bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the impact of a new central venous access device training progam for nurses: A quasi-experimental evaluation study
Authors: Burt Wendy , Spowart Lucy
Published: January 2021

Background:

Central venous access devices (CVAD) are widely used for both long- and short-term purposes within healthcare and are suitable for both hospital and community management. Training is essential in the prevention of complications such as infection.

Objectives:

To assess the impact of a new standardised education programme on clinical practice and patient care. The new education programme was introduced to all registered nurses working in one care group within an acute healthcare Trust with the aim of improving knowledge and skills and reduce CVAD-related complications.

Methods:

This retrospective quasi-experimental evaluation study analyses the impact of the programme on direct patient care. Secondary data sources such as infection incidence rates and CVAD clinical audits were used to identify and measure the relationship between staff confidence, infection incidence and care audit results. Data spanning a two-year period were used to capture an accurate representation of the patient group.

Results:

Improvements in audited care elements and a reduction of infection incidences were evident during and after implementation of the education programme. This was reflective of the self-reported increased confidence and knowledge and skill acquisition from staff who attended the programme.

Discussion:

Recommendations have been made including a review of the education content to target all key elements and promotion of an end goal with regular feedback to staff reinforcing the importance. The challenge of using secondary data sources also highlighted the need for quality improvements in the current care audit process.
What Is Creativity in Education? A Qualitative Study of International Curricula
Authors: Patston Timothy J. , Kaufman James C. , Cropley Arthur J. , Marrone Rebecca
Published: January 2021

The concept of “creativity” as a desirable attribute within education is long-standing. The fields of education and creativity have developed, and periodically intersected with, government reports, policies, commentaries, and advice. Recently, an increasing number of countries have emphasized creativity in their official curricula. However, the journey from openly acknowledging the importance of creativity to systematically and purposefully supporting its promotion in the classroom is a long one. The research reported in this article focuses on what might be regarded as the first step in this journey: school curriculum. This article analyzes curricula in 12 countries and asks three key questions: if and how creativity is defined, where is it placed in the curriculum, and what concrete advice is provided for teachers? Despite widespread interest and a productive field of research in creativity, our examination reveals little support for teachers to turn policy into practice.
The Stress of Motherhood and Intimate Partner Violence During Emerging Adulthood
Authors: Nash Sue P. , Sevareid Eric E. , Longmore Monica A. , Manning Wendy D. , Giordano Peggy C.
Published: January 2021

Intimate partner violence is a serious social and public health problem for women. Researchers have shown the context in which intimate partner violence occurs matters, yet, prior work has not examined specifically whether motherhood, and the relationship context of motherhood, are associated with physical violence. Drawing on the Toledo Adolescent Relationships Study (TARS) (n = 492), and the stress process framework, we compared emerging adult mothers’ (mothers with one child and mothers with multiple children) and non-mothers’ reports of physical violence. Using negative binomial regression models, we found that mothers with multiple children compared with nonmothers reported more instances of relationship violence. We also found women in dating relationships with one child compared to non-mothers reported substantially more physical violence. These findings underscore the nature of stress and motherhood during emerging adulthood and the need for intervention strategies that target new mothers.
Estrogen-related receptors: novel potential regulators of osteoarthritis pathogenesis
Authors: Tang Jinshuo , Liu Tong , Wen Xinggui , Zhou Zhongsheng , Yan Jingtong , Gao Jianpeng , Zuo Jianlin
Published: January 2021

Osteoarthritis (OA) is a chronic inflammatory disease that is associated with articular cartilage destruction, subchondral bone alterations, synovitis, and even joint deformity and the loss of joint function. Although current basic research on the pathogenesis of OA has made remarkable progress, our understanding of this disease still needs to be further improved. Recent studies have shown that the estrogen-related receptor (ERR) family members ERRα and ERRγ may play significant roles in the pathogenesis of OA. In this review, we refer to the latest research on ERRs and the pathogenesis of OA, elucidate the structure and physiopathological functions of the ERR orphan nuclear receptor family, and systematically examine the relationship between ERRs and OA at the molecular level. Moreover, we also discuss and predict the capacity of ERRs as potential targets in the clinical treatment of OA.
Relationships between inappropriate eating habits and problematic alcohol use, cigarette and waterpipe dependence among male adolescents in Lebanon
Authors: Berro Jana , Akel Marwan , Hallit Souheil , Obeid Sahar
Published: January 2021

