Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism With Intellectual Disability: An Observational Study.

Catatonia is a highly morbid psychomotor and affective disorder, which can affect autistic individuals with and without intellectual disability. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments in autistic individuals has not been described. We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1, 2021 to May 31, 2024.

Lip Augmentation in Patients with Fitzpatrick Skin Type V and VI: Use of a Validated Lip Fullness Scale and Determining Preinjection Lip Size Preference and Postinjection Patient Satisfaction.

There is limited literature assessing cosmetic lip size preferences in darker-skinned individuals. To measure preinjection lip augmentation preferences and postinjection satisfaction using the revised Lip Fullness Scale (LFS) in female participants with Fitzpatrick Skin Type V and VI. Females, aged 21 and over, with Fitzpatrick Skin Type V and VI desiring lip augmentation were recruited from a high-volume outpatient facial plastic surgery clinic.

The safety and efficacy of cannabinoids for the treatment of mental health and substance use disorders: protocol for a systematic review and meta-analysis.

There has been a global increase in the use of cannabinoids as a treatment for mental health (MH) and substance use disorders (SUD). In 2016, an Australian government-funded review found that although medicinal cannabinoids accounted for a small reduction in MH symptoms, the results varied according to study design. There has since been a rise in randomised controlled trials (RCTs) aiming to examine the efficacy of cannabinoids for the treatment of MH and SUD.

Branched endosomal disruptor (BEND) lipids mediate delivery of mRNA and CRISPR-Cas9 ribonucleoprotein complex for hepatic gene editing and T cell engineering.

Lipid nanoparticles (LNPs) are the preeminent non-viral drug delivery vehicle for mRNA-based therapies. Immense effort has been placed on optimizing the ionizable lipid (IL) structure, which contains an amine core conjugated to lipid tails, as small molecular adjustments can result in substantial changes in the overall efficacy of the resulting LNPs. However, despite some advancements, a major barrier for LNP delivery is endosomal escape.

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

A nuanced scrutiny of the segmental renal artery spectral Doppler in "Pickering" the right diagnosis.

Approximately 5-10% of patients with hypertension have secondary hypertension. We describe a case of secondary hypertension from bilateral renal artery stenosis (RAS): "Pickering syndrome." This is a case of hypertension secondary to bilateral RAS which provides an opportunity to review secondary hypertension with a specific focus on RAS, in terms of when to consider work up, causes of secondary hypertension, diagnostic testing, and treatment.

Social Networks, Health Support, and Dietary Intake in Mothers Receiving Home Visiting Services.

Home visiting programs (HVPs) provide services to pregnant individuals and parents of young children to improve families' health and well-being. However, little is known about these families' social contexts. This study explores the social networks and dietary intake of mothers enrolled in a HVP, focusing on health support and health undermining.

Concussion and depressive symptoms in high school students: impact of physical activity and substance use.

Objective: To investigate the association between concussion history and depressive symptoms after adjusting for physical activity, substance use, and illicit drug use.

Methods: We analysed data from the Adolescent Behaviour and Experiences Survey, a nationally representative survey of adolescents in the USA. Our independent variables were history of concussion in the 12 months preceding survey completion; self-reported weekly physical activity (days per week with >60 min of physical activity, 0-7 scale); substance use over the past 30 days (yes vs no) and illicit drug use throughout lifetime (yes vs no).

Optimizing Prescribing for Individuals With Type 2 Diabetes and Chronic Kidney Disease Through the Development and Validation of Algorithms for Community Pharmacists.

Background: Diabetes is the leading cause of kidney disease and contributes to 38% of kidney failure requiring dialysis. A gap in detection and management of type 2 diabetes (T2D) in chronic kidney disease (CKD) exists in primary care. Community pharmacists are positioned to support those not able to access kidney care through traditional pathways.

Exosomes in Facial Plastic Surgery.

Exosomes have emerged as a promising therapeutic frontier in facial plastic surgery. Preclinical studies have demonstrated their ability to modulate wound healing, skin rejuvenation, hair growth, and nerve regeneration. Early clinical evidence suggests potential benefits in enhancing recovery after laser resurfacing, treating acne scars, and promoting hair growth.

Sex Differences in the Comorbidity between Attention Deficit-Hyperactivity Disorder and Posttraumatic Stress Disorder: A Systematic Literature Review and Meta-Analysis.

Objective: Attention Deficit-Hyperactivity Disorder (ADHD) and Posttraumatic Stress Disorder (PTSD) are often comorbid and share a common core of symptoms. However, sex and gender-related factors significantly influence their prevalence, clinical presentation, and diagnosis. Here, we conducted a systematic literature review and meta-analysis to examine sex differences in ADHD/PTSD comorbidity during childhood and adulthood.

Understanding Age Differences in Well-Being: Pathways From Present Time Orientation to Mindfulness and Savoring the Moment.

