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Effect of vitamin D on clinical outcomes in patients with thermal injury

Abstract

Evaluating complications and mortality risks in burn patients is crucial for effective treatment planning and improving survival rates. This study investigated the relationship between the serum vitamin D level and the clinical outcomes of adult burns patients. This was a prospective cohort of adult patients hospitalized due to thermal burns at a burn centre in the north of Iran. Based on the level of 25 hydroxyvitamin D measured upon admission, patients were divided into two groups of patients with sufficient 25 hydroxyvitamin D level and insufficient 25 hydroxyvitamin D level. Descriptive statistics were used for baseline demographics. Univariate analysis was conducted using Mann–Whitney U, Chi-square, independent samples, and Fisher's exact tests. A multivariate logistic regression was performed to adjust for the effects of confounding variables. Statistical analyses were conducted using SPSS 28.0 software. A total of 220 patients were included in the study. The average total body surface area burned was 30.52 ± 9.34. Patients with insufficient vitamin D levels had longer hospital stays (12.53 vs. 11.45) and longer stays in the intensive care unit (ICU) (3.32 vs. 2.40) than those with appropriate vitamin D levels. Participants with insufficient vitamin D levels exhibited a numerically higher incidence of infections than those with adequate levels (p < 0.05). The multivariate regression found that vitamin D deficiency levels were associated with increased infection rates and prolonged hospital stay. This study suggests that vitamin D deficiency is a significant risk factor for adverse clinical outcomes in burn patients. Further research is needed to confirm these associations and to explore potential interventions to optimize vitamin D status in this patient population.

Real-world prescription of anti-COVID-19 drugs in hospitalized patients with COVID-19 in Japan

by Haruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama

Objective

Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan.

Design

The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan.

Participants

Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021.

Exposures

The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine.

Results

We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period.

Conclusions and relevance

This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.

Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1

by Dimitrios G. Anastasakis, Daniel Benhalevy, Nicolas Çuburu, Nihal Altan-Bonnet, Markus Hafner

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.

Implementation of antimicrobial stewardship programs: A study of prescribers’ perspective of facilitators and barriers

by Emelda E. Chukwu, Dennis Abuh, Ifeoma E. Idigbe, Kazeem A. Osuolale, Vivian Chuka-Ebene, Oluwatoyin Awoderu, Rosemary A. Audu, Folasade T. Ogunsola

Background

Despite promising signs of the benefits associated with Antimicrobial Stewardship Programs (ASPs), there remains limited knowledge on how to implement ASPs in peculiar settings for a more elaborate impact. This study explored prescriber experiences and perceptions of the usefulness, and feasibility of strategies employed for the implementation of antimicrobial stewardship (AMS) interventions as well as challenges encountered.

Methods

This is a cross-sectional mixed-method survey of prescribers’ perspective of the facilitators and barriers of implementing ASP. The quantitative approach comprised of a semi-structured questionnaire and data collected were analyzed using SPSS version 26 while the qualitative approach used focus group discussions followed by content analysis.

Results

Out of the thirty people that participated in the workshop, twenty-five completed the questionnaires which were analyzed. The respondents included 15 (60.0%) medical doctors and 10 (40.0%) pharmacists. The mean age of the respondents was 36.39±7.23 years with mean year of practice of 9.48±6.01 years. Majority of them (84.0%) were in a position to provide input on the implementation of AMS in their facilities, although their managements had the final decision. The pharmacists (100%) were more likely to agree that antibiotic resistance was a problem for their practice than the medical doctors (78.6%) while equal number (80.0%) of respondents (pharmacists and medical doctors) believed that inappropriate prescribing was a problem. Having a specialized and dedicated team with effective monitoring was recognized as crucial for effective ASP while inadequate personnel was identified as a major barrier. We identified stakeholder’s engagement, policies and regulation, as well as education as themes for improving AMS in the country.

