bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards the prediction of non-peptidic epitopes
Authors: Zierep Paul F. , Vita Randi , Blazeska Nina , Moumbock Aurélien F. A. , Greenbaum Jason A. , Peters Bjoern , Günther Stefan
Published: February 2022

In-silico methods for the prediction of epitopes can support and improve workflows for vaccine design, antibody production, and disease therapy. So far, the scope of B cell and T cell epitope prediction has been directed exclusively towards peptidic antigens. Nevertheless, various non-peptidic molecular classes can be recognized by immune cells. These compounds have not been systematically studied yet, and prediction approaches are lacking. The ability to predict the epitope activity of non-peptidic compounds could have vast implications; for example, for immunogenic risk assessment of the vast number of drugs and other xenobiotics. Here we present the first general attempt to predict the epitope activity of non-peptidic compounds using the Immune Epitope Database (IEDB) as a source for positive samples. The molecules stored in the Chemical Entities of Biological Interest (ChEBI) database were chosen as background samples. The molecules were clustered into eight homogeneous molecular groups, and classifiers were built for each cluster with the aim of separating the epitopes from the background. Different molecular feature encoding schemes and machine learning models were compared against each other. For those models where a high performance could be achieved based on simple decision rules, the molecular features were then further investigated. Additionally, the findings were used to build a web server that allows for the immunogenic investigation of non-peptidic molecules (http://tools-staging.iedb.org/np_epitope_predictor). The prediction quality was tested with samples from independent evaluation datasets, and the implemented method received noteworthy Receiver Operating Characteristic-Area Under Curve (ROC-AUC) values, ranging from 0.69–0.96 depending on the molecule cluster.
Specificity of Loxosceles α clade phospholipase D enzymes for choline-containing lipids: Role of a conserved aromatic cage
Authors: Moutoussamy Emmanuel E. , Waheed Qaiser , Binford Greta J. , Khan Hanif M. , Moran Shane M. , Eitel Anna R. , Cordes Matthew H. J. , Reuter Nathalie
Published: February 2022

Spider venom GDPD-like phospholipases D (SicTox) have been identified to be one of the major toxins in recluse spider venom. They are divided into two major clades: the α clade and the β clade. Most α clade toxins present high activity against lipids with choline head groups such as sphingomyelin, while activities in β clade toxins vary and include preference for substrates containing ethanolamine headgroups (Sicarius terrosus, St_βIB1). A structural comparison of available structures of phospholipases D (PLDs) reveals a conserved aromatic cage in the α clade. To test the potential influence of the aromatic cage on membrane-lipid specificity we performed molecular dynamics (MD) simulations of the binding of several PLDs onto lipid bilayers containing choline headgroups; two SicTox from the α clade, Loxosceles intermedia αIA1 (Li_αIA) and Loxosceles laeta αIII1 (Ll_αIII1), and one from the β clade, St_βIB1. The simulation results reveal that the aromatic cage captures a choline-headgroup and suggest that the cage plays a major role in lipid specificity. We also simulated an engineered St_βIB1, where we introduced the aromatic cage, and this led to binding with choline-containing lipids. Moreover, a multiple sequence alignment revealed the conservation of the aromatic cage among the α clade PLDs. Here, we confirmed that the i-face of α and β clade PLDs is involved in their binding to choline and ethanolamine-containing bilayers, respectively. Furthermore, our results suggest a major role in choline lipid recognition of the aromatic cage of the α clade PLDs. The MD simulation results are supported by in vitro liposome binding assay experiments.
Sleep quality and its correlates among undergraduate medical students in Nepal: A cross-sectional study
Authors: Paudel Kiran , Adhikari Tara Ballav , Khanal Pratik , Bhatta Ramesh , Paudel Rajan , Bhusal Sandesh , Basel Prem
Published: February 2022

Poor sleep quality has been found to affect students’ learning abilities, academic performance, and interpersonal relationships. However, little is known about this issue in Nepal. This study aimed to identify the factors associated with poor sleep quality among undergraduate medical students in Nepal. A web-based survey was conducted in March 2021 among 212 undergraduate medical students at the Institute of Medicine, Kathmandu, Nepal. Sleep quality was measured using a 19-item Pittsburgh Sleep Quality Index (PSQI). Multivariable logistic regression analysis was done to assess the factors associated with sleep quality. In the study participants, 38.2% of the students were identified as poor sleepers. Factors like being depressed (AOR = 4.5, 95% CI; 1.2–5.4), current alcohol use (AOR = 2.5, 95% CI; 1.8–10.8), poor academic achievement (AOR = 3.4, 95% CI; 1.1–10.9), and being a fourth-year student (AOR = 3.6, 95% CI; 1.1–11.8) were significantly associated with poor sleep quality. Poor sleep quality was common among undergraduate medical students. Routine screening of sleep quality and depressive symptoms is necessary to mitigate their impact among medical students. Medical students of the fourth year, current alcohol users, and those who did not have good academic achievement had poor sleep quality. Special attention on these population subgroups is thus needed to enhance sleep quality.
Avoiding data loss: Synthetic MRIs generated from diffusion imaging can replace corrupted structural acquisitions for freesurfer-seeded tractography
Authors: Beaumont Jeremy , Gambarota Giulio , Prior Marita , Fripp Jurgen , Reid Lee B.
Published: February 2022

