Femoral intramedullary nail extraction using the kissing nail technique when primary measures fail.

Introduction: Intramedullary femoral nails (IMFNs) need to be removed for subsequent joint replacement, refracture, nonunion, or infection. The tools used to extract newer IMFNs may not be suited for removal of older implants, especially if broken. The purpose of this study was to describe a novel technique in femoral nail extraction when primary measures fail and a report on 6 cases where it was used.

Maladaptive but malleable: Gender-science stereotypes emerge early but are modifiable by language.

Gender-science stereotypes emerge early in childhood, but little is known about the developmental processes by which they arise. The present study tested the hypothesis that language implying scientists are a special and distinct kind of person contributes to the development of gender-science stereotypes, even when it does not communicate stereotypic content. One cross-sectional and two longitudinal studies with racially and geographically diverse children (primarily from the United States; ages 4-5; N = 872, tested 2020-2022) revealed that gender stereotypes about science versus art (a) emerge before elementary school, (b) arise from commonplace identity-emphasizing language, especially among girls, and (c) can be durably disrupted by subtle changes to language.

Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation.

Conjugation chemistries are a major enabling technology for the development of drug delivery systems, from antibody-drug conjugates to antibody-targeted lipid nanoparticles inspired by the success of the COVID-19 vaccine. However, here it is shown that for antibody-targeted nanoparticles, the most popular conjugation chemistries directly participate in the activation of the complement cascade of plasma proteins. Their activation of complement leads to large changes in the biodistribution of nanoparticles (up to 140-fold increased uptake into phagocytes of the lungs) and multiple toxicities, including a 50% drop in platelet count.

Multi-stage-mixing to create a core-then-shell structure improves DNA-loaded lipid nanoparticles' transfection by orders of magnitude.

The unprecedented success of mRNA-lipid nanoparticles (LNPs) has highlighted their power for protein expression, but the hours-long half-life of mRNA severely limits their use in chronic diseases. In contrast, DNA LNPs display months-long expression and genetically encode cell type specificity, but their use has been hindered by poor protein expression (orders of magnitude lower than mRNA LNPs). To overcome this, we introduce multi-stage mixing (MSM) microfluidics to control the internal structure of LNPs and use it to create core-then-shell (CTS) structured DNA LNPs.

Long-Term Cognitive, Functional, and Patient-Reported Outcomes in Patients With Anti-NMDAR Encephalitis.

Background And Objectives: Anti-NMDA receptor (anti-NMDAR) encephalitis generally manifests in young adults. Although 80%-90% returns to independence, the majority experience persistent cognitive and psychosocial difficulties. Studies have demonstrated that cognitive recovery may continue for years; the temporal trajectory is largely unknown, as are factors influencing cognitive/psychosocial recovery.

Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance.

Background And Objectives: Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) encompass a heterogeneous group of antibody-associated disorders. Both the number of syndromes and commercially available antibody tests have increased considerably over the past decade. High-quality population-based data on epidemiology of these disorders and real-world performance of antibody tests are needed.

A percolation-type criticality threshold controls immune protein coating of surfaces.

When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, "deciding" whether to attack? We focus on the "complement" system of ∼40 blood proteins that bind microbes, nanoparticles, and medical devices, initiating inflammation. We show a sharp threshold for complement activation upon varying a fundamental material parameter, the surface density of potential complement attachment points.

Accelerated 3YMD programs: the last decade of growth of the Consortium of Accelerated Medical Pathway Programs (CAMPP).

Introduction: Over the past decade, the growth of accelerated three-year MD (3YMD) programs has flourished. In 2015, with support from the Josiah Macy Jr. Foundation, the Consortium of Medical Pathway Programs (CAMPP) started with eight North American medical schools.

Peer-Reviewed Publications by Successfully Matched Orthopedic Surgery Residency Applicants in the 2022-2023 Match.

Background: The Orthopaedic Surgery Match is highly competitive, with more applicants than residency spots. With the Step 1 Exam moving to a pass/fail result, residency programs and applicants have fewer objective data to determine applicants' relative competitiveness. Through this study, we sought to provide the mean number of accepted publications on PubMed a successfully matched orthopedic surgery applicant has by the time of submission of their application.

Recommendations to address and research systemic bias in assessment: perspectives from directors of research in medical education.

Introduction: Addressing systemic bias in medical school assessment is an urgent task for medical education. This paper outlines recommendations on topic areas for further research on systemic bias, developed from a workshop discussion at the 2023 annual meeting of the Society of Directors of Research in Medical Education.

Materials And Methods: During the workshop, directors engaged in small-group discussions on guidelines to address bias in assessment practices following a proposed categorization of 'Do's,' 'Don'ts,' and 'Don't knows' and listed their insights using anonymous sticky notes, which were shared and discussed with the larger group of participants.

Neutrophil-avid nanocarrier uptake by STAT3 dominant-negative hyper-IgE syndrome patient neutrophils.