Conclusion

The results gave insight into the prescribers’ perspective on the facilitators and barriers to antimicrobial stewardship; challenges and possible solutions to implementing ASPs in health facilities in Lagos State. We further identified pertinent contextual factors that need to be addressed when developing ASPs in healthcare facilities in a resource-poor setting.

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

by Sergei A. Fedotov, Maria S. Khrabrova, Elena S. Vashukova, Andrey S. Glotov, Anastasia O. Anpilova, Vladimir A. Dobronravov, Maria E. Velizhanina, Aleksandr A. Rubel

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30–100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

Exploring knowledge, perceptions, and practices of antimicrobials, and their resistance among medicine dispensers and community members in Kavrepalanchok District of Nepal

by Sabina Marasini, Sudim Sharma, Anjali Joshi, Surakshya Kunwar, Roshan Kumar Mahato, Archana Shrestha, Biraj Karmacharya

Background

Inappropriate use of antimicrobials is a global public health issue, particularly in developing countries, including Nepal, where over-the-counter sales and self-medication of antimicrobials are common.

Objectives

To explore knowledge, perceptions, and practices of antimicrobials and their resistance among medicine dispensers and community members in Nepal.

Methods

The study was conducted in three rural and five urban municipalities of the Kavrepalanchok district from May 2021 to August 2021. Data were collected using two qualitative approaches: In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). Data were analyzed using thematic analysis that combined deductive and inductive approaches to identify codes under pre-specified themes.

Results

A total of 16 In-depth interviews with medicine dispensers and 3 focus group discussions with community members were conducted. Knowledge regarding antimicrobial resistance varied among dispensers. Those with a prior educational background in pharmacy often had good knowledge about the causes and consequences of antimicrobial resistance. Meanwhile, consumers were less aware of antimicrobial resistance. Community members perceived antimicrobials as effective medicines but not long-term solution for treating diseases. They reported that dispensing without a prescription was common and that both consumers and dispensers were responsible for the inappropriate use of antimicrobials. On the contrary, several dispensers said that self-medication was common among the consumers, especially among more educated groups. The medicine dispensers and consumers expressed concerns about the weak enforcement of policies regarding pharmacy drug use and dispensing practices.

Conclusion

Promoting and strengthening the appropriate use of antimicrobials among medicine dispensers and community members is crucial. Bold policies and collective implementation of regulations could help combat antimicrobial resistance.

Evaluating deep learning-based melanoma classification using immunohistochemistry and routine histology: A three center study

by Christoph Wies, Lucas Schneider, Sarah Haggenmüller, Tabea-Clara Bucher, Sarah Hobelsberger, Markus V. Heppt, Gerardo Ferrara, Eva I. Krieghoff-Henning, Titus J. Brinker

Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine.

A non-lethal stable isotope analysis of valued freshwater predatory fish using blood and fin tissues as alternatives to muscle tissue

by Lukáš Vejřík, Ivana Vejříková, Zuzana Sajdlová, Luboš Kočvara, Tomáš Kolařík, Daniel Bartoň, Tomáš Jůza, Petr Blabolil, Jiří Peterka, Martin Čech, Mojmír Vašek

Stable isotope analysis (SIA) is widely used to study trophic ecology and food webs in aquatic ecosystems. In the case of fish, muscle tissue is generally preferred for SIA, and the method is lethal in most cases. We tested whether blood and fin clips can be used as non-lethal alternatives to muscle tissue for examining the isotopic composition of two freshwater predatory fish, European catfish (Silurus glanis) and Northern pike (Esox lucius), species of high value for many freshwater systems as well as invasive species in many others. Blood samples from the caudal vein, anal fin clips, and dorsal muscle obtained by biopsy punch were collected from four catfish and pike populations (14–18 individuals per population). Subsequently, these samples were analyzed for δ13C and δ15N. The effects of alternative tissues, study site, and fish body mass on the isotopic offset were investigated. Both species showed a correlation between the isotopic offset and the tissue type, as well as the study site, but no significant relationship with the body mass. The isotopic offsets between tissues were used to calculate the conversion equations. The results demonstrated that both blood and fin clips are suitable and less invasive alternative to muscle in SIA studies focused on European catfish and Northern pike. Blood provided better correspondence to muscle isotope values. However, our results clearly demonstrated that isotopic offsets between tissues vary significantly among populations of the same species. Therefore, obtaining a muscle biopsy from several individuals in any population is advisable to gain initial insights and establish a possible population-specific inter-tissue conversion.

