bluuebunny/crossref_metadata_2025 huggingface dataset:
Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas
Authors: Baptista Barbara Oliveira , de Souza Ana Beatriz Lopes , Riccio Evelyn Kety Pratt , Bianco-Junior Cesare , Totino Paulo Renato Rivas , Martins da Silva João Hermínio , Theisen Michael , Singh Susheel Kumar , Amoah Linda Eva , Ribeiro-Alves Marcelo , Souza Rodrigo Medeiros , Lima-Junior Josué Costa , Daniel-Ribeiro Cláudio Tadeu , Pratt-Riccio Lilian Rose
Published: January 2022

Background

The GMZ2.6c malaria vaccine candidate is a multi-stagePlasmodium falciparumchimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated.

Methods

This study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specific IgG, IgM, IgA and IgE antibodies and IgG subclasses were detected by Enzyme-Linked Immunosorbent Assay.

Results

The results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies. Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to parasite immunity.

Conclusions

The data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine.
Circular RNA ciRs-126 promotes hypoxia/reoxygenation cardiac injury possibly through miR-21
Authors: Tan Changming , Li Jianming , Yuan Zhaoshun , Mu Yongxin
Published: January 2022

Background

This study aimed to analyze the role of circular RNA ciRs-126 in hypoxia/reoxygenation cardiac injury (H/R).

Methods

Expression of ciRs-126 and miR-21 in plasma samples from patients with H/R and healthy controls was determined by RT-qPCR. Correlations were analyzed by linear regression. Overexpression of ciRs-126 and miR-21 was achieved in cardiomyocytes to explore their crosstalk. The roles of ciRs-126 and miR-21 in H/R-induced apoptosis of cardiomyocytes were analyzed using cell apoptosis assay.

Results

CiRs-126 was upregulated and miR-21 was downregulated in H/R patients. They were inversely correlated across plasma samples from H/R patients. In H/R cardiomyocytes, ciRs-126 was upregulated and miR-21 was downregulated. In cardiomyocytes, ciRs-126 overexpression decreased miR-21 level and reduced the inhibitory effects of miR-21 overexpression on H/R-induced cell apoptosis.

Conclusions

Circular RNA ciRs-126 may suppress miR-21 expression to promote H/R cardiac injury.
microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82
Authors: Song Li , Luan Bin , Xu Qingrong , Shi Ruihe , Wang Xiufang
Published: January 2022

Objective

Exosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82).

Methods

miR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model.

Results

miR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis.

Conclusion

The study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.
Hypoxia increases expression of selected blood–brain barrier transporters GLUT-1, P-gp, SLC7A5 and TFRC, while maintaining barrier integrity, in brain capillary endothelial monolayers
Authors: Ozgür Burak , Helms Hans Christian Cederberg , Tornabene Erica , Brodin Birger
Published: January 2022

Background

Brain capillary endothelial cells (BCECs) experience hypoxic conditions during early brain development. The newly formed capillaries are tight and functional before astrocytes and pericytes join the capillaries and establish the neurovascular unit. Brain endothelial cell phenotype markers P-gp (ABCB1), LAT-1(SLC7A5), GLUT-1(SLC2A1), and TFR(TFRC) have all been described to be hypoxia sensitive. Therefore, we hypothesized that monolayers of BCECs, cultured under hypoxic conditions, would show an increase in LAT-1, GLUT-1 and TFR expression and display tight endothelial barriers.

Methods and results

Primary bovine BCECs were cultured under normoxic and hypoxic conditions. Chronic hypoxia induced HIF-1α stabilization and translocation to the nucleus, as judged by immunocytochemistry and confocal laser scanning imaging. Endothelial cell morphology, claudin-5 and ZO-1 localization and barrier integrity were unaffected by hypoxia, indicating that the tight junctions in the BBB model were not compromised. SLC7A5, SLC2A1, and TFRC-mRNA levels were increased in hypoxic cultures, while ABCB1 remained unchanged as shown by real-time qPCR. P-gp, TfR and GLUT-1 were found to be significantly increased at protein levels. An increase in uptake of [3H]-glucose was demonstrated, while a non-significant increase in the efflux ratio of the P-gp substrate [3H]-digoxin was observed in hypoxic cells. No changes were observed in functional LAT-1 as judged by uptake studies of [3H]-leucine. Stabilization of HIF-1α under normoxic conditions with desferrioxamine (DFO) mimicked the effects of hypoxia on endothelial cells. Furthermore, low concentrations of DFO caused an increase in transendothelial electrical resistance (TEER), suggesting that a slight activation of the HIF-1α system may actually increase brain endothelial monolayer tightness. Moreover, exposure of confluent monolayers to hypoxia resulted in markedly increase in TEER after 24 and 48 h, which corresponded to a higher transcript level of CLDN5.

