bluuebunny/crossref_metadata_2025 huggingface dataset:
Filamentous tangles with nemaline rods in MYH2 myopathy: a novel phenotype
Authors: Madigan Nicolas N. , Polzin Michael J. , Cui Gaofeng , Liewluck Teerin , Alsharabati Mohammad H. , Klein Christopher J. , Windebank Anthony J. , Mer Georges , Milone Margherita
Published: April 2021

The MYH2 gene encodes the skeletal muscle myosin heavy chain IIA (MyHC-IIA) isoform, which is expressed in the fast twitch type 2A fibers. Autosomal dominant or recessive pathogenic variants in MYH2 lead to congenital myopathy clinically featured by ophthalmoparesis and predominantly proximal weakness. MYH2-myopathy is pathologically characterized by loss and atrophy of type 2A fibers. Additional myopathological abnormalities have included rimmed vacuoles containing small p62 positive inclusions, 15–20 nm tubulofilaments, minicores and dystrophic changes. We report an adult patient with late-pediatric onset MYH2-myopathy caused by two heterozygous pathogenic variants: c.3331C>T, p.Gln1111* predicted to result in truncation of the proximal tail region of MyHC-IIA, and c.1546T>G, p.Phe516Val, affecting a highly conserved amino acid within the highly conserved catalytic motor head relay loop. This missense variant is predicted to result in a less compact loop domain and in turn could affect the protein affinity state. The patient’s genotype is accompanied by a novel myopathological phenotype characterized by centralized large myofilamentous tangles associated with clusters of nemaline rods, and ring fibers, in addition to the previously reported rimmed vacuoles, paucity and atrophy of type 2A fibers. Electron microscopy demonstrated wide areas of disorganized myofibrils which were oriented in various planes of direction and entrapped multiple nemaline rods, as corresponding to the large tangles with rods seen on light microscopy. Nemaline rods were rarely observed also in nuclei. We speculate that the mutated MyHC-IIA may influence myofibril disorganization. While nemaline rods have been described in myopathies caused by pathogenic variants in genes encoding several sarcomeric proteins, to our knowledge, nemaline rods have not been previously described in MYH2-myopathy.
The effects of tobacco taxation and pricing on the prevalence of smoking in Africa
Authors: Immurana Mustapha , Boachie Micheal Kofi , Iddrisu Abdul-Aziz
Published: April 2021

Background

Tobacco use continues to kill millions of people globally, making it one of the major causes of preventable deaths. Notwithstanding, there has been a very marginal fall in the prevalence of tobacco smoking in Africa. Since taxes (hence prices) are part of the main measures suggested to decrease the demand for tobacco products, this study investigates how tobacco taxation and pricing influence the prevalence of smoking in 24 African countries.

Methods

Using panel data on 24 African countries sourced from the World Health Organization (WHO) and the World Bank databases for the period 2010 to 2016, this study employs the system Generalized Method of Moments (GMM) estimator to investigate the effects of tobacco taxation and pricing on the prevalence of smoking. The system GMM estimator is used due its ability to deal with potential endogeneity of tobacco taxation and pricing: the likelihood that the prevalence of smoking can influence tobacco taxation and pricing which may lead to biased estimates.

Results

Tobacco taxation and pricing have negative significant effects on the prevalence of smoking among the selected countries after controlling for growth of Gross Domestic Product (GDP) per capita, urbanization, death rate and net inflows of Foreign Direct Investment (FDI). Specifically, a percentage increase in tobacco price is found to decrease the prevalence of smoking by between 0.11 to 0.14%, while a percentage increase in tobacco tax decreases the prevalence of smoking by between 0.25 to 0.36%, all at 1% level of significance.

Conclusion

Since tobacco taxation and pricing are found to have negative significant effects on the prevalence of smoking, the implication is that, their use can be intensified by African policy makers towards achieving the WHO Framework Convention on Tobacco Control (FCTC) recommended targets and hence decrease the prevalence of tobacco smoking in Africa. Doing so may therefore help in achieving the Sustainable Development Goal (SDG) 3.5 (prevention and treatment of substance abuse), thereby reducing the colossal number of smoking attributable deaths.
Correction to: Recent developments in photoacoustic imaging and sensing for nondestructive testing and evaluation
Authors: Chen Sung-Liang , Tian Chao
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Relationships Between 24-hour LH and Testosterone Concentrations and With Other Pituitary Hormones in Healthy Older Men
Authors: van der Spoel Evie , Roelfsema Ferdinand , van Heemst Diana
Published: April 2021

Objective

To investigate the relationship between LH and testosterone (T), which characteristics associate with the strength of this relationship, and their interrelationships with GH, TSH, cortisol, and ACTH.

Design

Hormones were measured in serum samples collected every 10 minutes during 24 hours from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between 2 timeseries for all possible time shifts.