Development and validation of a multi-dimensional diagnosis-based comorbidity index that improves prediction of death in men with prostate cancer: Nationwide, population-based register study

by Marcus Westerberg, Sandra Irenaeus, Hans Garmo, Pär Stattin, Rolf Gedeborg

Assessment of comorbidity is crucial for confounding adjustment and prediction of mortality in register-based studies, but the commonly used Charlson comorbidity index is not sufficiently predictive. We aimed to develop a multidimensional diagnosis-based comorbidity index (MDCI) that captures comorbidity better than the Charlson Comorbidity index. The index was developed based on 286,688 men free of prostate cancer randomly selected from the Swedish general population, and validated in 54,539 men without and 68,357 men with prostate cancer. All ICD-10 codes from inpatient and outpatient discharges during 10 years prior to the index date were used to define variables indicating frequency of code occurrence, recency, and total duration of related hospital admissions. Penalized Cox regression was used to predict 10-year all-cause mortality. The MDCI predicted risk of death better than the Charlson comorbidity index, with a c-index of 0.756 (95% confidence interval [CI] = 0.751, 0.762) vs 0.688 (95% CI = 0.683, 0.693) in the validation cohort of men without prostate cancer. Men in the lowest vs highest MDCI quartile had distinctively different survival in the validation cohort of men with prostate cancer, with an overall hazard ratio [HR] of 5.08 (95% CI = 4.90, 5.26). This was also consistent within strata of age and Charlson comorbidity index, e.g. HR = 5.90 (95% CI = 4.65, 7.50) in men younger than 60 years with CCI 0. These results indicate that comorbidity assessment in register-based studies can be improved by use of all ICD-10 codes and taking related frequency, recency, and duration of hospital admissions into account.

High-resolution genomic analysis to investigate the impact of the invasive brushtail possum (<i>Trichosurus vulpecula</i>) and other wildlife on microbial water quality assessments

by Marie Moinet, Lynn Rogers, Patrick Biggs, Jonathan Marshall, Richard Muirhead, Megan Devane, Rebecca Stott, Adrian Cookson

Escherichia coli are routine indicators of fecal contamination in water quality assessments. Contrary to livestock and human activities, brushtail possums (Trichosurus vulpecula), common invasive marsupials in Aotearoa/New Zealand, have not been thoroughly studied as a source of fecal contamination in freshwater. To investigate their potential role, Escherichia spp. isolates (n = 420) were recovered from possum gut contents and feces and were compared to those from water, soil, sediment, and periphyton samples, and from birds and other introduced mammals collected within the Mākirikiri Reserve, Dannevirke. Isolates were characterized using E. coli-specific real-time PCR targeting the uidA gene, Sanger sequencing of a partial gnd PCR product to generate a gnd sequence type (gST), and for 101 isolates, whole genome sequencing. Escherichia populations from 106 animal and environmental sample enrichments were analyzed using gnd metabarcoding. The alpha diversity of Escherichia gSTs was significantly lower in possums and animals compared with aquatic environmental samples, and some gSTs were shared between sample types, e.g., gST535 (in 85% of samples) and gST258 (71%). Forty percent of isolates gnd-typed and 75% of reads obtained by metabarcoding had gSTs shared between possums, other animals, and the environment. Core-genome single nucleotide polymorphism (SNP) analysis showed limited variation between several animal and environmental isolates (Escherichia clones are shared between possums, other wildlife, water, and the wider environment. These findings support the potential role of possums as contributors to fecal contamination in Aotearoa/New Zealand freshwater. Our study deepens the current knowledge of Escherichia populations in under-sampled wildlife. It presents a successful application of high-resolution genomic methods for fecal source tracking, thereby broadening the analytical toolbox available to water quality managers. Phylogenetic analysis of isolates and profiling of Escherichia populations provided useful information on the source(s) of fecal contamination and suggest that comprehensive invasive species management strategies may assist in restoring not only ecosystem health but also water health where microbial water quality is compromised.

