"I'm still a me:" challenges and changes to the relational-self following the onset of aphasia, a grounded theory study.

Purpose: People with post-stroke aphasia experience relationship changes which can lead to an altered relational self. The aim of this research was to explore the experiences of a group of people with post-stroke aphasia regarding changes to the relational self.

Method: A constructivist grounded theory approach was used.

Appropriateness of lumbar spine imaging in patients presenting to the emergency department with low back pain in a Western Australian tertiary hospital.

Background: The Australian Rheumatology Association identified the use of imaging in patients with low back pain without indication of serious pathology as a low-value practice.

Aims: To determine the appropriateness of diagnostic lumbar spine imaging requests in patients with low back pain presenting to a Western Australian hospital's emergency department.

Methods: We conducted a retrospective review of all adult patients (18 years and older) who presented with low back pain to the Fiona Stanley Hospital emergency department from 1 July 2020 to 31 December 2020.

Barriers and Enablers in the Implementation of Physical Activity Improvement for Pregnant Women With Gestational Diabetes Mellitus: A Mixed-Methods Study.

Aim: To identify the barriers and enablers in the implementation of evidence-based physical activity (PA) programmes for the improvement of health outcomes among pregnant women with gestational diabetes mellitus (GDM), and to develop strategies for implementing this evidence in clinical practice.

Methods: A convergent mixed-methods study was conducted, integrating a descriptive qualitative research design with a cross-sectional survey. In-depth interview was used to collect the views and cognitions about physical activity from medical staff, leaders and pregnant women.

4D light sheet imaging, computational reconstruction, and cell tracking in mouse embryos.

As light sheet fluorescence microscopy (LSFM) becomes widely available, reconstruction of time-lapse imaging will further our understanding of complex biological processes at cellular resolution. Here, we present a comprehensive workflow for in toto capture, processing, and analysis of multi-view LSFM experiments using the ex vivo mouse embryo as a model system of development. Our protocol describes imaging on a commercial LSFM instrument followed by computational analysis in discrete segments, using open-source software.

Using language to evaluate curricular impact: a novel approach in assessing clinical reasoning curricula.

Objectives: Published clinical reasoning curricula are limited, and measuring curricular impact has proven difficult. This study aims to evaluate the impact of a broad-reaching, multi-level reasoning curricula by measuring utilization of clinical reasoning terminology in published abstracts.

Methods: In 2014, the University of Pittsburgh Medical Center (UPMC) created a clinical reasoning curriculum with interventions at the student, resident, and faculty levels with the goal of bringing reasoning education to the forefront.

A prospective, phase II, neoadjuvant study based on chemotherapy sensitivity in HR+/HER2- breast cancer-FINEST study.

Background: Hormone receptor-positive (HR+)/humaal growth factor receptor 2-negative (HER2-) breast cancer, the most common breast cancer type, has variable prognosis and high recurrence risk. Neoadjuvant therapy is recommended for median-high risk HR+/HER2- patients. This phase II, single-arm, prospective study aimed to explore appropriate neoadjuvant treatment strategies for HR+/HER2- breast cancer patients.

Unveiling the Burden of Sickle Cell Anemia: A Pilot Study Validating Dried Blood Spots for Newborn Screening.

This hospital-based cross-sectional study aimed to screen newborns for sickle cell anemia immediately after birth and validate dried blood spot (DBS) samples against conventional venous blood samples (CBS) for hemoglobin variant analysis by HPLC. Among 751 newborns, 2.93% were found to have sickle cell trait.

Cannabidiol (CBD) potentiates physiological and behavioral markers of hypothalamic-pituitary-adrenal (HPA) axis responsivity in female and male mice.

Rationale: Clinical literature indicates there may be a therapeutic use of cannabidiol (CBD) for stress-related disorders. Preclinical literature remains conflicted regarding the underlying neurobehavioral mechanisms, reporting mixed effects of CBD (increased, decreased, or no effect) on anxiety- and fear-related behaviors. Preclinical data demonstrated that CBD modulates hypothalamus-pituitary-adrenal (HPA) axis gene expression; it is unknown whether CBD changes HPA axis responsivity and how this relates to altered behavior.

Parents' Early Concerns about Their Child with Autism: Relation to Age of Diagnosis.

There is a substantial time gap between when parents develop concerns about their child (ages 1-2) and when they receive a diagnosis of autism (ages 3-5), delaying the onset of critical interventions. Few studies have examined how the timing, type, and quantity of early parental concerns are associated with age of diagnosis. The aims of this study were to describe characteristics of parents' concerns in a large community-based sample and explore how characteristics of concerns relate to age of diagnosis.

Treadmill intervention attenuates motor deficit with 6-OHDA-induced Parkinson's disease rat via changes in lipid profiles in brain and muscle.

One of the key hallmarks of Parkinson's disease is the disruption of lipid homeostasis in the brain, which plays a critical role in neuronal membrane integrity and function. Understanding how treadmill training impacts lipid restructuring and its subsequent influence on motor function could provide a basis for developing targeted non-pharmacological interventions for individuals living with early stage of PD. This study aims to investigate the effects of a treadmill training intervention on motor deficits induced by 6-OHDA in rats model of PD.

Characterization of DNA methylation clock algorithms applied to diverse tissue types.

Background: DNA methylation (DNAm) data from human samples has been leveraged to develop "epigenetic clock" algorithms that predict age and other aging-related phenotypes. Some DNAm clocks were trained using DNAm obtained from blood cells, while other clocks were trained using data from diverse tissue/cell types. To assess how DNAm clocks perform across non-blood tissue types, we applied DNAm algorithms to DNAm data generated from 9 different human tissue types.

