Lin , Zhang Li , Guo Jialiang , Zhang Ruipeng , Yin Yingchao , Hou Zhiyong , Zhang Yingze
Published: December 2020

Background: Plain radiographs are rarely used in the imaging evaluation of lumbar disc herniation (LDH). The L5 lamina is the important skeletal structure at the back of the lower lumbar vertebra. This study investigated the association between the height of L5 lamina under anteroposterior lumbar spine X-ray and lower LDH, to determine its significance to the onset of LDH in young adults.Methods: We conducted a retrospective study of 160 patients aged 18 to 39 years with lower LDH and 160 healthy controls. The anteroposterior lumbar spine X-ray was used to image features of the L5 lamina. The height of L5 lamina (“h”) and of the space between L4 and S1 lamina (“H”) were measured. The difference in height of L5 lamina in each study group was assessed as the ratio of “h/H”. Results: There was no significant difference in sex, age, occupation type, body mass index (BMI), family history or smoking status (p>0.05) between LDH group and the control group. The mean ratio (95% CI) of “h/H” in LDH and control group was 0.28 (0.26, 0.31) and 0.35 (0.32, 0.38) respectively, with statistical difference (p<0.05). The diagnostic accuracy of “h/H” ratio was investigated using the receiver operating characteristic (ROC) curve. The area under the curve was 0.835 (95% CI 0.789, 0.881), using a cut-off of 0.315 (sensitivity 0.806, specificity 0.794). A decrease in the “h/H” ratio, showed an increasing linear trend in the protrusion proportion of L4/5 segments (Z=5.943, p<0.05).Conclusions: Young adults with developmental defects of L5 lamina are more likely to develop lower LDH. Assessment of “h/H” ratio could be used for screening or prediction of asymptomatic or mildly symptomatic lower LDH in young adults.
Role of a Novel Insulin Resistance Index based on Combined Levels of C-peptide and Insulin in Assessment of the Heterogeneity of Diabetes Mellitus
Authors: Dai Hao , Fu Qi , Chen Heng , Zhang Mei , Sun Min , Gu Yong , Shi Yun , Yang Tao
Published: December 2020

Background The C-peptide-to-insulin ratio (C/I) is associated with hepatic insulin clearance and insulin resistance. We established a novel C-peptide-to-insulin ratio index (CPIRI) and explored its application in the heterogeneity of non-autoimmune diabetes.Methods A total of 865 adults diagnosed with new-onset diabetes mellitus (DM) within 1 year and 54 healthy controls (HC) were recruited. Our CPIRI model was established with fasting C/I as the independent variable and homeostasis model assessment of insulin resistance (HOMA-IR) as the dependent variable. Patients with negative-autoantibodies against pancreatic islets were subclassified according to CPIRI, age of onset , hemoglobin A1c (HbA1c), body mass index (BMI) and homeostatic model assessment of β-cell function (HOMA-β) via cluster analysis.Results Fasting C/I and HOMA-IR in both diabetic and healthy subjects were hyperbolically correlated, and log(C/I) and log(HOMA-IR) were linearly and negatively correlated; the correlation coefficient was −0.83 (P = 0.000) and −0.76 (P = 0.000), respectively. Finally, we obtained the equations CPIRI(DM) = 670/(C/I) 2.24 + 0.25 and CPIRI(HC) = 670/(C/I) 2.24 − 1 (F = 1904.39, P = 0.000). Pancreatic islet autoantibody-negative patients were further subclassified into three subtypes; subtype 1 (13.8%) had severe insulin resistance, subtype 2 (42.1%) suffered elderly-onset DM with slight symptoms, and subtype 3 (44.1%) suffered severe dysfunction of pancreatic islets. Each subtype exhibited different clinical characteristics and complications.Conclusions CPIRI can be used to effectively evaluate insulin resistance. Adult-onset non-autoimmune diabetes can be subclassified into 3 subtypes according to CPIRI along with other symptom-based characteristics of diabetic progression.
Improved adulticidal activity against Aedes aegypti (L.), and Aedes albopictus (Skuse), from synergy between Cinnamomum spp. essential oils
Authors: Aungtikun Jirapon , Soonwera Mayura
Published: December 2020

