Conectar
To determine the community’s perception on the magnitude of Xeroderma pigmentosum (XP) disease and healthcare-seeking practices in Micheweni, Pemba in response to the public widespread information on the increased burden of the disease.
Mixed-methods cross-sectional study.
Micheweni district, Pemba.
211 male and female adults in the household survey, three caretakers/parents of patients with XP in the case study, 20 key community leaders/influential people and health workers in in-depth interviews and 50 community members and other leaders in six focus groups.
This study has revealed that XP disease exists in few families of which some of them have more than one child affected. The record review showed that there were a total of 17 patients who were diagnosed with the disease for the past 3 years, however only 10 were alive during the time of the survey. Findings from the community members revealed that several patients were believed to have XP disease and perceived causes include inheritance, food types, beliefs and other sociocultural practices. Stigma and discrimination were reported by caretakers and religious leaders. However, some cases believed to be XP were identified as other skin conditions when clinical examination was performed by the team of our researchers. There is a great confusion about XP and other skin diseases.
The study has shown that XP affects only few families, hence termed as concentrated rather than a generalised disease. Due to the rareness of the disease, majority of people in the district are unaware of the disease, hence confusing it with other skin conditions. There is a need for the government in collaboration with other stakeholders to provide educational programme to community members about the disease to address the misconception about the magnitude of the disease.
by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz
ContextPotentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.
ObjectivesThe objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.
MethodsThe D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.
ConclusionThis large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.
To better understand healthcare and social/community service providers’ learning needs associated with supporting transgender and gender diverse (trans) persons who have experienced intimate partner violence (IPV).
An online survey was distributed through the trans-LINK Network in Ontario, Canada.
163 of 225 healthcare and social/community service providers completed the survey (72.4% response rate) between November 2022 and February 2023.
Expertise, training, workplace practices and learning needs related to supporting trans survivors of IPV.
Quantitative survey results were analysed descriptively and open-ended responses were organised thematically. In March 2022, survey results were shared with 33 stakeholders who helped define goals and objectives for an e-learning curriculum using Jamboard, data from which were collated and organised into themes.
Most (66.3%) survey respondents described having provided professional support to trans survivors of IPV, but only one-third (38.0%) reported having received relevant training, and many of the trainings cited were in fact focused on other forms of violence or trans health generally. The majority reported a mid (44.9%) or low-mid (28.5%) level of expertise and almost unanimously agreed that they would benefit from (further) training (99.4%). The most commonly recommended goal/objective for a curriculum emerging from the stakeholder consultation was to facilitate collaboration, knowledge sharing and (safe) referrals among organisations.
The results of this study highlight the critical need for an IPV curriculum specific to trans survivors and responsive to the needs of providers. As no one profession can address this complex issue in isolation, it is important that the curriculum aims to facilitate collaboration across sectors. In the absence of appropriate training and referrals, practitioners may perpetuate harm when caring for trans survivors of IPV.
This study aimed to examine the association between home meal preparer and salt intake among haemodialysis patients, including daily dietary status. We hypothesised that salt intake is higher among individuals who rely on meal preparation from others than those who prepare meals by themselves.
Cross-sectional study.
Two medical facilities in Fukushima Prefecture, Japan.
237 haemodialysis outpatients who visited one of the medical facilities between February 2020 and August 2021 and were diagnosed with anuria, defined as urination of
Salt intake amount was calculated from the results of predialysis and postdialysis blood draws, using Watson’s formula based on predialysis weight, predialysis serum sodium level, postdialysis weight and serum sodium level at the end of dialysis.
Salt intake was significantly higher in participants who relied on meal preparation from others (‘relying on others’) than those who prepared meals by themselves (‘self-prepared’) (B=1.359; 95% CI: 0.495 to 2.222). No statistical difference was found between individuals who ate out or ate takeout (‘outsourcing’) and those who prepared their own meals (‘self-prepared’). These results were robust after adjustment for confounding factors.
The present study revealed an association between self-preparation of meals at home and reduced salt intake among dialysis patients. Our findings suggest that whoever is the home meal preparer is possibly a social determinant of salt intake. To improve the prognosis of haemodialysis patients, actively reaching out to the family and assessing their social environment, such as identifying the home meal preparer and, if the patient relies on others for meal preparation, conducting nutritional/dietary guidance for that person, are effective in enhancing salt reduction.
Tuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse pregnancy outcomes. This study aimed to determine risk factors for an adverse pregnancy outcome among pregnant women diagnosed with TB.