Background

it is important to investigate the relationship between disordered eating in male adolescents and smoking and alcohol consumption as they are risk factors to other diseases as well. For example, high levels of alcohol accompanied by the acidic damage and nutritional deficit exhibited in people with disordered eating habits - due to induced vomiting - has been shown to increase risk of esophageal cancer. Considering the very few studies done on disordered eating prevailing in males and the prevalence of smoking and drinking habits, our study aims to investigate the correlation between inappropriate eating habits and one’s dependence on cigarettes, waterpipes, and alcohol all the while focusing on male adolescents.

Methods

This was a cross-sectional observational study that enrolled 389 male students (13–17 years of age) drawn from five Lebanese schools between October and December 2019.

Results

The MANCOVA analysis was performed taking the addiction scales as the dependent variables and the EAT-26 score as an independent variable, adjusting for the covariates (age, BMI and household crowding index). Higher EAT-26 scores (more inappropriate eating attitudes) were significantly associated with higher waterpipe dependence (B = 0.11; CI 0.06–0.17) and more problematic alcohol use (B = 0.08; CI 0.04–0.12), but not cigarette dependence.

Conclusions

This study revealed an association between inappropriate eating and increased drinking and smoking the waterpipe, but not cigarettes. The manifestation of inappropriate eating habits was found to be significant among male adolescents; in the literature, this is also true for female adolescents. In Lebanon, the engagement of adolescents in alcohol drinking and waterpipe smoking is frequent as they are accessible due to the lack of law enforcement and supervision in the country. In addition, while this study found an association between inappropriate eating habits and dependency on smoking and drinking, further investigation should be done on the role of one’s psychology in their exhibition of disordered eating as means to prevent the manifestation of these habits.
Analysing the effectiveness of topical bleeding care following tooth extraction in patients receiving dual antiplatelet therapy-retrospective observational study
Authors: Lewandowski Bogumił , Myszka Aleksander , Migut Małgorzata , Czenczek-Lewandowska Ewelina , Brodowski Robert
Published: January 2021

Background

Patients using antiplatelet drugs following infarctions, acute coronary syndrome or stroke pose a significant clinical problem if it is necessary to perform surgery, including dental surgery, since they are at risk of prolonged or secondary post-extraction bleeding. Discontinuation of this therapy is associated with a high risk of serious thromboembolic complications. The purpose of this study was to assess the effectiveness of TachoSil fibrin-collagen patches in stopping and preventing of secondary post-extraction bleeding in patients undergoing chronic antiplatelet therapy.

Methods

The study was conducted through retrospective examination of the medical records of 153 patients using chronic antiplatelet therapy and those qualified for tooth extraction. The largest group comprised 74 patients using aspirin and clopidogrel as dual platelet antiaggregation therapy; in this group 75 tooth extractions were carried out. In all of the patients TachoSil fibrin-collagen patches and stiches were applied to the wounds resulting from tooth removal.

Results

Following tooth extraction, primary bleeding was stopped in all the patients and their wounds closed via coagulation within 20–30 min. In eight cases, accounting for 4.9% of the patients, secondary bleeding occurred and was successfully stopped only by applying a pressure dressing soaked in tranexamic acid. Secondary bleeding occurred in three patients on the second day and in five patients on the third day following tooth removal.

Conclusion

Topical application of TachoSil patches following tooth removal in patients using single or dual antiplatelet therapy effectively stopped bleeding and prevented secondary bleeding after tooth extraction.
Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p
Authors: Liu Jianhui , Zhu Shaoliang , Tang Wei , Huang Qinghua , Mei Yan , Yang Huawei
Published: January 2021

Background

Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM.