Improved natural adulticidal agents against mosquito vectors are in urgent need, and essential oils from Cinnamomum plants can assume this role quite readily. Cinnamomum verum, C. cassia, and C. loureiroi essential oils (EOs) were extracted from the barks and evaluated for their chemical composition by GC-MS. The major constituent of the three EOs was cinnamaldehyde. WHO susceptibility tests on individual and combined EOs as well as cinnamaldehyde were conducted against female adults of Aedes aegypti and Aedes albopictus. All EO combinations exhibited a synergistic effect, manifesting a higher toxicity, with a synergistic value ranging from 2.9-6.7. Their increasing mortality value was improved between 16.0 to 41.7%. The highest synergistic effect was achieved by an EO combination of 0.5% C. cassia + 0.5% C. loureiroi, while the highest insecticidal activity was achieved by 2.5% C. verum + 2.5% C. cassia and 1% cinnamaldehyde, with a knockdown and mortality rate of 100% and a KT50 between 0.7-2.1 min. This combination was more toxic to both mosquito species than 1% w/v cypermethrin. These findings demonstrate that cinnamaldehyde and synergistic combinations of C. verum + C. cassia EOs and C. cassia + C. loureiroi EOs have a high insecticidal efficacy against Aedes populations.
Do Changes in Pulse Pressure Variation and Inferior Vena Cava Distensibility During Passive Leg Raising and Tidal Volume Challenge Detect Preload Responsiveness in Case of Low Tidal Volume Ventilation?
Authors: Taccheri Temistocle , Gavelli Francesco , Teboul Jean-Louis , Shi Rui , Monnet Xavier
Published: December 2020

BackgroundIn patients ventilated with tidal volume (Vt) <8 mL/kg, pulse pressure variation (PPV) and, likely, the distensibility of the inferior vena cava diameter (IVCV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt=6mL/kg, the effects of PLR could be assessed through changes in PPV or in IVCV rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCV rather than changes in PPV.MethodsIn 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt=6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥10% defined preload responsiveness.ResultsAt baseline, IVCV was not different between preload responders (n=15) and non-responders. Compared to non-responders, PPV and IVCV decreased more during PLR (by -38±16% and -26±28%, respectively) and increased more during the Vt challenge (by 64±42% and 91±72%, respectively) in responders. ∆PPVPLR, expressed either as absolute or percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98±0.02 for both). ∆IVCVPLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76±0.10), not in relative changes. ∆PPVVt, expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98±0.02 and 0.94±0.04, respectively). This was also the case for ∆IVCVVt but, the diagnostic threshold (1 point or 4%) was below the least significant change of IVCV (9[3-18]%).ConclusionsDuring mechanical ventilation with Vt=6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCV is used, it should be expressed in percent and not in absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCV, since the diagnostic threshold is too small with regards to the reproducibility of this variable.Trial registrationIDRCB: 2016-A00893-48
A qualitative study of factors that protect against pregnancy among sexually-active teens in the South African Birth to Twenty Plus cohort
Authors: Bosire Edna N , Chiseri Katharine , Comeau Dawn L , Richter Linda , Stein Aryeh D , Norris Shane A
Published: December 2020

Background: Risky sexual behaviors contribute to increased risk of adolescent pregnancy and HIV infections. This qualitative study sought to understand factors that might buffer this risk amongst sexually-active adolescents in Soweto, South Africa.Methods: We used purposive sampling to recruit women at age 24 years from Soweto, South Africa, who self-reported having sexual debut by age 15 years. Twenty women were recruited into 2 equal groups: (i) those who did not become pregnant before 18 years (n=10) and (ii) those who became pregnant before 18 years (n=10). In-depth qualitative interviews were conducted with the two groups of women to understand their family backgrounds, the conversations about sex to which they are exposed, sexual behaviors and steps they took, or didn’t take, during adolescence to prevent early pregnancies. Interviews were transcribed verbatim and thematically analyzed with the aid of MAXQDA software.Results: Both groups of adolescents reported predisposing risks to early pregnancy including influence from peers and older friends to engage in early sex; unstable family relationships and limited conversations about sex. Key factors that differentiated the two groups were family structure and support, as well as, the adolescent’s ability to navigate choices and make decisions on consistent condom use, access to information and desire to complete schooling. Other supportive systems identified by those who did not become pregnant included life-orientation courses provided at school, access to health services, and positive peer influences. Conclusion: The family is a key institution in supporting adolescents’ decisions regarding their behaviors and choices, as are peers and exposures to formal or informal information they receive about sex. Policy makers should work closely with other social support systems such as schools, healthcare providers and peers to ensure that adolescents have access to relevant information, including sex education, and contraceptives.
Community Voice in Cross-Sector Alignment: Concepts and Strategies from a Scoping Review of the Health Collaboration Literature
Authors: Petiwala Aliza , Lanford Daniel , Landers Glenn , Minyard Karen
Published: December 2020