Magnetic Resonance Imaging (MRI) motion artefacts frequently complicate structural and diffusion MRI analyses. While diffusion imaging is easily ‘scrubbed’ of motion affected volumes, the same is not true for T1w or T2w ‘structural’ images. Structural images are critical to most diffusion-imaging pipelines thus their corruption can lead to disproportionate data loss. To enable diffusion-image processing when structural images are missing or have been corrupted, we propose a means by which synthetic structural images can be generated from diffusion MRI. This technique combines multi-tissue constrained spherical deconvolution, which is central to many existing diffusion analyses, with the Bloch equations that allow simulation of MRI intensities for given scanner parameters and magnetic resonance (MR) tissue properties. We applied this technique to 32 scans, including those acquired on different scanners, with different protocols and with pathology present. The resulting synthetic T1w and T2w images were visually convincing and exhibited similar tissue contrast to acquired structural images. These were also of sufficient quality to drive a Freesurfer-based tractographic analysis. In this analysis, probabilistic tractography connecting the thalamus to the primary sensorimotor cortex was delineated with Freesurfer, using either real or synthetic structural images. Tractography for real and synthetic conditions was largely identical in terms of both voxels encountered (Dice 0.88–0.95) and mean fractional anisotropy (intrasubject absolute difference 0.00–0.02). We provide executables for the proposed technique in the hope that these may aid the community in analysing datasets where structural image corruption is common, such as studies of children or cognitively impaired persons.
SGLT2 inhibitors therapy protects glucotoxicity-induced β-cell failure in a mouse model of human KATP-induced diabetes through mitigation of oxidative and ER stress
Authors: Shyr Zeenat A. , Yan Zihan , Ustione Alessandro , Egan Erin M. , Remedi Maria S.
Published: February 2022

Progressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the temporal progression and mechanisms underlying glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice rapidly developed severe diabetes followed by an unexpected loss of insulin content, decreased proinsulin processing and increased proinsulin at 2-weeks of diabetes. These early events were accompanied by a marked increase in β-cell oxidative and ER stress, without changes in islet cell identity. Strikingly, treatment with the SGLT2 inhibitor dapagliflozin restored insulin content, decreased proinsulin:insulin ratio and reduced oxidative and ER stress. However, despite reduction of blood glucose, dapagliflozin therapy was ineffective in restoring β-cell function in NDM mice when it was initiated at >40 days of diabetes, when loss of β-cell mass and identity had already occurred. Our data from mouse models demonstrate that: i) hyperglycemia per se, and not insulin hypersecretion, drives β-cell failure in diabetes, ii) recovery of β-cell function by SGLT2 inhibitors is potentially through reduction of oxidative and ER stress, iii) SGLT2 inhibitors revert/prevent β-cell failure when used in early stages of diabetes, but not when loss of β-cell mass/identity already occurred, iv) common execution pathways may underlie loss and recovery of β-cell function in different forms of diabetes. These results may have important clinical implications for optimal therapeutic interventions in individuals with diabetes, particularly for those with long-standing diabetes.
Infection and vaccination status of COVID-19 among healthcare professionals in academic platform: Prevision vs. reality of Bangladesh context
Authors: Banu Bilkis , Akter Nasrin , Chowdhury Sujana Haque , Islam Kazi Rakibul , Islam Md. Tanzeerul , Hossain Sarder Mahmud
Published: February 2022

COVID-19 posed the healthcare professionals at enormous risk during this pandemic era while vaccination was recommended as one of the effective preventive approaches. It was visualized that almost all health workforces would be under vaccination on a priority basis as they are the frontline fighters during this pandemic. This study was designed to explore the reality regarding infection and vaccination status of COVID-19 among healthcare professionals of Bangladesh. It was a web-based cross-sectional survey and conducted among 300 healthcare professionals available in the academic platform of Bangladesh. A multivariate logistic regression model was used for the analytical exploration. Adjusted and Unadjusted Odds Ratio (OR) with 95% confidence intervals (95% CI) were calculated for the specified setting indicators. A Chi-square test was used to observe the association. Ethical issues were maintained according to the guidance of the declaration of Helsinki. Study revealed that 41% of all respondents identified as COVID-19 positive whereas a significant number (18.3%) found as non-vaccinated due to registration issues as 52.70%, misconception regarding vaccination as 29.10%, and health-related issues as 18.20%. Respondents of more than 50 years of age found more significant on having positive infection rather than the younger age groups. Predictors for the non-vaccination guided that male respondents (COR/p = 3.49/0.01), allied health professionals, and respondents from the public organizations (p = 0.01) who were ≤29 (AOR/p = 4.45/0.01) years of age significantly identified as non-vaccinated. As the older female groups were found more infected and a significant number of health care professionals found as non-vaccinated, implementation of specific strategies and policies are needed to ensure the safety precautions and vaccination among such COVID-19 frontiers.
Experiences of criticism in adults with ADHD: A qualitative study
Authors: Beaton Danielle M. , Sirois Fuschia , Milne Elizabeth
Published: February 2022