Conclusions

Our findings collectively suggest that hypoxic conditions increase some BBB transporters' expression via HIF-1α stabilization, without compromising monolayer integrity. This may in part explain why brain capillaries show early maturation, in terms of barrier tightness and protein expression, during embryogenesis, and provides a novel methodological tool for optimal brain endothelial culture.
Considerations for lactation with Ehlers-Danlos syndrome: a narrative review
Authors: Francis Jimi , Dickton Darby D.
Published: January 2022

Background

Ehlers-Danlos syndrome (EDS) is a rare genetic connective tissue condition that is poorly understood in relation to lactation. As diagnostic methods improve, prevalence has increased. EDS, a disorder that impacts connective tissue, is characterized by skin extensibility, joint hypermobility, and fragile tissue which can affect every organ and body system leading to complications during pregnancy, delivery, and the postpartum period. Traits of this disease can cause mild to severe physiologic and functional obstacles during lactation. Unfortunately, there is little clinical evidence and minimal guidance for lactation management, and providers may feel uncomfortable and hesitant to address these concerns with patients due to a lack of readily available resources on the subject and inexperience with such patients. This narrative review describes and discusses the types of EDS, identifying symptoms, considerations, and precautions for care providers to implement during lactation and breastfeeding.

Methods

An electronic search of relevant citations was conducted using the databases Cochrane, PubMed, and Google Scholar from 1 January 2000 to 1 November 2021. Search terms used were Ehlers-Danlos syndrome, Hypermobility Syndrome, breastfeeding, lactation, breastmilk expression, breastmilk collection, human milk expression, human milk collection, and infant feeding. The search of these databases yielded zero results. As no research articles on EDS were directly related to lactation, this narrative review includes articles found that related to the health of mothers relevant to maternal function during lactation.

Discussion

For the healthcare provider, identifying characteristics of EDS can improve the management of lactation challenges. Mothers may experience generalized symptoms from gastrointestinal distress to fatigue or chronic pain, while they also may suffer from more specific joint complaints and injuries, such as dislocations / subluxations, or skin fragility. Such obstacles can generate impediments to breastfeeding and create unique challenges for breastfeeding mothers with EDS.

Unfortunately, new mothers with these symptoms may have them overlooked or not addressed, impacting a mother’s ability to meet her breastfeeding intentions. While there are some published research manuscripts on EDS and pregnancy, there is a lack of information regarding breastfeeding and lactation. Additional research is needed to help guide EDS mothers to achieve their breastfeeding intentions.
A self-efficacy-enhancing intervention for Chinese patients after total hip arthroplasty: study protocol for a randomized controlled trial with 6-month follow-up
Authors: Deng Bo , Chen Yumei , Meng Ya , Zhang Yiheng , Tan Xingxian , Zhou Xiaohong , Zhang Meifen
Published: January 2022

Background

Total hip arthroplasty (THA) is a common and effective surgical method for advanced hip arthritis. Rehabilitation exercises are important to improve joint function after THA and are usually conducted in a home-based program. Poor patient adherence limits improvements in pain and function, affecting quality of life. The increasing use of THA in the aging Chinese population underscores the need to develop strategies that maximize functional outcomes. The purpose of this pilot study is to develop and assess the feasibility of a self-efficacy-enhancing intervention (SEEI) to improve exercise adherence in patients undergoing THA.

Methods

This single-blinded, parallel, randomized control trial will recruit 150 patients after THA and randomly assign them to an intervention or control group using computer-generated block randomization. The control group will receive usual care using evidence-based guidelines. The intervention group will receive the 6-month SEEI comprising personalized exercise guidance and self-efficacy education delivered using one face-to-face education session and four telephone consultations, supplemented by written materials. Participants are encouraged to build confidence in their own abilities, set rehabilitation goals, and self-monitor their physical exercise.

Results

Assessments will be conducted at baseline and 1, 3, and 6 months postsurgery. The outcome indicators are exercise adherence, physical function, anxiety and depression, self-efficacy of rehabilitation, joint function, and quality of life.

Conclusions

This study will test a theory-based intervention program to improve self-efficacy in rehabilitation, which may significantly impact out-of-hospital rehabilitation. The results will provide evidence to inform the postoperative recovery of patients undergoing THA or similar procedures.