Recurrent infections are a hallmark of STAT3 dominant-negative hyper-IgE syndrome (STAT3 HIES), a rare immunodeficiency syndrome previously known as Jobs syndrome, along with elevated IgE levels and impaired neutrophil function. We have been developing nanoparticles with neutrophil trophism that home to the sites of infection via these first-responder leukocytes, named neutrophil-avid nanocarriers (NANs). Here, we demonstrate that human neutrophils can phagocytose nanogels (NGs), a type of NAN, with enhanced uptake after particle serum opsonization, comparing neutrophils from healthy individuals to those with STAT3 HIES, where both groups exhibit NG uptake; however, the patient group showed reduced phagocytosis efficiency with serum-opsonized NANs.

Marginated Neutrophils in the Lungs Effectively Compete for Nanoparticles Targeted to the Endothelium, Serving as a Part of the Reticuloendothelial System.

Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has yet to achieve this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such "endothelial-targeted" nanocarriers also effectively target the lungs' numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens.

Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy.

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers.

Return on Investment of Three-Year Accelerated Programs for Students, Medical Schools, Departments, and Community.

Building on the initial accelerated pathway programs in the 1970s to increase workforce, nearly 30 schools have launched accelerated 3-year pathways (A3YP) during the past decade. The authors based on their educational roles, experiences, and scholarship with A3YP provide this perspective of the argument for A3YP and potential disadvantages for each group-students, schools, residencies, departments, and community. When schools consider innovations, they might consider A3YPs for multiple reasons; this perspective helps provide justification for the program and broadly considers return on investment (ROI).

Higher Onset of Periprosthetic Joint Infections in Patients With Teeth Compared to Those Without Teeth.

Introduction: Bacteria can enter the bloodstream through simple actions such as brushing teeth, flossing, and even chewing food, increasing the chance of hematogenous seeding of prosthetic joints. Antibiotics before dental work in patients with orthopedic hardware is a topic of debate because of concerns for antibiotic resistance. Patients with dentures theoretically avoid this risk due to the lack of teeth and their maintenance.

Child Access Prevention Laws and Pediatric Firearm Injury: A Rapid Review.

Introduction: US child firearm fatality rates have risen since 2013. Child Access Prevention (CAP) laws aimed at reducing minors' access to firearms have existed since the 1980s. However, specific requirements for safe storage of firearms, standards of negligence, and penalties for offenders vary significantly by state, yielding a heterogeneous body of CAP legislation.

Improved Outcomes When Home-Dose Carbidopa-Levodopa Is Continued in the Geriatric Emergency Department in Patients With Parkinson's Disease.

Parkinson's disease (PD) is a debilitating condition that affects 1.8% of people 65 years of age and older. Patients with PD often require hospitalization and are frequently admitted through the emergency department (ED).

Enabling non-viral DNA delivery using lipid nanoparticles co-loaded with endogenous anti-inflammatory lipids.

Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway.

HPV-driven oncogenesis-much more than the E6 and E7 oncoproteins.

High-risk human papillomaviruses are well-established drivers of several cancer types including cervical, head and neck, penile as well as anal cancers. While the E6 and E7 viral oncoproteins have proven to be critical for malignant transformation, evidence is also beginning to emerge suggesting that both host pathways and additional viral genes may also be pivotal for malignant transformation. Here, we focus on the role of host APOBEC genes, which have an important role in molecular editing including in the response to the viral DNA and their role in HPV-driven carcinogenesis.

loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts in an mTORC1- and MNK1/2-reversible fashion.

Tuberous sclerosis complex (TSC) is an inherited neurodevelopmental disorder (NDD) with frequent manifestations of epilepsy and autism spectrum disorder (ASD). TSC is caused by inactivating mutations in or tumor suppressor genes, with encoded proteins hamartin (TSC1) and tuberin (TSC2) forming a functional complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. This has led to treatment with allosteric mTORC1 inhibitor rapamycin analogs ("rapalogs") for TSC tumors; however, rapalogs are ineffective for treating neurodevelopmental manifestations.

Targeting of nanoparticles to the cerebral vasculature after traumatic brain injury.

Traumatic brain injury has faced numerous challenges in drug development, primarily due to the difficulty of effectively delivering drugs to the brain. However, there is a potential solution in targeted drug delivery methods involving antibody-drug conjugates or nanocarriers conjugated with targeting antibodies. Following a TBI, the blood-brain barrier (BBB) becomes permeable, which can last for years and allow the leakage of harmful plasma proteins.

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABAR Antibodies: Implications for Return to Driving.

Background And Objectives: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABAR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months.

Neuron-level Prediction and Noise can Implement Flexible Reward-Seeking Behavior.

We show that neural networks can implement reward-seeking behavior using only local predictive updates and internal noise. These networks are capable of autonomous interaction with an environment and can switch between explore and exploit behavior, which we show is governed by attractor dynamics. Networks can adapt to changes in their architectures, environments, or motor interfaces without any external control signals.