People with ADHD are at high risk of receiving criticism from others, yet criticism has not been well researched in this population. This study aimed to provide a rich understanding of what experiences adults with ADHD traits have with criticism. As part of a larger study, 162 participants with ADHD and high ADHD traits provided a written response to an open question asking about their experiences of criticism from other people. Thematic analysis was used to identify five common themes in the responses. Behaviours associated with inattention were perceived as the most criticised, whilst impulsive behaviours were mostly criticised in social contexts. Criticism was perceived via numerous conducts and was reported to have negative consequences for self-worth and wellbeing. To cope, some participants avoided criticism or changed how they reacted, including trying to accept themselves as they are. The responses indicated that receiving understanding from others played an important role in whether criticism was perceived. Overall, the findings highlight the need for more knowledge, understanding and acceptance towards neurodiversity from the general population.
Media attention and Vaccine Hesitancy: Examining the mediating effects of Fear of COVID-19 and the moderating role of Trust in leadership
Authors: Zhou Lulin , Ampon-Wireko Sabina , Xu Xinglong , Quansah Prince Edwudzie , Larnyo Ebenezer
Published: February 2022

Vaccination has emerged as the most cost-effective public health strategy for maintaining population health, with various social and economic benefits. These vaccines, however, cannot be effective without widespread acceptance. The present study examines the effect of media attention on COVID-19 vaccine hesitancy by incorporating fear of COVID-19 as a mediator, whereas trust in leadership served as a moderator. An analytical cross-sectional study is performed among rural folks in the Wassa Amenfi Central of Ghana. Using a questionnaire survey, we were able to collect 3079 valid responses. The Smart PLS was used to estimate the relationship among the variables. The results revealed that media attention had a significant influence on vaccine hesitancy. Furthermore, the results showed that fear of COVID-19 played a significant mediating role in the relationship between media and vaccine hesitancy. However, trust in leadership had an insignificant moderating relationship on the fear of COVID-19 and vaccine hesitancy. The study suggests that the health management team can reduce vaccine hesitancy if they focus on lessening the negative impact of media and other antecedents like fear on trust in leadership.
Research on the prediction of longevity from both individual and family perspectives
Authors: Miao Lvqing , Yang Suyu , Yi Yuye , Tian Peipei , He Lichun
Published: February 2022

Increasing human longevity is of global interest. The present study explored the prediction of longevity from both individual perspective and family perspective based on demographic and psychosocial factors. A total of 186 longevous family members and 237 ordinary elderly family members participated in a cross-sectional study, and a sample of 62 longevous elderly and 57 ordinary elderly were selected for comparative research. The results showed that it was three times more female than male in longevous elderly group. Up to 71.2% of longevous elderly had no experience in education, which was significantly lower than that of ordinary elderly. Due to such extreme age, more widowed (81.4%) elderly than those in married (18.6%). Less than one-seventh of the longevous elderly maintained the habit of smoking, and about one-third of them liked drinking, both were significantly lower than that of ordinary elderly. In terms of psychosocial factors, longevous elderly showed lower neuroticism and social support, while higher extraversion, compared with the ordinary elderly. However, there were no significant differences between the two family groups in demographic and psychosocial variables, except longevous families showing lower scores in neuroticism. Regression analysis found that neuroticism, social support and smoking habit had significant impact on individuals’ life span, then, neuroticism and psychoticism were the key factor to predict families’ longevity. We conclude that good emotional management, benign interpersonal support, and moderation of habits are important factors for individual longevity, and the intergenerational influence of personality is closely related to family longevity.
Trend and burden of neural tube defects among cohort of pregnant women in Ethiopia: Where are we in the prevention and what is the way forward?
Authors: Berhane Anteneh , Belachew Tefera
Published: February 2022

Introduction

Neural tube defect is one of the top five most serious birth defects in the world. In Ethiopia an accurate estimate of the trend and burden of neural tube defects is still unknown. There hasn’t been much research done on the prevalence and trend of neural tube defects in Eastern Ethiopia. To complement previous efforts of studies, the purpose of this study is to estimate the trend and burden of neural tube defects in Eastern Ethiopia as well as to investigate the epidemiological implications of the findings.

Methods

A facility-based retrospective cohort study was carried out from cohort pregnant women who delivered in selected hospitals. File records of all babies who were found to have neural tube defects could be reached between 2017 and 2019. A structured checklist was used to collect data. The incidence of each case was calculated by dividing the number of cases per year by the total number of live births in each hospital. To determine the linear trend of neural tube defects over time, linear trend of Extended Mantel-Haenszel chi-square was performed. Data were presented using frequencies and percentages. Data were analyzed using SPSS for windows version 25.

