bluuebunny/crossref_metadata_2025 huggingface dataset:
An engineered factor Va prevents bleeding induced by direct-acting oral anticoagulants by different mechanisms
Authors: von Drygalski Annette , Bhat Vikas , Gale Andrew J. , Averell Patricia M. , Cramer Thomas J. , Elias Darlene J. , Griffin John H. , Mosnier Laurent O.
Published: August 2020

Control of bleeding with direct-acting oral anticoagulants (DOACs) remains an unmet clinical need. Activated superFactor V (superFVa) is an engineered activated protein C (APC)–resistant FVa variant with enhanced procoagulant activity resulting from an A2/A3 domain disulfide bond and was studied here for control of DOAC-induced bleeding. SuperFVa reversed bleeding induced by FXa inhibitors (rivaroxaban, apixaban), and the FIIa inhibitor dabigatran in BalbC mice. The blocking anti-protein C and APC [(A)PC] antibody SPC-54 also reduced FXa inhibitor induced bleeding similar to superFVa, whereas dabigatran-induced bleeding was not affected. This indicated that sufficient APC was generated to contribute to bleeding in the presence of FXa inhibitors, but not in the presence of dabigatran, suggesting that mechanisms contributing to bleeding differed for FXa and FIIa inhibitors. Despite different mechanisms contributing to bleeding, superFVa effectively reduced bleeding for all DOACs, indicating the versatility of superFVa’s properties that contribute to its universal prohemostatic effects for DOAC associated bleeding. Supported by thrombin generation assays on endothelial cells in normal plasma spiked with DOACs and patient plasma anticoagulated with DOACs, 3 complementary mechanisms were identified by which superFVa achieved DOAC class-independent prohemostatic efficiency. These mechanisms are resistance to inactivation by APC, overcoming the FV activation threshold, and maximizing the efficiency of the prothrombinase complex when the available FXa is increased by FVIIa-based prohemostatics. In summary, it is this versatility of superFVa that delineates it from other prohemostatic agents as a promising class-independent rescue agent in bleeding situations associated with DOACs.
Identification of a Major QTL and Candidate Gene Analysis of Salt Tolerance at the Bud Burst Stage in Rice (Oryza sativa L.) Using QTL-Seq and RNA-Seq
Authors: Lei Lei , Zheng Hongliang , Bi Yanli , Yang Luomiao , Liu Hualong , Wang Jingguo , Sun Jian , Zhao Hongwei , Li Xianwei , Li Jiaming , Lai Yongcai , Zou Detang
Published: August 2020

Background

Salt stress is one of the main abiotic stresses that limits rice production worldwide. Rice salt tolerance at the bud burst stage directly affects the seedling survival rate and the final yield in the direct seeding cultivation model. However, the reports on quantitative trait locus (QTL) mapping and map-based cloning for salt tolerance at the bud burst stage are limited.

Results

Here, an F2:3 population derived from a cross between IR36 (salt-sensitive) and Weiguo (salt-tolerant) was used to identify salt-tolerant QTL interval at the bud burst stage using a whole-genome sequencing-based QTL-seq containing 40 extreme salt-tolerant and 40 extreme salt-sensitive individuals. A major QTL, qRSL7, related to relative shoot length (RSL) was detected on chromosome 7 using ΔSNP index algorithms and Euclidean Distance (ED) algorithms. According to single nucleotide polymorphisms (SNPs) between the parents, 25 Kompetitive allele-specific PCR (KASP) markers were developed near qRSL7, and regional QTL mapping was performed using 199 individuals from the F2:3 population. We then confirmed and narrowed down qRSL7 to a 222 kb genome interval. Additionally, RNA sequencing (RNA-seq) was performed for IR36 and Weiguo at 36 h after salt stress and control condition at the bud burst stage, and 5 differentially expressed genes (DEGs) were detected in the candidate region. The qRT-PCR results showed the same expression patterns as the RNA-seq data. Furthermore, sequence analysis revealed a 1 bp Indel difference in Os07g0569700 (OsSAP16) between IR36 and Weiguo. OsSAP16 encodes a stress-associated protein whose expression is increased under drought stress.

Conclusion

These results indicate that OsSAP16 was the candidate gene of qRSL7. The results is useful for gene cloning of qRSL7 and for improving the salt tolerance of rice varieties by marker assisted selection (MAS).
A qualitative study on the implementation of family health team: the perspectives of providers and patients
Authors: Mohd Hanafiah Ainul Nadziha , Johari Mohammad Zabri , Azam Syafinas
Published: August 2020

Background

Malaysia has committed to the global call to achieve universal health coverage, and with the adoption of Sustainable Development Goals, is further strengthening the health system through the primary health care services, particularly the family doctor concept. The Enhanced Primary Health Care (EnPHC) initiative was implemented to address the worrying upward trend of non-communicable disease prevalence, and incorporates the Family Health Team (FHT) concept. The aim of this paper is to describe the implementation of the FHT as part of the EnPHC intervention.