Exploring perceptions of gender roles amongst sexually active adolescents in rural KwaZulu-Natal, South Africa

by Brett Marshall, Celia Mehou-Loko, Sindisiwe Mazibuko, Makhosazana Madladla, Lucia Knight, Hilton Humphries

Traditional gender and social norms reinforce asymmetrical power relations, increase the risk of experiencing gender-based violence and mediate poor engagement with sexual and reproductive health services. This study explored gender norms and expectations amongst cisgender adolescents in rural KwaZulu-Natal, South Africa. A purposive sample of 29 adolescents aged 16–19 years old were enrolled as part of a longitudinal qualitative study. The current analysis reports on the first round of in-depth interviews, which focused on the role of men and women in their community. A theoretically informed thematic analysis identified three broad themes: 1) Adolescent interpretation and understanding of gender identity, 2) Gendered essentialism and Gender roles (two sub-themes: Young men: Power through providing, and Young women: The domestication process which highlighted that gender roles were defined by being the provider for men, and the successful fulfilment of traditional domestic behaviours amongst women), 3) Gender and fertility highlighted how participants highly valued fertility as affirming of manhood/womanhood. These norms reinforce gender roles that maintain asymmetrical power relations, carrying them over into adulthood. The subtle social pressure to prove fertility could have unintended consequences for driving teenage pregnancy. Structural, gender-based interventions emphasising positive gender-role development in early childhood are needed.

Clinical evaluation of a fully electronic microfluidic white blood cell analyzer

by Jianye Sui, Zhongtian Lin, Shahriar Azizpour, Fei Chen, Sunanda Gaur, Kelly Keene, Farzad Soleimani, Tanaya Bhowmick, Zubaid Rafique, Mehdi Javanmard

The White Blood Cell (WBC) count is one of the key parameters signaling the health of the immune system. Abnormal WBC counts often signal a systemic insult to the body such as an underlying infection or an adverse side effect to medication. Typically, the blood collected is sent to a central lab for testing, and results come back within hours, which is often inconvenient and may delay time-sensitive diagnosis or treatment. Here, we present the CytoTracker, a fully electronic, microfluidic based instant WBC analyzer with the potential to be used at point-of-care. The CytoTracker is a lightweight, portable, affordable platform capable of quantifying WBCs within minutes using only 50 μl of blood (approximately one drop of blood). In this study, we clinically evaluated the accuracy and performance of CytoTracker in measuring WBC and granulocyte counts. A total of 210 adult patients were recruited in the study. We validated the CytoTracker against a standard benchtop analyzer (Horiba Point of Care Hematology Analyzer, ABX Micros 60). Linear dynamic ranges of 2.5 k/μl– 35 k/μl and 0.6 k/μl– 26 k/μl were achieved for total WBC count and granulocyte count with correlation coefficients of 0.97 and 0.98. In addition, we verified CytoTracker’s capability of identifying abnormal blood counts with above 90% sensitivity and specificity. The promising results of this clinical validation study demonstrate the potential for the use of the CytoTracker as a reliable and accurate point-of-care WBC analyzer.

