Prophylactic Antibiotic Choice and Deep Infection in Lower Extremity Endoprosthetic Reconstruction: Comparison of Cefazolin, Cefazolin-Vancomycin, and Alternative Regimens.

INTRODUCTION: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens. METHODS: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues. RESULTS: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively (P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) (P = 0.13) and 12% revision surgery rate (31/260) (P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy. CONCLUSION: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily.

Evaluating ChatGPT's Ability to Answer Common Patient Questions Regarding Hip Fracture.

INTRODUCTION: ChatGPT is an artificial intelligence chatbot software programmed for conversational applications using reinforcement learning techniques. With its growing popularity and overall versatility, it is likely that ChatGPT's applications will expand into health care especially because it relates to patients researching their injuries. The purpose of this study was to investigate ChatGPT's ability to accurately answer frequently asked questions regarding hip fractures. METHODS: Eleven frequently asked questions regarding hip fractures were posed to ChatGPT, and the responses were recorded in full. Five of these questions were determined to be high-yield based on the likelihood that a patient would ask the question to a chatbot software. The chatbot's responses were analyzed by five fellowship-trained orthopaedic trauma surgeons for their quality and accuracy using an evidence-based approach. The chatbot's answers were rated as "Excellent response requiring no clarification", "Satisfactory response requiring minimal clarification", "Satisfactory response requiring moderate clarification", or "Unsatisfactory response requiring significant clarification." RESULTS: Of the five high-yield questions posed to the chatbot, no question was determined to be unsatisfactory requiring significant clarification by the authors. The remaining responses were either satisfactory requiring minimal clarification (n = 3) or satisfactory requiring moderate clarification (n = 2). DISCUSSION: The chatbot was generally found to provide unbiased and evidence-based answers that would be clearly understood by most orthopaedic patients. These findings suggest that ChatGPT has the potential to be an effective patient education tool especially because it continues to grow and improve as a chatbot application. LEVEL OF EVIDENCE: Level IV study.

Gaussians for Electronic and Rovibrational Quantum Dynamics.

The assumptions underpinning the adiabatic Born-Oppenheimer (BO) approximation are broken for molecules interacting with attosecond laser pulses, which generate complicated coupled electronic-nuclear wave packets that generally will have components of electronic and dissociation continua as well as bound-state contributions. The conceptually most straightforward way to overcome this challenge is to treat the electronic and nuclear degrees of freedom on equal quantum-mechanical footing by not invoking the BO approximation at all. Explicitly correlated Gaussian (ECG) basis functions have proved successful for non-BO calculations of stationary molecular states and energies, reproducing rovibrational absorption spectra with very high accuracy. In this Article, we present a proof-of-principle study of the ability of fully flexible ECGs (FFECGs) to capture the intricate electronic and rovibrational dynamics generated by short, high-intensity laser pulses. By fitting linear combinations of FFECGs to accurate wave function histories obtained on a large real-space grid for a regularized 2D model of the hydrogen atom and for the 2D Morse potential, we demonstrate that FFECGs provide a very compact description of laser-driven electronic and rovibrational dynamics.

Modeling of High-Harmonic Generation in the C60 Fullerene Using Ab Initio, DFT-Based, and Semiempirical Methods.

We report calculations of the high-harmonic generation spectra of the C60 fullerene molecule carried out by employing a diverse set of real-time time-dependent quantum chemical methods. All methodologies involve expanding the propagated electronic wave function in bases consisting of the ground and singly excited time-independent eigenstates obtained through the solution of the corresponding linear-response equations. We identify the correlation and exchange effect in the spectra by comparing the results from methods relying on the Hartree-Fock reference determinant with those obtained using approaches based on the density functional theory with different exchange-correlation functionals. The effect of the full random-phase approximation treatment of the excited electronic states is also analyzed and compared with the configuration interaction singles and the Tamm-Dancoff approximation. We also showcase the fact that the real-time extension of the semiempirical method INDO/S can be effectively applied for an approximate description of laser-driven dynamics in large systems.

Can ChatGPT Answer Patient Questions Regarding Total Knee Arthroplasty?

The internet has introduced many resources frequently accessed by patients prior to orthopaedic visits. Recently, Chat Generative Pre-Trained Transformer, an artificial intelligence-based chat application, has become publicly and freely available. The interface uses deep learning technology to mimic human interaction and provide convincing answers to questions posed by users. With its rapidly expanding usership, it is reasonable to assume that patients will soon use this technology for preoperative education. Therefore, we sought to determine the accuracy of answers to frequently asked questions (FAQs) pertaining to total knee arthroplasty (TKA).Ten FAQs were posed to the chatbot during a single online interaction with no follow-up questions or repetition. All 10 FAQs were analyzed for accuracy using an evidence-based approach. Answers were then rated as "excellent response not requiring clarification," "satisfactory requiring minimal clarification," satisfactory requiring moderate clarification," or "unsatisfactory requiring substantial clarification."Of the 10 answers given by the chatbot, none received an "unsatisfactory" rating with the majority either requiring minimal (5) or moderate (4) clarification. While many answers required nuanced clarification, overall, answers tended to be unbiased and evidence-based, even when presented with controversial subjects.The chatbot does an excellent job of providing basic, evidence-based answers to patient FAQs prior to TKA. These data were presented in a manner that will be easily comprehendible by most patients and may serve as a useful clinical adjunct in the future.