Methods

Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA.

Results

Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM.

Conclusions

Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.
Triple threat: pancreatic cystic lesion presenting with spontaneous hemorrhage is found to harbor three distinct neoplasms
Authors: Cha Da Eun , Horn Callie , Passeri Michael
Published: January 2021

Background

Pancreatic serous cystadenoma (SCA) is a benign, cystic lesion with an indolent growth pattern. Complications such as spontaneous hemorrhage or malignant transformation from SCA are extremely rare. Our case report describes an unusual presentation of a patient with a previously diagnosed SCA, made unique by the presence of three separate neoplasms in the final specimen.

Case presentation

A 74-year-old male with a previous diagnosis of SCA presented emergently with epigastric pain and non-bilious vomiting. Laboratory results were notable for a hemoglobin of 8.3 g/dl. CT scan of the abdomen demonstrated a complex, solid-cystic mass in the pancreatic head with a large hematoma and questionable focus of active hemorrhage. Surgical resection was recommended due to the risk of malignancy, possibility of re-bleeding, and symptoms of severe duodenal compression. Pancreaticoduodenectomy was performed, and final pathology demonstrated three separate neoplasms: serous cystadenoma, intraductal papillary mucinous neoplasm, and neuroendocrine tumor.

Conclusion

While pancreatic SCA are benign tumors that can be observed safely in the majority of cases, surgical intervention is often indicated in patients with large, symptomatic cysts or when diagnosis is unclear. When undergoing surveillance, it is crucial for both the patient and the care team to be aware of the possibility of rare, but life-threatening complications, such as hemorrhage. Likewise, the possibility of misdiagnosis or concurrent neoplasia should be considered.
Alteration of transthyretin and thyroxine-binding globulin in major depressive disorder: multiple reaction monitoring-based proteomic analysis
Authors: Woo Hye In , Park Jisook , Lim Shinn-Won , Kim Doh Kwan , Lee Soo-Youn
Published: January 2021

Background

Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.

Methods

A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine).

Results

Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (P = 0.026). A few differences were observed in protein levels related to SSRIs treatment, although they were not statistically significant. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (P = 0.007).

Conclusions

In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.
Validation of multiplex PCR sequencing assay of SIV
Authors: Moriarty Ryan V. , Fesser Nicolas , Sutton Matthew S. , Venturi Vanessa , Davenport Miles P. , Schlub Timothy , O’Connor Shelby L.
Published: January 2021

Background

The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data.

Methods

We modified a multiplex PCR and sequencing approach to characterize populations of simian immunodeficiency virus (SIV) isolated from nonhuman primates. We chose this approach with the aim of reducing the number of required input templates while maintaining fidelity and sensitivity. We conducted replicate sequencing experiments using different numbers of quantified viral RNA (vRNA) or viral cDNA as input material. We performed assays with clonal SIVmac239 to detect false positives, and we mixed SIVmac239 and a variant with 24 point mutations (SIVmac239-24X) to measure variant detection sensitivity.

Results

We found that utilizing a starting material of quantified viral cDNA templates had a lower rate of false positives and increased reproducibility when compared to that of quantified vRNA templates. This study identifies the importance of rigorously validating deep sequencing methods and including replicate samples when using a new method to characterize low frequency variants in a population with a small number of templates.

Conclusions

Because the need to generate reproducible and accurate sequencing data from diverse viruses from low titer samples, we modified a multiplex PCR and sequencing approach to characterize SIV from populations from non-human primates. We found that increasing starting template numbers increased the reproducibility and decreased the number of false positives identified, and this was further seen when cDNA was used as a starting material. Ultimately, we highlight the importance of vigorously validating methods to prevent overinterpretation of low frequency variants in a sample.
Real-world evidence on Kovaltry (81-8973) in children with moderate or severe hemophilia A in Europe: a nested cohort analysis
Authors: O’Hara Jamie , Hirst Ceri , Cabre Marquez Jose Francisco , Burke Tom
Published: January 2021

Background

Untreated hemophilia A patients may experience recurrent bleeding events leading to debilitating joint damages. While RCT and pharmacokinetic data support the value of Kovaltry [an unmodified full-length recombinant factor VIII (FVIII) product], real world evidence in children is lacking. This report describes a descriptive and multivariate analysis of the effectiveness of Kovaltry in children with hemophilia A in the real-world setting, using data from medical chart abstraction and cross-sectional surveys of physicians, patients, and caregivers.