Trial registration

Chinese Clinical Trials Registry,ChiCTR2000029422, registered on 31 January 2020
Impact of achondroplasia on Latin American patients: a systematic review and meta-analysis of observational studies
Authors: Fano Virginia , Kim Chong A. , Rosselli Pablo , Dib Regina El , Shediac Renée , Magalhães Tatiana , Mesojedovas Debora , Llerena Juan
Published: January 2022

Background

Achondroplasia (ACH), the most common form of disproportionate short stature, is caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene. Recent advances in drug therapy for ACH have highlighted the importance of elucidating the natural history and socioeconomic burden of this condition. Recognition that there are many potential issues for the patient with ACH is the first step in planning cost-effective interventions in Latin America (LATAM), a vast geographic territory comprising countries with multicultural characteristics and wide socioeconomic differences. We conducted a systematic literature review to characterize the impact of ACH on affected individuals and on healthcare resources in LATAM countries.

Methods

Searches of the global medical literature as well as regional and local medical literature up to August 2020. Observational studies on patients with ACH from any LATAM country. Pairs of reviewers independently screened eligible articles, extracted data from included studies, and assessed their risk of bias.

Results

Fifty-three unique studies (28 case series and cross-sectional studies and 25 case reports) including data on 1604 patients were eligible. Of these studies, 11 had data available for meta-analysis. Both premature mortality and all-cause mortality in the pooled studies was 15% [95% Confidence Interval (CI) 1.0E−3 to 0.47; I2 = 82.9%, p = 0.0029; three studies, n = 99 patients]. Frequency of cardio-respiratory-metabolic disorders was 17% [95% CI 0.04–0.37; I2 = 90.3%, p < 0.0001; four studies, n = 230 patients]; nervous system disorders was 18% [95% CI 0.07–0.33; I2 = 84.6%, p < 0.0001; six studies, n = 262 patients]; ear, nose, throat and speech disorders was 32% [95% CI 0.18–0.48; I2 = 73.4%, p = 0.0046; five studies, n = 183 patients]; and spinal issues including stenosis, compression and associated pain was 24% [95% CI 0.07–0.47; I2 = 91.3%, p < 0.0001; five studies, n = 235 patients].

Conclusions

There is currently evidence of high clinical burden in ACH patients in LATAM countries. Establishing the impact of ACH provides the necessary foundation for planning tailored and effective public health interventions.
Postmarketing safety of orphan drugs: a longitudinal analysis of the US Food and Drug Administration database between 1999 and 2018
Authors: Fan Min , Chan Adrienne Y. L. , Yan Vincent K. C. , Tong Xinning , Lau Lauren K. W. , Wan Eric Y. F. , Tam Eliza Y. T. , Ip Patrick , Lum Terry Y. , Wong Ian C. K. , Li X.
Published: January 2022

Background

Information about the specific regulatory environment of orphan drugs is scarce and inconsistent. Uncertainties surrounding the postmarketing long-term safety of orphan drugs remain. This study aimed to evaluate the labelling changes of orphan drugs and to identify postmarketing safety-associated approval factors.

Methods

This retrospective cohort study includes all drugs with orphan drug designation approved by the Center for Drug Evaluation and Research of the US Food and Drug Administration between 1999 and 2018. Main outcomes are safety-related labelling changes up to 31 December 2019. We defined any safety-related labelling changes as postmarketing safety events (PMSE). Safety-related withdrawals, suspensions, and boxed warnings were further categorised as severe postmarketing safety events (SPSE). Outcome measurements include frequencies of PMSE, SPSE, and association between approval factors and the occurrence of safety events.

Results

Amongst the 214 drugs identified with orphan drug designation (25.7% biologics), 83.6% were approved through at least one expedited programme, and 29.4% were approved with boxed warnings. During a median follow-up of 6.74 years since approval, 69.2% and 14.5% of the analysed orphan drugs had PMSE and SPSE, respectively. Safety-related withdrawal (0%, 0/214), suspended marketing (0.46%, 1/214) and new boxed warnings are uncommon (3.7%, 8/214). The safety-related labelling changes were more frequent in the drugs approved with boxed warnings [Incidence rate ratio (IRR): 1.95 (1.02–3.73)] and approved for long-term use [IRR: 2.76 (1.52–5.00)].

Conclusions and Relevance

In this long-term postmarketing analysis, approximately 70% of FDA-approved orphan drugs had safety-related labelling changes although severe safety events were rare. While maintaining early access to orphan drugs, the drug regulatory body has taken timely regulatory action with postmarketing surveillance to ensure patient safety.
Usefulness of random-start progestin-primed ovarian stimulation for fertility preservation
Authors: Huang Haipeng , Itaya Yukiko , Samejima Kouki , Ichinose Shunichiro , Narita Tatsuya , Matsunaga Shigetaka , Saitoh Masahiro , Takai Yasushi
Published: January 2022

Background

Progestin-primed ovarian stimulation (PPOS) has been used in infertility cases in recent years, and several reports have stated that it has oocyte collection results similar to those of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. For emergency fertility preservation, random-start ovarian stimulation is usually recommended. Therefore we compared the clinical outcomes of random-start PPOS with those of conventional random-start GnRH-ant protocols in fertility-preserving cases.