Results

A total of 48,750 deliveries were recorded during the three years of the study considered for analyses with 522 women having neural tube defect giving an incidence rate of 107.5 per 10,000 live births in the three years. The most common types of neural tube defects found in the area were anencephaly and spina bifida accounting for 48.1% and 22.6%, respectively. The distribution of neural tube defects varied across the study hospitals, with Adama Medical College Hospital having the highest proportion (46.6%). Over half of the mothers (56.7%) live in cities. Mothers in the age group 25–34 (46.9%) and multigravida mothers had higher proportions (64.4%).of neural tube defects. None of the mothers took folic acid before conception, and only 19% took iron folic acid supplementation during their pregnancy.

Conclusion and recommendation

The findings showed that an increasing trend and burden of neural tube defects and preconception folic acid supplementation is insignificant in the region which showed that where we are in the prevention of neural tube defects. The finding suggests that preconception folic acid supplementation in conjunction with health care services should be considered to reduce the risk of neural tube defects in the region. Aside from that, intensive prevention efforts for long-term folate intake through dietary diversification and appropriate public health interventions are required. Furthermore, data must be properly recorded in order to address disparities in neonatal death due to neural tube defects, and the determinants of neural tube defects should be investigated using large scale prospective studies with biomarkers.
Factors predicting companies’ crisis in the engineering industry from the point of view of financial analysis
Authors: Lukáč Jozef , Olexová Cecília , Kudlová Zuzana
Published: February 2022

A key factor for business management is the assessment of the financial situation of companies. Nowadays, it is essential to monitor the liquidity crisis, which is closely linked to corporate crises. The aim of the paper is to analyse a selected sector of the economy from the perspective of the corporate crisis and to identify the factors of crisis. More than 2000 engineering companies in Slovakia were analysed during the period from 2015 to 2019 with the aim of analysing financial results, especially in the area of financial forecast for the future. In the analysis, statistical testing of the significance of relationships using the Spearman correlation coefficient, the significance of differences by the power of t-test, regression and clustering were used. A significant part of the paper is the analysis of selected indicators of the company’s crisis—Altman’s Z score and the IN05 index. The results indicate that engineering companies in Slovakia are achieving good results and their financial situation is improving within the years between 2015–2019. The results can also be used as a starting point for research concerning the impact of COVID-19 in this area. In the context of corporate crisis management, engineering companies behave in the same way but it is necessary to monitor individual factors that can detect a corporate crisis. Possible measures would thus lead to the stabilization of financial results and long-term sustainable positive prospects for companies in the future.
Experimental study on the effect of high-temperature oxidation coal mechanical characteristics
Authors: Wang Xiaoqi , Ma Heng , Qi Xiaohan , Gao Ke , Li Shengnan , Yang Xuesong
Published: February 2022

After long-term oxidation and energy storage, broken coal body borehole walls and drainage shaft walls may cause spontaneous combustion during gas extraction. The high-temperature thermal shock caused by the spontaneous combustion of coal incurs thermal damage on adjacent coal, which, in turn, causes changes in the mechanical properties of the coal. However, only a few studies have been conducted in this context, which has limited our understanding of the thermal damage characteristics of coal bodies in such situations. This study aimed to experimentally investigate the correlation between the crack evolution law and the mechanical properties of coal bodies at different temperatures (50–300°C) using heat-force loading considering Ping Mei No. 10 coal mine as the research object. The results suggest that the coal body experiences a large amount of visible damage, and becomes increasingly complex. At 50–300°C, some indexes (such as longitudinal wave velocity, Poisson’s ratio, compressive strength, elastic modulus, impact energy index, and pre-peak strain) are positively correlated with temperature. In addition, the dynamic failure time and temperature show a negative correlation, and the overall change slope is small. The relationship between each index and temperature at 200–300°C is opposite to that at 50–200°C, and the overall change slope is larger. Moreover, when the oxidation temperature exceeds 200°C, the destruction of the coal body changes from elastic brittleness to ductility-plasticity. High-temperature oxidation incurs irreversible thermal damage of coal. Hence, it is necessary to focus on the changes in mechanical properties of coal after a spontaneous combustion process is extinguished.
Real-time text message surveys reveal student perceptions of personnel resources throughout a course-based research experience
Authors: Olson Alyssa N. , Cotner Sehoya , Kirkpatrick Catherine , Thompson Seth , Hebert Sadie
Published: February 2022

