bluuebunny/crossref_metadata_2025 huggingface dataset:
Indicators for mode of delivery in pregnant women with uteruses scarred by prior caesarean section: a retrospective study of 679 pregnant women
Authors: Hua Zhifen , El Oualja Fadwa
Published: November 2019

Background

The delivery mode for pregnant women with uteruses scarred by prior caesarean section (CS) is a controversial issue, even though the CS rate has risen in the past 20 years. We performed this retrospective study to identify the factors associated with preference for CS or vaginal birth after CS (VBAC).

Methods

Pregnant women (n = 679) with scarred uteruses from Moulay Ali Cherif Provincial Hospital, Rashidiya, Morocco, were enrolled. Gestational age, comorbidity, fetal position, gravidity and parity, abnormal amniotic fluid, macrosomia, placenta previa or abruptio, abnormal fetal presentation, premature rupture of fetal membrane with labor failure, poor progression in delivery, and fetal outcomes were recorded.

Results

Out of 679 pregnant women ≥28 gestational weeks, 351 (51.69%) had a preference for CS. Pregnant women showed preference for CS if they were older (95% CI 1.010–1.097), had higher gestational age (95% CI 1.024–1.286), and a shorter period had passed since the last CS (95% CI 0.842–0.992). Prior gravidity (95% CI 0.638–1.166), parity (95% CI 0.453–1.235), vaginal delivery history (95% CI 0.717–1.818), and birth weight (95% CI 1.000–1.001) did not influence CS preference. In comparison with fetal preference, maternal preference was the prior indicator for CS. Correlation analysis showed that pregnant women with longer intervals since the last CS and history of gravidity, parity, and vaginal delivery showed good progress in the first and second stages of vaginal delivery.

Conclusions

We concluded that maternal and gestational age and interval since the last CS promoted CS preference among pregnant women with scarred uteruses.
Risk factors for placenta accreta spectrum: findings from the Japan environment and Children’s study
Authors:   the Japan Environment and Children’s Study (JECS) Group, Kyozuka Hyo , Yamaguchi Akiko , Suzuki Daisuke , Fujimori Keiya , Hosoya Mitsuaki , Yasumura Seiji , Yokoyama Tadahiko , Sato Akiko , Hashimoto Koichi
Published: November 2019

Background

Placenta accreta spectrum (PAS) is a life-threating complication in the field of obstetrics. Sometimes we face with unexpected PAS cases which is potentially higher maternal mortality and morbidity compared with expected cases. The present study was conducted to examine the prevalence of PAS and to elucidate its risk factors using a large Japanese birth cohort study.

Methods

We reviewed the results of a nationwide prospective birth cohort study in Japan, and identified 90,554 participants treated from 2011 to 2014 in 15 regional centers. Multiple regression models were created to identify the risk factors for PAS. These data were obtained from self-reported questionnaires or patient medical records.

Results

This analysis consisted of 202 cases of PAS (18 with placenta previa and 184 without placenta previa) and 90,352 cases without PAS. The multiple logistic regression analysis showed that placenta previa (adjusted odds ratio [aOR]: 12.86, 95% confidence interval [CI] 7.70–21.45, P < 0.001), assisted reproductive technology-related pregnancies (aOR: 6.78, 95% CI 4.54–10.14, P < 0.001), smoking during pregnancy (aOR: 1.95, 95% CI 1.15–3.31, P = 0.013), more than two previous cesarean sections (aOR: 2.51, 95% CI 1.35–4.67, P = 0.004), and uterine anomalies (aOR: 3.97, 95% CI 1.24–12.68, P = 0.020) increased the risk of PAS.

Conclusion

In general population, placenta previa, assisted reproductive technology-related pregnancy, smoking during pregnancy, repeated cesarean sections, and uterine anomalies were risk factors for PAS in the Japanese population.
Increased risk of lymphoid malignancy in patients with herpes zoster: a longitudinal follow-up study using a national cohort
Authors: Choi Hyo Geun , Zehnder James L. , Lee Young Kyung , Lim Hyun , Kim Miyoung
Published: November 2019

Background

The association between herpes zoster and the risk of lymphoid neoplasms in Asian populations has not yet been established. We performed a longitudinal follow-up study using a nationwide cohort to assess the risk of lymphoid neoplasms arising after herpes zoster infection in the adult Korean population.

Methods

Data from participants ≥20 years of age who were registered in the Korean National Health Insurance Service-National Sample Cohort database between 2002 and 2013 were collected. We extracted the data of participants with herpes zoster (n = 59,495) as well as those of matched references at a ratio of 1:4 (n = 237,980) and investigated the subsequent occurrence of lymphoid neoplasms. A stratified Cox proportional hazards model was used to calculate unadjusted hazard ratios (HRs) as well as those adjusted for the Charlson comorbidity index score.