Methods

We retrospectively examined 86 cycles of oocyte collection, of which 56 were random-start GnRH-ant and 30 were random-start PPOS for fertility preservation at our hospital between January 2016 and April 2021. The primary outcome was the number of mature oocytes per cycle. The secondary outcome was the number of vitrified blastocysts per cycle for embryo freezing cases.

Results

No significant differences were noted in the number of days of stimulation, total dose of gonadotropin preparation, and the number of mature oocytes and vitrified blastocysts. The number of hospital visits for monitoring was significantly lower in the PPOS group. The start of menstruation before oocyte collection was significantly less in the PPOS group.

Conclusions

Random-start PPOS and GnRH-ant were similar in oocyte collection results. PPOS can reduce the number of hospital visits, thus reducing patient stress. PPOS at the start of the luteal phase can prevent the start of menstruation during ovarian stimulation.
Germline HOXB13 mutation p.G84E do not confer an increased bladder or kidney cancer risk in polish population
Authors: Złowocka-Perłowska Elżbieta , Tołoczko-Grabarek Aleksandra , Lubiński Jan
Published: January 2022

Introduction

The role of HOXB13 in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of HOXB13 p.G84E mutation in bladder and kidney cancer patients from Poland.

Materials and methods

1418 patients with bladder cancer and 813 cases with kidney cancer and 4497 controls were genotyped for HOXB13 p.G84E.

Results

p.G84E mutation of HOXB13 gene was detected in three of 1418 (0.2%) bladder cancer cases and in six of 4497 controls (odds ratio [OR], 1.6; 95% CI 0.39–6.36; p = 0.8). Among 813 kidney cancer cases HOXB13 mutations was reported in three patients (0,4%) (odds ratio [OR], (OR = 2,8; 95% CI 0.69–11.11; p = 0.3). In cases with mutations in the HOXB13 gene, the family history of cancer was negative.

Conclusion

HOXB13 mutation was not associated with bladder or kidney cancer. Mutation p.G84E in HOXB13 seem not to play a role in bladder and kidney cancer development in Polish patients.
Persistence of live virus in critically ill patients infected with SARS-COV-2: a prospective observational study
Authors: Funk Duane J. , Bullard Jared , Lother Sylvan , Grande Gloria Vazquez , Garnett Lauren , Doan Kaylie , Dust Kerry , Kumar Anand , Poliquin Guillaume , Strong Jim
Published: January 2022

Background

Research on the duration of infectivity of ICU patients with COVID-19 has been sparse. Tests based on Reverse Transcriptase polymerase chain reaction (RT-PCR) detect both live virus and non-infectious viral RNA. We aimed to determine the duration of infectiousness based on viral culture of nasopharyngeal samples of patients with COVID-19.

Methods

Prospective observational study in adult intensive care units with a diagnosis of COVID-19 Pneumonia. Patients had repeated nasopharyngeal sampling performed after day 10 of ICU admission. Culture positive rate (based on viral culture on Vero cells in a level 4 lab) and Cycle threshold from RT-PCR were measured.

Results

Nine patients of the 108 samples (8.3%, 95% CI 3.9–15.2%) grew live virus at a median of 13 days (interquartile range 11–19) after their initial positive test. 74.1% of patients were RT-PCR positive but culture negative, and the remaining (17.6%) were RT-PCR and culture negative. Cycle threshold showed excellent ability to predict the presence of live virus, with a Ct < 25 with an AUC of 0.90 (95% CI 0.83–0.97, p < 0.001). The specificity of a Ct > 25 to predict negative viral culture was 100% (95% CI 70–100%).

Conclusion

8.3% of our ICU patients with COVID-19 grew live virus at a median of 13 days post-initial positive RT-PCR test. Severity of illness, use of mechanical ventilation, and time between tests did not predict the presence of live virus. Cycle threshold of > 25 had the best ability to determine the lack of live virus in these patents.
Efficacy of acupuncture and its influence on the emotional network in adult insomnia patients: protocol for a randomized controlled clinical trial
Authors: Jiang Tongfei , Zhang Qi , Yuan Fang , Zhang Fan , Guo Jing
Published: January 2022

Introduction

Insomnia disorder (ID) is characterized by dissatisfaction with the quantity or quality of sleep and is often accompanied by negative emotions such as anxiety and depression. Patients with insomnia become trapped in a vicious circle of bad moods and poor sleep. Resting-state functional magnetic resonance imaging (r-fMRI) studies have shown abnormalities in emotion-related brain networks in patients with ID. And it has been proven that reducing negative emotions improves sleep quality. As a traditional alternative therapy, acupuncture has been demonstrated to be effective not only in improving sleep quality but also in stabilizing emotions; however, the mode of action needs to be further explored. Therefore, a clinical trial was designed to explore the effect of acupuncture in improving sleep and mood and to intuitively investigate the regulation of the emotional network using fMRI.