Methods

In-depth interviews and focus group discussions were conducted with the intervention design team, healthcare providers and patients in two rounds during the implementation period. A total of 121 individuals in the two rounds, split into different groups, where some of the participants of the FGD were also interviewed individually. Data were analysed using a thematic analysis, with codes being organised into larger themes.

Results

Themes that emerged from the data were around the process of FHT implementation and the advantages of the FHT, which included continuity of health care and improved quality of care. Patients and health care providers were receptive to the FHT concept, and took the effort to adapt the concept in the local settings.

Conclusions

The FHT concept implemented at 20 public primary health clinics has benefits appreciated by health care providers and patients. Addressing the viable shortcomings would better prepare the current primary healthcare system to scale up the FHT concept nationwide and enhance its feasibility and sustainability.

Trial registration

The study is registered with the National Medical Research Register, Ministry of Health Malaysia (NMRR-17-295-34711).
Agreement between self-reported morbidity and pharmacy claims data for prescribed medications in an older community based population
Authors: Mannion Clionadh , Hughes John , Moriarty Frank , Bennett Kathleen , Cahir Caitriona
Published: August 2020

Background

Studies have indicated variability around prevalence estimates of multimorbidity due to poor consensus regarding its definition and measurement. Medication-based measures of morbidity may be valuable resources in the primary-care setting where access to medical data can be limited. We compare the agreement between patient self-reported and medication-based morbidity; and examine potential patient-level predictors of discordance between these two measures of morbidity in an older (≥ 50 years) community-based population.

Methods

A retrospective cohort study was performed using national pharmacy claims data linked to The Irish LongituDinal study on Ageing (TILDA). Morbidity was measured by patient self-report (TILDA) and two medication-based measures, the Rx-Risk (< 65 years) and Rx-Risk-V (≥65 years), which classify drug claims into chronic disease classes. The kappa statistic measured agreement between self-reported and medication-based morbidity at the individual patient-level. Multivariate logistic regression was used to examine patient-level characteristics associated with discordance between measures of morbidity.

Results

Two thousand nine hundred twenty-five patients were included (< 65 years:N = 1095, 37.44%; and ≥ 65 years:N = 1830 62.56%). Hypertension and high cholesterol were the most prevalent self-reported morbidities in both age cohorts. Agreement was good or very good (κ = 0.61–0.81) for diabetes, osteoporosis and glaucoma; and moderate for high cholesterol, asthma, Parkinson’s and angina (κ = 0.44–0.56). All other conditions had fair or poor agreement. Age, gender, marital status, education, poor-delayed recall, depression and polypharmacy were significantly associated with discordance between morbidity measures.

Conclusions

Most conditions achieved only moderate or fair agreement between self-reported and medication-based morbidity. In order to improve the accuracy in prevalence estimates of multimorbidity, multiple measures of multimorbidity may be necessary. Future research should update the current Rx-Risk algorithms in-line with current treatment guidelines, and re-assess the feasibility of using these indices alone, or in combination with other methods, to yield more accurate estimates of multimorbidity.
Place of death associated with types of long-term care services near the end-of-life for home-dwelling older people in Japan: a pooled cross-sectional study
Authors: Abe Kazuhiro , Miyawaki Atsushi , Kobayashi Yasuki , Watanabe Taeko , Tamiya Nanako
Published: August 2020

Background

Many older people wish to die at home. However, there is still a huge gap between the place where older adults wish to die and the place where they, in fact, do die. We aimed to assess the association between each type of long-term care (LTC) services that home-dwelling older individuals utilized at their end of life and place of death.

Methods

A pooled cross-sectional study at the point of death was used for the analysis. Participants included beneficiaries of long-term care insurance in Japan, aged 65 years and above, who passed away between January 2008 and December 2013, excluding those who died due to external factors and those who were using residential services at their time of death. We conducted a multivariate Poisson regression analysis with robust standard errors adjusting for potential confounders and examined the association between the use of each type of LTC service for home-dwelling recipients, including in-home services, day services, and short-stay services, with the interaction terms being time of death (exposure) and home death (outcome). We calculated the adjusted probability of home deaths for each combination pattern of LTC services for home-dwelling recipients using standard marginalization.

Results

We analyzed 2,035,657 beneficiaries. The use of in-home services, day services, and short-stay services were associated with an increased probability of home deaths; the incident rate ratio (IRR) was 13.40 (with a 95% confidence interval (CI): 13.23–13.57) for in-home services, the IRR was 6.32 (6.19–6.45) for day services, and the IRR was 1.25 (1.16–1.34) for short-stay services. Those who used day or short-stay services with in-home services exhibited a higher probability of home deaths than those who used only day or short-stay services.