Results

The rate of lymphoid neoplasms was higher in the herpes zoster group (0.15% [90/59,495]) than in the reference group (0.08% [212/237,980], P < 0.001). The unadjusted and adjusted HRs of herpes zoster in patients with lymphoid neoplasms were 1.68 (95% confidence interval [CI] = 1.31–2.15) and 1.58 (95% CI = 1.23–2.02), respectively (P < 0.001 for both). On subgroup analyses according to age and sex, herpes zoster was associated with an increased risk of lymphoid neoplasms in all subgroups; the adjusted HRs were 1.53 (95% CI = 1.05–2.24) for patients < 60 years old, 1.58 (95% CI = 1.14–2.20) for patients ≥60 years old, 1.64 (95% CI = 1.16–2.31) for men, and 1.51 (95% CI = 1.06–2.16) for women (P < 0.05 for all). On subgroup analysis of lymphoid neoplasm subtypes, herpes zoster was associated with the risk of Hodgkin’s disease (adjusted HR: 3.23 [95% CI = 1.17–8.93]) and multiple myeloma/malignant plasma cell neoplasms (adjusted HR: 2.17 [95% CI = 1.33–3.54]) (P < 0.05 for both).

Conclusion

Herpes zoster is associated with lymphoid neoplasm development in the Korean population irrespective of age and sex. The risks of Hodgkin’s disease and plasma cell neoplasms are significantly elevated in patients with herpes zoster.
Low lean mass and chemotherapy toxicity risk in the elderly: the Fraction study protocol
Authors: Steinmeyer Zara , Gérard Stéphane , Filleron Thomas , Lozano Stéphanie , Brechemier Delphine , Abellan Van Kan Gabor , Mourey Loic , Cristol-Dalstein Laurence , De Decker Laure , Rolland Yves , Balardy Laurent
Published: November 2019

Background

Half of cancer cases occur in patients aged 70 and above. Majority of older patients are eligible for chemotherapy but evidence for treating this population is sparse and severe toxicities affect more than half of them. Determining prognostic biomarkers able to predict poor chemotherapy tolerance remains one of the major issues in geriatric oncology. Ageing is associated with body composition changes (increase of fat mass and loss of lean mass) independently of weight-loss. Previous studies suggest that body composition parameters (particularly muscle mass) may predict poor chemotherapy tolerance. However, studies specifically including older adults on this subject remain sparse and the majority of them study body composition based on computed tomography (CT) scanner (axial L3 section) muscle mass estimation. This method is to date not validated in elderly cancer patients.

Methods

This trial (Fraction) will evaluate the discriminative ability of appendicular lean mass measured by dual-energy X-ray absorptiometry (DXA) to predict severe toxicity incidence in older cancer-patients treated with first-line chemotherapy. DXA is considered the gold standard in body composition assessment in older adults.

Patient’s aged ≥70 diagnosed with solid neoplasms or lymphomas at a locally advanced or metastatic stage treated for first-line chemotherapy were recruited. Patients completed a pre-chemotherapy assessment that recorded socio-demographics, tumor/treatment variables, laboratory test results, geriatric assessment variables (function, comorbidity, cognition, social support and nutritional status), oncological risk scores and body composition with DXA. Appendicular lean mass was standardized using evidence based international criteria. Participants underwent short follow-up geriatric assessments within the first 3 months, 6 months and a year after inclusion. Grade 3 to 5 chemotherapy-related toxicities, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) were assessed at each chemotherapy cycle.

Discussion

The finding that body composition is associated with poor tolerance of chemotherapy could lead to consider these parameters as well as improve current decision-making algorithms when treating older adults.

Trial registration

ClinicalTrials.gov Identifier:NCT02806154registered on October 2016.
A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort
Authors: Carbunaru Samuel , Nettey Oluwarotimi S. , Gogana Pooja , Helenowski Irene B. , Jovanovic Borko , Ruden Maria , Hollowell Courtney M. P. , Sharifi Roohollah , Kittles Rick A. , Schaeffer Edward , Gann Peter , Murphy Adam B.
Published: November 2019

Background

Predictive models that take race into account like the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) and the new Prostate Biopsy Collaborative Group (PBCG) RC have been developed to equitably mitigate the overdiagnosis of prostate specific antigen (PSA) screening. Few studies have compared the performance of both calculators across racial groups.

Methods

From 1485 prospectively recruited participants, 954 men were identified undergoing initial prostate biopsy for abnormal PSA or digital rectal examination in five Chicago hospitals between 2009 and 2014. Discrimination, calibration, and frequency of avoided biopsies were calculated to assess the performance of both risk calculators.

Results

Of 954 participants, 463 (48.5%) were Black, 355 (37.2%) were White, and 136 (14.2%) identified as Other. Biopsy results were as follows: 310 (32.5%) exhibited no cancer, 323 (33.9%) indolent prostate cancer, and 321 (33.6%) clinically significant prostate cancer (csPCa). Differences in area under the curve (AUC)s for the detection of csPCa between PCPT and PBCG were not statistically different across all racial groups. PBCG did not improve calibration plots in Blacks and Others, as it showed higher levels of overprediction at most risk thresholds. PCPT led to an increased number of avoidable biopsies in minorities compared to PBCG at the 30% threshold (68% vs. 28% of all patients) with roughly similar rates of missed csPCa (23% vs. 20%).