Methods and analysis

A total of 60 participants with ID will be randomly allocated to a spirit-regulating group or a control group using non-effective acupoints acupuncture at a ratio of 1:1. All participants will receive 3 acupuncture treatment sessions per week for 4 weeks. In addition, 30 healthy individuals will be included in the healthy group. The primary outcome is the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes are the Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), the Hyperarousal Scale (HAS), and the Fatigue Scale-14 (FS-14), r-fMRI data, sleep diary, and actigraphy. The data will be collected prior to treatment, following treatment, and during the 12-week follow-up period; a sleep diary will be kept during the entire process.

Ethics and dissemination

This protocol has been approved by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine (Bejing TCM Hospital). The results will be published in peer-reviewed journals or presented at academic conferences.

Trial registration

Chinese Clinical Trials Register ChiCTR1800015282.

Protocol version: Version 1.0. Date: Dec.2020
Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms
Authors: Chi Ya-Hui , Wang Wan-Ping , Hung Ming-Chun , Liou Gunn-Guang , Wang Jing-Ya , Chao Pen-Hsiu Grace
Published: January 2022

The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFβ1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFβ1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, clustering at the nuclear periphery and reintegrating into the nucleoplasm. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFβ1-induced compositional changes in the chromatin and nuclear lamina.
Influence of lincomycin-spectinomycin treatment on the outcome of Enterococcus cecorum infection and on the cecal microbiota in broilers
Authors: Schreier Jana , Karasova Daniela , Crhanova Magdalena , Rychlik Ivan , Rautenschlein Silke , Jung Arne
Published: January 2022

Background

Enterococcus cecorum(EC) is one of the main reasons for skeletal disease in meat type chickens. Intervention strategies are still rare and focus mainly on early antibiotic treatment of the disease, although there are no data available concerning the effectivity of this procedure. The present study aimed to investigate the effectivity of early lincomycin-spectinomycin treatment during the first week of life after EC-infection. Furthermore, the impact of lincomycin-spectinomycin treatment and EC infection on the development of cecal microbiota was investigated.

Methods

A total of 383 day-old broiler chicks were randomly assigned to four groups (non-infected and non-treated, non-infected and treated, EC-infected and non-treated, and EC-infected and treated). The EC-infected groups were inoculated orally with an EC suspension at the day of arrival and at study day 3. The treatment groups were treated with lincomycin-spectinomycin via the drinking water for six consecutive days, starting two hours after the first inoculation. Necropsy of 20 chickens per group was performed at study days 7, 14, 21, and 42. Bacteriological examination via culture and real-time PCR was performed to detect EC in different extraintestinal organs. Cecal samples of nine chickens per group and necropsy day were analyzed to characterize the composition of the cecal microbiota.

Results

No clinical signs or pathologic lesions were found at necropsy, and EC was not detected in extraintestinal organs of the EC-infected and treated birds. Lincomycin-spectinomycin promoted the growth of the bacterial genusEscherichia/Shigellaand reduced the amount of potentially beneficialLactobacillus spp.in the ceca regardless of EC-infection. Unexpectedly, the highest abundances of the genus Enterococcus were found directly after ending antibiotic treatment in both treatment groups, suggesting the growth of resistant enterococcal species. EC was not detected among the most abundant members of the genusEnterococcus.Oral EC-infection at the first day of life did not influence the development of cecal microbiota in the present study.

Conclusions

Lincomycin-spectinomycin treatment during the first week of life can prevent the EC-associated disease in broiler type chickens and has a direct impact on the development of the cecal microbiota. The low abundance of EC in the ceca of infected chickens underlines the pathogenic nature of the disease-causing EC strains. Further research on alternative prevention and intervention strategies is needed with regard to current efforts on reducing the use of antibiotics in livestock animals.
Genomic characteristics and comparative genomics of Salmonella enterica subsp. enterica serovar Schwarzengrund strain S16 isolated from chicken feces
Authors: Yang Seung-Min , Kim Eiseul , Lee Woojung , Kim Hae-Yeong
Published: January 2022

Background

Salmonella enterica subsp. enterica serovar Schwarzengrund (S. Schwarzengrund) is most frequently isolated from commensals humans or poultry. Here we report S. Schwarzengrund strain S16, the first sequenced genome in the Republic of Korea. Additionally, genome sequencing for strain S16 was performed and compared with other S. Schwarzengrund genomes obtained from public database.