Using TB programmatic data, this retrospective cohort analysis included all women who were routinely diagnosed with TB in the public sector between October 2018 and March 2020 in two health subdistricts of Cape Town, and who were documented to be pregnant during their TB episode. Adverse pregnancy outcome was defined as either a live birth of an infant weighing
Of 248 pregnant women, half (52%) were living with HIV; all were on antiretroviral therapy at the time of their TB diagnosis. Pregnancy outcomes were documented in 215 (87%) women, of whom 74 (34%) had an adverse pregnancy outcome. Being older (35–44 years vs 25–34 years (adjusted OR (aOR): 3.99; 95% CI: 1.37 to 11.57), living with HIV (aOR: 2.72; 95% CI: 0.99 to 4.63), having an unfavourable TB outcome (aOR: 2.29; 95% CI: 1.03 to 5.08) and having presented to antenatal services ≤1 month prior to delivery (aOR: 10.57; 95% CI: 4.01 to 27.89) were associated with higher odds of an adverse pregnancy outcome.
Pregnancy outcomes among women with TB were poor, irrespective of HIV status. Pregnant women with TB are a complex population who need additional support prior to, during and after TB treatment to improve TB treatment and pregnancy outcomes. Pregnancy status should be considered for inclusion in TB registries.
Critically ill patients are at high risk of acquiring ventilator-associated pneumonia (VAP), which occurs in approximately 20% of mechanically ventilated patients. VAP results either from aspiration of pathogen-contaminated oropharyngeal secretions or contaminated biofilms that form on endotracheal tubes (ETTs) after intubation. VAP results in increased duration of mechanical ventilation, increased intensive care unit and hospital length of stay, increased risk of death and increased healthcare costs. Because of its impact on patient outcomes and the healthcare system, VAP is regarded as an important patient safety issue and there is an urgent need for better evidence on the efficacy of prevention strategies. Modified ETTs that reduce aspiration of oropharyngeal secretions with subglottic secretion drainage or reduce the occurrence of biofilm with a coating of ceragenins (CSAs) are available for clinical use in Canada. In this implementation study, we will evaluate the efficacy of these two types of Health Canada-licensed ETTs on the occurrence of VAP, and impact on patient-centred outcomes.
In this ongoing, pragmatic, prospective, longitudinal, interrupted time, cross-over implementation study, we will compare the efficacy of a CSA-coated ETT (CeraShield N8 Pharma) with an ETT with subglottic secretion drainage (Taper Guard, Covidien). The study periods consist of four alternating time periods of 11 or 12 weeks or a total of 23 weeks for each ETT. All patients intubated with the study ETT in each time period will be included in an intention-to-treat analysis. Outcomes will include VAP incidence, mortality and health services utilisation including antibiotic use and length of stay.
This study has been approved by the Health Sciences Research Ethics Board at Queen’s University. The results of this study will be actively disseminated through manuscript publication and conference presentations.
by Richard Okyere Boadu, Godwin Adzakpah, Nathan Kumasenu Mensah, Kwame Adu Okyere Boadu, Jonathan Kissi, Christiana Dziyaba, Rosemary Bermaa Abrefa
BackgroundInformation and communication technology (ICT) has significantly advanced global healthcare, with electronic health (e-Health) applications improving health records and delivery. These innovations, including electronic health records, strengthen healthcare systems. The study investigates healthcare professionals’ perceptions of health information applications and their associated factors in the Cape Coast Metropolis of Ghana’s health facilities.
MethodsWe used a descriptive cross-sectional study design to collect data from 632 healthcare professionals (HCPs), in the three purposively selected health facilities in the Cape Coast municipality of Ghana, in July 2022. Shapiro-Wilk test was used to check the normality of dependent variables. Descriptive statistics were used to report means with corresponding standard deviations for continuous variables. Proportions were also reported for categorical variables. Bivariate regression analysis was conducted to determine the factors influencing the Benefits of Information Technology (BoIT); Barriers to Information Technology Use (BITU); and Motives of Information Technology Use (MoITU) in healthcare delivery. Stata SE version 15 was used for the analysis. A p-value of less than 0.05 served as the basis for considering a statistically significant accepting hypothesis.
ResultsHealthcare professionals (HCPs) generally perceived moderate benefits (Mean score (M) = 5.67) from information technology (IT) in healthcare. However, they slightly agreed that barriers like insufficient computers (M = 5.11), frequent system downtime (M = 5.09), low system performance (M = 5.04), and inadequate staff training (M = 4.88) hindered IT utilization. Respondents slightly agreed that training (M = 5.56), technical support (M = 5.46), and changes in work procedures (M = 5.10) motivated their IT use. Bivariate regression analysis revealed significant influences of education, working experience, healthcare profession, and IT training on attitudes towards IT utilization in healthcare delivery (BoIT, BITU, and MoITU). Additionally, the age of healthcare providers, education, and working experience significantly influenced BITU. Ultimately, age, education, working experience, healthcare profession, and IT training significantly influenced MoITU in healthcare delivery.