BackgroundHealth care access is an important driver of population health, and factors beyond health care also drive health outcomes. Recognizing the importance of the social determinants of health (SDOH), different actors in the health care, public health, and social service sectors are increasingly collaborating to improve health outcomes in communities. To support such collaboration, the Robert Wood Johnson Foundation recently developed the cross-sector alignment theory of change. According to the cross-sector alignment theory of change, community voice is critical for helping collaboratives address community health needs. Yet research on health collaboratives offers little guidance on how community voice should be understood, or which community voice strategies are most effective.MethodsThis study addresses a gap in the literature with a systematic scoping review of research on health-oriented collaboration and community voice. By scanning key academic journals, searching three academic databases, and obtaining documents from across our professional networks, we identified 36 documents that address community voice in health collaboratives. The review reveals several concepts of community voice and a range of community voice strategies.ResultsWe find that community voice strategies fall into two broad approaches: active and passive. These vary in the level of engagement required from the community and in the level of power shared between communities and collaborators, and this in turn has implications for community health outcomes. We also find that while most strategies are discussed in the context of short-term collaboration, many also lend themselves to adoption in the context of sustainable collaboration and, ultimately, cross-sector alignment.ConclusionThis review provides a characterization and conceptualization of community voice in health-oriented collaborations that provides a new theoretical basis for future research. Passive and active community voice strategies can be studied in more detail for their expected impact on health outcomes and disparities. The increased attention to active community voice can help practitioners achieve improved health outcomes and researchers understand the pathways to health improvement through collaboration.
Discrimination Due to Sexual Orientation and Associated Factors Among Men Who have Sex with Men in 12 Brazilian Cities: A Respondent-Driven Sampling Survey
Authors: Magno Laio , Dourado Inês , Leal Andrea Fachel , Knauth Daniela , Guimarães Mark Drew Crosland , Bermúdez Ximena Pamela Díaz , Rocha Gustavo Machado , Veras Maria Amélia , Kendall Carl , de Brito Ana Maria , Kerr Lígia
Published: December 2020

BackgroundDiscrimination due to sexual orientation (DDSO) has an important association with health outcomes among men who have sex with men (MSM). This study aimed to analyse factors associated with DDSO among MSM in 12 Brazilian cities.MethodsA cross-sectional study with 4,176 MSM participants recruited in 2016 through respondent-driven sampling in 12 Brazilian cities. In this analysis, ordinal logistic regression was used to assess associations with previously identified levels of DDSO, which were based on latent class analysis (LCA) on 13 variables from the discrimination section of the questionnaire. Weighted odds ratios and their respective 95% confidence interval were estimated using Gile estimator. ResultsMost participants were young, single, had a religious affiliation, a post-primary education, were black or mixed race and had a high and average socio-economic status. More than half reported DDSO in the previous 12 months (65%). DDSO was then classified into four latent classes (very high, high, average or low). We observed an independent association among the four latent classes of DDSO and the following variables: age< 25 years old, white skin color, experience of sexual or physical violence, revealing to a father his sexual orientation as MSM, experienced suicidal ideation in the previous two weeks and had taken illicit drugs in the last six months. ConclusionWe observed that sociodemographic characteristics, previous violence experiences, family knowledge about sexual orientation and mental health issues were associated with DDSO. Monitoring DDSO throws into sharp relief our broad social, political, and moral failings. These results should be used for the purposes of surveillance and protection for the human rights.
Association of the CFTR Gene With Asthma and Airway Mucus Hypersecretion
Authors: Lessmann Astrid Crespo , Bernal Sara , Río Elisabeth del , Rojas Ester , Martínez-Rivera Carlos , Malanda Nuria Marina , Pallarés-Sanmartín Abel , Pascual Silvia , García Juan Luis , Padilla Alicia , Curto Elena , Cisneros Carolina , Serrano Jose , Baiget Montserrat , Plaza Vicente
Published: December 2020

IntroductionAirway mucus hypersecretion is an undercharacterized phenotype of asthma. Objectives(1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the characteristics of the asthma phenotype with airway mucus hypersecretion.MethodComparative cross-sectional multicentre study including 39 hypersecretors and 61 non-hypersecretors asthma patients. Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least three months in two successive years. Spirometry, fractional exhaled nitric oxide, induced sputum cell count, blood test and questionnaires were performed. Blood DNA samples were sequenced using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis.ResultsGenetic differences were observed in the c.1680-870T>A genetic variant of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p=0.036). Asthma hypersecretors were older (57.4 years vs. 49.4 years; p=0.004) and had greater asthma severity (58.9% vs. 23.7%; p=0.005), greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p=0.041), poorer asthma control (60% vs. 29%; p=0.021), and lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p=0.003).ConclusionPatients with asthma and with mucus hypersecretion may have a different disease mechanism produced by an intronic genetic variant in the CFTR gene (NM_000492.3:c.1680-870T>A). They present a more severe disease, poorer asthma control and a non-allergic inflammatory phenotype.
Convergence of Scaffold Guided Bone Regeneration and RIA Bone Grafting for the Treatment of a Critical-Sized Bone Defect of the Femoral Shaft
Authors: Kobbe Philipp , Laubach Markus , Hutmacher Dietmar W , Alabdulrahman Hatem , Sellei Richard M , Hildebrand Frank
Published: December 2020