D-dimer levels to exclude pulmonary embolism and reduce the need for CT angiography in COVID-19 in an outpatient population

by Anita Kovács, Dóra Hantosi, Nikoletta Szabó, Annamária Letoha, Csaba Lengyel, Imre Földesi, Katalin Burián, András Palkó, Dániel Veréb, Zsigmond Tamás Kincses

Objectives

Emerging results indicate that, in COVID-19, thromboembolic complications contribute to the high mortality and morbidity. Previous research showed that the prevalence of pulmonary embolism (PE) is between 25–50% in COVID-19 patients, however, most of these reports are based on data from patients with severe pneumonia, treated in intensive care units.

Materials and methods

We conducted a retrospective, single-center, observational study to estimate the prevalence of PE in COVID-19 patients who underwent CT angiography and to identify the most important predictors.Adult outpatients with COVID-19, who presented at our COVID Outpatient Clinic between 1st and 31st of March in 2021 and underwent CTA examination were included in this study. Multiple linear regression analysis was used to identify predictors of PE in COVID-19 patients. The predictors were: age, gender, disease duration, CT severity index and log-transformed quantitative D-dimer (logQDDIM) value.

Results

843 COVID-19 patients were included into the study. 82.56% (693 patients) of the infected patients had a pulmonary CTA examination and D-dimer levels (mean age: 59.82 years ± 15.66). 7.61% (53 patients) of the patients had PE. 2.02% (14 patients) of the patients had main branch or lobar PE.The multiple regression analysis found that only logQDDIM was a significant predictor. A logQDDIM cut-off value of 0.0169 (1.0171 ug/ml serum D-dimer) predicted PE with 99% sensitivity (p Conclusions

We demonstrated in a large cohort of COVID-19 patients that a cut-off value of QDDIM of 1ug/ml can exclude pulmonary embolism in an outpatient setting, implicating that QDDIM might potentially supersede CTA as a screening approach in COVID-19 outpatient clinics.

Dislodgement resistance and structural changes of tricalcium silicate-based cements after exposure to different chelating agents

by Özgür İlke Ulusoy, Nidambur Vasudev Ballal, Rajkumar Narkedamalli, Nuran Ulusoy, Krishna Prasad Shetty, Alexander Maniangat Luke

This study aimed to evaluate the dislodgement resistance and structural changes of different mineral trioxide aggregate cements (MTA) like Pro-Root MTA, Ortho MTA, and Retro MTA after exposure to sodium hypochlorite (NaOCl), NaOCl-Ethylenediaminetetraacetic acid (EDTA), 1-hydroxyethylidene-1, 1-bisphosphonate (Dual Rinse HEDP), and NaOCl-Maleic acid (MA). The root canal spaces of 150 dentine slices were obturated using tricalcium silicate cements and divided into 3 groups (n = 50): Group1: ProRoot MTA, Group2: Retro MTA, and Group3: Ortho MTA. The samples in each group were further subdivided into four experimental (n = 10) and one control groups (n = 10): 2.5% NaOCl-17% EDTA, Dual Rinse HEDP, 2.5% NaOCl-7% Maleic acid, 2.5% NaOCl, distilled water (control). The dislodgement resistance and structural changes of cements were measured. Use of DR HEDP resulted in higher dislodgement resistance compared to17% EDTA and 7% MA in the samples obturated with Ortho MTA and Pro-Root MTA (p

Trends of inequality in DPT3 immunization services utilization in Ethiopia and its determinant factors: Evidence from Ethiopian demographic and health surveys, 2000–2019

by Hailu Fekadu, Wubegzier Mekonnen, Aynalem Adugna, Helmut Kloos, Damen Hailemariam

Background

Low levels of diphtheria, tetanus toxoid, pertussis (DPT3) immunization services utilization and high deaths among under five children are concentrated in economically and socially disadvantaged groups, especially in low and middle-income countries, including Ethiopia. Hence, the aim of this study is to assess levels and trends in DPT3 immunization services utilization in Ethiopia and identify inequalities.