Results

Mean (95% CI) maximal correlation was 0.21 (0.10-0.31) at lag time of 60 minutes between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared with men with no cross-correlation, lower fat mass (18.5 [14.9-19.7] vs. 22.3 [18.4-29.4] kg), waist circumference (93.6 [5.7] vs. 103.1 [12.0] cm), high-sensitivity C-reactive protein (0.7 [0.4-1.3] vs. 1.8 [0.8-12.3] mg/L), IL-6 (0.8 [0.6-1.0] vs. 1.2 [0.9-3.0] pg/mL), and 24-hour mean LH (4.3 [2.0] vs. 6.1 [1.5] U/L), and stronger LH-T feedforward synchrony (1.5 [0.3] vs. 1.9 [0.2]). Furthermore, T was positively cross-correlated with TSH (0.32 [0.21-0.43]), cortisol (0.26 [0.19-0.33]), and ACTH (0.26 [0.19-0.32]).

Conclusions

LH is followed by T with a delay of 60 minutes in healthy older men. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, LH levels, and LH-T feedforward synchrony. We observed positive correlations between T and TSH, cortisol, and ACTH.
Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway
Authors: Wang Hui , Wang Chengdong , Long Qi , Zhang Yuan , Wang Meiling , Liu Jie , Qi Xufeng , Cai Dongqing , Lu Gang , Sun Jianmin , Yao Yong-Gang , Chan Wood Yee , Chan Wai Yee , Deng Yi , Zhao Hui
Published: April 2021

The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin 2 (Fermt2) is widely expressed in mouse embryos, and its absence causes lethality at the peri-implantation stage due to the failure to trigger integrin activation. The function of kindlin2 during embryogenesis has not yet been fully elucidated as a result of this early embryonic lethality. Here, we showed that kindlin2 is essential for neural crest (NC) formation in Xenopus embryos. Loss-of-function assays performed with kindlin2-specific morpholino antisense oligos (MOs) or with CRISPR/Cas9 techniques in Xenopus embryos severely inhibit the specification of the NC. Moreover, integrin-binding-deficient mutants of Kindlin2 rescued the phenotype caused by loss of kindlin2, suggesting that the function of kindlin2 during NC specification is independent of integrins. Mechanistically, we found that Kindlin2 regulates the fibroblast growth factor (FGF) pathway, and promotes the stability of FGF receptor 1. Our study reveals a novel function of Kindlin2 in regulating the FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.
A novel injury paradigm in the central nervous system of adult Drosophila: molecular, cellular and functional aspects
Authors: Losada-Pérez María , García-Guillén Nuria , Casas-Tintó Sergio
Published: April 2021

The mammalian central nervous system (CNS) exhibits limited regenerative capacity and the mechanisms that mediate its regeneration are not fully understood. Here, we present a novel experimental design to damage the CNS by using a contusion injury paradigm. The design of this protocol allows the study of long-term and short-term cellular responses, including those of the CNS and the immune system, and of any implications regarding functional recovery. We demonstrate for the first time that adult Drosophilamelanogaster glial cells undergo spontaneous functional recovery following crush injury. This crush injury leads to an intermediate level of functional recovery after damage, which is ideal to screen for genes that facilitate or prevent the regeneration process. Here, we validate this model and analyse the immune responses of glial cells as a central regulator of functional regeneration. Additionally, we demonstrate that glial cells and macrophages contribute to functional regeneration through mechanisms involving the Jun N-terminal kinase (JNK) pathway and the Drosophila protein Draper (Drpr), characteristic of other neural injury paradigms. We show that macrophages are recruited to the injury site and are required for functional recovery. Further, we show that the proteins Grindelwald and Drpr in Drosophila glial cells mediate activation of JNK, and that expression of drpr is dependent on JNK activation. Finally, we link neuron-glial communication and the requirement of neuronal vesicular transport to regulation of the JNK pathway and functional recovery.

This article has an associated First Person interview with the first author of the paper.
Counseling at all contacts for postpartum contraceptive use: can paper-based tools help community health workers improve continuity of care? A qualitative study from Ethiopia
Authors: Mossie Muluneh Yigzaw , Pfitzer Anne , Yusuf Yousra , Wondimu China , Bazant Eva , Bansal Vaiddehi , Mackenzie Devon , Sitrin Deborah , Pleah Tsigue
Published: April 2021

Background: Globally, there has been a resurgence of interest in postpartum family planning (PPFP) to advance reproductive health outcomes. Few programs have systematically utilized all contacts a woman and her baby have with the health system, from pregnancy through the first year postpartum, to promote PPFP. Nested into a larger study covering two districts, this study assessed the use, acceptability, and feasibility of tools for tracking women’s decision-making and use of PPFP in the community health system in Oromia region, Ethiopia. Community-level tracking tools included a modified Integrated Maternal and Child Health (IMCH) card with new PPFP content, and a newly developed tool for pregnant and postpartum women for use by Women Development Armies (WDAs). Proper completion of the tools was monitored during supervision visits.

Methods: In-depth interviews and focus group discussions were conducted with health officials, health extension workers, and volunteers. A total of 34 audio-files were transcribed and translated into English, double-coded using MAXQDA, and analyzed using a thematic approach.

Results: The results describe how HEWs used the modified IMCH card to track women’s decision making through the continuum of care, to assess pregnancy risk and to strengthen client-provider interaction. Supervision data demonstrated how well HEWs completed the modified IMCH card. The WDA tool was intended to promote PPFP and encourage multiple contacts with facilities from pregnancy to extended postpartum period. HEWs have reservations about the engagement of WDAs and their use of the WDA tool.