BackgroundCritical-sized bone defects, mainly from trauma, infection or tumor resection are a challenging condition, often resulting in prolonged, complicated course of treatment. Autografts are considered as the gold standard to replace lost bone. However, limited amount of bone graft volume and donor site morbidity have established the need for the development of alternative methods such as scaffold-based Tissue Engineering (TE). The emerging market of additive manufacturing (3D-printing) has markedly influenced the manufacturing of scaffolds out of a variety of biodegradable materials. Particularly medical-grade polycaprolactone and tricalcium phosphate (mPCL-TCP) scaffolds show appropriate biocompatibility and osteoconduction with good biomechanical strength in large preclinical animal models. This case report aims to show first evidence of the feasibility, safety, and efficacy of mPCL-TCP scaffolds applied in a patient with a long bone segmental defect.Case presentationThe presented case comprises a 29-year-old patient who has suffered a left-sided II° open femoral shaft fracture. After initial external fixation and subsequent conversion to reamed antegrade femoral nailing the patient presented with an infection in the area of the formerly open fracture. Multiple revision surgeries followed to eradicate microbial colonization and attempt to achieve bone healing. However, 18 months after the index event, still insufficient diaphyseal bone formation was observed with circumferential bony defect measuring 6 cm at the medial and 11 cm at the lateral aspect of the femur. Therefore, the patient received a patient-specific mPCL-TCP scaffold, fitting the exact anatomical defect and the inserted nail, combined with autologous bone graft (ABG) harvested with the Reamer Irrigator Aspirator system (RIA – Synthes®) as well as bone morphogenetic protein-2. Radiographic follow-up 12 months after implantation of the TE scaffold shows advanced bony fusion and bone formation inside and outside the fully interconnected scaffold architecture.ConclusionThis case report shows a promising translation of scaffold-based TE from bench to bedside. Preliminary evidence indicates that the use of medical-grade scaffolds is safe and has the potential to improve bone healing. Further, its synergistic effects when combined with ABG show the potential of mPCL-TCP scaffolds to support new bone formation in segmental long bone defects.
Analysis of Structure Indicators Influencing 3-h and 6-h Compliance with the Surviving Sepsis Campaign Guidelines in China: A Systematic Review
Authors: Wang Lu , Ma Xudong , He Huaiwu , Su Longxiang , Guo Yanhong , Shan Guangliang , Zhou Xiang , Liu Dawei , Long Yun
Published: December 2020

Background: Compliance with the surviving sepsis campaign (SSC) guidelines (Cssc) is a key factor affecting the effects of sepsis treatment. We designed this study to investigate the relationships of the structure indicators of ICU on 3-h and 6-h Cssc in China. A total of 1854 hospitals were enrolled in a survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018, through December 31, 2018.Methods: We investigated the 1854 hospitals’ 3-h and 6-h Cssc, including compliance with each specific measure of the 3-h and 6-h SSC bundles. We also investigated the actual level of the structure indicators of ICU, released by China-NCCQC in 2015.The outcomes were in adherence with the SSC guidelines (2016). Monitoring indicators included 3-h and 6-h Cssc.Results: In the subgroup, the rate of broad-spectrum antibiotic therapy was the highest, and the rate of CVP and ScvO2 measurement was the lowest. Structure indicators related to 3-h and 6-h Cssc include the predicted mortality rate and the standardized mortality ratio (SMR). The relationships between 3-h and 6-h Cssc and the proportion of ICU in total inpatient bed occupancy, the proportion of acute physiology and chronic health evaluation (APACHE) II score ≥15 in all ICU patients were uncertain. There was no relationship of 3-h and 6-h Cssc with the proportion of ICU patients among total inpatients.Conclusions: Structure indicators influencing 3-h and 6-h Cssc in China are the predicted mortality rate and the standardized mortality rate.
Implementation of the Connect for Health Pediatric Weight Management Program: Study Protocol and Baseline Characteristics
Authors: Simione Meg , Farrar-Muir Haley , Mini Fernanda Neri , Perkins Meghan E , Luo Man , Frost Holly , Orav E. John , Metlay Joshua , Zai Adrian H , Kistin Caroline J , Sease Kerry , Hambidge Simon J , Taveras Elsie M
Published: December 2020

Background: Promising approaches for reduction of childhood obesity include interventions such as Connect for Health, a scalable, primary care-based intervention to improve family-centered outcomes for children ages 2-12 years. Substantial gaps remain in the adoption of proven-effective interventions particularly in settings that care for low-income children. Methods: We used the Consolidated Framework for Implementation Research to examine contextual determinants of implementation of Connect for Health in four organizations that deliver primary care to low-income children in Boston, MA, Denver, CO, and Greenville, SC. The Connect for Health program includes (1) electronic health record (EHR)-based clinical decision support tools to guide clinicians; (2) family educational materials; and (3) text messages for parents to support behavior change. We used the RE-AIM framework to guide our mixed-methods evaluation. Using a quasi-experimental design, we will examine the effectiveness of stakeholder-informed strategies in supporting program adoption and child outcomes. At baseline, we abstracted EHR data from the organizations to describe characteristics of children ages 2-12 years with a BMI ≥ 85th percentile.Results: During the 15-month period prior to implementation, 26,161 children with a BMI ≥ 85th percentile ages 2-12 years were seen for a primary care visit. Across the organizations, 79% of children with a BMI ≥ 85th percentile had public insurance, 49% were Hispanic, and 18% were Black. Approximately 37% of children had a BMI ≥ 95th percentile and 15% had a BMI in the severe obesity category. Childhood obesity ICD-10 diagnostic codes were used more for children with obesity (44%) and severe obesity (60%) than children with overweight (17%); nutrition (7%) and physical activity (6%) counseling codes were seldom used. Referrals for weight management programs were less than 17% and less than 16% for nutrition services. Laboratory evaluations were ordered more often for children with obesity (39%) and severe obesity (64%) than children with overweight (29%)Discussion: A majority of children with overweight and obesity lacked recommended diagnosis codes, referrals, and laboratory evaluations for assessment and management of obesity and related co-morbidities. These findings suggest the need to augment current approaches to increase uptake of proven-effective weight management programs. Trial Registration: Clinicaltrials.gov, NCT04042493, Registered on August 2, 2019; https://clinicaltrials.gov/ct2/show/NCT04042493
GJA1 rs2071165 A>G Variant Increased Gastric Cancer Risk in Females of Northwest China: A Case-control Study
Authors: yuan lijuan , Wei Gang , Yang Ping , Lu Jianguo , Peng Shujia , Yang Zhengyu , Yang Lin , He Xianli , Bao Guoqiang
Published: December 2020