Results

Strain S16 was isolated from chicken feces. The complete genome consists of one chromosome and one plasmid. The genome size is 4,822,755 bp with 4852 coding sequences. Strain S16 was determined as serovar Schwarzengrund by in silico serotyping and typed as sequence type (ST) 96. Forty-six S. Schwarzengrund genomes yielded a pangenome of 7112 genes, core-genome of 3374 genes, accessory-genome of 2906 genes, and unique-genome of 835 genes. Eighty-one genes were unique to strain S16, including hypothetical proteins and transcriptional regulators. Genotypic analysis of antibiotic resistance of strain S16 confirmed resistance to amikacin, ciprofloxacin, sulfamethoxazole, streptomycin, and tetracycline. Unlike other S. Schwarzengrund genomes, strain S16 had a mutation of gyrB. Moreover, similar to other S. Schwarzengrund genomes reported in other countries, strain S16 was harbored for 153 virulence genes including Saf operon and cdtB gene. All the antibiotic resistance genes and virulence genes were present in the core- or accessory-genomes.

Conclusions

Complete genome of strain S16 was sequenced. Comparative genomic analysis revealed several genes responsible for antibiotic resistance and specific genomic features of strain S16 and identified virulence factors that might contribute to the human and animal pathogenicity of other S. Schwarzengrund genomes.
Delineating the autistic phenotype in children with neurofibromatosis type 1
Authors: Chisholm Anita K. , Haebich Kristina M. , Pride Natalie A. , Walsh Karin S. , Lami Francesca , Ure Alex , Maloof Tiba , Brignell Amanda , Rouel Melissa , Granader Yael , Maier Alice , Barton Belinda , Darke Hayley , Dabscheck Gabriel , Anderson Vicki A. , Williams Katrina , North Kathryn N. , Payne Jonathan M.
Published: January 2022

Background

Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics.

Methods

Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score ≥ 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires.

Results

The study cohort comprised 68 children (3–15 years). Sixty-three per cent met the ADOS-2 ‘autism spectrum’ cut-off, and 34% exceeded the more stringent threshold for ‘autistic disorder’ on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by ‘insistence on sameness’ (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs.

Limitations

Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood.

Conclusions

Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management.
Sodium–glucose cotransporter 2 inhibitor-induced euglycemic diabetic ketoacidosis in a patient with coronavirus disease 2019: a case report
Authors: Yii Edwin Sze Sian , Azli Athirah Wan , Sitaram Premela Naidu
Published: January 2022

Background

Sodium–glucose cotransporter 2 inhibitors are among the new-generation oral antihyperglycemic agents that have been used in the treatment of type 2 diabetes mellitus. With the recent coronavirus disease 2019 pandemic and rise of cases in the third wave, diagnosis of life-threatening euglycemic diabetic ketoacidosis may easily be overlooked or missed.

Case presentation

We present the case of a 37-year-old Malay gentleman with underlying type 2 diabetes mellitus on empagliflozin, who presented to our hospital with symptomatic coronavirus disease 2019 infection and diabetic ketoacidosis. He developed severe rebound euglycemic diabetic ketoacidosis due to the continuous usage of empagliflozin for glycemic control alongside intravenous insulin.

Conclusions

Physicians should have a high index of suspicion in diagnosing and managing euglycemic diabetic ketoacidosis, including withholding treatment of sodium–glucose cotransporter 2 inhibitors during the acute management of diabetic ketoacidosis.
Equalities and inequalities for several variables mappings
Authors: Bodaghi Abasalt
Published: January 2022

In this paper, some special mappings of several variables such as the multicubic and the multimixed quadratic–cubic mappings are introduced. Then, the systems of equations defining a multicubic and a multimixed quadratic–cubic mapping are unified to a single equation. Under some mild conditions, it is shown that a multimixed quadratic–cubic mapping can be multiquadratic, multicubic and multiquadratic–cubic. Furthermore, by applying a known fixed-point theorem, the Hyers–Ulam stability of multimixed quadratic–cubic, multiquadratic, multicubic and multiquadratic–cubic are studied in non-Archimedean normed spaces.
A note on optimal Hermite interpolation in Sobolev spaces
Authors: Xu Guiqiao , Yu Xiaochen
Published: January 2022