Methods

This study used data from 2000, 2005, 2011, 2016, and 2019 Ethiopian Demographic Health Surveys (EDHSs). The 2019 updated version of the world health organization (WHO’s) Health Equity Assessment Toolkit (HEAT) software was used to analyze the data. Six measure of inequality was calculated: ratio (R), differences (D), relative index of inequality (RII), slope index of inequality (SII), population attributable fraction (PAF) and population attributable risk (PAR). The findings were disaggregated by the five equity stratifiers: economic status, education, place of residence, regions and sex of the child.

Results

This study showed an erratic distribution of DPT3 immunization services utilization in Ethiopia. The trends in national DPT3 immunization coverage increased from 21% in (2000) to 62% in (2019) (by 41 percentage points). Regarding economic inequality, DPT3 immunization coverages for the poorest quintiles over 20 years were 15.3% (2000), and 47.7% (2019), for the richest quintiles coverage were 43.1 (2000), and 83.4% (2019). However, the service utilization among the poorest groups were increased three fold compared to the richest groups. Regarding educational status, inequality (RII) show decreasing pattern from 7.2% (2000) to 1.5% in(2019). Concerning DPT3 immunization inequality related to sex, (PAR) show that, sex related inequality is zero in 2000, 2005 and in 2019. However, based on the subnational region level, significance difference (PAR) was found in all surveys: 59.7 (2000), 51.1 (2005), 52.2 (2011), 42.5 (2016) and 30.7 (2019). The interesting point of this finding was that, the value of absolute inequality measures (PAR) and (PAF), are shown a decreasing trends from 2000 to 2019, and the gap among the better of regions and poor regions becoming narrowed over the last 20 years. Concerning individual and community level factors, household wealth index, education of the mother, age of respondent, antenatal care, and place of delivery show statically significant with outcome variable. Keeping the other variables constant the odds of an average child in Amhara Region getting DPT3 immunization was 54% less than for a child who lived in Addis Ababa (OR: 0.46, 95% CI: 0.34 – 0.63). Respondents from households with the richest and richer wealth status had 1.21, and 1.26 times higher odds of DPT3 immunization services utilization compared to their counterpart (OR: 1.21, 95% CI: 1.04 -1.41) and (OR: 1.26, 95% CI: 1.13 – 1.40) respectively.

Conclusion

We conclude that DPT3 immunization coverage shows a growing trend over 20 years in Ethiopia. But inequalities in utilization of DPT3 immunization services among five equality stratifies studied persisted. Reasons for this could be complex and multifactorial and depending on economic, social, maternal education, place of residence, and healthcare context. Therefore, policy has to be structured and be implemented in a ways that address context specific barriers to achieving equality among population sub-groups and regions.

Application of in-silico drug discovery techniques to discover a novel hit for target-specific inhibition of SARS-CoV-2 Mpro’s revealed allosteric binding with MAO-B receptor: A theoretical study to find a cure for post-covid neurological disorder

by Magdi E. A. Zaki, Sami A. AL-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Vijay H. Masand, Rahul G. Ingle, Vivek Digamber Rathod, Nikita Maruti Gaikwad, Summya Rashid, Pravin N. Khatale, Pramod V. Burakale, Rahul D. Jawarkar

Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R2 = 0.800–793, Q2LOO = 0.734–0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit’s docking score (-8.208 kcal/mol) and PIC50 (7.85 M) demonstrated a significant affinity for SARS-CoV-2’s main protease. Based on post-covid neurodegenerative episodes in Alzheimer’s and Parkinson’s-like disorders and MAO-B’s role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2’s primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR’s COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness.