Course-based research experiences (CREs) are designed to engage students in authentic scientific experiences that are embedded into a standard curriculum. CREs provide valuable research experiences to large numbers of undergraduate biology students, however, CRE implementation can require many personnel. Because limited personnel may be a barrier to widespread CRE implementation, our goal was to discover which personnel students valued throughout a CRE and the ways they were valuable. We investigated students’ perceptions of personnel resources throughout a semester-long CRE using two survey approaches. Using a text message survey administered multiple times per week, real-time data was collected about which personnel resource students perceived to be the most helpful. Using a web-based survey administered five times throughout the semester, retrospective data was collected about how often students used each personnel resource and how helpful students perceived each personnel resource to be. Graduate teaching assistants (TAs) were consistently selected as the most helpful personnel resource by the majority of respondents throughout the semester, with most respondents describing graduate TAs providing project-specific feedback. Although less frequently, undergraduate TAs were also consistently selected as the most helpful personnel resource. Respondents described undergraduate TAs providing project-specific feedback, general feedback, and project-specific resources. Data from the retrospective, web-based survey largely mirrored the real-time, text message survey data. Throughout the semester, most respondents reported using graduate TAs “Often” or “Always” and that graduate TAs were “Very” or “Extremely” helpful. Throughout most of the semester, most respondents also reported using undergraduate TAs “Often” or “Always” and that undergraduate TAs were “Very” or “Extremely” helpful. The results of this descriptive study underscore the importance of graduate and undergraduate TAs in the development and implementation of CREs, emphasizing the need for departments and course coordinators to be intentional in planning TA training that prepares TAs to fulfill their critical role in CRE implementation.
Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia
Authors: Gebremariam Girma Tekle , Biratu Selam , Alemayehu Metasebia , Welie Abraham Gebregziabiher , Beyene Kebede , Sander Beate , Gebretekle Gebremedhin Beedemariam
Published: February 2022

Background

Type 2 diabetes mellitus (T2DM) and its treatment impact patients’ physical health as well as emotional and social wellbeing. This study aimed to assess health-related quality of life (HRQoL) and associated factors among patients with T2DM at a tertiary care hospital in Ethiopia.

Methods

A face-to-face cross-sectional survey was conducted among patients with T2DM at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. We collected data using a validated Amharic version of the 5-level EuroQoL-5 dimensions (EQ-5D-5L) questionnaire. Descriptive statistics were used to present patient characteristics. Kruskal-Wallis and Mann-Whitney U tests were performed to explore differences in the median scores of EQ-5D-5L utility and visual analog scale (EQ-VAS). Multivariable Tobit regression models were used to identify predictors of HRQoL. Utility scores were calculated using disutility weights of the Ethiopian general population. Statistical significance was determined at p < 0.05.

Results

A total of 360 patients with T2DM participated. Mean (SD) age was 64.43(10.61) years. Reported health problems were mostly in the pain/discomfort (67.3%) dimension followed by mobility (60.5%), whereas the usual activities domain (34.1%) was the least health problem being reported. The median (IQR) EQ-5D-5L utility and EQ-VAS scores were 0.95 (0.88–0.96) and 80 (75.0–85.0), respectively. In multivariable Tobit regression models older age, having poor glycemic control, longer duration of diabetes, insulin usage, obesity, and having diabetes-related complications were significant negative predictors of HRQoL.

Conclusions

Overall, patients with T2DM had lower HRQoL than the general population, which was attributed to being older age, longer duration of diabetes, insulin use, obesity, inadequate glycemic control, and diabetes-related complications. The utility index we generated can be used in future economic evaluations to inform decisions about alternative interventions and resource allocation.
H2B.V demarcates divergent strand-switch regions, some tDNA loci, and genome compartments in Trypanosoma cruzi and affects parasite differentiation and host cell invasion
Authors: Rosón Juliana Nunes , Vitarelli Marcela de Oliveira , Costa-Silva Héllida Marina , Pereira Kamille Schmitt , Pires David da Silva , Lopes Leticia de Sousa , Cordeiro Barbara , Kraus Amelie J. , Cruz Karin Navarro Tozzi , Calderano Simone Guedes , Fragoso Stenio Perdigão , Siegel T. Nicolai , Elias Maria Carolina , da Cunha Julia Pinheiro Chagas
Published: February 2022

Histone variants play a crucial role in chromatin structure organization and gene expression. Trypanosomatids have an unusual H2B variant (H2B.V) that is known to dimerize with the variant H2A.Z generating unstable nucleosomes. Previously, we found that H2B.V protein is enriched in tissue-derived trypomastigote (TCT) life forms, a nonreplicative stage ofTrypanosoma cruzi, suggesting that this variant may contribute to the differences in chromatin structure and global transcription rates observed among parasite life forms. Here, we performed the first genome-wide profiling of histone localization inT.cruziusing epimastigotes and TCT life forms, and we found that H2B.V was preferentially located at the edges of divergent transcriptional strand switch regions, which encompass putative transcriptional start regions; at some tDNA loci; and between the conserved and disrupted genome compartments, mainly at trans-sialidase, mucin and MASP genes. Remarkably, the chromatin of TCT forms was depleted of H2B.V-enriched peaks in comparison to epimastigote forms. Interactome assays indicated that H2B.V associated specifically with H2A.Z, bromodomain factor 2, nucleolar proteins and a histone chaperone, among others. Parasites expressing reduced H2B.V levels were associated with higher rates of parasite differentiation and mammalian cell infectivity. Taken together, H2B.V demarcates critical genomic regions and associates with regulatory chromatin proteins, suggesting a scenario wherein local chromatin structures associated with parasite differentiation and invasion are regulated during the parasite life cycle.
CovS inactivation reduces CovR promoter binding at diverse virulence factor encoding genes in group A Streptococcus
Authors: Horstmann Nicola , Myers Kevin S. , Tran Chau Nguyen , Flores Anthony R. , Shelburne III Samuel A.
Published: February 2022