Conclusions

We demonstrated that home-dwelling older persons who used LTC services near end-of-life had a higher probability of home deaths as compared to those who did not. Our findings can clarify the importance of providing and integrating such services to support care recipients who wish to die at home as well as for the benefit of their informal caregivers.
Mediolateral damping of an overhead body weight support system assists stability during treadmill walking
Authors: Bannwart M. , Bayer S. L. , König Ignasiak N. , Bolliger M. , Rauter G. , Easthope C. A.
Published: August 2020

Background

Body weight support systems with three or more degrees of freedom (3-DoF) are permissive and safe environments that provide unloading and allow unrestricted movement in any direction. This enables training of walking and balance control at an early stage in rehabilitation. Transparent systems generate a support force vector that is near vertical at all positions in the workspace to only minimally interfere with natural movement patterns. Patients with impaired balance, however, may benefit from additional mediolateral support that can be adjusted according to their capacity. An elegant solution for providing balance support might be by rendering viscous damping along the mediolateral axis via the software controller. Before use with patients, we evaluated if control-rendered mediolateral damping evokes the desired stability enhancement in able-bodied individuals.

Methods

A transparent, cable-driven robotic body weight support system (FLOAT) was used to provide transparent body weight support with and without mediolateral damping to 21 able-bodied volunteers while walking at preferred gait velocity on a treadmill. Stability metrics reflecting resistance to small and large perturbations were derived from walking kinematics and compared between conditions and to free walking.

Results

Compared to free walking, the application of body weight support per-se resulted in gait alterations typically associated with body weight support, namely increased step length and swing phase. Frontal plane dynamic stability, measured by kinematic variability and nonlinear dynamics of the center of mass, was increased under body weight support, indicating reduced balance requirements in both damped and undamped support conditions. Adding damping to the body weight support resulted in a greater increase of frontal plane stability.

Conclusion

Adding mediolateral damping to 3-DoF body weight support systems is an effective method of increasing frontal plane stability during walking in able-bodied participants. Building on these results, adjustable mediolateral damping could enable therapists to select combinations of unloading and stability specifically for each patient and to adapt this in a task specific manner. This could extend the impact of transparent 3-DoF body weight support systems, enabling training of gait and active balance from an early time point onwards in the rehabilitation process for a wide range of mobility activities of daily life.
Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism
Authors: Chao Owen Y. , Pathak Salil S. , Zhang Hao , Dunaway Nathan , Li Jay-Shake , Mattern Claudia , Nikolaus Susanne , Huston Joseph P. , Yang Yi-Mei
Published: August 2020

The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T+Itpr3tf/J (BTBR) mice and Fragile X Mental Retardation 1 knockout (Fmr1-KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6 J wild-type ones. In contrast, Fmr1-KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher “complexity” and lower “texture”. Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1-KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.
Ferroptosis, necroptosis, and pyroptosis in anticancer immunity
Authors: Tang Rong , Xu Jin , Zhang Bo , Liu Jiang , Liang Chen , Hua Jie , Meng Qingcai , Yu Xianjun , Shi Si
Published: August 2020

In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by the fact that only one third of patients with most types of cancer respond to these agents. The induction of cell death mechanisms other than apoptosis has gradually emerged as a new cancer treatment strategy because most tumors harbor innate resistance to apoptosis. However, to date, the possibility of combining these two modalities has not been discussed systematically. Recently, a few studies revealed crosstalk between distinct cell death mechanisms and antitumor immunity. The induction of pyroptosis, ferroptosis, and necroptosis combined with ICIs showed synergistically enhanced antitumor activity, even in ICI-resistant tumors. Immunotherapy-activated CD8+ T cells are traditionally believed to induce tumor cell death via the following two main pathways: (i) perforin-granzyme and (ii) Fas-FasL. However, recent studies identified a new mechanism by which CD8+ T cells suppress tumor growth by inducing ferroptosis and pyroptosis, which provoked a review of the relationship between tumor cell death mechanisms and immune system activation. Hence, in this review, we summarize knowledge of the reciprocal interaction between antitumor immunity and distinct cell death mechanisms, particularly necroptosis, ferroptosis, and pyroptosis, which are the three potentially novel mechanisms of immunogenic cell death. Because most evidence is derived from studies using animal and cell models, we also reviewed related bioinformatics data available for human tissues in public databases, which partially confirmed the presence of interactions between tumor cell death and the activation of antitumor immunity.
MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4
Authors: Lin Ji , Huang Huijuan , Lin Liheng , Li Weiwei , Huang Jianfen
Published: August 2020

Background

MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells.

Results

Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway.