Background: Gastric cancer (GC) is one of the most common malignancies and its incidence rates vary widely between men and women. Previous studies have suggested that Cx43 and SCAMP1 are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated.Methods: A total of three SNPs among 681 GC patients and 756 controls were tested using the Agena Mass ARRAY RS1000 system including GJA1 rs2071165, SCAMP1 rs4530741, and rs6874309. The strength of the association with cancer risk was assessed by the odds ratios and 95% confidence intervals generated from the logistic regression model. Kaplan-Meier Curve, long-rank tests, and a multivariate Cox proportional hazard model were used for prognosis analysis. The expression of GJA1 was assessed by immunohistochemistry.Results: The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (odds ratio [OR] =1.55, 95% confidence interval, 95%CI] = 1.03–2.32, p = 0.034). Furthermore, the risk effect of rs2071165 was more evident in the subgroups of female patients with GC, stratified by age, clinical stage, tumor size, and recurrence/metastasis. However, no obvious differences in Cx43 expression in GC tissues were observed between males and females. Furthermore, no significant association between rs4530741 and rs6874309 polymorphisms in SCAMP1 and GC risk or prognosis was observed. Conclusion: In conclusion, this study suggests that GJA1 rs2071165 polymorphisms are associated with increased GC risk in females for the first time, which showed a potential new clinical marker for assessing GC risk in females.
Downregulation of GIRK2 Mediated by PPARγ Inhibition in DRG Contributes to the Neuropathic Pain Induced by Spare Nerve Injury
Authors: Mai Jing-Wen , Ji Yan-Qin , Luo Dexing
Published: December 2020

Neuropathic pain, as the most common chronic and intractable neurological disorder, seriously endangers the health and even life of patients. Due to the unclear mechanism, there is no effective treatment for neuropathic pain at present. Here, we used spared nerve injury (SNI) rat model to investigate the underlying mechanism involved in neuropathic pain. We found that SNI significantly decreased the expression of G protein-coupled inwardly rectifying potassium channel subunit 2 (GIRK2) and peroxisome proliferation-activated receptor gamma (PPARγ) in dorsal root ganglion (DRG). Activation of GIRK2 by intrathecal injection of activators-ML-297 or overexpression of GIRK2 by intrathecal injection of adenovirus associated virus (AAVs)-AAV-GIRK2-EGFP remarkably attenuated the mechanical allodynia induced by SNI in rats. Similarly, activation or overexpression of PPARγ also relieved the SNI-induced mechanical allodynia. We further found that the expression of PPARγ was co-localized with GIRK2-positive neurons, and overexpression of PPARγ rescued the down-regulation of GIRK2 induced by SNI. The results of chromatin immunoprecipitation (ChIP) assays further showed that PPARγ was bound to the potential binding site in the promoter region of GIRK2, and overexpression of PPARγ recovered the binding in GIRK2 promoter region in DRG, which was decreased by SNI. Altogether, our results suggested that the reduction of PPARγ induced downregulation of GIRK2 in DRG, whichwas involved in SNI-induced mechanical allodynia.
The Core Outcome Development for Carrier Screening (CODECS) Study: Protocol for Development of a Core Outcome Set
Authors: Richardson Ebony Joanne , McEwen Alison , Newton-John Toby , Manera Karine , Jacobs Chris
Published: December 2020