Results

Male patients aged < 18 years with moderate or severe hemophilia A, residing in five European countries and treated with FVIII were studied. The co-primary endpoints were the annualized bleeding rate (ABR) and the annual FVIII utilization rate. Twenty nine patients treated with Kovaltry were included, of whom 93% had severe disease and 75% were on continuous prophylactic treatment. The mean ABR was 2.66 ± 2.06, with rates decreasing with age. The children received on average 2.45 infusions per week, consistent across age groups (median 3; range 1–3). There were no reports of inhibitor development or adverse events in the study (AEs), and all patients were satisfied or very satisfied with the treatment. An exploratory multivariate analysis suggests no significant difference in ABR or units utilized between Kovaltry and some extended half life products in children with severe hemophilia A, though characteristics of these patient cohorts were markedly different.

Conclusion

This analysis demonstrates the effectiveness and safety of Kovaltry in a pan-European pediatric population with severe hemophilia A.
Exome sequencing in paediatric patients with movement disorders
Authors: Kwong Anna Ka-Yee , Tsang Mandy Ho-Yin , Fung Jasmine Lee-Fong , Mak Christopher Chun-Yu , Chan Kate Lok-San , Rodenburg Richard J. T. , Lek Monkol , Huang Shushu , Pajusalu Sander , Yau Man-Mut , Tsoi Cheung , Fung Sharon , Liu Kam-Tim , Ma Che-Kwan , Wong Sheila , Yau Eric Kin-Cheong , Tai Shuk-Mui , Fung Eva Lai-Wah , Wu Nick Shun-Ping , Tsung Li-Yan , Smeitink Jan , Chung Brian Hon-Yin , Fung Cheuk-Wing
Published: January 2021

Background

Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.

Results

We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.

Conclusions

A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
The identification of novel immunogenic antigens as potential Shigella vaccine components
Authors: de Alwis Ruklanthi , Liang Li , Taghavian Omid , Werner Emma , The Hao Chung , Thu Trang Nguyen Hoang , Duong Vu Thuy , Davies D. Huw , Felgner Philip L. , Baker Stephen
Published: January 2021

Background

Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen.

Methods

Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections.

Results

Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody.

Conclusions

These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.
Increased levels of YKL-40 in patients with diabetes mellitus: a systematic review and meta-analysis
Authors: Luo Wanwan , Zhang Lingmin , Sheng Lingling , Zhang Zhencheng , Yang Zaixing
Published: January 2021

Background

Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.

Methods

Pubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case–control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese. Finally, twenty-five studies were included in this meta-analysis.

Results

Compared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD = 1.62, 95% CI 1.08 to 2.25, P = 0.000; GDM: SMD = 2.85, 95% CI 1.01 to 4.70, P = 0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD = 1.58, 95% CI 0.59 to 2.56, P = 0.002; microalbuminuria: SMD = 2.57, 95% CI 0.92 to 4.22, P = 0.002; macroalbuminuria: SMD = 2.69, 95% CI 1.40 to 3.98, P = 0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD = 1.49, 95% CI 0.28 to 2.71, P = 0.016; macroalbuminuria vs microalbuminuria: SMD = 0.93, 95% CI 0.34 to 1.52, P = 0.002).