Conclusions

In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.
Structural basis of the anti-ageing effects of polyphenolics: mitigation of oxidative stress
Authors: Rolt Adam , Cox Lynne S.
Published: August 2020

Ageing, and particularly the onset of age-related diseases, is associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Polyphenolic natural products such as stilbenoids, flavonoids and chalcones have been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis and cellular senescence, both in vitro and in vivo. Here we aim to identify the structural basis underlying the pharmacology of polyphenols towards ROS and related biochemical pathways involved in age-related disease. We compile and describe SAR trends across different polyphenol chemotypes including stilbenoids, flavonoids and chalcones, review their different molecular targets and indications, and identify common structural ground between chemotypes and mechanisms of action. In particular, we focus on the structural requirements for the direct scavenging of reactive oxygen/nitrogen species such as radicals as well as coordination of a broader antioxidant response. We further suggest that it is important to consider multiple (rather than single) biological activities when identifying and developing new medicinal chemistry entities with utility in modulating complex biological properties such as cell ageing.
Biomethanation processes: new insights on the effect of a high H2 partial pressure on microbial communities
Authors: Braga Nan Lucia , Trably Eric , Santa-Catalina Gaëlle , Bernet Nicolas , Delgenès Jean-Philippe , Escudié Renaud
Published: August 2020

Background

Biomethanation is a promising solution to upgrade the CH4 content in biogas. This process consists in the injection of H2 into an anaerobic digester, using the capacity of indigenous hydrogenotrophic methanogens for converting the injected H2 and the CO2 generated from the anaerobic digestion process into CH4. However, the injection of H2 could cause process disturbances by impacting the microbial communities of the anaerobic digester. Better understanding on how the indigenous microbial community can adapt to high H2 partial pressures is therefore required.

Results

Seven microbial inocula issued from industrial bioprocesses treating different types of waste were exposed to a high H2 partial pressure in semi-continuous reactors. After 12 days of operation, even though both CH4 and volatile fatty acids (VFA) were produced as end products, one of them was the main product. Acetate was the most abundant VFA, representing up to 94% of the total VFA production. VFA accumulation strongly anti-correlated with CH4 production according to the source of inoculum. Three clusters of inocula were distinguished: (1) inocula leading to CH4 production, (2) inocula leading to the production of methane and VFA in a low proportion, and (3) inocula leading to the accumulation of mostly VFA, mainly acetate. Interestingly, VFA accumulation was highly correlated to a low proportion of archaea in the inocula, a higher amount of homoacetogens than hydrogenotrophic methanogens and, the absence or the very low abundance in members from the Methanosarcinales order. The best methanogenic performances were obtained when hydrogenotrophic methanogens and Methanosarcina sp. co-dominated all along the operation.

Conclusions

New insights on the microbial community response to high H2 partial pressure are provided in this work. H2 injection in semi-continuous reactors showed a significant impact on microbial communities and their associated metabolic patterns. Hydrogenotrophic methanogens, Methanobacterium sp. or Methanoculleus sp. were highly selected in the reactors, but the presence of co-dominant Methanosarcinales related species were required to produce higher amounts of CH4 than VFA.
Distribution and prevalence of ticks and tick-borne disease on sheep and cattle farms in Great Britain
Authors: Lihou Katie , Rose Vineer Hannah , Wall Richard
Published: August 2020

Introduction

The most abundant and widespread tick species in Great Britain,Ixodes ricinus, is responsible for the transmission of a range of pathogens that cause disease in livestock. Empirical data on tick distribution and prevalence are required to inform farm management strategies. However, such data are largely unavailable; previous surveys have been rare and are usually relatively localised.

Methods

A retrospective questionnaire survey of farmers was used to assess the reported prevalence of ticks on livestock across Great Britain. Spatial scan statistics and kernel density maps were used to assess spatial clustering and identify areas of significantly elevated risk, independent of the underlying distribution of respondents. Logistic regression models were used to identify risk factors for tick presence.

Results

Tick infection risk to livestock is shown to be spatially aggregated, with areas of significantly elevated risk in north Wales, northwest England and western Scotland. Overall, the prevalence of farms reporting tick presence was 13% for sheep farms and 6% for cattle farms, but in “hot spot” clusters prevalence ranged between 48–100%. The prevalence of farms reporting tick-borne disease overall was 6% for sheep and 2% for cattle, but on farms reporting ticks, prevalence was 44% and 33% for sheep and cattle farms, respectively. Upland farming, larger flock sizes, region and the presence of sheep on cattle farms were all significant risk factors for tick presence.