Conclusion

Significant improvements were noticed in PBCG’s calibrations and net benefits in Whites compared to PCPT. Since PBCG’s improvements in Blacks are disputable and potentially biases a greater number of low risk Black and Other men towards unnecessary biopsies, PCPT may lead to better biopsy decisions in racial minority groups. Further comparisons of commonly used risk calculators across racial groups is warranted to minimize excessive biopsies and overdiagnosis in ethnic minorities.
The precursor for nerve growth factor (proNGF) is not a serum or biopsy-rinse biomarker for thyroid cancer diagnosis
Authors: Rowe Christopher W. , Faulkner Sam , Paul Jonathan W. , Tolosa Jorge M. , Gedye Craig , Bendinelli Cino , Wynne Katie , McGrath Shaun , Attia John , Smith Roger , Hondermarck Hubert
Published: November 2019

Background

Nerves and neurotrophic growth factors are emerging promoters of cancer growth. The precursor for Nerve Growth Factor (proNGF) is overexpressed in thyroid cancer, but its potential role as a clinical biomarker has not been reported. Here we have examined the value of proNGF as a serum and biopsy-rinse biomarker for thyroid cancer diagnosis.

Methods

Patients presenting for thyroid surgery or biopsy were enrolled in separate cohorts examining serum (n = 204, including 46 cases of thyroid cancer) and biopsy-rinse specimens (n = 188, including 26 cases of thyroid cancer). ProNGF levels in clinical samples were analysed by ELISA. Univariate and multivariate statistical analyses were used to compare proNGF levels with malignancy status and clinicopathological parameters.

Results

ProNGF was not detected in the majority of serum samples (176/204, 86%) and the detection of proNGF was not associated with thyroid cancer diagnosis. In the few cases where proNGF was detected in the serum, thyroidectomy did not affect proNGF concentration, demonstrating that the thyroid was not the source of serum proNGF. Intriguingly, an association between hyperthyroidism and serum proNGF was observed (OR 3.3, 95% CI 1.6–8.7 p = 0.02). In biopsy-rinse, proNGF was detected in 73/188 (39%) cases, with no association between proNGF and thyroid cancer. However, a significant positive association between follicular lesions and biopsy-rinse proNGF was found (OR 3.3, 95% CI 1.2–8.7, p = 0.02).

Conclusions

ProNGF levels in serum and biopsy-rinse are not increased in thyroid cancer and therefore proNGF is not a clinical biomarker for this condition.
Modeling patients’ time, travel, and monitoring costs in anticoagulation management: societal savings achievable with the shift from warfarin to direct oral anticoagulants
Authors: Leminen Aapeli , Pyykönen Mikko , Tynkkynen Juho , Tykkyläinen Markku , Laatikainen Tiina
Published: November 2019

Background

Anticoagulation therapy is used for atrial fibrillation (AF) patients for reducing the risk of cardioembolic complications such as stroke. The previously recommended anticoagulant, warfarin, has a narrow therapeutic window, and it requires regular laboratory monitoring, unlike direct oral anticoagulants (DOAC). From a societal perspective, it is important to measure time and travel costs associated with warfarin monitoring to better compare the total therapy costs of these two alternative forms of anticoagulation management. In this study we design a georeferenced cost model to investigate societal savings achievable with the shift from warfarin to DOACs in the study region of North Karelia in Eastern Finland.

Methods

Individual-level patient data of 6519 AF patients was obtained from the regional patient database. Patients’ geocoded home addresses and other GIS data were used to perform a network analysis for the optimal routes for warfarin monitoring visits. These measures of revealed accessibility were then used in the cost model to measure monetary time and travel costs in addition to direct healthcare costs of anticoagulation management.

Results

The share of time and travel costs in warfarin monitoring is 26.6% of the total therapy costs in our study region. With current drug retail prices in Finland, the societal expense of anticoagulation management is only 2.6% higher with DOACs than in the baseline with warfarin. However, when 25% lower distributor’s prices are used, the total societal cost decreases by 13.6% with DOACs.

Conclusions

Our results indicate that patients’ time and travel costs critically increase the societal cost of warfarin therapy; and despite the higher price of DOACs, they are already cost-efficient alternatives to warfarin in anticoagulation management. In the future, the cost of AF complications should be included in the cost comparison between warfarin and DOACs. Our modeling approach applies to different geographical regions and to different healthcare processes requiring patient monitoring.
Return of genetic and genomic research findings: experience of a pediatric biorepository
Authors: Papaz Tanya , Liston Eriskay , Zahavich Laura , Stavropoulos Dimitri J. , Jobling Rebekah K. , Kim Raymond H. , Reuter Miriam , Miron Anastasia , Oechslin Erwin , Mondal Tapas , Bergin Lynn , Smythe John F. , Altamirano-Diaz Luis , Lougheed Jane , Yao Roderick , Akinrinade Oyediran , Breckpot Jeroen , Mital Seema
Published: November 2019

Background

Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants.

Methods

Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed.

Results

Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included.

