Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility.

The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition.

Aberrant encoding of event saliency in the orbitofrontal cortex following loss of the psychiatric-associated circular RNA, circHomer1.

CircHomer1 is an activity-dependent circular RNA (circRNA) isoform produced from back-splicing of the Homer1 transcript. Homer1 isoforms are well-known regulators of homeostatic synaptic plasticity through post-synaptic density scaffold regulation. Homer1 polymorphisms have been associated with psychiatric diseases including schizophrenia (SCZ) and bipolar disorder (BD).

Knockout of AMPA receptor binding protein Neuron-Specific Gene 2 (NSG2) enhances associative learning and cognitive flexibility.

The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition.

Retrograde intramedullary nailing of AO/OTA 33C femur fractures in patients with below-knee amputations: technical note and case series.

Purpose: Intra-articular distal femur fractures in patients with a lower extremity amputation can present a technical challenge for the treating surgeon in what may be otherwise considered a routine procedure in non-amputees. Difficulties with positioning, fracture reduction, limb contractures, and stump osteoporosis can present challenges with treatment. Here, we describe the surgical technique and outcome of a case series of amputee patients with AO/OTA 33C femur fractures.

Does local fat thickness correlate with post-operative infection in open reduction and internal fixation of acetabulum fractures?

Purpose: Obesity is an epidemic which increases risk of many surgical procedures. Previous studies in spine and hip arthroplasty have shown that fat thickness measured on preoperative imaging may be as or more reliable in assessment of risk of post-operative infection and/or wound complications than body mass index (BMI). We hypothesized that, similarly, increased local fat thickness at the surgical site is a predictor of wound complication in acetabulum fracture surgery.

Neuron-specific gene NSG1 binds to and positively regulates sortilin ectodomain shedding via a metalloproteinase-dependent mechanism.

Increasing evidence suggests that aberrant regulation of sortilin ectodomain shedding can contribute to amyloid-β pathology and frontotemporal dementia, although the mechanism by which this occurs has not been elucidated. Here, we probed for novel binding partners of sortilin using multiple and complementary approaches and identified two proteins of the neuron-specific gene (NSG) family, NSG1 and NSG2, that physically interact and colocalize with sortilin. We show both NSG1 and NSG2 induce subcellular redistribution of sortilin to NSG1- and NSG2-enriched compartments.

Distribution and inflammatory cell response to intracranial delivery of radioluminescent Y2(SiO4)O:Ce particles.

Due to increasing advances in their manufacture and functionalization, nanoparticle-based systems have become a popular tool for in vivo drug delivery and biodetection. Recently, scintillating nanoparticles such as yttrium orthosilicate doped with cerium (Y2(SiO4)O:Ce) have come under study for their potential utility in optogenetic applications, as they emit photons upon low levels of stimulation from remote x-ray sources. The utility of such nanoparticles in vivo is hampered by rapid clearance from circulation by the mononuclear phagocytic system, which heavily restricts nanoparticle accumulation at target tissues.

Improved outcomes with "7+3" induction chemotherapy for acute myeloid leukemia over the past four decades: analysis of SWOG trial data.

We have previously shown that complete response (CR) rates and overall survival of patients with acute myeloid leukemia have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients aged 65 or younger randomized to "7+3" arms from five SWOG studies: S8600 (n=530), S9031 (n=98), S9333 (n=57), S0106 (n=301), and S1203 (n=261).

Anatomic Total Shoulder Arthroplasty: Component Size Prediction with 3-Dimensional Pre-Operative Digital Planning.

Background: The rate, complexity, and cost of total shoulder arthroplasty (TSA) continues to grow. Technology has advanced pre-operative templating. Reducing cost of TSA has positive impact for the patient, manufacturer, and hospital.

Global loss of Neuron-specific gene 1 causes alterations in motor coordination, increased anxiety, and diurnal hyperactivity in male mice.

The Neuron-specific gene family (NSG1-3) consists of small endolysosomal proteins that are critical for trafficking multiple receptors and signaling molecules in neurons. NSG1 has been shown to play a critical role in AMPAR recycling from endosomes to plasma membrane during synaptic plasticity. However, to date nothing is known about whether NSG1 is required for normal behavior at an organismal level.

Machine learning prediction and tau-based screening identifies potential Alzheimer's disease genes relevant to immunity.

With increased research funding for Alzheimer's disease (AD) and related disorders across the globe, large amounts of data are being generated. Several studies employed machine learning methods to understand the ever-growing omics data to enhance early diagnosis, map complex disease networks, or uncover potential drug targets. We describe results based on a Target Central Resource Database protein knowledge graph and evidence paths transformed into vectors by metapath matching.

Proteopathic tau primes and activates interleukin-1β via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway.

Pathological hyperphosphorylation and aggregation of tau (pTau) and neuroinflammation, driven by interleukin-1β (IL-1β), are the major hallmarks of tauopathies. Here, we show that pTau primes and activates IL-1β. First, RNA-sequence analysis suggests paired-helical filaments (PHFs) from human tauopathy brain primes nuclear factor κB (NF-κB), chemokine, and IL-1β signaling clusters in human primary microglia.

Comparison of k-wire insertion using oscillatory and unidirectional drilling modes under constant thrust force.