Glucagon-like Peptide-1 Agonists: What the Orthopaedic Surgeon Needs to Know.

¼ Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.¼ GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).¼ The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.¼ While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.¼ Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts.

HIV drug resistance among patients experiencing antiretroviral therapy failure in Russia, 2019-2021.

Increasing HIV drug resistance is an important public health concern. The current study aimed to assess HIV drug resistance among people who live with HIV (PLWH) experiencing virological failure. Blood samples and epidemiological characteristics were collected in four Siberian regions from PLWH experiencing ART failure. Partial pol gene sequences were obtained for the study individuals. Drug resistance mutations (DRMs) were predicted using the Stanford HIVdb Program. The association of HIV DRM with epidemiological characteristics was estimated using logistic regression analysis. Further analysis was performed for children (0-14 y old) and adults (≥15 y old) separately. In total, 815 (89.4%) patients were included in the final dataset. Overall, 501 (61.5%) patients had DRM detected. NRTI DRM was more common in children, while NRTI+NNRTI DRM was more frequent in adults (P < 0.001). Krasnoyarsk region, male sex and high viral load were positively associated with the presence of DRM in adults, while higher CD4 cell count and PI/INSTI-based ART had a negative association. No association between epidemiological characteristics and DRM was identified in children. The remaining 38.5% of patients with virological failure had no DRM detected; those patients were likely to have insufficient ART adherence. Most (55.5%) patients had HIV CRF63_02A6, followed by sub-subtype A6 (39.2%). This study revealed poor ART adherence as a main factor driving ART failure among PLWH in the Siberian region. DRM was detected in over 60% of PLWH experiencing ART failure. The current results highlight an urgent need for the introduction of special programs focusing on ART adherence improvement.

Assessing ChatGPT Responses to Common Patient Questions Regarding Total Hip Arthroplasty.

BACKGROUND: The contemporary patient has access to numerous resources on common orthopaedic procedures before ever presenting for a clinical evaluation. Recently, artificial intelligence (AI)-driven chatbots have become mainstream, allowing patients to engage with interfaces that supply convincing, human-like responses to prompts. ChatGPT (OpenAI), a recently developed AI-based chat technology, is one such application that has garnered rapid growth in popularity. Given the likelihood that patients may soon call on this technology for preoperative education, we sought to determine whether ChatGPT could appropriately answer frequently asked questions regarding total hip arthroplasty (THA). METHODS: Ten frequently asked questions regarding total hip arthroplasty were posed to the chatbot during a conversation thread, with no follow-up questions or repetition. Each response was analyzed for accuracy with use of an evidence-based approach. Responses were rated as "excellent response not requiring clarification," "satisfactory requiring minimal clarification," "satisfactory requiring moderate clarification," or "unsatisfactory requiring substantial clarification." RESULTS: Of the responses given by the chatbot, only 1 received an "unsatisfactory" rating; 2 did not require any correction, and the majority required either minimal (4 of 10) or moderate (3 of 10) clarification. Although several responses required nuanced clarification, the chatbot's responses were generally unbiased and evidence-based, even for controversial topics. CONCLUSIONS: The chatbot effectively provided evidence-based responses to questions commonly asked by patients prior to THA. The chatbot presented information in a way that most patients would be able to understand. This resource may serve as a valuable clinical tool for patient education and understanding prior to orthopaedic consultation in the future.

The novel questionnaire assessing occupational exposure to the risk factors of contact allergy among health professionals.

Introduction: Skin diseases account for about 7% of all occupational diseases in Europe. Allergic contact dermatitis (ACD) is one of the most common occupational skin diseases. Therefore, it constitutes the major health and economic problem. Increasing the detectability of ACD would significantly improve the quality of life of patients and their work efficiency. Aim: To design a questionnaire facilitating the diagnosis of ACD in work environment of healthcare providers. Material and methods: The initial questionnaire consisted of 53 questions related to ACD and exposure to various occupational hazards. On its basis, a scale of exposure to occupational skin diseases (OSDES-49) was created. The reliability of the scale was measured using the internal consistency test of the scale. It was assumed that individual items of the scale would be correlated with the total score if the Kleine and Nunnally criteria were met. Results: The Kleine and Nunnally criteria were met by 16 out of 49 items on the scale. OSDES-49 results were strongly correlated with the assessment using a questionnaire consisting of only 16 items (OSDES-16). Spearman's rank correlation coefficient was rho = 0.850 and p < 0.001. Conclusions: Results of the study showed that in any further screening tests, the OSDES-16 scale is reliable. The use of OSDES-16 reduces the time of initial diagnostics and simplifies it.