Genomic and Clinicopathological Characterization of CRLF2-Rearranged Mixed Phenotype Acute Leukemia.

Rearrangements of cytokine receptor-like factor 2 gene (CRLF2) are present in ∼50% of B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR::ABL1-like features. Herein, we report three patients with CRLF2-rearranged mixed phenotype acute leukemia (MPAL). All three cases were B/myeloid MPAL in young patients harboring P2RY8::CRLF2 or IGH::CRLF2 with additional genomic alterations in signaling (JAK and RAS) and cell cycle (CDKN2A/B) pathways, a genomic profile similar to that in BCR::ABL1-like B-ALL.

Folic and folinic acid load tests for dynamic assessments of compliance and metabolism in folate deficiency and hyperhomocysteinaemia patients unresponsive to high-dose folate replacement.

We describe the utility of 'folic and folinic acid load tests' in the investigation of a 26-year-old woman with persistently low serum folate and moderate hyperhomocysteinaemia unresponsive to folic acid supplements. Serum folate, plasma 5-methyltetrahydrofolate (5-MTHF), red cell 5-MTHF and plasma total homocysteine at baseline, 2-h, 4-h and 2- or 4-days (if applicable) post administration of a large dose of oral folic acid, or oral or parenteral folinic acid were measured. The tests confirmed non-compliance but also suggested an unsuspected possible defect in the folate pathway based on differential response to folic versus folinic acid supplements.

Haloperidol dopamine receptor occupancy and antagonism correspond to delirium agitation scores and EPS risk: A PBPK-PD modeling analysis.

Background: Delirium is a severe neuropsychiatric disorder associated with increased morbidity and mortality. Numerous precipitating factors and etiologies merge into the pathophysiology of this condition which can be marked by agitation and psychosis. Judicious use of antipsychotic medications such as intravenous haloperidol reduces these symptoms and distress in critically ill individuals.

Associations between structural brain changes and blood neurofilament light chain protein in treatment-resistant schizophrenia.

Objective: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia.

Behind the scenes of EQA-characteristics, capabilities, benefits and assets of external quality assessment (EQA).

The main stakeholders in external quality assessment (EQA) programs are the participants, in whose interests these challenges are ultimately organised. EQA schemes in the medical field contribute to improving the quality of patient care by evaluating the analytical and diagnostic quality of laboratory and point-of-care tests (POCT) by independent third parties and, if necessary, pointing out erroneous measurement results and analytical or diagnostic improvement potential. Other benefits include the option of using EQA samples for other important laboratory procedures, such as the verification or validation of diagnostic medical devices (IVD-MDs), a contribution to the estimation of measurement uncertainty, a means of training and educating laboratory staff through educational EQA programmes or samples, or even for independent and documented monitoring of staff competence, such as on samples with unusual or even exceptional characteristics.

Genomics Review of Selective RET Inhibitors Sensitivity in Thyroid Cancer Clinical Trials.

RET gene is a driver of thyroid cancer (TC) tumorigenesis. The incidence of TC has increased worldwide in the last few decades, both in medullary and follicular-derived subtypes. Several drugs, including multikinase and selective inhibitors, have been explored.

Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study Protocol and Rationale.

Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.

Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.

Atherosclerotic Cardiovascular Disease Risk Scores are Associated with Carotid Intima-Media Thickness.

Atherosclerotic cardiovascular disease (ASCVD) risk calculators estimate the 10-year incident risk of myocardial infarction (MI), coronary artery disease (CAD) death, or stroke; however, they lack comprehensiveness and accuracy. Carotid intima-media thickness (CIMT) is a surrogate marker that may improve risk estimation acumen. The objective of this study was to derive ASCVD risk scores from historical data and determine whether these risk scores are associated with the history of subclinical CAD and CIMT.

Do we Need to Perform Bone Marrow Examination in all Subjects Suspected of MDS? Evaluation and Validation of Non-Invasive (Web-Based) Diagnostic Algorithm.

Background: Bone marrow examination (BME) is the gold standard of diagnosing myelodysplastic syndromes (MDS).

Problems: it is invasive, painful, causing possible bleeding, inaccurate (aspirate hemodilution), and subjective (inter-observer interpretation discordance). We developed non-invasive diagnostic tools: A logistic regression formula [LeukRes 2018], then a web algorithm using 10 variables (age, gender, Hb, MCV, WBC, ANC, monocytes, PLT, glucose, creatinine) to diagnose/exclude MDS [BldAdv 2021].

Color Change and Cytotoxic Effects of a Bleaching Gel With 22% Carbamide Peroxide Catalyzed by Manganese Oxide.

Objectives: To evaluate the color change and trans-amelodentinal cytotoxicity of a 22% carbamide peroxide (CP) bleaching gel containing different concentration of manganese oxide (MnO).

Material And Methods: Enamel/dentin discs adapted to artificial pulp chambers were distributed according to treatments: CN-No treatment; CP22%-22%CP; CP22 + 2MnO-22%CP + 2 mg/mLMnO; CP22% + 6MnO-22%CP + 6 mg/mLMnO; CP22% + 10MnO-22%CP + 10 mg/mLMnO applied for 2 h for 15 days. Color change-CC (ΔE and ΔWI) (n = 8) was determined at 5, 10, and 15-day periods (ANOVA/Sidak).

A Splice Site Variant in SENP7 Results in a Severe Form of Arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is a heterogeneous disorder associated with 1/3000 to 1/5000 live births. We report a consanguineous family with multiple affected members with AMC and identified a recessive mutation in the highly conserved splice donor site, resulting in the mis-splicing of the affected exons. SENP7 is a deSUMOylase that is critical for sarcomere assembly and skeletal muscle contraction by regulating the transcriptional program in the skeletal muscle.