Conclusions: To conclude, the IMCH card improves counseling practices through the continuum of care and is acceptable and feasible to apply. Some elements have been incorporated into a revised national tool and can serve as example for other low-income countries with similar community health systems. Further study is warranted to determine how to engage WDAs in promoting PPFP.
Addressing implementation considerations when developing universal interventions for speech, language and communication needs in the ordinary classroom: a protocol for a scoping review
Authors: Gallagher Aoife , Murphy Carol-Anne , Fitzgerald Johanna , Law James
Published: April 2021

Background: Understanding the factors that influence the implementation of health interventions in the context of education is essential to improving outcomes for children and young people with speech and language needs (SLCN). Yet implementation considerations have not been adequately addressed when developing interventions for this context. The aim of this paper is to present a protocol for a scoping review of existing implementation frameworks that might guide SLCN intervention research in schools. 

Methods: In accordance with scoping review guidelines, the study will be conducted in six phases: (1) identification of the research question, (2) identification of potentially relevant studies of Implementation Science frameworks, (3) study screening and selection, (4) charting and extracting data from identified frameworks, (5) collating, summarising and reporting the results and (6) consultation with stakeholders. Two reviewers will conduct the screening and extraction stages independently. Identified frameworks will be collated, and described, and constructs from the IS frameworks will be categorised using domains from the Consolidated Framework for Implementation Research. A draft IS model will be proposed based on the findings of the scoping review.

Conclusions: The findings of this review will provide guidance for researchers in addressing implementation considerations when developing universal interventions for SLCN in the ordinary classroom, and ultimately will contribute towards improving outcomes for this vulnerable childhood population.
Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review
Authors: Odhiambo Mercy , Kariuki Symon M. , Newton Charles R.
Published: April 2021

Background: The treatment gap for epilepsy is large in low- and middle-income countries (LMICs) and the effectiveness and safety of the available anti-seizure medication (ASMs) is not fully understood. We conducted a systematic review to evaluate the extent of therapeutic drug monitoring (TDM) of ASM in LMIC, including purposes and methods used during monitoring.

Methods: A search was conducted on four main databases (PubMed, Psych-Info, CINAHL and Embase), with eligible articles screened using a PRISMA checklist and a set of exclusion and inclusion criteria. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Descriptive statistics were used to pool median distribution of TDM across studies.

Results: Of the 6,309 articles identified in the initial search, 65 (1.0%) met the eligibility criteria. TDM of ASMs was mostly done to assess toxicity (42.8%), but rarely to monitor adherence (9.0%). TDM differed by economic status and infrastructural status with majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). First generation ASMs (82.3%) were more likely to be monitored than second generation ASMs (17.6%) and carbamazepine was the most frequently monitored drug. Fluorescence Polarization Immunoassay (FPIA) was the most common technique used for TDM (41.5%) followed by High-Performance Liquid Chromatography (HPLC) (16.9%). In addition, FPIA was the cheapest method of TDM based on approximated costs ($1000, TDx system). Assay validation and quality control were reported variably, and reference ranges used during TDM of ASMs were relatively uniform.

Conclusions: TDM is mostly done to evaluate ASM toxicity, but rarely for other reasons such as evaluating adherence or assessing clinical efficacy. There is a need for more investment in comprehensive TDM in LMICs that incorporates dose titration of ASM using pharmacokinetics and pharmacodynamics modelling, for both first generation and second generation ASMs.
Percepciones y aprendizajes en un huerto educativo en Educación Primaria.
Authors: Suárez-López Rafael , Ramos-Truchero Guadalupe , Tutor David , Gutiérrez Claudia
Published: April 2021

Los huertos educativos son una herramienta y un contexto didáctico muy versátil y de gran potencial para diferentes propósitos educativos, como la enseñanza de las ciencias, la mejora de los hábitos alimentarios, o la formación de una ciudadanía sostenible, especialmente en sus dimensiones alimentaria y ambiental. Este trabajo investiga el impacto de un programa de Educación Ambiental realizado en huertos educativos con estudiantes de 5º curso de Educación Primaria de tres colegios de Valladolid. Para ello, se realizaron grupos focales de diez alumnos por colegio, antes y después del programa educativo. Las grabaciones de dichos grupos focales fueron transcritas y analizadas mediante el software MAXQDA para desarrollar un sistema de categorías y subcategorías, con el objetivo de detectar los cambios en el discurso de los estudiantes. Los estudiantes valoraron el tiempo de trabajo en el huerto positivamente como tiempo de aprendizaje, no obstante, algunos no lo percibieron como tiempo de clase. Aunque los estudiantes ya tenían un discurso elaborado sobre la relación entre alimentación y salud, se muestra que reforzaron y ampliaron sus conocimientos previos. Sin embargo, no desarrollaron conciencia sobre los impactos ambientales relacionados con la producción de alimentos. Los resultados muestran la importancia de los huertos educativos para la formación de una ciudadanía sostenible, pero también la importancia del diseño de los programas educativos.
Assigning Priorities (or Not) in Service Systems with Nonlinear Waiting Costs
Authors: Ouyang Huiyin , Taník Argon Nilay , Ziya Serhan
Published: April 2021