Conclusions

Our current meta-analysis demonstrates that serum level of YKL-40 is increased in DM and positively associated with the severe degree of albuminuria. Therefore, we suggest that YKL-40 could be considered to be detected, along with other inflammatory markers, if DM, especially DN, is suspected.
Radiation-induced toxicity in rectal epithelial stem cell contributes to acute radiation injury in rectum
Authors: Tirado Felipe Rodriguez , Bhanja Payel , Castro-Nallar Eduardo , Olea Ximena Diaz , Salamanca Catalina , Saha Subhrajit
Published: January 2021

Background

Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality and treatment outcome in patients with pelvic malignancies. Unlike small bowel and colon, effect of radiation in rectal stem cells has not been explored extensively. Here we demonstrate that Lgr5-positive rectal stem cells are radiosensitive and organoid-based transplantation of rectal stem cells mitigates radiation damage in rectum.

Methods

C57Bl6 male mice (JAX) at 24 h were exposed to pelvic irradiation (PIR) to determine the radiation effect in pelvic epithelium. Effect of PIR on Lgr5-positive rectal stem cells (RSCs) was determined in Lgr5-EGFP-Cre-ERT2 mice exposed to PIR. Effect of PIR or clinically relevant fractionated PIR on regenerative response of Lgr5-positive RSCs was examined by lineage tracing assay using Lgr5-eGFP-IRES-CreERT2; Rosa26-CAG-tdTomato mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from Lgr5-EGFP-Cre-ERT2 mice. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Organoids from Lgr5-EGFP-ires-CreERT2-TdT mice were transplanted in C57Bl6 male mice exposed to PIR. Engraftment and repopulation of Lgr5-positive RSCs were determined after tamoxifen administration to activate Cre recombinase in recipient mice. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test.

Result

Exposure to pelvic irradiation significantly damaged rectal epithelium with the loss of Lgr5+ve rectal stem cells. Radiosensitivity of rectal epithelium was also observed with exposure to clinically relevant fractionated pelvic irradiation. Regenerative capacity of Lgr5+ve rectal stem cells was compromised in response to fractionated pelvic irradiation. Ex vivo organoid study demonstrated that Lgr5+ve rectal stem cells are sensitive to both single and fractionated radiation. Organoid-based transplantation of Lgr5+ve rectal stem cells promotes repair and regeneration of rectal epithelium.

Conclusion

Lgr5-positive rectal stem cells are radiosensitive and contribute to radiation-induced rectal epithelial toxicity. Transplantation of Lgr5-positive rectal stem cells mitigates radiation-induced rectal injury and promotes repair and regeneration process in rectum.
Utilization of the Public Health Ordinance to prevent nosocomial spread in a case of acute measles-associated psychosis
Authors: Stein-Zamir Chen , Abramson Nitza , Sonnenfeld-Alroey Hagit , Charnes Jacob , Eckstein Dana , Dienstag Aryeh , Wolf Dana , Moses Allon E. , Weiss Yoram G.
Published: January 2021

Measles is a highly contagious disease. A 24 years old patient, recently exposed to measles (unvaccinated), presented in the emergency department with severe agitation, compatible with an acute psychotic episode, during the measles epidemic which spread in Israel in 2018–2019. Upon hospital admission, strict isolation was instructed, yet, without compliance, probably due to the patient’s status. Measles diagnosis was promptly confirmed. As measles transmission was eminent, public health measures were employed through immediate implementation of the section 15 of the Public Health Ordinance, allowing for compulsory short-term isolation. The patient’s condition improved within a few days and the measures were no longer necessary. This measles case occurred in the pre-Coronavirus disease 2019 (COVID-19) epidemic when use of a Public Health Ordinance was considered an extreme measure. This is in contrast to the current global use of Public Health laws to enforce strict quarantine and isolation on persons infected or potentially exposed to COVID-19. Nevertheless, minimizing infectious diseases transmission is a core function of public health law. Utilizing legal enforcement in circumstances of immediate public health hazard, such as nosocomial measles transmission, necessitates careful consideration. The integrative clinical and public health approach and prompt measures employed in this exceptional case, led to prevention of further infection spread.
Expression pattern analysis of three R2R3-MYB transcription factors for the production of anthocyanin in different vegetative stages of Arabidopsis leaves
Authors: Koo Yeonjong , Poethig R. Scott
Published: January 2021