Conclusions

Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.
The Latin American version of the internalized stigma of mental illness scale (LA-ISMI): a multicentric validation study from three Latin American countries
Authors: Caqueo-Urízar Alejandra , Urzúa Alfonso , Loundon Anderson , Boucekine Mohamed , Fond Guillaume , Boyer Laurent
Published: November 2019

Background

To date, no data have been available concerning the psychometric characteristics of the Internalized Stigma of Mental Illness scale (ISMI-29) in Latin American countries. The aim of this study was to validate a Latin American version of the ISMI in people with schizophrenia.

Methods

The study included 253 stabilized outpatients with schizophrenia from 3 Mental Health Services in three Latin American countries: Bolivia (N = 83), Chile (N = 85) and Peru (N = 85). We analyzed the psychometric properties using item response and classical test theories. An item reduction was then performed to improve the psychometric properties of the ISMI-29. The final version of the ISMI was tested for construct validity, reliability, external validity and differential item functioning (DIF).

Results

The five-factor structure of the ISMI-29 was not confirmed using confirmatory factor analysis (RMSEA = 0.12, CFI = 0.77, and WRMR = 2.20). Seventeen items were discarded to obtain a satisfactory psychometric version. The ISMI-12 evaluates 3 dimensions: social stigma (4 items), stigma experience (4), and self-stigma (3). The factor structure accounted for 68% of the total variance. Internal consistency was satisfactory. The scalability was satisfactory, with INFIT statistics within an acceptable range. In addition, the results confirmed the absence of DIF and supported the invariance of the item calibrations between countries.

Conclusion

The ISMI-29 is not valid in our sample and should not be used in Latin American countries. The ISMI-12 is the first internalized stigma questionnaire with satisfactory psychometric properties available in Latin American countries. Its brevity could facilitate its dissemination and use in clinical settings.
Implementation of government-directed policy in the hospital setting: a modified Delphi study
Authors: Havers S. M. , Martin E. , Wilson A. , Hall L.
Published: November 2019

Background

In the last 20 years governments have sought to introduce policy that improves the quality of care provided in hospitals, yet little research has been done to understand how these policies are implemented, factors that affect the implementation process or what should be considered by decision-makers during policy development or implementation planning. Experts with real-life experience in the introduction and implementation of policy are best placed to provide valuable insight into practical issues that affect implementation and the associated outcomes of these policies.

Methods

A modified Delphi study of experts in hospital policy development and implementation was undertaken to investigate factors influencing the implementation of government-directed policy in the hospital setting. This study built on the findings of two previous studies — a qualitative study of clinician perspectives of policy implementation and a systematic review and meta-synthesis, in which common contextual factors and policy characteristics associated with policy implementation were ascertained. International experts with extensive experience in government-directed policy implementation at global, national, corporate, jurisdictional and organisational levels were asked to provide opinions on predetermined factors and the feasibility of considering these in policy development and implementation planning. Survey design and analysis was guided by the Consolidated Framework for Implementation Research.

Results

Eleven experts from four countries and with different health system perspectives participated in the study. Consensus was reached on the importance of all predetermined factors in the first survey round with additional factors for investigation highlighted by participants for examination in subsequent rounds. On study completion, expert consensus was reached on 24 factors of importance; only 20 of these factors reached consensus for feasibility.

Conclusions

Study findings indicated that, whilst there are multiple factors of importance in policy implementation across all Consolidated Framework for Implementation Research domains, some factors, such as establishment of roles and responsibilities for implementation and organisational lines of accountability, are feasible for consideration at a hospital level only. In addition, four factors did not reach consensus in terms of feasibility, indicating that it may not be practical to consider all factors of importance when implementing policy; this has important implications for implementation planning and resource allocation.
Molecular and computational analysis of 45 samples with a serologic weak D phenotype detected among 132,479 blood donors in northeast China
Authors: Zhang Xu , Li Guiji , Zhou Zhuren , Shao Chaopeng , Huang Xuying , Li Lichun , Li Xiaofeng , Liu Ying , Fan Hua , Li Jianping
Published: November 2019

Background

RH1 is one of the most clinically important blood group antigens in the field of transfusion and in the prevention of fetal incompatibility. The molecular analysis and characterization of serologic weak D phenotypes is essential to ensuring transfusion safety.

Methods

Blood samples from a northeastern Chinese population were randomly screened for a serologic weak D phenotype. The nucleotide sequences of all 10 exons, adjacent flanking intronic regions, and partial 5′ and 3′ untranslated regions (UTRs) were detected for RHD genes. Predicted deleterious structural changes in missense mutations of serologicl weak D phenotypes were analyzed using SIFT, PROVEAN and PolyPhen2 software. The protein structure of serologic weak D phenotypes was predicted using Swiss-PdbViewer 4.0.1.

Results

A serologic weak D phenotype was found in 45 individuals (0.03%) among 132,479 blood donors. Seventeen distinct RHD mutation alleles were detected, with 11 weak D, four partial D and two DEL alleles. Further analyses resulted in the identification of two novel alleles (RHD weak D 1102A and 399C). The prediction of a three-dimensional structure showed that the protein conformation was disrupted in 16 serologic weak D phenotypes.