For a queueing system with multiple customer types differing in service-time distributions and waiting costs, it is well known that the cµ-rule is optimal if costs for waiting are incurred linearly with time. In this paper, we seek to identify policies that minimize the long-run average cost under nonlinear waiting cost functions within the set of fixed priority policies that only use the type identities of customers independently of the system state. For a single-server queueing system with Poisson arrivals and two or more customer types, we first show that some form of the cµ-rule holds with the caveat that the indices are complex, depending on the arrival rate, higher moments of service time, and proportions of customer types. Under quadratic cost functions, we provide a set of conditions that determine whether to give priority to one type over the other or not to give priority but serve them according to first-come, first-served (FCFS). These conditions lead to useful insights into when strict (and fixed) priority policies should be preferred over FCFS and when they should be avoided. For example, we find that, when traffic is heavy, service times are highly variable, and the customer types are not heterogenous, so then prioritizing one type over the other (especially a proportionally dominant type) would be worse than not assigning any priority. By means of a numerical study, we generate further insights into more specific conditions under which fixed priority policies can be considered as an alternative to FCFS.

This paper was accepted by Baris Ata, stochastic models and simulation.
Teacher-rated aggression and co-occurring behaviors and emotional problems among schoolchildren in four population-based European cohorts
Authors: Whipp Alyce M. , Vuoksimaa Eero , Bolhuis Koen , de Zeeuw Eveline L. , Korhonen Tellervo , Mauri Matteo , Pulkkinen Lea , Rimfeld Kaili , Rose Richard J. , Beijsterveldt Catharina (Toos) E. M. van , Bartels Meike , Plomin Robert , Tiemeier Henning , Kaprio Jaakko , Boomsma Dorret I.
Published: April 2021

Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7–14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47–0.80) and lower with internalizing problems (r: 0.02–0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the higher mean levels of aggressive behavior in boys, the correlations were notably similar for boys and girls (e.g., aggressive-hyperactivity correlations: 0.51–0.75 boys, 0.47–0.70 girls) and did not vary greatly with respect to age, instrument or cohort. Thus, teacher-rated aggressive behavior rarely occurs in isolation; boys and girls with problems of aggressive behavior likely require help with other behavioral and emotional problems. Important to note, higher aggressive behavior is not only associated with higher amounts of other externalizing and internalizing problems but also with lower levels of prosocial behavior.
MR. Estimator, a toolbox to determine intrinsic timescales from subsampled spiking activity
Authors: Spitzner F. P. , Dehning J. , Wilting J. , Hagemann A. , P. Neto J. , Zierenberg J. , Priesemann V.
Published: April 2021

Here we present our Python toolbox “MR. Estimator” to reliably estimate the intrinsic timescale from electrophysiologal recordings of heavily subsampled systems. Originally intended for the analysis of time series from neuronal spiking activity, our toolbox is applicable to a wide range of systems where subsampling—the difficulty to observe the whole system in full detail—limits our capability to record. Applications range from epidemic spreading to any system that can be represented by an autoregressive process. In the context of neuroscience, the intrinsic timescale can be thought of as the duration over which any perturbation reverberates within the network; it has been used as a key observable to investigate a functional hierarchy across the primate cortex and serves as a measure of working memory. It is also a proxy for the distance to criticality and quantifies a system’s dynamic working point.
Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks
Authors: Arnold David T. , Donald Charmaine , Lyon Max , Hamilton Fergus W. , Morley Anna J. , Attwood Marie , Dipper Alexandra , Barratt Shaney L.
Published: April 2021

Introduction

Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up.

Methods

Prospective single centre observational study.

Results

Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml).

Conclusions

The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.
Castration causes an increase in lysosomal size and upregulation of cathepsin D expression in principal cells along with increased secretion of procathepsin D and prosaposin oligomers in adult rat epididymis
Authors: Carvelli Lorena , Aguilera Andrea Carolina , Zyla Leila , Pereyra Laura Lucía , Morales Carlos R. , Hermo Louis , Sosa Miguel A.
Published: April 2021

In the epididymis, lysosomal proteins of the epithelial cells are normally targeted from the Golgi apparatus to lysosomes for degradation, although their secretion into the epididymal lumen has been documented and associated with sperm maturation. In this study, cathepsin D (CatD) and prosaposin (PSAP) were examined in adult epididymis of control, and 2-day castrated rats without (Ct) and with testosterone replacement (Ct+T) to evaluate their expression and regulation within epididymal epithelial cells. By light microscope-immunocytochemistry, a quantitative increase in size of lysosomes in principal cells of Ct animals was noted from the distal initial segment to the proximal cauda. Androgen replacement did not restore the size of lysosomes to control levels. Western blot analysis revealed a significant increase in CatD expression in the epididymis of Ct animals, which suggested an upregulation of its expression in principal cells; androgens restored levels of CatD to that of controls. In contrast, PSAP expression in Ct animals was not altered from controls. Additionally, an increase in procathepsin D levels was noted from samples of the epididymal fluid of Ct compared to control animals, accompanied by an increased complex formation with PSAP. Moreover, an increased oligomerization of prosaposin was observed in the epididymal lumen of Ct rats, with changes reverted to controls in Ct+T animals. Taken together these data suggest castration causes an increased uptake of substrates that are acted upon by CatD in lysosomes of principal cells and in the lumen by procathepsin D. These substrates may be derived from apoptotic cells noted in the lumen of proximal regions and possibly by degenerating sperm in distal regions of the epididymis of Ct animals. Exploring the mechanisms by which lysosomal enzymes are synthesized and secreted by the epididymis may help resolve some of the issues originating from epididymal dysfunctions with relevance to sperm maturation.
Altered metabolism by autophagy defection affect liver regeneration
Authors: Chen Yi , Xu Zhiwei , Zeng Yanli , Liu Junping , Wang Xuemei , Kang Yi
Published: April 2021