Anthocyanin is a type of flavonoid that appears purple in plants. PAP1, PAP2, and MYB113 are the three major R2R3-MYB transcription factors that regulate flavonoid biosynthesis inArabidopsis thaliana. In this study, we found that the three MYB genes regulate anthocyanin accumulation in different leaf stages. Under limited nutrient conditions, PAP1 and PAP2 genes were highly induced in juvenile leaves. Conversely, MYB113 was expressed mainly in adult leaves. In addition, we investigated the role of trans-acting siRNA4 (TAS4) in the post-transcriptional regulation of anthocyanin expression in Arabidopsis leaves. In plant growth, the inhibition of PAP1 and PAP2 gene expression by TAS4 was observed only in juvenile leaves, and MYB113 inhibition was observed in adult leaves. In conclusion, we found that transcription and transcript repression of the three MYB genes is differentially regulated by TAS4 in leaf developmental stages. Our results improve the understanding of the regulation of plant anthocyanin production under stress conditions.
Analysis of ethoxyquin and its oxidation products in swine tissues by gas chromatography-tandem mass spectrometry for evaluating the feed-to-animal tissue transfer of ethoxyquin and its metabolites
Authors: Zhang Chi , Gai Xiangrong , Tian Ying , Wang Jiayi , He Dongting , Yang Wenjun , Zhang Liying , Chen Yiqiang
Published: January 2021

Background

Ethoxyquin (EQ) is a common antioxidant which is widely used in animal feed. But the supplement of EQ in animal feed may lead to the residues of EQ and its major oxidation products: ethoxyquin quinone imine (EQI) and ethoxyquin dimer (EQDM) in animal tissue. Thus, it would pose potential health hazards to consumers. However, the method for the simultaneous determination of EQ, EQI and EQDM in animal tissues is currently not available, and the accumulation extend of these chemicals in animal tissues after EQ administration remains to be evaluated.

Results

A gas chromatography-tandem mass spectrometry method was successfully developed for the simultaneous determination of EQ, EQI and EQDM in swine tissues. The quantitative limits of EQ, EQI and EQDM can achieve to 0.5, 5.0 and 5.0 μg/kg in swine tissues, respectively. The spiked-recovery ratios of the three analytes (5–2000 μg/kg) were in the range of 64.7%–100.7% with relative standard deviations below 11.6%. Moreover, the utilization of this method for the analysis of actual swine tissue samples revealed that the application of commercial EQ additive in swine diet would produce the residues of all the three chemicals (EQ, EQI and EQDM) in fat, kidney, liver and muscle.

Conclusions

The assay accuracy and precision of this GC-MS/MS method can meet the requirement of quantitative analysis. Meanwhile, the safety of EQ as a feed additive should be seriously considered with regard to food safety concerns since the oxidation product of EQ may have potential carcinogenicity.
HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals
Authors: Masenga Sepiso K. , Kirabo Annet , Hamooya Benson M. , Nzala Selestine , Kwenda Geoffrey , Heimburger Douglas C. , Mutale Wilbroad , Koethe John R. , Pilic Leta , Munsaka Sody M.
Published: January 2021

Background

High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population.

Methods

We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor.

Results

The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001).

Conclusions

The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.
Assessment of antibiosis potential of Bacillus sp. against the soil-borne fungal pathogen Sclerotium rolfsii Sacc. (Athelia rolfsii (Curzi) Tu & Kimbrough)
Authors: Kumari Puja , Bishnoi Santosh Kumar , Chandra Sheela
Published: January 2021

Background

This study aimed to investigate the rhizosphere bacterial isolates’ antagonistic property against the soil-borne fungal phytopathogen,Sclerotium rolfsiiSacc. (Athelia rolfsii(Curzi) Tu & Kimbrough). The chemical control of the disease caused byS.rolfsiiis economically and environmentally unsustainable, and therefore, a bio-control agent in the form of rhizospheric bacteria is gaining importance.