This paper investigates the optimal Hermite interpolation of Sobolev spaces$W_{\infty }^{n}[a,b]$W∞n[a,b],$n\in \mathbb{N}$n∈Nin space$L_{\infty }[a,b]$L∞[a,b]and weighted spaces$L_{p,\omega }[a,b]$Lp,ω[a,b],$1\le p< \infty $1≤p<∞withωa continuous-integrable weight function in$(a,b)$(a,b)when the amount of Hermite data isn. We proved that the Lagrange interpolation algorithms based on the zeros of polynomial of degreenwith the leading coefficient 1 of the least deviation from zero in$L_{\infty }$L∞(or$L_{p,\omega }[a,b]$Lp,ω[a,b],$1\le p<\infty $1≤p<∞) are optimal for$W_{\infty }^{n}[a,b]$W∞n[a,b]in$L_{\infty }[a,b]$L∞[a,b](or$L_{p,\omega }[a,b]$Lp,ω[a,b],$1\le p<\infty $1≤p<∞). We also give the optimal Hermite interpolation algorithms when we assume the endpoints are included in the interpolation systems.
A variational inequality arising from optimal surrender of variable annuity with lookback benefit
Authors: Jeon Junkee , Kwak Minsuk
Published: January 2022

We introduce a variable annuity (VA) contract with a surrender option and lookback benefit, that is, the benefit of the VA contract is linked to the maximum process of the policyholder’s account value. In contrast to the constant guarantee model provided in Bernard et al. (Insur. Math. Econ. 55:116–128, 2014), it is optimal for the policyholder of the VA contract with lookback benefit to surrender the VA contract when the policyholder’s account value is below or equal to the optimal surrender boundary. Thus, from the perspective of the insurer to construct a portfolio of VA contracts, utilizing the VA contracts with lookback benefit along with VA contracts with constant guarantee provides the diversification of early surrenders. The valuation of this contract can be described as a two-dimensional parabolic variational inequality. By converting this into the one-dimensional problem, we obtain the integral equations for the value function and the free boundary. The recursive integration method is applied to obtain the numerical solutions. We also provide comparative statics of the optimal surrender boundaries with respect to various parameters.
On three-term conjugate gradient method for optimization problems with applications on COVID-19 model and robotic motion control
Authors: Sulaiman Ibrahim Mohammed , Malik Maulana , Awwal Aliyu Muhammed , Kumam Poom , Mamat Mustafa , Al-Ahmad Shadi
Published: January 2022

The three-term conjugate gradient (CG) algorithms are among the efficient variants of CG algorithms for solving optimization models. This is due to their simplicity and low memory requirements. On the other hand, the regression model is one of the statistical relationship models whose solution is obtained using one of the least square methods including the CG-like method. In this paper, we present a modification of a three-term conjugate gradient method for unconstrained optimization models and further establish the global convergence under inexact line search. The proposed method was extended to formulate a regression model for the novel coronavirus (COVID-19). The study considers the globally infected cases from January to October 2020 in parameterizing the model. Preliminary results have shown that the proposed method is promising and produces efficient regression model for COVID-19 pandemic. Also, the method was extended to solve a motion control problem involving a two-joint planar robot.
Evaluating the long-term care insurance policy from medical expenses and health security equity perspective: evidence from China
Authors: Liu Huan , Hu Tiantian
Published: January 2022

Background

Since the national long-term care (LTCI) policy pilot in 2016 of China, the LTCI policy has had significant impact on the residents in the pilot area.

Methods

From the perspective of medical expenses and health security equity, this study selects tracking survey data from the CHARLS database in 2013, 2015, and 2018 and empirically investigates the effect of LTCI policy pilot by using differences-in-differences method (DID). Moreover, this study measures the economic distribution and health equity of the treated and untreated groups using the concentration and Theil indices.

Results

The results showed that group heterogeneity of medical expenses and health level of elderly in the treatment group were narrowing. Moreover, the policy results showed that the LTCI policy pilot significantly affects the outpatient, hospital expenses, and length of stay of elders. Residence registration, income level, and basic medical insurance play a significant regulatory role. Additionally, LTCI policy pilot significantly improved the overall health of the elderly.

Conclusions

The measurement results of inequality show that the policy increases the income of low-income people, lowers the inequality level of outpatient and inpatient reimbursement, and reduces the concentration index of ADL disability and serious diseases. However, the inequality of serious diseases is becoming higher. Based on this, this paper provides several suggestions on optimizing the pilot policy of LTCI.
COVID-19: information access, trust and adherence to health advice among migrants in Norway
Authors: Madar Ahmed A. , Benavente Pierina , Czapka Elżbieta , Herrero-Arias Raquel , Haj-Younes Jasmin , Hasha Wegdan , Deeb George , Møen Kathy A. , Ortiz-Barreda Gaby , Diaz Esperanza
Published: January 2022

Background

Migrants in Norway bear a higher burden of COVID-19 infections and hospitalization as compared to non-migrants. The aim of our study was to understand how migrants perceive their own health risk, how they access information regarding the preventive measures, the degree of trust in this information, in the Norwegian authorities and the news media, and migrants’ adherence to authorities’ recommendations regarding the pandemic.

Methods

An online survey was performed between May and July 2020 among 529 Polish, Arabic, Somali, Tamil, and Spanish-speaking migrants in Norway. For each outcome presented in the aims, unweighted and weighted descriptive analyses were performed for all migrants together and for each language group.