Autophagy is the primary intracellular catabolic process for degrading and recycling long-lived proteins and damaged organelles, which maintains cellular homeostasis. Autophagy has key roles in development and differentiation. By using the mouse with liver specific knockout of autophagy related gene 5 (Atg5), a gene essential for autophagy, we investigated the possible role of autophagy in liver regeneration after 70% partial hepatectomy (PHx). Ablation of autophagy significantly impaired mouse liver regeneration, and this impairment was associated with reduced hepatocellular proliferation rate, down-regulated expression of cyclins and tumor suppressors, and increased hepatocellular apoptosis via the intrinsic apoptotic pathway. Ablation of autophagy does not affect IL-6 and TNF-α response after PHx, but the altered hepatic and systemic metabolic responses were observed in these mice, including reduced ATP and hepatic free fatty acid levels in the liver tissue, increased glucose level in the serum. Autophagy is required to promote hepatocellular proliferation by maintaining normal hepatic and systemic metabolism and suppress hepatocellular apoptosis in liver regeneration.
Acidic amino acids as counterions of ciprofloxacin: Effect on growth and pigment production in Staphylococcus aureus NCTC 8325 and Pseudomonas aeruginosa PAO1
Authors: Warraich Annsar Ahmad , Mohammed Afzal Ur Rahman , Gibson Hazel , Hussain Majad , Rahman Ayesha Sabah
Published: April 2021

Antimicrobial resistance (AMR) is emerging as a global threat to public health. One of the strategies employed to combat AMR is the use of adjuvants which act to enhance or reinstate antimicrobial activity by inhibiting resistance mechanisms. However, these adjuvants are themselves not immune to selecting resistant phenotypes. Thus, there is a need to utilise mechanisms which are either less likely to or unable to trigger resistance. One commonly employed mechanism of resistance by microorganisms is to prevent antimicrobial uptake or efflux the antibiotic which manages to permeate its membrane. Here we propose amino acids as antimicrobial adjuvants that may be utilizing alternate mechanisms to fight AMR. We used a modified ethidium bromide (EtBr) efflux assay to determine its efflux in the presence of ciprofloxacin within Staphylococcus aureus (NCTC 8325) and Pseudomonas aeruginosa (PAO1). In this study, aspartic acid and glutamic acid were found to inhibit growth of both bacterial species. Moreover, a reduced production of toxic pigments, pyocyanin and pyoverdine by P. aeruginosa was also observed. As evident from similar findings with tetracycline, these adjuvants, may be a way forward towards tackling antimicrobial resistance.
Effect of a scaled-up quality improvement intervention on health workers’ competence on neonatal resuscitation in simulated settings in public hospitals: A pre-post study in Nepal
Authors: Chaulagain Dipak Raj , K. C. Ashish , Wrammert Johan , Brunell Olivia , Basnet Omkar , Malqvist Mats
Published: April 2021

Background

Helping Babies Breathe (HBB) training improves bag and mask ventilation and reduces neonatal mortality and fresh stillbirths. Quality improvement (QI) interventions can improve retention of neonatal resuscitation knowledge and skills. This study aimed to evaluate the effect of a scaled-up QI intervention package on uptake and retention of neonatal resuscitation knowledge and skills in simulated settings.

Methods

This was a pre-post study in 12 public hospitals of Nepal. Knowledge and skills of trainees on neonatal resuscitation were evaluated against the set standard before and after the introduction of QI interventions.

Results

Altogether 380 participants were included for knowledge evaluation and 286 for skill evaluation. The overall knowledge test score increased from 14.12 (pre-basic) to 15.91 (post-basic) during basic training (p < 0.001). The knowledge score decreased over time; 15.91 (post-basic) vs. 15.33 (pre-refresher) (p < 0.001). Overall skill score during basic training (16.98 ± 1.79) deteriorated over time to 16.44 ± 1.99 during refresher training (p < 0.001). The proportion of trainees passing the knowledge test increased to 91.1% (post-basic) from 67.9% (pre-basic) which decreased to 86.6% during refresher training after six months. The knowledge and skill scores were maintained above the set standard (>14.0) over time at all hospitals during refresher training.

Conclusion

HBB training together with QI tools improves health workers’ knowledge and skills on neonatal resuscitation, irrespective of size and type of hospitals. The knowledge and skills deteriorate over time but do not fall below the standard. The HBB training together with QI interventions can be scaled up in other public hospitals.