Heat generation during the Kirschner wire (K-wire) insertion process, under either unidirectional or oscillatory drilling mode, places bone at risk of thermal osteonecrosis which can lead to infection. There is a lack of quantitative understanding of the heat generation difference between the two drilling modes and knowledge of optimal thrust force level under each mode is missing. The goal of this study is to investigate the effects of drilling modes and thrust force levels on the bone drilling outcomes.

Management of Open Segmental Tibial Fractures.

Open segmental tibial fractures are difficult injuries fraught with potential for complications. Delays or missteps in treatment and soft tissue coverage can lead to disastrous outcomes. This article and the accompanying video demonstrate an example of a timely, team-based approach for management of an open segmental tibial shaft fracture with complex osseous fixation and soft tissue reconstruction.

Retrograde Intramedullary Nail for Distal Femur Fracture, Through a Total Knee Arthroplasty.

Distal femur fractures are common in the elderly population. The risk of sustaining a distal femur fracture is increased with the presence of total knee arthroplasty components. Fixation with a retrograde intramedullary nail is a viable option for treatment of these injuries.

Reported Technical Aspects of Type II SLAP Lesion Repairs in Athletes.

Purpose: To systematically review the available literature to further describe and report the available data on SLAP repair techniques and the association with outcomes.

Methods: A systematic review of literature was performed on manuscripts describing type II SLAP repairs in athletes. Selection criteria included studies reporting exclusively type II SLAP tears without concomitant pathology, minimum 2-year postoperative follow-up, use of anchor fixation, and return to previous level of play data available.

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics.

Non-invasive light delivery into the brain is needed foroptogenetics to avoid physical damage. An innovative strategy could employ x-ray activation of radioluminescent particles (RLPs) to emit localized light. However, modulation of neuronal or synaptic function by x-ray induced radioluminescence from RLPs has not yet been demonstrated.

Associations between complete remission and 2- to 3-year survival following 7 + 3 induction for acute myeloid leukemia.

Among acute myeloid leukemia (AML) patients treated with 7 + 3 induction, we evaluate the association between complete morphologic remission (CR) and long-term overall survival (OS) over four decades. We analyzed 1247 patients age 65 randomized to 7 + 3 arms from five SWOG studies. OS has improved over the four decades.

Transcriptomic changes due to early, chronic intermittent alcohol exposure during forebrain development implicate WNT signaling, cell-type specification, and cortical regionalization as primary determinants of fetal alcohol syndrome.

Background: Fetal alcohol syndrome (FAS) due to gestational alcohol exposure represents one of the most common causes of nonheritable lifelong disability worldwide. In vitro and in vivo models have successfully recapitulated multiple facets of the disorder, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic mechanisms underlying FAS.

Methods: In this study, we utilized an in vitro human pluripotent stem cell-based (hPSC) model of corticogenesis to probe the effects of early, chronic intermittent alcohol exposure on the transcriptome of first trimester-equivalent cortical neurons.

Osseous Healing With Nonrigid Suture Fixation in the Arthroscopic Latarjet Procedure.

Background: The Latarjet procedure is a popular means to surgically address anterior glenohumeral joint instability. Although the Latarjet procedure is becoming increasingly common, challenges persist and include postoperative complications secondary to use of the conventional 2 bicortical fixation screws. Recently, a novel surgical technique using a guided surgical approach for graft positioning with nonrigid fixation via a suture suspensory system has been described.

Optical induction of autophagy via Transcription factor EB (TFEB) reduces pathological tau in neurons.

Pathological accumulation of microtubule associated protein tau in neurons is a major neuropathological hallmark of Alzheimer's disease (AD) and related tauopathies. Several attempts have been made to promote clearance of pathological tau (p-Tau) from neurons. Transcription factor EB (TFEB) has shown to clear p-Tau from neurons via autophagy.

Arthroscopic Rotator Cuff Repair: A General Instructional Course Lecture.

Rotator cuff pathology is one of the most common reasons for patients to seek orthopaedic consultation. Although in many cases these issues can be resolved with proper conservative management, many of these patients benefit from surgical treatment. The goal of this instructional course lecture is to identify factors that can potentially lead to worse outcomes following repair, describe the history and techniques behind transosseous anchorless repairs, discuss subscapularis tears and their management, and to analyze the most current data regarding double-row rotator cuff repairs.

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition.

Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC).

Exosomal secretion of a psychosis-altered miRNA that regulates glutamate receptor expression is affected by antipsychotics.

The ability of small secretory microvesicles known as exosomes to influence neuronal and glial function via their microRNA (miRNA) cargo has positioned them as a novel and effective method of cell-to-cell communication. However, little is known about the role of exosome-secreted miRNAs in the regulation of glutamate receptor gene expression and their relevance for schizophrenia (SCZ) and bipolar disorder (BD). Using mature miRNA profiling and quantitative real-time PCR (qRT-PCR) in the orbitofrontal cortex (OFC) of SCZ (N = 29; 20 male and 9 female), BD (N = 26; 12 male and 14 female), and unaffected control (N = 25; 21 male and 4 female) subjects, we uncovered that miR-223, an exosome-secreted miRNA that targets glutamate receptors, was increased at the mature miRNA level in the OFC of SCZ and BD patients with positive history of psychosis at the time of death and was inversely associated with deficits in the expression of its targets glutamate ionotropic receptor NMDA-type subunit 2B (GRIN2B) and glutamate ionotropic receptor AMPA-type subunit 2 (GRIA2).