Background: Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for ‘what to measure’ in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention. Objectives: The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice.Methods: In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: i) A systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement ii) A systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes iii) Semi-structured focus groups and interviews with patients who have undertaken reproductive genetic carrier screening to identify outcomes of importance to them iv) Delphi survey of key stakeholders, including patients, clinicians, and researchers, to refine and prioritise the list of outcomes generated from the previous steps v) A virtual consensus meeting with a purposive sample of key stakeholders to finalise the core outcome set for reporting.Discussion: This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET core outcome set registration: http://www.comet-initiative.org/Studies/Details/1381
TGR5 activation attenuates neuroinflammation via Pellino3 inhibition of Caspase-8/NLRP3 after middle cerebral artery occlusion in rats
Authors: Liang Hui , Matei Nathanael , Devin W. McBride , Xu Yang , Zhou Zhenhua , Tang Jiping , Luo Benyan , Zhang John H.
Published: December 2020

Background NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3) plays an important role in mediating inflammatory responses during ischemic stroke. Bile acid receptor TGR5 has been identified as an important component in regulating inflammatory response in brain. In this study, we investigated the mechanism of TGR5 on alleviating neuroinflammation after middle cerebral artery occlusion (MCAO).Methods—Sprague-Dawley rats were subjected to MCAO and INT777 was administered intranasally 1 hour after MCAO. Small interfering RNA for TGR5 and Pellino3 were administered through intracerebroventricular injection 48 hours before MCAO. Infarct volumes, neurological scores, ELISA,flow cytometry༌ immunofluorescence staining, Western blot and co-immunoprecipitation were evaluated.Results— Endogenous TGR5 and Pellino3 expressions were increased after MCAO.TGR5 activation by INT777 significantly decreased pro-inflammatory cytokines levels, reduced cleaved caspase-8 and NLRP3 expressions, thereby reducing brain infarction, improving both short- and long-term neurobehavioral assessment. Ischemic damage induced interaction of TGR5 with Pellino3. Knockdown of either TGR5 or Pellino3 increased expressions of cleaved caspase-8 and NLRP3, aggravated brain impairments, abolished the anti-inflammatory effects of INT777 after MCAO.Conclusions—TGR5 activation attenuated brain injury by inhibiting neuroinflammation after MCAO, which may be mediated by Pellino3 inhibition of Caspase-8/NLRP3.
Systemic administration of β-glucan induces immune training in microglia
Authors: Heng Yang , Zhang Xiaoming , Borggrewe Malte , Weering Hilmar R.J. van , Brummer Maaike L. , Nijboer Tjalling W. , Joosten Leo A.B. , Netea Mihai G. , Boddeke Erik W.G.M. , Laman Jon D. , Eggen Bart J.L.
Published: December 2020

BackgroundAn innate immune memory response can manifest in two ways: immune training and immune tolerance, which refers to an enhanced or suppressed immune response to a second challenge, respectively. Exposing monocytes to moderate-to-high amounts of bacterial lipopolysaccharide (LPS) induces immune tolerance, whereas fungal β-glucan (BG) induces immune training. In microglia, it has been shown that different LPS inocula in vivo can induce either immune training or tolerance. Few studies focused on impact of BG on microglia and were only performed in vitro. The aim of the current study was to determine whether BG activates and induces immune memory in microglia upon peripheral administration in vivo.MethodsTwo experimental designs were used. In the acute design, mice received an intraperitoneal (i.p.) injection with PBS, 1 mg/kg LPS or 20 mg/kg BG and were terminated after 3 h, 1 or 2 days. In the preconditioning design, animals were first challenged i.p. with PBS, 1 mg/kg LPS or 20 mg/kg BG. After 2, 7 or 14 days, mice received a second injection with PBS or 1 mg/kg LPS and were sacrificed 3 h later. Microglia were isolated by fluorescence-activated cell sorting, and cytokine gene expression levels were determined. In addition, a self-developed program was used to analyze microglia morphological changes. Cytokine concentrations in serum were determined by a cytokine array.ResultsMicroglia exhibited a classical inflammatory response to LPS, showing significant upregulation of Tnf, Il6, Il1β, Ccl2, Ccl3 and Csf1 expression, three h after injection, and obvious morphological changes 1 and 2 days after injection. With an interval of 2 days between two challenges, both BG and LPS induced immune training in microglia. The training effect of LPS changed into immune tolerance after a 7-day interval between 2 LPS challenges. Preconditioning with BG and LPS resulted in increased morphological changes in microglia in response to a systemic LPS challenge compared to naïve microglia.ConclusionsOur results demonstrate that preconditioning with BG and LPS both induced immune training of microglia at two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning resulted in immune tolerance in microglia.
Activated STAT3 Signaling Pathway by Ligature-induced Periodontitis Could Contribute to Neuroinflammation and Cognitive Impairment in Rats
Authors: Hu Yi , Zhang Xu , Zhang Jing , Xia Xinyi , Li Huxiao , Qiu Che , Liao Yue , Chen Huiwen , He Zhiyan , Song Zhongchen , Zhou Wei
Published: December 2020