Conclusions

These data have important implications for assessing both the risk of tick-borne disease in livestock and optimising approaches to disease management. In particular, the study highlights the need for effective livestock tick control in upland regions and the southwest, and provides evidence for the importance of sheep as tick maintenance hosts.
Prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) phenotypes of Pseudomonas aeruginosa and Acinetobacter baumannii isolated in clinical samples from Northeast of Iran
Authors: Mirzaei Bahman , Bazgir Zahra Norouzi , Goli Hamid Reza , Iranpour Fatemeh , Mohammadi Fatemeh , Babaei Ryhaneh
Published: August 2020

Objective

Multi and extensively drug-resistant (MDR and XDR), Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) are two main causative agents of nosocomial infections leading to increased morbidity and mortality. We aim to study the prevalence of MDR and XDR-A. baumannii and P. aeruginosa phenotypes in clinical specimens. We conducted this for 1 year (2017–2018) and isolated bacteria from the clinical samples. Then, XDR and MDR strains were determined by susceptibility testing (disc diffusion).

Results

Out of 3248 clinical samples, A. baumannii and P. aeruginosa strains were detected in 309(9.51%) of them. Susceptibility testing indicated that (16.50%) and (15.53%) of the P. aeruginosa and (74.75%) and (73.13%) of the A. baumannii isolates were screened as the MDR and XDR strains. The frequency of MDR isolates was higher in wound samples 222 (71.8%). This rate in behavioral intensive care unit (BICU) and restoration ward, were 187 (60.5%) and 63 (20.4%). The frequency of XDR isolates in BICU 187 (59.54%), restoration 58(18.77%), and burns 30 (9.70%) were assessed as well. Considering high isolation rates of MDR and XDR of mentioned strains, it is necessary to apply prevention criteria for eradication of the mentioned bacteria from hospital wards.
Activin/Nodal signaling mediates dorsal–ventral axis formation before third quartet formation in embryos of the annelid Chaetopterus pergamentaceus
Authors: Lanza Alexis R. , Seaver Elaine C.
Published: August 2020

Background

The clade of protostome animals known as the Spiralia (e.g., mollusks, annelids, nemerteans and polyclad flatworms) shares a highly conserved program of early development. This includes shared arrangement of cells in the early-stage embryo and fates of descendant cells into embryonic quadrants. In spiralian embryos, a single cell in the D quadrant functions as an embryonic organizer to pattern the body axes. The precise timing of the organizing signal and its cellular identity varies among spiralians. Previous experiments in the annelid Chaetopterus pergamentaceus Cuvier, 1830 demonstrated that the D quadrant possesses an organizing role in body axes formation; however, the molecular signal and exact cellular identity of the organizer were unknown.

Results

In this study, the timing of the signal and the specific signaling pathway that mediates organizing activity in C. pergamentaceus was investigated through short exposures to chemical inhibitors during early cleavage stages. Chemical interference of the Activin/Nodal pathway but not the BMP or MAPK pathways results in larvae that lack a detectable dorsal–ventral axis. Furthermore, these data show that the duration of organizing activity encompasses the 16 cell stage and is completed before the 32 cell stage.

Conclusions

The timing and molecular signaling pathway of the C. pergamentaceus organizer is comparable to that of another annelid, Capitella teleta, whose organizing signal is required through the 16 cell stage and localizes to micromere 2d. Since C. pergamentaceus is an early branching annelid, these data in conjunction with functional genomic investigations in C. teleta hint that the ancestral state of annelid dorsal–ventral axis patterning involved an organizing signal that occurs one to two cell divisions earlier than the organizing signal identified in mollusks, and that the signal is mediated by Activin/Nodal signaling. Our findings have significant evolutionary implications within the Spiralia, and furthermore suggest that global body patterning mechanisms may not be as conserved across bilaterians as was previously thought.
Educational initiatives and implementation of electroencephalography into the acute care environment: a protocol of a systematic review
Authors: Taran Shaurya , Ahmed Wael , Bui Esther , Prisco Lara , Hahn Cecil D. , McCredie Victoria A.
Published: August 2020

Background

Use of electroencephalography (EEG) is currently recommended by the American Clinical Neurophysiology Society for a wide range of indications, including diagnosis of nonconvulsive status epilepticus and evaluation of unexplained disorders of consciousness. Data interpretation usually occurs by expert personnel (e.g., epileptologists, neurophysiologists), with information relayed to the primary care team. However, data cannot always be read in time-sensitive fashion, leading to potential delays in EEG interpretation and patient management. Multiple training programs have recently been described to enable non-experts to rapidly interpret EEG at the bedside. A comprehensive review of these training programs, including the tools used, outcomes obtained, and potential pitfalls, is currently lacking. Therefore, the optimum training program and implementation strategy remain unknown.