Trial registration

This study was part of the larger Nepal Perinatal Quality Improvement Project (NePeriQIP) with International Standard Randomised Controlled Trial Number, ISRCTN30829654, registered 17th of May, 2017.
Impacts of a sugar sweetened beverage tax on body mass index and obesity in Thailand: A modelling study
Authors: Phonsuk Payao , Vongmongkol Vuthiphan , Ponguttha Suladda , Suphanchaimat Rapeepong , Rojroongwasinkul Nipa , Swinburn Boyd Anthony
Published: April 2021

Background

The World Health Organization (WHO) recommends sugar-sweetened beverage (SSB) taxes to address obesity. Thailand has just launched the new tax rates for SSB in 2017; however, the existing tax rate is not as high as the 20% recommended by the WHO. The objective for this study was to estimate the impacts of an SSB tax on body mass index (BMI) and obesity prevalence in Thailand under three different scenarios based on existing SSB and recommended tax rates.

Methods

A base model was built to estimate the impacts of an SSB tax on SSB consumption, energy intake, BMI, and obesity prevalence. Literature review was conducted to estimate pass on rate, price elasticity, energy compensation, and energy balance to weight change. Different tax rates (11%, 20% and 25%) were used in the model. The model assumed no substitution effects, model values were based on international data since there was no empirical Thai data available. Differential effects by income groups were not estimated.

Findings

When applying 11%, 20%, and 25% tax rates together with 100% pass on rate and an -1.30 own-price elasticity, the SSB consumption decreased by 14%, 26%, and 32%, respectively. The 20% and 25% price increase in SSB price tended to reduce higher energy intake, weight status and BMI, when compared with an 11% increase in existing price increase of SSB. The percentage changes of obesity prevalence of 11%, 20% and 25% SSB tax rates were estimated to be 1.73%, 3.83%, and 4.91%, respectively.

Conclusions

A higher SSB tax (20% and 25%) was estimated to reduce consumption and consequently decrease obesity prevalence. Since Thailand has already endorsed the excise tax structure, the new excise tax structure for SSB should be scaled up to a 20% or 25% tax rate if the SSB consumption change does not meet a favourable goal.
Development of multiplex real-time RT-PCR assay for the detection of SARS-CoV-2
Authors: Tombuloglu Huseyin , Sabit Hussein , Al-Suhaimi Ebtesam , Al Jindan Reem , Alkharsah Khaled R.
Published: April 2021

The outbreak of the new human coronavirus SARS-CoV-2 (also known as 2019-nCoV) continues to increase globally. The real-time reverse transcription polymerase chain reaction (rRT-PCR) is the most used technique in virus detection. However, possible false-negative and false-positive results produce misleading consequences, making it necessary to improve existing methods. Here, we developed a multiplex rRT-PCR diagnostic method, which targets two viral genes (RdRPandE) and one human gene (RP) simultaneously. The reaction was tested by usingpseudoviralRNA and human target mRNA sequences as a template. Also, the protocol was validated by using 14 clinical SARS-CoV-2 positive samples. The results are in good agreement with the CDC authorized Cepheid`s Xpert®Xpress SARS-CoV-2 diagnostic system (100%). Unlike single gene targeting strategies, the current method provides the amplification of two viral regions in the same PCR reaction. Therefore, an accurate SARS-CoV-2 diagnostic assay was provided, which allows testing of 91 samples in 96-well plates in per run. Thanks to this strategy, fast, reliable, and easy-to-use rRT-PCR method is obtained to diagnose SARS-CoV-2.
Increased expression of Netrin-4 is associated with allodynia in a trigeminal neuropathic pain model rats by infraorbital nerve injury
Authors: Honjo Yuka , Fujita Yuki , Niwa Hitoshi , Yamashita Toshihide
Published: April 2021

Neuropathic pain refers to pain caused by lesions or diseases of the somatosensory nervous system that is characteristically different from nociceptive pain. Moreover, neuropathic pain occurs in the maxillofacial region due to various factors and is treated using tricyclic antidepressants and nerve block therapy; however, some cases do not fully recover. Netrin is a secreted protein crucially involved in neural circuit formation during development, including cell migration, cell death, neurite formation, and synapse formation. Recent studies show Netrin-4 expressed in the dorsal horn of the spinal cord is associated with chronic pain. Here we found involvement of Netrin-4 in neuropathic pain in the maxillofacial region. Netrin-4, along with one of its receptors, Unc5B, are expressed in the caudal subnucleus of the trigeminal spinal tract nucleus. Inhibition of its binding by anti-Netrin-4 antibodies not only shows a behavioral analgesic effect but also neuronal activity suppression. There was increased Netrin-4 expression at 14 days after infraorbital nerve injury. Our findings suggest that Netrin-4 induced by peripheral nerve injury causes neuropathic pain via Unc5B.
Should homes and workplaces purchase portable air filters to reduce the transmission of SARS-CoV-2 and other respiratory infections? A systematic review
Authors: Hammond Ashley , Khalid Tanzeela , Thornton Hannah V. , Woodall Claire A. , Hay Alastair D.
Published: April 2021