Conclusions

Two novel and 15 rare RHD alleles were identified. Weak D type 15, DVI Type 3, and RHD1227A were the most prevalent D variant alleles in a northeastern Chinese population. Although the frequencies of the D variant alleles presented herein were low, their phenotypic and genotypic descriptions add to the repertoire of reported RHD alleles. Bioinformatics analysis on RhD protein can give us more interpretation of missense variants of RHD gene.
Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice
Authors: Wang Chao , Zhang Lu , Ndong Jean De La Croix , Hettinghouse Aubryanna , Sun Guodong , Chen Changhong , Zhang Chen , Liu Ronghan , Liu Chuan-ju
Published: November 2019

Purpose

Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI.

Methods

PGRN-deficient (Gr−/−) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique. Local PGRN expression following injury was evaluated by Western blotting and immunofluorescence. Basso Mouse Scale (BMS), inclined grid walking test, and inclined plane test were conducted at indicated time points to assess neurological recovery. Inflammation and apoptosis were examined by histology (Hematoxylin and Eosin (H&E) staining and Nissl staining, TUNEL assays, and immunofluorescence), Western blotting (from whole tissue protein for iNOS/p-p65/Bax/Bcl-2), and ex vivo ELISA (for TNFα/IL-1β/IL-6/IL-10). To identify the prophylactic and therapeutic potential of targeting PGRN, a PGRN derived small protein, Atsttrin, was conjugated to PLGA-PEG-PLGA thermosensitive hydrogel and injected into intrathecal space prior to SCI. BMS was recorded for neurological recovery and Western blotting was applied to detect the inflammatory and apoptotic proteins.

Results

After SCI, PGRN was highly expressed in activated macrophage/microglia and peaked at day 7 post-injury.Grn−/−mice showed a delayed neurological recovery after SCI at day 21, 28, 35, and 42 post-injury relative to WT controls. Histology, TUNEL assay, immunofluorescence, Western blotting, and ELISA all indicated thatGrn−/−mice manifested uncontrolled and expanded inflammation and apoptosis. Administration of control-released Atsttrin could improve the neurological recovery and the pro-inflammatory/pro-apoptotic effect of PGRN deficiency.

Conclusion

PGRN deficiency exacerbates SCI by promoting neuroinflammation and cellular apoptosis, which can be alleviated by Atsttrin. Collectively, our data provide novel evidence of using PGRN derivatives as a promising therapeutic approach to improve the functional recovery for patients with spinal cord injury.
Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis
Authors: Zhou Ruixi , Yang Xiaoyan , Li Xihong , Qu Yi , Huang Qun , Sun Xuemei , Mu Dezhi
Published: November 2019

Background

Sepsis is a critical disease associated with extremely high mortality. Some severe forms of sepsis can induce brain injury, thus causing behavioral and cognitive dysfunction. Pyroptosis is a type of cell death that differs from apoptosis and plays an important role in the occurrence and development of infectious diseases, nervous system-related diseases. A recent study has found that there is pyroptosis in the hippocampus of sepsis-induced brain injury, but its mechanism and treatment scheme have not been evaluated.

Methods

We established immediately a septic rat model by cecal ligation and perforation (CLP) after administration with recombinant club cell protein (rCC16) and/or U46619 in different groups. The clinical performance, survival percentage, vital signs, and neurobehavioral scores were monitored at different time points. Cortical pathological changes were also examined. The expression of cortical nucleotide-binding domain leucine-rich repeat-containing pyrin domain-containing 3 (NLRP3), caspase-1, (p)-p38 mitogen-activated protein kinase (MAPK), and (p)-extracellular signal-related kinase (ERK) was detected by western blotting and immunofluorescence analysis. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha in the cortical supernatant were detected by enzyme-linked immunosorbent assay.

Results

Compared with the sham group, the clinical performance, survival percentage, vital signs, and severe cortical pathological changes in the CLP group were worse; NLRP3, caspase-1, and inflammatory factor levels were increased; and phosphorylation of p38 MAPK and ERK was also increased. Meanwhile, multiple indicators were deteriorated further after administration of U46619 in CLP rats. The clinical performance of CLP rats, however, was better after rCC16 administration; cortical pathological changes were attenuated; and NLRP3, caspase-1, and inflammatory factor levels and the phosphorylation of signaling pathway proteins (p38 MAPK and ERK) were reduced. Interestingly, the CLP rats showed the opposite changes in all indicators after administration with both rCC16 and U46619 when compared with those administered rCC16 alone.

Conclusions

In sepsis, rCC16 inhibits cortical pyroptosis through p38 MAPK and ERK signaling pathways. Meanwhile, rCC16 has a protective effect on newborn rats with sepsis, but it is not clear whether its mechanism is directly related to pyroptosis.
HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia
Authors: Berggrund Malin , Gustavsson Inger , Aarnio Riina , Hedlund-Lindberg Julia , Sanner Karin , Wikström Ingrid , Enroth Stefan , Olovsson Matts , Gyllensten Ulf
Published: November 2019

Objective

This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

Methods

We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3–6 months later and were included in the present study.

Results

Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + .

Conclusions

The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.
Comparison of four nanoparticle monitoring instruments relevant for occupational hygiene applications
Authors: Jørgensen Rikke Bramming
Published: November 2019

Background

The aim of this study is to make a comparison of a new small sized nanoparticle monitoring instrument, Nanoscan  SMPS, with more traditional large size instruments, known to be precise and accurate [Scanning Mobility Particle Sampler (SMPS) and Fast Mobility Particle Sizer (FMPS)], and with an older small size instrument with bulk measurements of 10–1000 nm particles (CPC3007). The comparisons are made during simulated exposure scenarios relevant to occupational hygiene studies.

Methods

Four scenarios were investigated: metal inert gas (MIG) welding, polyvinyl chloride (PVC) welding, cooking, and candle-burning. Ratios between results are compaed and Pearsson correlations analysis was performed.

Results

The highest correlation between the results is found between Nanoscan and SMPS, with Pearsson correlation coefficients above 0.9 for all scenarios. However, Nanoscan tended to overestimate the results from the SMPS; the ratio between the UFP concentrations vary between 1.44 and 2.01, and ratios of total concentrations between 1.18 and 2.33. CPC 3007 did not show comparable results with the remaining instruments.

Conclusion

Based on the results of this study, the choice of measurement equipment may be crucial when evaluating measurement results against a reference value or a limit value for nanoparticle exposure. This stresses the need for method development, standardisation, and harmonisation of particle sampling protocols before reference values are introduced. Until this is established, the SMPS instruments are the most reliable for quantification of the concentrations of UFP, but in a more practical occupational hygiene context, the Nanoscan SMPS should be further tested.
IARC 2019: “Night shift work” is probably carcinogenic: What about disturbed chronobiology in all walks of life?
Authors: Erren Thomas C. , Morfeld Peter , Groß J. Valérie , Wild Ursula , Lewis Philip
Published: November 2019

In June of 2019, a working group convened by the International Agency for Research on Cancer [IARC] concluded that “night shift work” is probably carcinogenic to humans (a Group 2A carcinogen). This was based on sufficient evidence of cancer and strong mechanistic evidence in experimental animals and limited evidence from human epidemiological studies. The biological basis from experimental work is clear and compelling: Disturbed chronobiology such as due to alterations in the light-dark schedule which shift-workers experience is associated with carcinogenicity. But is it correct to assume in epidemiological studies that “night shift work” provides the same dose of disturbed chronobiology to all night workers and that disturbed chronobiology from activities outside of work does not count? Both chronobiological theory and supporting evidence suggest that much-needed future epidemiology should address these questions and should consider disturbed chronobiology in all walks of life.
Can a multicomponent multidisciplinary implementation package change physicians’ and nurses’ perceptions and practices regarding thrombolysis for acute ischemic stroke? An exploratory analysis of a cluster-randomized trial
Authors: Hasnain Md Golam , Levi Christopher R. , Ryan Annika , Hubbard Isobel J. , Hall Alix , Oldmeadow Christopher , Grady Alice , Jayakody Amanda , Attia John R. , Paul Christine L.
Published: November 2019

Background

The Thrombolysis ImPlementation in Stroke (TIPS) trial tested the effect of a multicomponent, multidisciplinary, collaborative intervention designed to increase the rates of intravenous thrombolysis via a cluster randomized controlled trial at 20 Australian hospitals (ten intervention, ten control). This sub-study investigated changes in self-reported perceptions and practices of physicians and nurses working in acute stroke care at the participating hospitals.

Methods

A survey with 74 statements was administered during the pre- and post-intervention periods to staff at 19 of the 20 hospitals. An exploratory factor analysis identified the structure of the survey items and linear mixed modeling was applied to the final survey domain scores to explore the differences between groups over time.

Result

The response rate was 45% for both the pre- (503 out of 1127 eligible staff from 19 hospitals) and post-intervention (414 out of 919 eligible staff from 18 hospitals) period. Four survey domains were identified: (1) hospital performance indicators, feedback, and training; (2) personal perceptions about thrombolysis evidence and implementation; (3) personal stroke skills and hospital stroke care policies; and (4) emergency and ambulance procedures. There was a significant pre- to post-intervention mean increase (0.21 95% CI 0.09; 0.34; p < 0.01) in scores relating to hospital performance indicators, feedback, and training; for the intervention hospitals compared to control hospitals. There was a corresponding increase in mean scores regarding perceptions about the thrombolysis evidence and implementation (0.21, 95% CI 0.06; 0.36; p < 0.05). Sub-group analysis indicated that the improvements were restricted to nurses’ responses.

Conclusion

TIPS resulted in changes in some aspects of nurses’ perceptions relating to the evidence for intravenous thrombolysis and its implementation and hospital performance indicators, feedback, and training. However, there is a need to explore further strategies for influencing the views of physicians given limited statistical power in the physician sample.

Trial registration

ACTRN12613000939796, UTN: U1111–1145-6762.
Targeting adaptability to improve Medication Therapy Management (MTM) implementation in community pharmacy
Authors: Hohmeier Kenneth C. , Wheeler James S. , Turner Kea , Vick Jarrod S. , Marchetti Merrill L. , Crain Jeremy , Brookhart Andrea
Published: November 2019

Objectives

(1) To develop an adaptation framework for MTM delivery for pharmacists (the MTM Adaptability Framework), (2) to examine the impact of an educational intervention informed by the MTM Adaptability Framework on MTM completion rates over a 2-year period, and (3) to explore pharmacists’ perceptions regarding knowledge and beliefs about MTM and MTM implementation self-efficacy pre- and post-intervention.