Background: Increasing evidence suggests a causal link between periodontitis and cognitive disorders. Systemic inflammation initiated by periodontitis may mediate the development of cognitive impairment. Our study aims to investigate the effect of ligature-induced periodontitis on cognitive function and the role of Signal transducers and activators of transcription 3 (STAT3) in this process.Materials and Methods: Ligature-induced periodontitis was established, and the rats were treated intraperitoneally with/without the pSTAT3 inhibitor cryptotanshinone (CTS). Alveolar bone resorption and periodontal inflammation were detected by micro-computed tomography (micro-CT) analysis and histopathological evaluation. Locomotor activity and cognitive function were evaluated by the Open field test (OFT) and the Morris water maze test (MWM), respectively. The activation of microglia and astrocytes in hippocampus and cortex was assessed by immunohistochemistry (IHC). The expression of interleukins (IL-1β, IL-6, IL-8, IL-21) in both periphery and cortex was evaluated by RT-PCR and ELISA. The expression of pSTAT3 and the activation of the STAT3 signaling pathway (JAK2, STAT3, and pSTAT3) in both oral cavity and cortex was assessed by IHC and Western blotting. The expression of amyloid precursor protein (APP) and its key secretase enzymes were evaluated by RT-PCR. The level of amyloid β-protein (Aβ) and the ratio of Aβ1-40/1-42 were measured via ELISA in plasma and cortex while IHC was used to detect the level of Aβ1-42 in brain.Results: In periodontal ligature rats, significant alveolar bone resorption and local inflammatory cell infiltration were present. Apparent increases in inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-21) were detected. in both periphery and brain. Additionally, spatial learning and memory ability was impaired, while locomotor activity was not affected. Activated microglia and astrocytes were found in the cortex and hippocampus, presenting as enlarged cell bodies and irregular protrusions. The STAT3 signaling pathway was activated in both oral cavity and cortex and the processing of APP by β- and γ-secretases was promoted. Change mentioned above could be relieved by the pSTAT3 inhibitor CTS. Conclusions: Ligature-induced periodontitis in rats resulted in systemic inflammation and further abnormal APP processing, leading to cognitive impairments. In this progress, the activation of the STAT3 signaling pathway may play an important role by increasing inflammatory load and promoting neuroinflammation.
Drug Resistance Profile and Clonality of Plasmodium Falciparum Parasites in Cape Verde: The 2017 Malaria Outbreak
Authors: Leal Silvânia da Veiga , Ward Daniel , Campino Susana , Benavente Ernest Diez , Ibrahim Amy , Andrade Tânia , Varela Isaías , Clark Taane G. , Monteiro Davidson , Gonçalves Luzia , Valdez Tomas , Lima Maria da Luz Mendonça , Silveira Henrique , Nogueira Fatima
Published: December 2020

BackgroundCape Verde is an archipelago located off the West African coast, and is in a pre-elimination phase of malaria control. Since 2010, less than 20 Plasmodium falciparum malaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulating P. falciparum to inform on drug resistance, potential transmission networks, and sources of infection, including parasite importation.MethodsEnrolled subjects involved malaria patients admitted to Dr. Agostinho Neto Hospital at Praia city, Santiago island, Cape Verde, between July and October 2017. Neighbours and family members of enrolled cases were assessed for the presence of anti-P. falciparum antibodies. Sanger sequencing and real time PCR was used to identify SNPs in genes associated with drug resistance (e.g. pfdhfr, pfdhps, pfmdr1, pfk13, pfcrt), and whole genome sequencing data was generated to investigate the population structure of P. falciparum parasites.ResultsWe analysed 190 parasite samples, 187 indigenous and three from imported infections. Malaria cases were distributed throughout Praia city. There were no cases of severe malaria, and all patients had an adequate clinical and parasitological response after treatment. Anti-P. falciparum antibodies were not detected in the 137 neighbours and family members tested. No mutations were detected in pfdhps. The triple mutation S108N/N51I/C59R in pfdhfr and the chloroquine resistant CVIET haplotype in the pfcrt gene were detected in almost all samples. Variations in pfk13 were identified in only one sample (R645T, E668K). The haplotype NFD for pfmdr1 was detected in the majority of samples (89.7%).ConclusionsPolymorphisms in pfk13 associated with ACTs tolerance in Southeast Asia were not detected, but the majority of the tested samples carried the pfmdr1 haplotype NFD and antimalarial associated mutations in the the pfcrt and pfdhfr genes. We performed the first WGS for Cape Verdean parasites that showed that the samples cluster together, have a very high level of similarity and are close to other parasites populations from West Africa.
Do Clinicians in Areas of Declining Malaria Transmission Adhere to Malaria Diagnosis Guidelines? A Cross-sectional Study From Kampala, Uganda.
Authors: Angella Atukunda , Deogratius Mwaka Amos , Arinaitwe Emmanuel , Orishaba Phillip , Kamya Moses R. , Nankabirwa Joaniter I.
Published: December 2020