Methods

We will conduct a systematic review of descriptive studies, case series, cohort studies, and randomized controlled trials assessing training programs for EEG interpretation by non-experts. Our primary objective is to comprehensively review educational programs in this domain and report their structure, patterns of implementation, limitations, and trainee feedback. Our secondary objective will be to compare the performance of non-experts for EEG interpretation with a gold standard (e.g., interpretation by a certified electroencephalographers). Studies will be limited to those performed in acute care settings in both adult and pediatric populations (intensive care unit, emergency department, or post-anesthesia care units). Comprehensive search strategies will be developed for MEDLINE, EMBASE, WoS, CINAHL, and CENTRAL to identify studies for review. The gray literature will be scanned for further eligible studies. Two reviewers will independently screen the search results to identify studies for inclusion. A standardized data extraction form will be used to collect important data from each study. If possible, we will attempt to meta-analyze the quantitative data. If heterogeneity between studies is too high, we will present meaningful quantitative comparisons of secondary outcomes as per the synthesis without meta-analysis (SWiM) reporting guidelines.

Discussion

We will aim to summarize the current literature in this domain to understand the structure, patterns, and pitfalls of EEG training programs for non-experts. This review is undertaken with a view to inform future education designs, potentially enabling rapid detection of EEG abnormalities, and timely intervention by the treating physician.

PROSPERO registration

Submitted and undergoing review. Registration ID: CRD42020171208.
Enterococcus faecium: from microbiological insights to practical recommendations for infection control and diagnostics
Authors: Zhou Xuewei , Willems Rob J. L. , Friedrich Alexander W. , Rossen John W. A. , Bathoorn Erik
Published: August 2020

Early in its evolution,Enterococcus faeciumacquired traits that allowed it to become a successful nosocomial pathogen.E. faeciuminherent tenacity to build resistance to antibiotics and environmental stressors that allows the species to thrive in hospital environments. The continual wide use of antibiotics in medicine has been an important driver in the evolution ofE. faeciumbecoming a highly proficient hospital pathogen.

For successful prevention and reduction of nosocomial infections with vancomycin resistantE. faecium(VREfm), it is essential to focus on reducing VREfm carriage and spread. The aim of this review is to incorporate microbiological insights ofE. faeciuminto practical infection control recommendations, to reduce the spread of hospital-acquired VREfm (carriage and infections). The spread of VREfm can be controlled by intensified cleaning procedures, antibiotic stewardship, rapid screening of VREfm carriage focused on high-risk populations, and identification of transmission routes through accurate detection and typing methods in outbreak situations. Further, for successful management ofE. faecium,continual innovation in the fields of diagnostics, treatment, and eradication is necessary.
Multidisciplinary inpatient rehabilitation improves the long-term functional status of geriatric hip-fracture patients
Authors: Pfeufer Daniel , Kammerlander Christian , Stadler Christian , Roth Tobias , Blauth Michael , Neuerburg Carl , Böcker Wolfgang , Zeckey Christian , Lechleitner Monika , Gosch Markus
Published: August 2020

Background

As the world population ages, the number of hip-related fractures in the elderly is steadily increasing. These fractures generate a major worldwide healthcare problem and frequently lead to deterioration of life quality, mobility and independence in activity of daily life of geriatric patients. At present, many studies have investigated and proved benefits of multidisciplinary orthogeriatric care for elderly hip-fracture patients. Only few studies however, have analyzed treatment concepts for those patients directly following discharge from hospital in specialized rehabilitation centers. The aim of this study was to evaluate effects of a multidisciplinary inpatient rehabilitation on the short- and long-term functional status of geriatric patients who suffered from hip fracture.

Methods

A total of 161 hip-fracture patients aged 80 years and above, or additionally 70 years and above suffering from age-typical multimorbidity were included in this study. Patients who had an initial Barthel Index lower than 30 points were excluded from this study, as most of these patients were not able to attend a therapy at the rehabilitation center due to a poor functional status. The patients were separated into two subgroups dependent on the availability of treatment spots at the rehabilitation center. No other item was used to discriminate between the groups. Group A (n = 95) stayed an average of 21 days at an inpatient rehabilitation center that specialized in geriatric patients. Group B (n = 66) underwent the standard postoperative treatment and were sent home with further treatment by their general practitioner, nursing staff and physiotherapists. To evaluate the patients’ functional status over the course of time we used the Barthel Index, which was evaluated for every patient on the day of discharge, as well as during checkups after 3, 6 and 12 months.

Results

The average Barthel Index at the day of discharge was 57.79 ± 14.92 points for Group A and 56.82 ± 18.76 points for Group B (p = 0.431). After 3 months, the average Barthel Index was 82.43 points for Group A and 73.11 points for group B (p = 0.005). In the 6-month checkup Group A’s average Barthel Index was 83.95 points and Group B’s was 74.02 points (p = 0.002). After 12 months, patients from Group A had an average Barthel Index of 81.21 while patients from Group B had an average Barthel Index of 69.85 (p = 0.005).