Respiratory infections, including SARS-CoV-2, are spread via inhalation or ingestion of airborne pathogens. Airborne transmission is difficult to control, particularly indoors. Manufacturers of high efficiency particulate air (HEPA) filters claim they remove almost all small particles including airborne bacteria and viruses. This study investigates whether modern portable, commercially available air filters reduce the incidence of respiratory infections and/or remove bacteria and viruses from indoor air. We systematically searched Medline, Embase and Cochrane for studies published between January 2000 and September 2020. Studies were eligible for inclusion if they included a portable, commercially available air filter in any indoor setting including care homes, schools or healthcare settings, investigating either associations with incidence of respiratory infections or removal and/or capture of aerosolised bacteria and viruses from the air within the filters. Dual data screening and extraction with narrative synthesis. No studies were found investigating the effects of air filters on the incidence of respiratory infections. Two studies investigated bacterial capture within filters and bacterial load in indoor air. One reported higher numbers of viable bacteria in the HEPA filter than in floor dust samples. The other reported HEPA filtration combined with ultraviolet light reduced bacterial load in the air by 41% (sampling time not reported). Neither paper investigated effects on viruses. There is an important absence of evidence regarding the effectiveness of a potentially cost-efficient intervention for indoor transmission of respiratory infections, including SARS-CoV-2. Two studies provide ‘proof of principle’ that air filters can capture airborne bacteria in an indoor setting. Randomised controlled trials are urgently needed to investigate effects of portable HEPA filters on incidence of respiratory infections.
Crescimento com Base nas Exportações depois da COVID-19
Authors: Naudé Wim , Cameron Martin
Published: April 2021

A pandemia COVID‑19 foi disruptiva para o comércio internacional e as cadeias de valor globais. Pequenas economias abertas como a Portuguesa são particularmente vulneráveis. Neste artigo consideramos o impacto da pandemia nas exportações do país, argumentando que uma recuperação liderada pelas exportações é possível. O desafio é o de identificar oportunidades de exportação viáveis, uma vez que uma das consequências da pandemia COVID‑19 é a de ter fechado e restringido as oportunidades de exportação globalmente. Não obstante, nós mostramos que ainda há oportunidades de exportação subutilizadas em Portugal. Usamos as grandes bases de dados UN_COMTRADE e CEPII BACI às quais aplicámos 4 filtros para identificar 45.593 oportunidades de exportação realistas. Estas oportunidades foram avaliadas em €286,6 mil milhões de euros em receitas potenciais inexploradas. Os maiores mercados para estes produtos estão em países como os Estados Unidos, Alemanha, China, Reino Unido, França e Japão. Discutem‑se ainda implicações para políticas de facilitação do comércio e industriais que possam utilizar estas oportunidades no contexto da literatura relevante em comércio e desenvolvimento.
Efectos del crecimiento urbano sobre humedales costero-continentales del ambiente semiárido de Tierra del Fuego, Argentina
Authors: Iturraspe Rodolfo Javier , Fank Lucía , Urciuolo Adriana Beatriz , Lofiego Rita
Published: April 2021

La conjunción de humedales costeros y continentales en zonas semiáridas y en adyacencias urbanas, representa un valioso patrimonio socio-ambiental, sujeto a las tensiones que la expansión urbana genera, especialmente si se manifiesta con altas tasas de crecimiento. El presente artículo aborda el problema de los cambios físicos sobre humedales provocados por la expansión urbana acelerada en el contexto mencionado, identificando factores agravantes. Se estudió el caso de Río Grande, ciudad costera de la estepa de Tierra del Fuego, Argentina, cuyo crecimiento fue impulsado desde 1972 por políticas de promoción industrial. Los humedales fueron identificados, clasificados y cartografiados mediante análisis multiespectral de imágenes de satélite. La expansión urbana se delimitó según tres períodos vinculados a variantes en las políticas de promoción. El análisis espacio-temporal evidencia correspondencia entre pulsos de fluctuación de las políticas, con la dinámica de la expansión urbana y ocupación de áreas naturales. Un tercio de la expansión urbana fue a expensas de la desaparición de humedales, con saldo adicional de unidades fragmentadas. Se analizan externalidades, no siempre evidentes, resultantes de la urbanización de estos ecosistemas y se concluye en la significación de los asentamientos informales, así como la falta de planificación como factores que incrementan la pérdida de humedales.
Comparative analysis of canine mesenchymal stem cells and bone marrow-derived mononuclear cells
Authors: Maeta Noritaka , Tamura Katsutoshi , Ezuka Fuuna , Takemitsu Hiroshi
Published: April 2021

Background and Aim: Mesenchymal stem cells (MSCs), which have multi-lineage differentiation potentials, are a promising source for regenerative medicine. However, the focus of study of MSCs is shifting from the characterization of the differentiation potential to their secretion potential for cell transplantation. Tissue regeneration and the attenuation of immune responses are thought to be affected by the secretion of multiple growth factors and cytokines by MSCs. However, the secretion potential of MSCs profiling remains incompletely characterized. In this study, we focused on the secretion ability related and protein mRNA expression of dog adipose tissue-derived MSCs (AT-MSC), bone marrow (BM)-derived MSCs, and BM-derived mononuclear cells (BM-MNC).

Materials and Methods: Real-time polymerase chain reaction analyses revealed mRNA expression of nine growth factors and seven interleukins in these types of cells and three growth factors protein expression were determined using Enzyme-linked immunosorbent assay.