Methods

This study is a prospective, mixed-methods research study including a quasi-experimental, one-group pretest-posttest quantitative study with a sequential explanatory qualitative study arm featuring semi-structured key informant interviews. US supermarket pharmacy chain setting included 93 community pharmacy sites located in Tennessee, Kentucky, and Alabama. MTM completion rates are reported as percentage of completed comprehensive medication reviews (CMRs) and targeted medication reviews (TMRs) and pharmacist perceptions.

Results

An 11.4% absolute increase in MTM completion rates was seen after the educational intervention targeting adaptation of MTM in the community pharmacy setting. This was found to be significant (46.92% vs. 58.3%;p< 0.001). Responses to the semi-structured interviews were mapped against CFIR and included themes: “knowledge and beliefs about MTM (pre-intervention),” “self-efficacy for MTM implementation (pre-intervention),” “knowledge and beliefs about MTM (post-intervention),” and “self-efficacy for MTM implementation (post-intervention).” Data convergence was found across these methodologies and suggested that targeting adaptability of MTM delivery increases MTM completion rates (quantitative data) and positively changes perceptions of MTM feasibility and self-efficacy (interviews).

Conclusion

The use of an educational intervention about adaptation of MTM to influence adaptation of MTM to a chain community pharmacy setting part of an implementation strategy improved MTM completion rates significantly. Future research should investigate combined implementation strategies and their impact on MTM implementation success.
Effect of sIL-13Rα2-Fc on the progression of rat tail intervertebral disc degeneration
Authors: Wang Xin , Sun Junhao , Tan Jianshi , Fang Pengzhong , Chen Jinlei , Yuan Wen , Chen Huajiang , Liu Yang
Published: November 2019

Background

The incidence of degenerative disc disease caused by intervertebral disc injury is increasing annually, seriously affecting the quality of life of patients and increasing the disease burden on society. The mechanisms of intervertebral disc degeneration include changes in extracellular matrix (ECM) deposition and tissue fibrosis. sIL-13Rα2-Fc potently inhibits interleukin (IL)-13, as well as blocks related cell signaling pathways and inhibits fibrosis in certain tissues. However, it is unknown whether sIL-13Rα2-Fc inhibits fibrosis in injured intervertebral discs and slows the process of degeneration. We hypothesized that sIL-13Rα2-Fc delays the progression of intervertebral disc degeneration by inhibiting intervertebral disc fibrosis and improving ECM deposition.

Methods

A rat tail intervertebral disc degeneration model was established. Pathological changes in rat intervertebral disc tissue were observed by hematoxylin and eosin staining and Masson staining. Glycosaminoglycan (GAG), chondroitin sulfate (CS), keratan sulfate (KS), and hyaluronic acid (HA) contents were quantitatively analyzed by enzyme-linked immunosorbent assay. Type I and type II collagen expression levels were analyzed by reverse transcription-PCR and western blotting.

Results

Hematoxylin and eosin staining and Masson staining revealed annulus fibrosus rupture, disordered arrangement, decreased nucleus pulposus tissue, and decreased collagen fiber in the rat intervertebral disc tissue. Following treatment with sIL-13Rα2-Fc, pathological changes in the rat intervertebral disc were reduced. Rat intervertebral disc tissue showed decreased GAG, CS-KS, and (HA) contents, increased type I collagen levels, and decreased type II collagen levels in degenerated intervertebral discs. sIL-13Rα2-Fc intervention increased the contents of GAG, CS, KS, and HA; inhibited the expression of type I collagen; and promoted the expression of type II collagen.

Conclusion

These results demonstrate that intervertebral disc degeneration is associated with tissue fibrosis. sIL-13Rα2-Fc can regulate type I and type II collagen expression levels by increasing GAG, CS, KS, and HA contents, thereby slowing the progression of intervertebral disc degeneration.
Comparison of ceramic-on-ceramic bearing vs ceramic-on-highly cross-linked polyethylene-bearing surfaces in total hip arthroplasty for avascular necrosis of femoral head: a prospective cohort study with a mid-term follow-up
Authors: Feng Bin , Ren Yi , Cao Shiliang , Lin Jin , Jin Jin , Qian Wenwei , Weng Xisheng
Published: November 2019

Background

The ideal bearing surface for patients of avascular necrosis (AVN) undergoing total hip arthroplasty (THA) remains controversial. The purpose of this study is to evaluate the clinical outcomes, health-related quality of life (HRQL), and wear of the bearing surface between ceramic-on-ceramic (CoC) and ceramic-on-highly cross-linked polyethylene (CoXPE) THA for patients of AVN after midterm follow-up.