Main body

Five rhizosphericBacillusspecies viz.B.subtilissubsp.Subtilisstr.168 (accession no. MH283878),B.siamensisstrain PDA 10 (accession no. MH283879),B.amyloliquefaciensstrain 1034 (accession no. MH283880),B.velezensisstrain FZB42165 (accession no. MH283881), andB.atrophaeusstrain NBRC 15539 (accession no. MH283882) were assessed for their antagonistic potential againstS.rolfsiibased on 3 different screening methods. Among these, 100% fungal growth inhibition by all 5Bacillusspp. was observed in the novel ring method, whereas in the dual culture method, the maximum growth inhibition was (58%) exhibited by the strain NBRC 15539 ofB.atrophaeus. The antagonistic activity showed by the modified dual culture method was also relatively high, and the highest activity (93.7%) was shown by the strain NBRC 15539 ofB.atrophaeus. Besides, theBacillussp. was also evaluated for their plant growth-promoting attributes and other properties such as the production of siderophore, HCN, amylase, protease, lipase, and ammonia, including their assessment for chitinase and cellulase activity.

Conclusion

The study provided empirical evidence ofBacillussp. antagonistic potential againstS.rolfsiiand should be of contributive value in developing a biocontrol agent for this highly important crop fungal pathogen.
Development of a test for assessment of the lipreading ability for children in the Arabic-speaking countries
Authors: Hegazi Mona Abdel-Fattah , Saad Aya Mohammed , Khodeir Mona Sameeh
Published: January 2021

Background

Lipreading is considered an important skill that varies considerably among normal-hearing (NH) and hearing-impaired (HI) children. It is well known that normal-hearing children use audition as the primary sensory modality for speech perception, whereas HI children use lipreading cues as the primary sensory modality for speech perception. Moreover, speech perception is a multisensory process that involves attention to auditory signals as well as visual articulatory movements, and the integration of auditory and visual signals occurs naturally and automatically in normal individuals of all ages. Most researches proved that lipreading is a natural and important skill needed for language acquisition in HI children. Lipreading also helps HI children to perceive speech, acquire spoken language, and acquire phonology. In the Arabic language, tools are deficient for assessing the lipreading ability for HI children, so this study was conducted to develop a test suitable for assessing the lipreading ability of hearing-impaired children among Arabic-speaking countries. The constructed lipreading test was administered to 160 Arabic-speaking Egyptian children including 100 typically developing NH children and 60 HI children. Participants’ responses were statistically analyzed to assess the validity and reliability and to compare the lipreading ability between the NH and HI children. Ranks of percentiles were established to provide an estimate of the lipreading ability in children.

Results

Statistically significant differences were found between the normal-hearing and HI children as regards all subtotal and total scores of the Arabic lipreading test, with good validity and reliability of the test.

Conclusions

The Arabic lipreading test is a valid and reliable test that can be applied to assess the lipreading ability among Arabic-speaking children with HI.
Mental health services for children in care: investigation to elicit outcomes of direct and indirect interventions
Authors: Deuchar Samuel , Majumder Pallab
Published: January 2021

Aims and method

The aim of this study was to compare the efficacy of direct therapy and indirect consultation for treating mental health difficulties among looked after children (LAC), and also to identify any demographic or clinical predictor variables for outcomes in this cohort. A retrospective evaluation of mental health outcomes for 104 LAC was conducted. All children received network consultation in combination with or without direct therapeutic work. Outcomes were compared between the groups with and without direct therapeutic intervention.

Results

Those receiving both treatments displayed significantly greater Strengths and Difficulties Questionnaire (SDQ)-rated improvements than those receiving just consultation. Nonetheless, improvements in scores for the latter group were significant relative to baseline. Treatment duration, younger age at referral and start SDQ were all correlated with positive outcomes, while number of address changes predicted higher start SDQ scores.