Results: For the BM-MNC growth factors, the mRNA expression of transforming growth factor-β (TGF-β) was the highest. For the BM-derived MSC (BM-MSC) and AT-MSC growth factors, the mRNA expression of vascular endothelial growth factor (VEGF) was highest. BM-MSCs and AT-MSCs showed similar expression profiles. In contrast, BM-MNCs showed unique expression profiles for hepatocyte growth factor and epidermal growth factor. The three types of cells showed a similar expression of TGF-β.

Conclusion: We conclude that expression of cytokine proteins and mRNAs suggests involvement in tissue repair and protection.
Profil Klinis dan Faktor Risiko Mortalitas pada Anak dengan Hidrosefalus di RSUD dr. Soetomo Surabaya
Authors: Ariyati Nabila Fitri , Gunawan Prastiya Indra , Sustini Florentina
Published: April 2021

Latar belakang. Hidrosefalus merupakan kelainan sistem saraf pusat yang paling umum terjadi baik pada bayi, anak, maupun remaja dan dapat menyebabkan konsekuensi serius berupa mortalitas. Informasi yang menyediakan faktor risiko mortalitas pada anak dengan hidrosefalus masih sangat terbatas.Tujuan. Mengevaluasi dan mengidentifikasi faktor risiko yang berhubungan dengan terjadinya mortalitas pada anak dengan hidrosefalus.Metode. Penelitian analitik observasional pada 89 pasien anak yang menderita hidrosefalus dengan menggunakan data rekam medis pasien anak yang dirawat di bagian instalasi rawat inap RSUD dr. Soetomo periode Januari 2014 hingga September 2016. Analisis menggunakan chi-square dan regresi logistik.Hasil. Didapatkan 89 subjek yang memenuhi kriteria inklusi. Mortalitas pasien anak dengan hidrosefalus adalah 17,97%. Analisis bivariat menunjukkan adanya hasil signifikan pada infeksi meningoensefalitis dengan OR 8,12 (95% CI 2,38-27,6) p=0,001. Sepsis memiliki OR 6,18 (95% CI 1,53-24,9) p=0,01. Kelainan struktur SSP berupa brain edema memiliki OR 4,27 (95% CI 1,25-14,6) p=0,02. Gagal nafas memiliki OR 56,0 (95% CI 6,16-508,9) p=0,001. Hasil analisis multivariat menunjukkan gagal nafas dan brain edema memiliki nilai OR (95% CI) berturut-turut 192,8 (9,92-3745,8) dan 10,07(1,23-82,5) dengan nilai p<0,05.Kesimpulan. Gagal nafas dan brain edema merupakan faktor risiko mortalitas pada anak dengan hidrosefalus.
Kultúra és teljesítmény a közigazgatásban (Culture and performance in the public administration)
Authors: Hajnal György
Published: April 2021

A szerző dolgozatában egy közigazgatásban végzett kérdőíves vizsgálat eredményeit összegezi. A kutatás alapkérdése: a közigazgatási szervezetek körében hogyan befolyásolja a szervezeti kultúra a szervezeti teljesítményt? A kutatás e kérdést egy hat magyar minisztériumban folytatott kérdőíves vizsgálat révén kísérli meg megválaszolni. ____ In his study the author presents the results of a questionnaire survey of the Hungarian public administration. The main issue of this survey was how to influence the organizational culture the organizational performance in the public administration? This survey would try to answer this issue.
Vállalati struktúrák változásai a földgázellátó szektorban
Authors: Horánszky Beáta
Published: April 2021

A szerző tanulmányában a hazai gázellátás szervezeti rendszerét mutatja be a kezdetektől napjainkig. Elemzi azokat a struktúraváltozásokat, melyek e szektorban és ennek vállalatainál bekövetkeztek.
Identification of a small-scale pig farm infected with Brucella suis linked to a clinical case of human brucellosis in Buenos Aires province, Argentina
Authors: BENCE Angel Ricardo , MORAN María Celeste , CACCIATO Claudio Santiago , SOTO Javier , GUTIERREZ Silvina Elena , ESTEIN Silvia Marcela
Published: April 2021

Here we report a case of human brucellosis due to Brucella suis in a person who worked in a small-scale pig farm. The farm had no history of clinical brucellosis, and signs of the disease were not observed upon clinical examination of the animals. Serum from all the 3 boars, 16/22 sows and 9/25 gilts was obtained for serological examination by Buffered Plate Agglutination Test (BPAT), Rose Bengal Test (RBT) and Fluorescent Polarization Assay (FPA). Bacteriological culture and Direct Fluorescence Antibody Test (DFAT) were performed in tissue samples from a seropositive boar and a sow. Specific antibodies were detected in 53 % (10/19) adult pigs, while all sampled gilts were seronegative. B. suis biovar 1 was isolated from one boar. In contrast, while the bacterium was not isolated from any tissue from a seropositive sow, it was detected by DFAT. From the bacteriological and serological evidence of B. suis endemic infection in the pig farm and the lack of preventive measures and biosecurity practices, it is concluded that the person most likely acquired the disease from the infected animals or by contact with contaminated environment in the farm.