ConclusionsHealthcare professionals acknowledge moderate benefits of IT in healthcare but encounter barriers like inadequate resources and training. Motives for IT use include staff training and support. Bivariate regression analysis shows education, working experience, profession, and IT training significantly influence attitudes towards IT adoption. Targeted interventions and policies can enhance IT utilization in the Cape Coast Metropolis, Ghana.
by Bartłomiej Baran, Dariusz Majerek, Piotr Szyszka, Dariusz Wójcik, Tomasz Rymarczyk
Robust and reliable diagnostic methods are desired in various types of industries. This article presents a novel approach to object detection in industrial or general ultrasound tomography. The key idea is to analyze the time-dependent ultrasonic signal recorded by three independent transducers of an experimental system. It focuses on finding common or related characteristics of these signals using custom-designed deep neural network models. In principle, models use convolution layers to extract common features of signals, which are passed to dense layers responsible for predicting the number of objects or their locations and sizes. Predicting the number and properties of objects are characterized by a high value of the coefficient of determination R2 = 99.8% and R2 = 98.4%, respectively. The proposed solution can result in a reliable and low-cost method of object detection for various industry sectors.by Kaho Yamasaki, Ayaka Sampei, Hiromitsu Miyata
ObjectivesRumination is suggested to exacerbate psychological health, but there is room for investigating the potential protecting factors for individuals with high ruminative tendencies against psychological symptoms. The present cross-sectional study aimed to uncover the associations between rumination as a maladaptive dimension of self-focus, self-compassion, and psychological health, and whether and how components of self-compassion may moderate the associations between rumination and psychological health in Japanese undergraduate students.
MethodsA questionnaire survey was conducted by using both an online platform and a paper-based questionnaire. The survey included established Japanese versions of psychological scales on rumination, self-compassion, perceived stress, trait anxiety, and depression.
ResultsThe results revealed statistically significant positive correlations between rumination and negative dimensions of self-compassion, and rumination and psychological symptoms. Positive dimensions of self-compassion were significantly negatively correlated with both rumination and psychological symptoms. Reflection as a positive dimension of self-focus did not show significant correlations with most psychological variables. Furthermore, hierarchical multiple regression analyses involving subscales of self-compassion and their interactions with rumination as predictors revealed that the interactions between rumination and components of self-compassion, i.e., over-identification and mindfulness, significantly predicted trait anxiety. Higher rumination predicted higher anxiety when over-identification was high, but not when over-identification was low. Also, lower rumination predicted lower anxiety when mindfulness was high, but not when mindfulness was low.
ConclusionsThe results suggest significant associations between rumination, components of self-compassion, and psychological health in a population of Japanese undergraduate students. The data also suggest that components of self-compassion play moderating roles in the relationship between rumination and psychological health, potentially serving as aggravating/protective factors for psychological health. Longitudinal studies and comparisons between different cultures should be conducted in the future quest.