Conclusion

The results of this study reveal a significantly better outcome concerning both, short-term and long-term functional status after 3, 6 and 12 months for geriatric hip-fracture patients, who underwent an inpatient treatment in a rehabilitation center following the initial therapy.
Fatal case of newborn Lassa fever virus infection mimicking late onset neonatal sepsis: a case report from northern Nigeria
Authors: Ogunkunle Taofik Oluwaseun , Bello Surajudeen Oyeleke , Anderson Chinwe Immaculata , Musa Rashida , Olaosebikan Rasaq , Imam Abdulazeez
Published: August 2020

Background

Lassa fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa fever infections are rare in scientific literature. We report a fatal case of Lassa fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis.

Case presentation

The patient is a 26-day-old neonate who was admitted with a day history of fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting the need to evaluate for Lassa fever using reverse transcription polymerase chain reaction (RT-PCR). He died 31 h into admission and RT-PCR result was positive for Lassa fever.

Conclusions

Neonatal Lassa fever infection is highly fatal and can mimic neonatal sepsis. High index of suspicion is needed particularly for atypical presentations of neonatal sepsis in Lassa fever endemic areas.
Temporal trends in areas at risk for concomitant tuberculosis in a hyperendemic municipality in the Amazon region of Brazil
Authors: Bruce Alexandre Tadashi Inomata , Berra Thais Zamboni , dos Santos Felipe Lima , Alves Yan Mathias , Souza Ludmilla Leidianne Limirio , Ramos Antônio Carlos Vieira , Arroyo Luiz Henrique , de Almeida Crispim Juliane , Pinto Ione Carvalho , Palha Pedro Fredemir , Monroe Aline Aparecida , Yamamura Mellina , Fiorati Regina Célia , Moncaio Ana Carolina Scarpel , de Oliveira Gomes Dulce Maria , Arcêncio Ricardo Alexandre
Published: August 2020

Background

Although preventable and curable, tuberculosis (TB) still occurs in poor or developing countries, mainly in metropolitan regions of larger cities. The disease is a serious public health problem, and is directly linked to social issues. We analyzed temporal trend variations in areas at risk for concomitant TB, and characterized the clinical and epidemiological profiles of cases in a hyperendemic municipality in the Amazon region of Brazil.

Methods

This ecological study was performed in the municipality of Manaus, in northern Brazil. The population comprised cases with concomitant pulmonary and extrapulmonary TB, registered on the Notifiable Diseases Information System (SINAN), between January 1, 2009 and December 31, 2018. For risk cluster detection, spatial and spatiotemporal scanning statistical techniques were used. The Spatial Variation in Temporal Trends (SVTT) approach was used to detect and infer clusters for significantly different time trends.

Results

Between 2009 and 2018, 873 concomitant TB cases were registered in Manaus. By using purely spatial scanning statistics, we identified two risk clusters. The relative risk (RR) of the clusters was 2.21 (95% confidence interval [CI]: 1.57–2.88; P = 0.0031) and 2.03 (95% CI: 1.58–2.58; P = 0.0029). Using space-time scanning, we identified a risk cluster with an RR of 3.57 (95% CI: 2.84–4.41; P = 0.014), between 2017 and 2018. For SVTT analyses, three clusters with spatial variations were detected in the significant temporal trends: SVTT 1 (P = 0.042), SVTT 2 (P = 0.046) and SVTT 3 (P = 0.036).

Conclusions

In Brazil, several TB-determining factors such as race/color, gender, low educational level and low income overlap in needy urban areas and communities, demonstrating that it is unlikely to reach the goals, agreed and launched with the END TB Strategy within the deadlines of international agreements, if there is no reduction in existing inequities determinants and risk of illness in the country.
The BONEBRIDGE active transcutaneous bone conduction implant: Effects of location, lifts and screws on sound transmission
Authors: Rohani Seyed Alireza , Bartling Mandolin Li , Ladak Hanif M. , Agrawal Sumit K.
Published: August 2020

Background

The BONEBRIDGE (MED-EL, Innsbruck, Austria) is a bone-conduction implant used in the treatment of conductive and mixed hearing loss. The BONEBRIDGE consists of an external audio processor and a bone-conduction floating mass transducer that is surgically implanted into the skull in either the transmastoid, retrosigmoid or middle fossa regions. The manufacturer includes self-tapping screws to secure the transducer; however, self-drilling screws have also been used with success. In cases where the skull is not thick enough to house the transducer, lifts are available in a variety of sizes to elevate the transducer away from the skull. The objective of the present study was to investigate the effects of screw type, lift thickness, and implant location on the sound transmission of the BONEBRIDGE.