Well-being has been shown to improve with age, but underlying mechanisms are unclear. We tested a conceptual model that posited that age-related increases in present time orientation foster greater dispositional mindfulness and savoring the moment, and that these psychological processes are pathways that link older age to better well-being. U.

Opioid-related harms and experiences of care among people in justice settings in New South Wales, Australia: evidence from the National Ambulance Surveillance System.

Background: People in justice settings experience higher rates of psychiatric morbidity, including alcohol and drug use disorders, compared with the general population. However, our understanding of opioid-related harms in justice settings is limited. This study used ambulance data to examine opioid-related harms and experiences of care in New South Wales (NSW), Australia, during periods of incarceration or detention.

Rapid Parallel Adaptation in Distinct Invasions of Ambrosia Artemisiifolia Is Driven by Large-Effect Structural Variants.

When introduced to multiple distinct ranges, invasive species provide a compelling natural experiment for understanding the repeatability of adaptation. Ambrosia artemisiifolia is an invasive, noxious weed, and chief cause of hay fever. Leveraging over 400 whole-genome sequences spanning the native-range in North America and 2 invasions in Europe and Australia, we inferred demographically distinct invasion histories on each continent.

Direct, non-medical out-of-pocket expenditures for mothers of moderate or late preterm infants in a level II NICU: Comparison of Alberta Family Integrated Care versus standard care.

Objective: To compare direct, non-medical out-of-pocket expenditures (OOPE) between mothers receiving Alberta Family Integrated Care (FICare™) versus standard care (SC) during their infant's neonatal intensive care unit (NICU) admission and explore factors influencing spending extremes.

Methods: In this exploratory, concurrent mixed-methods sub-study, we compared mother-reported OOPE from Alberta FICare™ and SC parent journals. We thematically analyzed hand-written notes from 30 journals with the highest and lowest 5 % of OOPE.

Coronal Malalignment Is Infrequently Present in Patients With Aseptic Tibial Loosening.

Background: Coronal lower extremity malalignment and improper implant position have been described as risk factors for aseptic tibial loosening following primary total knee arthroplasty (TKA). However, several prior studies have shown no association between alignment and implant loosening. Meanwhile, there is increasing interest in kinematic alignment.

Tenecteplase for the Treatment of Pediatric Arterial Ischemic Stroke: A Safety Surveillance Report.

Objectives: Intravenous tenecteplase (TNK) is increasingly used to treat adult patients with acute arterial ischemic stroke, but the risk profile of TNK in childhood stroke is unknown. This study aims to prospectively gather safety data regarding TNK administration in children.

Methods: Since December 2023, a monthly email survey was sent to participants recruited from the International Pediatric Stroke Study and Pediatric Neurocritical Care Research Group querying recent experience with TNK in childhood stroke.

A building block for science talk: Educational TV supports parent-child conversations during an engineering activity.

We investigated the impact of parents' open-ended questions during collaborative science activities. Specifically, we randomly assigned 116 parents (69.8% mothers; 89.

Implementation of an Anxiety Management Process in Pediatric Primary Care: An Evidence-Based Practice Quality Improvement Initiative.

Introduction: Pediatric anxiety is rapidly increasing, and in 2022, the US Preventive Services Task Force recommended universal anxiety screening using a validated tool for children 8-18 years.

Method: This evidence-based practice quality improvement initiative integrated an educational process, a validated anxiety screening tool, and a Caregiver Satisfaction Survey into all primary care wellness visits for patients aged 8-18 years.

Results: Significant increases in screening and referrals for mental healthcare were observed postinitiative implementation, especially in ages 8-11 years.

Outcomes associated with local treatment of nasal planum squamous cell carcinoma in dogs: 89 cases (2003-2020).

Objective: To describe the clinical characteristics, treatments, complications, and outcomes in dogs with nasal planum squamous cell carcinoma (SCC) undergoing local treatment.

Methods: A retrospective, multi-institutional study was performed. Medical records were searched to identify dogs diagnosed with nasal planum SCC.

Parent Perceptions of Behavior Analytic Interventions.

Unlabelled: Current trends in the general American population favor parenting strategies with a relationship-focused approach highlighting secure attachment, respecting children, parenting proactively, showing empathic leadership, and using positive discipline. However, these strategies generally have not been validated by the research literature or may be based on behavior analytic strategies without reference to their origins. Although behavior analytic strategies have been shown to be effective throughout decades of research, these approaches have acquired a negative reputation in many communities with the perception of applied behavior analysis (ABA) being cold, harsh, and robotic.

Impact of Order Set on Exocrine Pancreatic Insufficiency in Chronic Pancreatitis, Pancreatic Cancer, and Pancreatic Resection.

Background And Aims: Enzyme insufficiency (EPI) is common in chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and after pancreatic resection. 40%-50% of CP patients and 70%-80% of PDAC patients develop EPI. 1/3rd of these patients are prescribed Pancreatic enzyme replacement therapy (PERT), often at an inadequate dose, with evidence that this leads to increased morbidity and mortality.

Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available.