by Lisa Jung, Sonja Hillemacher, Inga Tiemann, Mascha Lepke, Dirk Hinrichs
In commercial laying hens, keel bone damage (KBD) is a severe health and welfare problem leading to pain, reduced mobility and decreased laying performance. Flocks of all production systems and hybrid lines can be affected. KBD is a multifactorial welfare issue and, among other factors, associated with a high laying performance which negatively affects the calcium deposit in the medullary bones. Therefore, mature hens of local breeds with much lower egg production than commercial hybrids may be expected to show less or even no keel bone damage. This study evaluates (i) the prevalence of KBD in local breeds, (ii) the difference in type and level of damages, and (iii) if roosters and pullets are also affected. In total, we palpated 343 mature hens, 40 pullets, and 18 roosters of 13 different local breeds and one commercial hybrid. The animals were kept on eight different farms in free-range or floor-housing systems. Our results showed that on average 44.2% of mature hens per local breed were affected by KBD (range: 11.1%-84.7%). We found deviation of less than 1 cm in 26.9%, deviations of more than 1 cm in 6.4% and palpable fractures in 23.8% of the mature hens of local breeds. The tip was damaged in 23.6% of the mature hens. Also, pullets and roosters were affected by KBD. Finally, we found that KBD also occurs in local breeds. Therefore, we conclude that even the low laying performance of local breeds does not prevent them from the occurrence of KBD.KBD in local breeds may rather be associated with genetics (breed) as well as management and housing. Thus, breeders of local breeds should include bone health as a selection trait. Owners of local breeds should also pay attention to the condition of the keel and ought to be trained about preventive measures.by Ihssan S. Masad, Amin Alqudah, Shoroq Qazan
Sleep stages classification is one of the new topics in studying human life quality because it plays a crucial role in getting a healthy lifestyle. Abnormal changes or absence of normal sleep may lead to different diseases such as heart-related diseases, diabetes, and obesity. In general, sleep staging analysis can be performed using electroencephalography (EEG) signals. This study proposes a convolutional neural network (CNN) based methodology for sleep stage classification using EEG signals taken by six channels and transformed into time-frequency analysis images. The proposed methodology consists of three major steps: (i) segment the EEG signal into epochs with 30 seconds in length, (ii) convert epochs into 2D representation using time-frequency analysis, and (iii) feed the 2D time-frequency analysis to the 2D CNN. The results showed that the proposed methodology is robust and achieved a very high accuracy of 99.39% for channel C4-A1. All other channels have accuracy values above 98.5%, which indicates that any channel can be used for sleep stage classification with high accuracy. The proposed methodology outperformed the methods in the literature in terms of overall accuracy or single channel accuracy. It is expected to provide a great benefit for physicians, especially neurologists; by providing them with a new powerful tool to support the clinical diagnosis of sleep-related diseases.by Reenu Thomas, Claude Ondongo-Ezhet, Nini Motsoaledi, Mike Sharland, Michelle Clements, Sithembiso Velaphi
ObjectiveTo determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa.
MethodsSingle-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available.
ResultsThere were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5–0.7];p = Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];pStaphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%–2%],pCandida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated.
ConclusionsThere has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.
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.by Olivia de Villiers, Claudia Elliot-Wilson, Kevin G. F. Thomas, Patrick L. Semple, Thurandrie Naiker, Michelle Henry, Ian L. Ross
Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients’ cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter.by Anita Kovács, Dóra Hantosi, Nikoletta Szabó, Annamária Letoha, Csaba Lengyel, Imre Földesi, Katalin Burián, András Palkó, Dániel Veréb, Zsigmond Tamás Kincses
ObjectivesEmerging 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 methodsWe 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.
Results843 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.
by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri
The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.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.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.by Ursula Just, Helmut Burtscher, Sylvia Jeratsch, Meike Fischer, Carol Stocking, Jens Preussner, Mario Looso, Ralf Schwanbeck, Stefan Günther, Ralf Huss, Lynne Mullen, Thomas Braun
Brain metastasis leads to increased mortality and is a major site of relapse for several cancers, yet the molecular mechanisms of brain metastasis are not well understood. In this study, we established and characterized a new leukemic cell line, FIA10, that metastasizes into the central nervous system (CNS) following injection into the tail vein of syngeneic mice. Mice injected with FIA10 cells developed neurological symptoms such as loss of balance, tremor, ataxic gait and seizures, leading to death within 3 months. Histopathology coupled with PCR analysis clearly showed infiltration of leukemic FIA10 cells into the brain parenchyma of diseased mice, with little involvement of bone marrow, peripheral blood and other organs. To define pathways that contribute to CNS metastasis, global transcriptome and proteome analysis was performed on FIA10 cells and compared with that of the parental stem cell line FDCP-Mix and the related FIA18 cells, which give rise to myeloid leukemia without CNS involvement. 188 expressed genes (RNA level) and 189 proteins were upregulated (log2 ratio FIA10/FIA18 ≥ 1) and 120 mRNAs and 177 proteins were downregulated (log2 ratio FIA10/FIA18 ≤ 1) in FIA10 cells compared with FIA18 cells. Major upregulated pathways in FIA10 cells revealed by biofunctional analyses involved immune response components, adhesion molecules and enzymes implicated in extracellular matrix remodeling, opening and crossing the blood-brain barrier (BBB), molecules supporting migration within the brain parenchyma, alterations in metabolism necessary for growth within the brain microenvironment, and regulators for these functions. Downregulated RNA and protein included several tumor suppressors and DNA repair enzymes. In line with the function of FIA10 cells to specifically infiltrate the brain, FIA10 cells have acquired a phenotype that permits crossing the BBB and adapting to the brain microenvironment thereby escaping immune surveillance. These data and our model system FIA10 will be valuable resources to study the occurrence of brain metastases and may help in the development of potential therapies against brain invasion.Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy.
This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people’s lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations.
The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications.
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