The control of virulence gene regulator (CovR), also called caspsule synthesis regulator (CsrR), is critical to how the major human pathogen group A Streptococcus fine-tunes virulence factor production. CovR phosphorylation (CovR~P) levels are determined by its cognate sensor kinase CovS, and functional abrogating mutations in CovS can occur in invasive GAS isolates leading to hypervirulence. Presently, the mechanism of CovR-DNA binding specificity is unclear, and the impact of CovS inactivation on global CovR binding has not been assessed. Thus, we performed CovR chromatin immunoprecipitation sequencing (ChIP-seq) analysis in the emm1 strain MGAS2221 and its CovS kinase deficient derivative strain 2221-CovS-E281A. We identified that CovR bound in the promoter regions of nearly all virulence factor encoding genes in the CovR regulon. Additionally, direct CovR binding was observed for numerous genes encoding proteins involved in amino acid metabolism, but we found limited direct CovR binding to genes encoding other transcriptional regulators. The consensus sequence AATRANAAAARVABTAAA was present in the promoters of genes directly regulated by CovR, and mutations of highly conserved positions within this motif relieved CovR repression of the hasA and MGAS2221_0187 promoters. Analysis of strain 2221-CovS-E281A revealed that binding of CovR at repressed, but not activated, promoters is highly dependent on CovR~P state. CovR repressed virulence factor encoding genes could be grouped dependent on how CovR~P dependent variation in DNA binding correlated with gene transcript levels. Taken together, the data show that CovR repression of virulence factor encoding genes is primarily direct in nature, involves binding to a newly-identified DNA binding motif, and is relieved by CovS inactivation. These data provide new mechanistic insights into one of the most important bacterial virulence regulators and allow for subsequent focused investigations into how CovR-DNA interaction at directly controlled promoters impacts GAS pathogenesis.
El perfeccionismo postkantiano y la izquierda hegeliana
Authors: Moggach Douglas
Published: February 2022

La ética política de la Escuela hegeliana se caracteriza por el perfeccionismo post-kantiano, un enfoque que difiere de las teorías perfeccionistas precedentes en que tiene por objeto la promoción de la libertad y las condiciones de su ejercicio. Las ideas de actividad espontánea o iniciada por sí misma desplazan los puntos de vista antiguos de la felicidad o la prosperidad (eudaimonia), basados en concepciones fijas de la naturaleza humana. Las nuevas teorías están también pendientes de los intereses conflictivos en la sociedad civil moderna emergente y de la necesidad de transformar sus prácticas e instituciones. Dentro de este enfoque se distinguen dos variantes en la década de 1840, las de Bauer y Marx, de las cuales aquí se examinan sus respectivos compromisos normativos y metaéticos.
Francisco de Vitoria y Emmanuel Lévinas: la doctrina sobre los indios y los derechos del otro humano
Authors: Campà Molist Joan Enric
Published: February 2022

Si bien los Derechos Humanos se han edificado desde el principio de libertad e igualdad a la hora de mediar un encuentro interidentitario, tal como se expone en el postulado de Francisco de Vitoria, con el pensamiento de Emmanuel Lévinas pueden sufrir una conversión para ser erigidos desde otros principios: la responsabilidad y la illeidad. Ésta puede ser una importante conversión si la consideramos en un encuentro entre civilizaciones tan importante como el dado en 1492, cómo no, en la isla de Bohío (actual República Dominicana). Asimismo, desde la Doctrina sobre los indios de Francisco de Vitoria, se descifran puntos de sintonía y divergencia que ayudan a la reflexión levinasiana de los Derechos Humanos: los Derechos del otro humano.
Ética y turismo en el marco de las ‘tribus morales’: el potencial moral indirecto de la actividad turística desde una perspectiva evolutiva
Authors: Suárez-Ruíz E. Joaquín
Published: February 2022

El objetivo de este trabajo es analizar una concepción del vínculo entre ética y turismo que puede ser pensada como alternativa a la predominante en la teoría del turismo actual. Para ello, se partirá de la perspectiva evolutiva de la moral de dos filósofos contemporáneos: Peter Singer y Joshua Greene. Según se argumentará, paralelamente a la ética del turismo y al turismo ético, también puede hablarse de una potencialidad moral del turismo cultural de masas, la cual no surge de una aplicación de preceptos éticos al turismo, sino que es inherente a este último.
Miguel de Unamuno: del instinto de perpetuación al de comunión
Authors: San Román Gómez Álvaro
Published: February 2022

El presente artículo se propone hacer hincapié en la importancia que para Unamuno adquiere la experiencia de la comunidad a lo largo de su vida y obra, así como en la relación que esta guarda con la individualidad y la inmortalidad. Para ello estudiaremos lo que llamamos “instinto de comunión”, con el fin de ampliar la investigación en un área del pensamiento de Unamuno cuya interpretación ha quedado relegada a un segundo plano en favor de su famoso “instinto de perpetuación”. Ello nos permitirá concluir con una defensa antipositivista del sujeto y de la comunidad conformada por los seres humanos y la naturaleza.
A Study of Vitamin D Levels in HIV Seropositive Patients
Authors: K. Chandrashekar , K.H. Vinod Gowda , Ganteppanavar Chetan K. , Hubballi Veeresh B. , Hasabi Ishwar S.
Published: February 2022