Educational technologies for teaching hand hygiene: Systematic review

by Daiane Rubinato Fernandes, Bruna Nogueira dos Santos, Carolina Scoqui Guimarães, Elaine Barros Ferreira, Amanda Salles Margatho, Paula Elaine Diniz dos Reis, Didier Pittet, Renata Cristina de Campos Pereira Silveira

Aim

To gather available scientific evidence on technologies used to teach hand hygiene to professional populations and lays involved in health care in the hospital setting. This systematic review was designed as proposed by Preferred Reporting Items for Systematic Reviews and Meta-Analysis, included studies reporting primary, original, quantitative research findings with no date limit and written in English, Spanish or Portuguese. The search was performed in the following electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica dataBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde, US National Library of Medicine, Scopus, Web of Science, Google Scholar and ProQuest. The eligibility criteria were applied independently by two reviewers to select the studies, first by reading the titles and abstracts on the Rayyan platform and then by full text reading of the eligible studies. After a descriptive analysis, the studies were subjected to critical evaluation of their methodological quality using JBI tools.

Results

Seven studies were included, addressing various methods for teaching hand hygiene using different technological resources, such as audiovisual electronic devices, videos, virtual reality, and gamification using tablets and smartphones, in different populations.

Conclusion

Using technologies to teach hand hygiene considerably helps patients, visitors, and relatives in learning the procedures and efficiently improves hand hygiene compliance rates among healthcare professionals, creating evidence-based repetitive learning opportunities for patients and caregivers.

Refinement of the motorised laminectomy-assisted rat spinal cord injury model by analgesic treatment

by Harikrishnan Vijayakumar Sreelatha, Hamza Palekkodan, Ansar Fasaludeen, Lissy K. Krishnan, Klas S. P. Abelson

Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.

Intraorbital pressure–volume characteristics in a piglet model: In vivo pilot study

by Yasin Hamarat, Laimonas Bartusis, Vilma Putnynaite, Rolandas Zakelis, Mantas Deimantavicius, Vilma Zigmantaite, Ramunė Grigaleviciute, Audrius Kucinskas, Evaldas Kalvaitis, Arminas Ragauskas

Intracranial pressure measurement is frequently used for diagnosis in neurocritical care but cannot always accurately predict neurological deterioration. Intracranial compliance plays a significant role in maintaining cerebral blood flow, cerebral perfusion pressure, and intracranial pressure. This study’s objective was to investigate the feasibility of transferring external pressure into the eye orbit in a large-animal model while maintaining a clinically acceptable pressure gradient between intraorbital and external pressures. The experimental system comprised a specifically designed pressure applicator that can be placed and tightly fastened onto the eye. A pressure chamber made from thin, elastic, non-allergenic film was attached to the lower part of the applicator and placed in contact with the eyelid and surrounding tissues of piglets’ eyeballs. External pressure was increased from 0 to 20 mmHg with steps of 1 mmHg, from 20 to 30 mmHg with steps of 2 mmHg, and from 30 to 50 mmHg with steps of 5 mmHg. An invasive pressure sensor was used to measure intraorbital pressure directly. An equation was derived from measured intraorbital and external pressures (intraorbital pressure = 0.82 × external pressure + 3.12) and demonstrated that external pressure can be linearly transferred to orbit tissues with a bias (systematic error) of 3.12 mmHg. This is close to the initial intraorbital pressure within the range of pressures tested. We determined the relationship between intraorbital compliance and externally applied pressure. Our findings indicate that intraorbital compliance can be controlled across a wide range of 1.55 to 0.15 ml/mmHg. We observed that external pressure transfer into the orbit can be achieved while maintaining a clinically acceptable pressure gradient between intraorbital and external pressures.

AGO2-RIP-Seq reveals miR-34/miR-449 cluster targetome in sinonasal cancers

by Marco Tomasetti, Federica Monaco, Corrado Rubini, Marzia Rossato, Concetta De Quattro, Cristina Beltrami, Giacomo Sollini, Ernesto Pasquini, Monica Amati, Gaia Goteri, Lory Santarelli, Massimo Re

Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.
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