Manipulation of mitochondrial poly(A) polymerase family proteins in impacts mRNA termini processing.

RNA-specific nucleotidyltransferases (rNTrs) add nontemplated nucleotides to the 3 end of RNA. Two noncanonical rNTRs that are thought to be poly(A) polymerases (PAPs) have been identified in the mitochondria of trypanosomes - KPAP1 and KPAP2. KPAP1 is the primary polymerase that adds adenines (As) to trypanosome mitochondrial mRNA 3 tails, while KPAP2 is a non-essential putative polymerase whose role in the mitochondria is ambiguous.

Pathogen presence, prevalence, and diversity in and mammal hosts at their expanding northern range limits.

With climate and land use changes, tick-borne pathogens are expected to become more widely distributed in Canada. Pathogen spread and transmission in this region is modulated by changes in the abundance and distribution of tick and host populations. Here, we assessed the relationships between pathogens detected in and mammal hosts at sites of different levels of disease risk using data from summer field surveys in Ontario and Quebec, Canada.

iSurgARy: A mobile augmented reality solution for ventriculostomy in resource-limited settings.

Global disparities in neurosurgical care necessitate innovations addressing affordability and accuracy, particularly for critical procedures like ventriculostomy. This intervention, vital for managing life-threatening intracranial pressure increases, is associated with catheter misplacement rates exceeding 30% when using a freehand technique. Such misplacements hold severe consequences including haemorrhage, infection, prolonged hospital stays, and even morbidity and mortality.

Focusing on antimicrobial resistant infections -are we missing the forest for the trees and the patients for pathogens?

Antimicrobial resistance (AMR) is a challenge because it is associated with worse patient outcomes. To solve the problem will take development of interventions and policies which improve patient outcomes by prolonging survival, improving patient symptoms, function and quality of life. Logically, we should look to focusing resources in areas that would have the greatest impact on public health.

Residential childcare worker perceptions of work-related achievement and pride.

Introduction: Multiple risk and protective factors influence the wellbeing and retention of child protective and youth justice professionals. Less attention has been given to empirically understand how residential childcare workers (RCW) experience these factors. A sense of pride and of achievement may be related to competence and satisfaction, which have been identified as protective factors against staff turnover.

Models and Biomarkers for Local Response Prediction in Early-Stage and Oligometastatic Non-small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy Using Machine Learning.

Background A minority of patients receiving stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) are not good responders. Radiomic features can be used to generate predictive algorithms and biomarkers that can determine treatment outcomes and stratify patients to their therapeutic options. This study investigated and attempted to validate the radiomic and clinical features obtained from early-stage and oligometastatic NSCLC patients who underwent SBRT, to predict local response.

Establishing a standardized murine orthotopic intra-rectal model for the study of colorectal adenocarcinoma.

Background: Orthotopic models offer a more accurate representation of colorectal cancer (CRC) compared to subcutaneous models. Despite promising results from the reported intra-rectal models, establishing a standardized method for CRC research remains challenging due to model variability, hindering comprehensive studies on CRC pathogenesis and treatment modalities, such as brachytherapy. This study aimed to establish a standardized workflow for an orthotopic intra-rectal animal model to induce the growth of colorectal adenocarcinoma in male and female mice.

The Future Hospital in Global Health Systems: The Future Hospital Within the Healthcare System.

Future hospitals must be able to adapt in many ways to the changing demands on their roles and functions within evolving healthcare delivery infrastructures. These include changing population structures and needs, new models of healthcare provision, technological advances, and innovations in design, all while enhancing their environmental sustainability. This article sets out the issues that those determining healthcare policy and designing future hospitals must consider if they are to become and remain fit for purpose within the wider health and social care system.

Oncoproteins E6/E7 of the human papillomavirus types 16 & 18 synergize in modulating oncogenes and tumor suppressor proteins in colorectal cancer.

Objective: Our study presents a novel analysis of the oncogenes and tumor suppressor proteins directly modulated by E6/E7 of high-risk HPV types 16 and 18, in colorectal cancer (CRC).

Methods: HCT 116 (KRAS mutant) & HT-29 (TP53 mutant) cell models of CRC were transduced with E6/E7 of HPV16 and HPV18, individually and in combination. Further, we utilized a liquid chromatography mass spectrometry (LC-MS/MS) approach to analyze and compare the proteomes of both CRC cell models.

Malnutrition in Spine Oncology: Where Are We and What Are We Measuring?

Study Design: Scoping review.

Objective: To identify which markers are used as surrogates for malnutrition in metastatic spine disease and which are the most studied outcomes associated with it.

Methods: A scoping review was performed by searching the PubMed/Medline, EMBASE, and Web of Science databases up to July 2022.

Bullying in adolescents across three years in the context of the COVID-19 pandemic: a repeated cross-sectional and prospective analysis.