Method

Six cadaveric temporal bones were embalmed and dried for use in this study. In each sample, a hole was drilled in each of the three implant locations to house the implant transducer. At the middle fossa, six pairs of screw holes were pre-drilled; four pairs to be used with self-tapping screws and lifts (1, 2, 3, and 4 mm thick lifts, respectively), one pair with self-tapping screws and no lifts, and one pair with self-drilling screws and no lifts. At the transmastoid and retrosigmoid locations, one pair of screw holes were pre-drilled in each for the use of the self-tapping screws. The vibration of transmitted sound to the cochlea was measured using a laser Doppler vibrometry technique. The measurements were performed on the cochlear promontory at eight discrete frequencies (0.5, 0.75, 1, 1.5, 2, 3, 4 and 6 kHz). Vibration velocity of the cochlear wall was measured in all samples. Measurements were analyzed using a single-factor ANOVA to investigate the effect of each modification.

Results

No significant differences were found related to either screw type, lift thickness, or implant location.

Conclusions

This is the first known study to evaluate the effect of screw type, lift thickness, and implant location on the sound transmission produced by the BONEBRIDGE bone-conduction implant. Further studies may benefit from analysis using fresh cadaveric samples or in-vivo measurements.
Tracheoesophageal voice prosthesis management in laryngectomy patients during the COVID-19 pandemic
Authors: Goldstein David P. , Ralph Gilbert , de Almeida John R. , Jethwa Ashok R. , Irish Jonathan , Chepeha Douglas B. , Brown Dale , Gullane Patrick , Waldron John , Aziza Elana , Durkin Lisa
Published: August 2020

With the COVID-19 pandemic, there has been significant changes and challenges in the management of oncology patients. One of the major strategies to reduce transmission of the virus between patients and healthcare workers is deferral of follow-up visits. However, deferral may not be possible in total laryngectomy patients. Urgent procedures may be necessary to prevent complications related to ill-fitting tracheoesophageal puncture (TEP) voice prostheses, such as aspiration or loss of voicing. In this paper, we describe the Princess Margaret Cancer Center's approach to managing this unique patient population.
P53 aggregation, interactions with tau, and impaired DNA damage response in Alzheimer’s disease
Authors: Farmer Kathleen M. , Ghag Gaurav , Puangmalai Nicha , Montalbano Mauro , Bhatt Nemil , Kayed Rakez
Published: August 2020

The transcription factor, p53, is critical for many important cellular functions involved in genome integrity, including cell cycle control, DNA damage response, and apoptosis. Disruption of p53 results in a wide range of disorders including cancer, metabolic diseases, and neurodegenerative diseases. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregates that contribute to disease pathology. Although p53 is known to aggregate, its propensity to aggregate in AD has never been assessed. Moreover, AD neuropathology includes lethal cell cycle re-entry, excessive DNA damage, and abnormal cell death which are all controlled by p53. Here, we show p53 forms oligomers and fibrils in human AD brain, but not control brain. p53 oligomers can also be detected in htau and P301L mouse models. Additionally, we demonstrate that p53 interacts with tau, specifically tau oligomers, in AD brain and can be recapitulated by in vitro exogenous tau oligomer treatment in C57BL/6 primary neurons. p53 oligomers also colocalize, potentially seeding, endogenous p53 in primary neurons. Lastly, we demonstrate that in the presence of DNA damage, phosphorylated p53 is mislocalized outside the nucleus and p53-mediated DNA damage responders are significantly decreased in AD brain. Control brain shows a healthy DNA damage response, indicating a loss of nuclear p53 function in AD may be due to p53 aggregation and/or interactions with tau oligomers. Given the critical role of p53 in cellular physiology, the disruption of this crucial transcription factor may set an irreversible course towards neurodegeneration in AD and potentially other tauopathies, warranting further investigation.
Antimicrobial activity of some plant essential oils and an antimicrobial-peptide against some clinically isolated pathogens
Authors: Tanhaeian Abbas , Sekhavati Mohammad Hadi , Moghaddam Mohammad
Published: August 2020

Background

Essential oils and antimicrobial peptides are two well-known safe and natural products that have been considered as alternatives to antibiotics. In the present study, the antibacterial activity of four plant essential oils and one lactoferrin-derived peptide was investigated.

Results

The chemical profile of each essential oil was determined by GC and GC–MS. Antimicrobial activity was shown against seven clinically isolated veterinary pathogens. MIC and MBC assessment of the essential oils and cLFchimera exhibited different antibacterial properties (MIC from a range of 62.5 to 500 µg/mL and 3.5 to 39.0 µg/mL for essential oils and cLFchimera, respectively). Compared to the essential oils, cLFchimera showed more significant antibacterial activity. Among the essential oils, Vitex agnus-castus and Salvia officinalis showed relatively better antibacterial activity.

Conclusions

The in vitro results reported here suggested that, for animals suffering from these pathogens, cLFchimera and the essential oils particularly Vitex agnus-castus could be considered as potential antimicrobial agents.