Clinical implications

Despite the retrospective design of this study, its results can be considered as preliminary findings to guide treatment decisions in LAC.
Cost-Effectiveness of Temozolamide for Treatment of Glioblastoma Multiforme in India
Authors: Gupta Nidhi , Prinja Shankar , Patil Vijay , Bahuguna Pankaj
Published: January 2021

PURPOSE

Glioblastoma multiforme (GBM) has poor outcomes following surgery and radiation. Adjuvant temozolamide along with radiation therapy has been shown to improve survival. In this paper, we evaluate the cost-effectiveness of concomitant temozolamide with radiation and maintenance temozolamide for 6 months of treatment for GBM in India.

MATERIALS AND METHODS

We used a Markov model to evaluate the lifetime costs and consequences of treating GBM with radiation alone versus radiation with adjuvant temozolamide. The model was calibrated using the published evidence from European Organisation for Research and Treatment of Cancer-NCIC trial on progression-free survival and overall survival to estimate the life years (LYs) and quality-adjusted LYs (QALYs). Cost of treatment and management of complications were estimated using the data from the National Health System Cost Database and Indian studies. Future cost and consequences were discounted at 3%. Incremental cost per QALY gained with temozolamide was estimated to assess cost effectiveness.

RESULTS

Temozolamide resulted in an increase of 0.59 (0.53-0.66) LY and 0.33 (0.29-0.40) QALY per person at an incremental cost of ₹75,120 in Indian national rupee (INR) (59,337-93,960). Overall, the use of temozolamide incurs an incremental cost of ₹212,020 INR (138,127-401,466) per QALY gained, which has a 4.7% probability to be cost-effective at 1-time per capita Gross Domestic Product (GDP) threshold. In case the current price of temozolamide could be decreased by 90%, the probability of its use for GBM being cost-effective increases to 80%.

CONCLUSION

Temozolamide is not cost-effective for treatment of patients with GBM in India. This evidence should be used while framing guidelines for treatment and price regulation.
Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD
Authors: Watkins Benjamin , Qayed Muna , McCracken Courtney , Bratrude Brandi , Betz Kayla , Suessmuth Yvonne , Yu Alison , Sinclair Shauna , Furlan Scott , Bosinger Steven , Tkachev Victor , Rhodes James , Tumlin Audrey Grizzle , Narayan Alexandria , Cribbin Kayla , Gillespie Scott , Gooley Ted A. , Pasquini Marcelo C. , Hebert Kyle , Kapoor Urvi , Rogatko Andre , Tighiouart Mourad , Kim Sungjin , Bresee Catherine , Choi Sung W. , Davis Jeffrey , Duncan Christine , Giller Roger , Grimley Michael , Harris Andrew C. , Jacobsohn David , Lalefar Nahal , Norkin Maxim , Farhadfar Nosha , Pulsipher Michael A. , Shenoy Shalini , Petrovic Aleksandra , Schultz Kirk R. , Yanik Gregory A. , Waller Edmund K. , Levine John E. , Ferrara James L. , Blazar Bruce R. , Langston Amelia , Horan John T. , Kean Leslie S.
Published: January 2021

PURPOSE

Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD.

METHODS

ABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days).

RESULTS

In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) ( P = .13, hazard ratio = 0.45). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo, P = .05). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%, P < .001), and the SGFS was better (97.7% v 58.7%, P < .001). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients.

CONCLUSION

Adding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.
Racial Disparities in Intravenous Bisphosphonate Use Among Older Patients With Multiple Myeloma Enrolled in Medicare
Authors: Zhou Jifang , Sweiss Karen , Nutescu Edith A. , Han Jin , Patel Pritesh R. , Ko Naomi Y. , Lee Todd A. , Chiu Brian C.-H. , Calip Gregory S.
Published: January 2021

PURPOSE:

Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM.

METHODS:

We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation.

RESULTS:

We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19).

CONCLUSION:

Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.