Background: Uganda clinical management guidelines recommend a malaria laboratory test in all patients presenting with fever, and only those with a positive test receive antimalarial treatment. However, the current practice in areas with declining malaria transmission remains unknown. We assessed the clinicians’ diagnostic practices, the factors associated with recommending a test, and the risk of missing a malaria case when a test is not recommended in patients presenting with fever in Kampala, an area of declining malaria transmission in Uganda. Methods: Between January and March 2020, 383 participants aged > 12 years and presenting to Kisenyi Health Centre IV with fever were enrolled in the study. A questionnaire was administered during exit interviews, routine diagnostic practices were recorded from participant clinical notes, and a research blood slide was obtained for later reading. Results: Of the enrolled participants, 356 (93%) had a malaria diagnostic test recommended by the managing clinician. Factors associated with increasing prevalence of having a test recommended included; history of overnight travel (adjusted prevalence ratio [aPR] 1.07, 95% confidence interval [CI] 1.02 – 1.13, p=0.011), being married (aPR=1.07, 95% CI 1.01 – 1.13, p=0.022), and having tertiary education (aPR=1.09 95% CI 1.01 – 1.17, p=0.031). Among the 27 participants where a malaria diagnostic test was not recommended, 4 (14.8%) had a positive study smear. Conclusion: Despite having significant declines in malaria transmission in Kampala in the last decade, clinicians at the study health facility highly adhered to the clinical management guidelines, recommending a malaria test in almost all patients presenting with fever. However, a significant proportion of malaria cases was missed when a test was not recommended. These results highlight the importance of laboratory testing for malaria in all patients who present with fevers and live in endemic setting even when transmission has significantly declined.
Arthroscopy Mini-plate Fixation with the Posterior Trans-septal Portal for Treating Posterior Cruciate Ligament Tibial Avulsion Fractures
Authors: Wang Chunlei , Zhang Haisen , Li Longjie , Chen Si , Liu Chang
Published: December 2020

Background Posterior cruciate ligament (PCL) avulsion fractures are rare and difficult to treat. The present work aimed to examine the effect of an innovative arthroscopy method for the treatment of PCL tibial avulsion fractures using mini-plate reduction and fixation through two tibial tunnels and the posterior trans-septal portal.Methods Totally 19 patients (median age, 33 years; range, 23–43 years) with PCL tibial avulsion fractures who underwent treatment with an arthroscopic suture bridge method were retrospectively assessed. Knee function pre-operation and at last follow up was assessed via Lysholm and Tegner scores. A KT-2000 arthrometer was employed for determining knee stability, the range of motion (ROM), and side-to-side differences. Plain radiography and International Knee Documentation Committee (IKDC) exams were performed for patient evaluation.Results No patient was switched to conventional open surgery due to difficult intraoperative procedures. Mean post-surgical Lysholm and Tegner scores (P < 0.001) were significantly improved in comparison with presurgical values. KT-2000 examination revealed markedly reduced side-to-side differences at last follow-up than observed preoperatively (1.2 ± 0.6 VS. 9.3 ± 2.2; P < 0.001). Radiography at the final follow up revealed solid union at the fracture site in the totality of 19 cases.Conclusions This new arthroscopy mini-plate fixation and posterior trans-septal method for posterior cruciate ligament tibial avulsion fractures resulted in good clinico-radiological outcomes, with adequate stability and fracture site healing. It could be employed to repair avulsion fragments of various sizes.Level of evidence IV
Relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors at the unit level: A correlational study
Authors: Nurmeksela Anu , Mikkonen Santtu , Kinnunen Juha , Kvist Tarja
Published: December 2020

Background Nurse managers play a critical role in enhancing nursing and patient outcomes. A nurse manager’s work, which can be described as a middle-manager at a health care organization, is complex and changes from day to day. Only a few studies have clarified how nurse managers divide their time across various work activities. This study aimed to describe the relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors at the hospital unit level. Methods A cross-sectional and correlational study design was used. The data were collected from nurse managers (n= 29), nursing staff (n=306), and patients (n=651) from 28 units across three Finnish acute care hospitals between April and November in year 2017. In addition, data concerning medication errors over one calendar year (2017) were acquired from the hospitals’ incident reporting register. Analysis of covariance (ANCOVA) was used to estimate relationships between data from subareas of Nurse Managers’ Work Content Questionnaire, Kuopio University Hospital Job Satisfaction Scale, and Revised Humane Caring Scale, along with medication errors reports. Significance level of 95% was used to estimate strength of covariances. Unstandardized coefficients (B) estimates were used to explain the relationship of variables.Results Multiple relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors were identified. Nurse managers’ work activities had both positive and negative relationships on the other studied variables. The Requiring factors of work (p< .001) subarea of nurses’ job satisfaction, total patient satisfaction (p< .001), and medication errors (p< .001) were found to be the variables most significantly affected by other factors.Conclusions The findings suggest that nurse managers should focus on improving nursing practices by managing and organizing nurses’ work in a way that makes their employees feel supported, motivated and secure. Furthemore, nurse managers should adopt a leadership style that emphasizes safe and patient-centered care. The results also suggest that the administration of today’s health care organizations should actively evaluate nurse managers’ share of work activities to ensure that their daily work is in line with the organizational goals.