Results

Sixty-one percent of migrants perceived their health as excellent or very good, with the lowest value (42%) in the Tamil group and the highest among Somalians (85%). The majority of respondents (82%) felt they had received sufficient information. Press conferences from the government, health authorities’ websites, and Norwegian news media were the preferred channels of information for all groups. Most migrants reported a high level of adherence to preventive measures (88%) and trust in Norwegian authorities (79%). However, there were variations among groups regarding the importance of sources of information and level of trust, which was lowest for the Polish group.

Conclusion

Migrants in Norway reported receiving sufficient information about COVID-19 and high adherence to preventive measures. However, the levels of trust in the information sources, the services and the authorities varied among the groups. Understanding how migrants are dealing with this pandemic is crucial to improve the dissemination of information and trust in the health authorities for the different groups.
Effect of checklist based box system interventions on improving institutional delivery among reproductive age women in Northwest Ethiopia: generalized structural equation modeling
Authors: Andargie Netsanet Belete , Debelew Gurmesa Tura
Published: January 2022

Background

Previous studies have shown that there is low utilization of institutional delivery in Ethiopia, as well as various factors contributing to this low utilization. Notably, there is paucity around interventions to improve institutional delivery. Hence, this study examines the effectiveness of checklist-based box system intervention on improving institutional delivery and to investigate the association through which the intervention is linked to institutional delivery.

Method

The study used data from a larger trial, on the effectiveness of checklist-based box system intervention on improving maternal health service utilization. In the intervention arm, mothers received regular community-level pregnancy screening and referral, service utilization monitoring boxes, drop-out tracing mechanisms, regular communication between health centers and health posts, and person-centered health education for mothers. This study used the existing government-led maternal health program as a control arm. A total of 1062 mothers who gave birth one-year before the survey were included in the final analysis. A difference-in-difference estimator was used to test the effectiveness of the intervention. Generalized structural equation modeling was used to examine the direct and/ indirect associations between the intervention and institutional delivery.

Result

Among participants, 403 (79.5%) mothers from intervention and 323 (58.2%) mothers from control clusters gave birth at health facilities. The result of the study revealed a 19% increase in institutional delivery in the intervention arm (19, 95%CI: 11.4-27.3%). In this study the pathway from checklist-based box system intervention to institutional delivery was mainly direct - (AOR = 3.32, 95%CI: 2.36-4.66), however, 33% of the effect was partially mediated by attendance of antenatal care four visits (AOR = 1.39, 95%CI: 1.02-1.92). The influence of significant others (AOR = 0.25, 95%CI: 0.15-0.43) and age (AOR = 0.03, 95%CI: 0.01- 0.09) had an inverse relation with institutional delivery.

Conclusion

The implementation of a checklist-based box system significantly increased institutional delivery utilization, both directly and indirectly by improving antenatal care four attendance. A larger-scale implementation of the intervention was recommended, taking the continuum of care approach into account.

Trial registration

ClinicalTrials.gov, NCT03891030, Retrospectively registered on 26 March, 2019.
COVID-19 denial in Turkmenistan veiling the real situation
Authors: Hashim Hashim Talib , El Rassoul Ahed El Abed , Bchara John , Ahmadi Attaullah , Lucero-Prisno Don Eliseo
Published: January 2022

Coronavirus disease 2019 (COVID-19) emerged in late 2019, with the first case identified in Wuhan City, Hubei Province, China, on 12 December 2019. In order to perceive the comprehensive impact of this pandemic, we have to know that misinformation and denials about COVID-19 have surely exacerbated its diffusion and hindered the response against it. Turkmenistan remains one of the very few countries in the world that lacks reports about emerging cases of the novel coronavirus. Turkmen authorities claim that they have adopted all attainable measures required in order to combat the virus, asserting that COVID-19 has yet to reach their country. Despite the government’s reported absence of COVID-19 in the country, rumors, media reports and independent sources suggest the spread of the pandemic in Turkmenistan. By mid-June 2020, the outbreak was referred to as being serious with patients suffering extreme health risks, and following its state of disrepair and unethical practices, many of those anticipated to be COVID-19 infected tend to suffer at home, discouraging any interaction with the healthcare system. The civil society in Turkmenistan, for the time being, takes full part of the government’s duty in the process of informing and educating the public regarding the COVID-19 pandemic, and endeavors to keep the government and WHO accountable for behaving in such repressive ways that could lead to rather preventable loss of human life in Turkmenistan. Yet, efforts hang fire before unveiling the real situation, and Turkmenistan’s government owning up to the negations and roaming speculations, not only regarding the coronavirus crisis, but every public-related issue itself.