BACKGROUND Vitamin D has an extensive role in immune function and regulation. Cardiovascular disease, Insulin resistance, cell-mediated immunity, autoimmune disease, infections like tuberculosis Vitamin D has a significant role. In autophagy, active form of vitamin D is found to have a role. Low vitamin D levels among HIV infected patients are associated with an increase in mortality, morbidity with a positive correlation between vitamin D levels and CD4 T cells. We wanted to study vitamin D levels in HIV patients, the correlation between CD4 counts and vitamin D levels, the correlation between vitamin D levels and opportunistic infections and also severity of the disease in HIV patients. METHODS A total of 104 confirmed HIV positive patients in KIMS, Hubballi fulfilling inclusion and exclusion criteria were included in the study. Detailed history, examination and lab studies were conducted. RESULTS Among the 104 HIV positive patients, 54 were male and 50 were female patients. 94 (90.4 %) patients had hypovitaminosis D (< 30 ng/ml) and 10 (9.6 %) patients had normal vitamin D levels (> 30 ng/ml). Low vitamin D levels were associated with low CD4 counts with a positive correlation and Pearson correlation value of (+0.87). Low vitamin D levels were associated with severe HIV disease (WHO stage 3 and 4) and with opportunistic infections like TB and oral candidiasis. All these above correlations were found to be statistically significant (P < 0.001). CONCLUSIONS Vitamin D deficiency is frequently observed in HIV positive patients. Low vitamin D levels are associated with low CD4 counts, more severe disease and opportunistic infections. These suggest the importance of vitamin D in HIV positive patients in slowing disease progression and ultimately improving the quality of life and hence its levels need to be checked regularly. KEY WORDS HIV; TB; CD4 Counts; Vitamin D
Hepatitis B Vaccination Status of Dentists and Their Approach to Hepatitis B Infected Patients - A Questionnaire Based Survey from Maharashtra
Authors: Kuyare Sunil Suresh , Pai Nanda G. , Mankar Ashwini A. , Makwana Vidhi M. , Nataraj Gita
Published: February 2022

BACKGROUND Dentists are at high risk for Hepatitis B infection. Vaccination provides effective immunity. Not all dentists are vaccinated despite awareness and availability. Hepatitis B vaccination for health care workers is mandatory as per Biomedical Waste Management Rules, 2018. The present study was planned to determine the vaccination status amongst dentists and their approach to Hepatitis B infected patients. METHODS After the institutional ethics committee permission, the study was initiated. A Google form along with an online consent was emailed to all dentists registered with Maharashtra dental council (MDC). Post survey, a short information sheet was mailed to all, about the need for Hepatitis B vaccination and certain aspects related to it. The responses were automatically transferred to a Microsoft excel sheet and analyzed. RESULTS 16,418 emails were sent out. 371 (2.3 %) participants responded, 352 (2.1 %) working dentists were included. 78.2 % (N = 273) were from urban area. 56 % (N =192) participants were in the age group 22-30 years. Male to female ratio was 0.8:1. 52.2 % (N = 184) had own clinic and 34.4 % (N = 121) were private practitioners. 56.4 % (N = 195) were dental graduates and 43.6 % (N = 151) were postgraduates. The vaccination status of dentists was found to be 74.7 % (N = 263). Only 22.1 % (N = 58) had tested for antibody titre against Hepatitis B, 55.7 % (N = 196) dentists routinely carried out hepatitis B testing of their patients. If patients tested positive, 53.1 % (N =187) provided dental care in their own clinic. CONCLUSIONS Improving the hepatitis B vaccination amongst dentists will improve their safety and reduce their fear of managing infected patients. KEY WORDS Hepatitis B, Vaccination, Dentists, Survey.
Ocular Manifestations in Rheumatoid Arthritis Patients - A Hospital Based Cross Sectional Study
Authors: Satmiamma Nishi Raghu , Shobhana Sheeba Chellan , Antony Jacob , Swarna Bai Siji Vincent
Published: February 2022