Background: Bullying has been identified as a risk factor for many issues among adolescents. Although it was already considered a public health issue in Brazil before the COVID-19 pandemic, little is known about how the pandemic and associated public health measures have affected bullying behavior.

Objective: To explore changes in bullying victimization and perpetration among Brazilian high school students from 2019 to 2022.

Clouds reduce downwelling longwave radiation over land in a warming climate.

Clouds greatly influence the Earth's energy balance. Observationally constraining cloud radiative feedback, a notably uncertain climate feedback mechanism, is crucial for improving predictions of climate change but, so far, remains an elusive objective, and the feedback may be different over the ocean versus over land. Here we show a local negative surface longwave cloud feedback over land at the southern Great Plains site, constrained by direct long-term observation of spectrally resolved downwelling longwave radiance.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Community Views of Determinants of Men's Wellbeing in Guatemala: A Study Using Fuzzy Cognitive Mapping.

Background: In post-conflict Guatemala, Indigenous men's psychological distress has been linked to violence exposure, disrupted social support systems, and structural inequities.

Purpose: We aimed to document how communities themselves understand men's wellbeing and the factors that influence men's wellbeing.

Research Design And Study Sample: Fuzzy Cognitive Mapping with 20 stakeholder groups in Santiago Atitlán and Cuilco, Guatemala defined men's wellbeing in local terms and identified the influences community groups understood to promote and detract from men's wellbeing.

Penalized G-estimation for effect modifier selection in a structural nested mean model for repeated outcomes.

Effect modification occurs when the impact of the treatment on an outcome varies based on the levels of other covariates known as effect modifiers. Modeling these effect differences is important for etiological goals and for purposes of optimizing treatment. Structural nested mean models (SNMMs) are useful causal models for estimating the potentially heterogeneous effect of a time-varying exposure on the mean of an outcome in the presence of time-varying confounding.

Early environmental influences on the orbito-frontal cortex function and its effects on behavior.

Early-life adversity during pre- and early post-natal phases can impact brain development and lead to maladaptive changes in executive function related behaviors. This increases the risk for a range of psychopathologies and physical diseases. Importantly, exposure to adversities during these periods is also linked to alterations in the orbito-frontal cortex (OFC) which is a key player in these executive functions.

Diosmetin alleviates TNFα-induced liver inflammation by improving liver sinusoidal endothelial cell dysfunction.

Sterile inflammation contributes to the development of many liver diseases including non-alcoholic fatty liver disease. Tumor necrosis factor alpha (TNFα) is a key cytokine driving liver inflammation primarily through pro-inflammatory activation of liver sinusoidal endothelial cells (LSEC). The knowledge of whether modulating LSEC activation can alleviate liver inflammation is scarce.

Management of epilepsia partialis continua: A systematic review.

Purpose: Epilepsia partialis continua (EPC) is form of focal motor status epilepticus, with limited guidelines regarding effective pharmacological management. This systematic review aimed to describe previously utilized pharmacological management strategies for EPC, with a focus on patient outcomes.

Methods: A systematic review of the databases PubMed, EMBASE, and SCOPUS was performed from inception to May 2024.

Child Neurology: Severe -Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Pathogenic variants in cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.

Sex Differences in Natural History and Health Outcomes Among Individuals With Tic Disorders.

Objectives: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset.

Methods: The relationship between sex and clinical measures was explored in 2,403 participants (N = 2,109 with TS; N = 294 with PMVT) from the TAAICG dataset using generalized estimating equation regression models, and adjusted for age and family relationships.

Results: Female (vs male) participants with TS (25.

Feature selectivity of corticocortical feedback along the primate dorsal visual pathway.

Anatomical studies have revealed a prominent role for feedback projections in the primate visual cortex. Theoretical models suggest that these projections support important brain functions, like attention, prediction, and learning. However, these models make different predictions about the relationship between feedback connectivity and neuronal stimulus selectivity.

Continuous Instrument Tracking in a Cerebral Corticectomy Ex Vivo Calf Brain Simulation Model: Face and Content Validation.

Background And Objectives: Subpial corticectomy involving complete lesion resection while preserving pial membranes and avoiding injury to adjacent normal tissues is an essential bimanual task necessary for neurosurgical trainees to master. We sought to develop an ex vivo calf brain corticectomy simulation model with continuous assessment of surgical instrument movement during the simulation. A case series study of skilled participants was performed to assess face and content validity to gain insights into the utility of this training platform, along with determining if skilled and less skilled participants had statistical differences in validity assessment.

Interventions to Reduce Mental Health Stigma in Young People: A Systematic Review and Meta-Analysis.

Importance: Mental health stigma is a considerable barrier to help-seeking among young people.

Objective: To systematically review and meta-analyze randomized clinical trials (RCTs) of interventions aimed at reducing mental health stigma in young people.

Data Sources: Comprehensive searches were conducted in the CENTRAL, CINAHL, Embase, PubMed, and PsycINFO databases from inception to February 27, 2024.