Methods

We performed a retrospective case-control analysis of 93 CoC and 77 CoXPE consecutive THAs for patients of AVN. The cases were followed at a minimum 5 years follow-up (average 7 years). Harris hip score (HHS) score and bearing-related complications were assessed. The health-related quality of life (HRQL) was assessed with the Short Form 36 (SF-36). Plain radiographs and computed tomography (CT) were used for radiographic evaluation.

Results

Both the CoC group and CoXPE group showed statistically significant improvements in HHS scores with no difference between the two bearing surfaces. There was no significant difference as for SF-36 at the latest follow-up between two groups, except for significant higher scores in the dimensions of general health in the CoC group (75.7 vs 64.7, P = 0.032). No radiographic evidence of osteolysis and loosening was present at the final follow-up. The mean wear rate of the CoC was 0.0096 mm/year and the CoXPE was 0.047 mm/year after evaluation with reconstructed CT.

Conclusions

CoC THAs acts as well as CoXPE THAs for patients with femoral head avascular necrosis after midterm follow-up. CoC bearing can significantly decrease the wearing rate than CoXPE bearing.
Repair of a type B aortic dissection with a re-vascularization of the aberrant right subclavian artery in an adult patient
Authors: Abuharb Mahmoud Yousef Ibrahim , Ming Bian Xiao , Jian He
Published: November 2019

Background

An aberrant right subclavian artery which arises from the proximal descending aorta may result in aortic dissection. The dissection may occur at either the site of the primary intimal tear or from an aortic branch. These conditions may lead to blood flow limitation and possible aneurysmal degeneration in the future.

Case presentation

We described the clinical presentation and management of a 54-year old patient diagnosed with a rare case of an aberrant right subclavian artery with Stanford Type B aortic dissection. A hybrid surgical approach was successfully performed and the patient had an uneventful recovery.

Conclusion

Even though aortic dissection is often an incidental finding, this case highlighted that in rare situations, it can be associated with an aberrant right subclavian artery. It is important to disseminate this association as it has profound diagnostic and therapeutic implications in safeguarding the clinical outcomes of patients with such condition.
Autophagy protein NRBF2 has reduced expression in Alzheimer’s brains and modulates memory and amyloid-beta homeostasis in mice
Authors: Lachance Véronik , Wang Qian , Sweet Eric , Choi Insup , Cai Cui-Zan , Zhuang Xu-Xu , Zhang Yuanxi , Jiang Jessica Li , Blitzer Robert D. , Bozdagi-Gunal Ozlem , Zhang Bin , Lu Jia-Hong , Yue Zhenyu
Published: November 2019

Background

Dysfunctional autophagy is implicated in Alzheimer’s Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity of the changes confounds the role of autophagy in AD.

Methods

To further understand the autophagy alteration in AD brains, we analyzed transcriptomic (RNAseq) datasets of several brain regions (BA10, BA22, BA36 and BA44 in 223 patients compared to 59 healthy controls) and measured the expression of 130 ATGs. We used autophagy-deficient mouse models to assess the impact of the identified ATGs depletion on memory, autophagic activity and amyloid-β (Aβ) production.

Results

We observed significant downregulation of multiple components of two autophagy kinase complexes BECN1-PIK3C3 and ULK1/2-FIP200 specifically in the parahippocampal gyrus (BA36). Most importantly, we demonstrated that deletion of NRBF2, a component of the BECN1-PIK3C3 complex, which also associates with ULK1/2-FIP200 complex, impairs memory in mice, alters long-term potentiation (LTP), reduces autophagy in mouse hippocampus, and promotes Aβ accumulation. Furthermore, AAV-mediated NRBF2 overexpression in the hippocampus not only rescues the impaired autophagy and memory deficits in NRBF2-depleted mice, but also reduces β-amyloid levels and improves memory in an AD mouse model.

Conclusions

Our data not only implicates NRBF2 deficiency as a risk factor for cognitive impairment associated with AD, but also support the idea of NRBF2 as a potential therapeutic target for AD.
Directed evolution of the PcaV allosteric transcription factor to generate a biosensor for aromatic aldehydes
Authors: F. M. Machado Leopoldo , Currin Andrew , Dixon Neil
Published: November 2019

Background

Transcription factor-based biosensors are useful tools for the detection of metabolites and industrially valuable molecules, and present many potential applications in biotechnology and biomedicine. However, the most common approach to develop biosensors relies on employing a limited set of naturally occurring allosteric transcription factors (aTFs). Therefore, altering the ligand specificity of aTFs towards the detection of new effectors is an important goal.

Results

Here, the PcaV repressor, a member of the MarR aTF family, was used to develop a biosensor for the detection of hydroxyl-substituted benzoic acids, including protocatechuic acid (PCA). The PCA biosensor was further subjected to directed evolution to alter its ligand specificity towards vanillin and other closely related aromatic aldehydes, to generate the Van2 biosensor. Ligand recognition of Van2 was explored in vitro using a range of biochemical and biophysical analyses, and extensive in vivo genetic-phenotypic analysis was performed to determine the role of each amino acid change upon biosensor performance.

Conclusions

This is the first study to report directed evolution of a member of the MarR aTF family, and demonstrates the plasticity of the PCA biosensor by altering its ligand specificity to generate a biosensor for aromatic aldehydes.