BACKGROUND The prevalence of rheumatoid arthritis (RA) in India is 0.28% to 0.7%, 15-45% of patients with RA develop ocular manifestations. Ocular disabilities can be reduced with timely interference by an ophthalmologist. Keratoconjunctivitis sicca (Sjogren’s syndrome) is the most common ocular association of RA. This study was done to find out various ocular manifestations in rheumatoid arthritis patients. METHODS A cross sectional study was conducted among the patients attending the rheumatology clinic at Government Medical College, Trivandrum. Patients in the age group of 18-60 years were screened and further evaluated at regional institute of ophthalmology, Trivandrum. Screening for RA was done using the American Rheumatism Association criteria. A complete ophthalmic examination was done for those who satisfied the criteria. The various ocular manifestations in RA are described and presented as proportions. RESULTS Ocular manifestation was found in 38% of total patients attending the rheumatology clinic. There were 54 females (80.5%) and 13 males (19.4%). Age group mainly affected were in 46-50 yr (17.9%). The duration of rheumatoid arthritis ranged from few months to 25 years. Keratoconjunctivitis sicca was the commonest manifestation found, detected in 22(84%) patients, episcleritis was noted in two patients (7.6%), scleritis in 1 patient (3.8%) and marginal furrowing in 1 patient (3.8%). CONCLUSIONS In this clinic-based study there was a high proportion (38%) of ocular involvement in RA and hence it is essential to include ophthalmic evaluation as a routine in RA patients. The most common manifestation was keratoconjunctivitis sicca followed by episcleritis, diffuse anterior scleritis and marginal corneal furrowing. KEY WORDS Rheumatoid Arthritis, Keratoconjunctivitis Sicca, Ocular Manifestations, Scleritis, Episcleritis
Psychosocial Profile and Psychiatric Comorbidity in Patients with Chronic Headache
Authors: B. Jyostna , Vasireddy Niveditha
Published: February 2022

BACKGROUND Chronic daily headache is a common problem reported in tertiary centres and headache is more commonly comorbid with psychiatric disorders. Headache associated with psychopathology has exaggerated effects on quality of life and disability. Comorbid psychiatric illnesses are risk factors for headaches becoming chronic. Earlier studies on the comorbidity of headache and psychiatric disorders found that comorbidity was found among 90 % of the samples with chronic headaches. The objectives of the study were to evaluate psychiatric comorbidity of patients with chronic headache and the association between socio-demographic factors and psychiatric disorders in patients with chronic headache. METHODS The present study was done in tertiary care hospital, on psychosocial profile and psychiatric disorders in patients with chronic headaches. The subjects belonging to both sexes and above twenty years were included in the study. After obtaining the socio-demographic details of each subject as per pre-decided intake proforma, each subject was administered with M.I.N.I. Plus. The data obtained were analyzed by statistical methods and the results were compiled. RESULTS According to the study, young age group, females, married, illiterates, and people with low socioeconomic status were suffering from chronic headaches. The most common psychiatric comorbidity seen among the study population was major depressive disorder (MDD), dysthymia, panic disorder with agoraphobia and generalized anxiety disorder (GAD). CONCLUSIONS There is a need to assess psychiatric comorbidity among patients suffering from headaches as early diagnosis will help in the good prognosis of the individuals and better patient care. KEY WORDS Chronic Headache, Psychiatric Comorbidity, Major Depressive Disorder, Panic Disorder, Generalized Anxiety Disorder.
Prevention of Hypotension following Spinal Anaesthesia for Caesarean Section: Comparison of Pretreatment with Crystalloid and Ephedrine Infusion
Authors: M.S. Sajil , Ulahannan Reshma , S. Sree Sabari , Sathyan Nithin
Published: February 2022

BACKGROUND Regional anaesthesia has become the preferred technique for caesarean section because of higher incidence of maternal mortality and morbidity associated with general anaesthesia. Spinal hypotension occurs as a result of sympathetic blockade and decreased venous return due to decreased systemic vascular resistance and venous pooling. Such episodes of hypotension have been shown to cause decreased Apgar scores and foetal acidosis. Preloading with intravenous fluids, left uterine displacement and prophylactic/ therapeutic vasopressors have all been used in the prevention and management of hypotension traditionally. However no single method has been proved satisfactory. In terms of neonatal and maternal outcomes, prevention of hypotension is considered superior to treatment of established hypotension. In this study, we compare the efficacy of preloading of crystalloids with Ephedrine infusion in prevention of hypotension following spinal block in caesarean patients. Objectives- Primary objective is to determine the incidence of hypotension following spinal anaesthesia in patients receiving preloading with crystalloids and preloading with Ephedrine. Secondary objective is to compare intraoperative maternal and foetal adverse effects of pre-treatment with crystalloids and Ephedrine. METHODS An observational study was conducted in 90 patients belonging to ASA I and II categories undergoing elective LSCS. One category received 10ml/kg Ringer Lactate and other category 10mg Ephedrine in 10ml/kg Ringer Lactate 15-30 minutes prior to spinal block. All patients received SAB with 22.2ml 0.5% Bupivacaine heavy at L3-L4 space. HR and BP were monitored periodically and fall in MAP of ≥20% was noted and managed with rescue Ephedrine. Maternal adverse events, foetal APGAR scores and umbilical blood gas analysis noted. RESULTS Incidence of hypotension was significantly less in Ephedrine category as compared to crystalloid category. Incidence of maternal adverse events as well as foetal parameters was not significantly different. CONCLUSIONS Preloading with Ephedrine decreases the incidence of maternal hypotension when compared to crystalloids alone. KEY WORDS Caesarean Section, Crystalloids; Ephedrine, Foetal Acidosis, Mean Arterial BP, Preloading, Spinal Hypotension.