Understanding the impact of transformational leadership on nurse compassion provision through a time-lagged field study.

BACKGROUND: A large volume of literature identifies positive, rejuvenating benefits associated with giving compassion to others. However, the relationship between giving compassion and feelings of exhaustion remains underexplored. Understanding when giving compassion can potentially lead to feelings of emotional exhaustion is particularly important for nurses who are called upon to provide high levels of compassion to suffering patients in their daily work. We suggest that by engaging in transformational leadership behaviors, frontline supervisors can help nurses realize the positive benefits associated with giving compassion. PURPOSE: The aim of this study was to examine the impact of nurses' perceptions of transformational leadership offered by their supervisors on the relationship between the levels of compassionate behaviors nurses report engaging in with patients and feelings of emotional exhaustion and job satisfaction. METHODOLOGY/APPROACH: A time-lagged field survey was conducted across two waves of 112 full-time employed inpatient nurses within the United States. RESULTS: Providing high levels of compassionate behavior to patients was associated with reduced (increased) perceptions of emotional exhaustion and increased (decreased) job satisfaction when supervisors engaged in higher (lower) levels of transformational leadership. DISCUSSION: Transformational leadership serves as an important resource to help caregivers such that nurses feel invigorated and satisfied, as opposed to drained or fatigued, when engaging in high levels of compassionate behaviors toward suffering patients. PRACTICE IMPLICATIONS: For nurses to fully reap the established positive benefits associated with providing compassion to patients, frontline supervisors should be encouraged to engage in behaviors reflective of transformational leadership.

Distinct hippocampal-prefrontal neural assemblies coordinate memory encoding, maintenance, and recall.

Short-term memory enables incorporation of recent experience into subsequent decision-making. This processing recruits both the prefrontal cortex and hippocampus, where neurons encode task cues, rules, and outcomes. However, precisely which information is carried when, and by which neurons, remains unclear. Using population decoding of activity in rat medial prefrontal cortex (mPFC) and dorsal hippocampal CA1, we confirm that mPFC populations lead in maintaining sample information across delays of an operant non-match to sample task, despite individual neurons firing only transiently. During sample encoding, distinct mPFC subpopulations joined distributed CA1-mPFC cell assemblies hallmarked by 4-5 Hz rhythmic modulation; CA1-mPFC assemblies re-emerged during choice episodes but were not 4-5 Hz modulated. Delay-dependent errors arose when attenuated rhythmic assembly activity heralded collapse of sustained mPFC encoding. Our results map component processes of memory-guided decisions onto heterogeneous CA1-mPFC subpopulations and the dynamics of physiologically distinct, distributed cell assemblies.

Pan-cancer antagonistic inhibition pattern of ATM-driven G2/M checkpoint pathway vs other DNA repair pathways.

DNA repair mechanisms keep genome integrity and limit tumor-associated alterations and heterogeneity, but on the other hand they promote tumor survival after radiation and genotoxic chemotherapies. We screened pathway activation levels of 38 DNA repair pathways in nine human cancer types (gliomas, breast, colorectal, lung, thyroid, cervical, kidney, gastric, and pancreatic cancers). We took RNAseq profiles of the experimental 51 normal and 408 tumor samples, and from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium databases - of 500/407 normal and 5752/646 tumor samples, and also 573 normal and 984 tumor proteomic profiles from Proteomic Data Commons portal. For all the samplings we observed a congruent trend that all cancer types showed inhibition of G2/M arrest checkpoint pathway compared to the normal samples, and relatively low activities of p53-mediated pathways. In contrast, other DNA repair pathways were upregulated in most of the cancer types. The G2/M checkpoint pathway was statistically significantly downregulated compared to the other DNA repair pathways, and this inhibition was strongly impacted by antagonistic regulation of (i) promitotic genes CCNB and CDK1, and (ii) GADD45 genes promoting G2/M arrest. At the DNA level, we found that ATM, TP53, and CDKN1A genes accumulated loss of function mutations, and cyclin B complex genes - transforming mutations. These findings suggest importance of activation for most of DNA repair pathways in cancer progression, with remarkable exceptions of G2/M checkpoint and p53-related pathways which are downregulated and neutrally activated, respectively.

The Impact of the COVID-19 Pandemic on the Presentation of Patients With Spinal Metastases.

STUDY DESIGN: Retrospective review. OBJECTIVE: The aim was to determine if preoperative spinal instability neoplastic scores (SINSs) and Tokuhashi prognostication scores differed in patients receiving surgical care before and during the coronavirus disease-2019 (COVID-19) pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has caused delays in scheduling nonemergent surgeries. Delay in presentation and/or surgical treatment for oncology patients with metastatic spinal disease could result in progression of the disease, which can complicate surgical care and worsen patient outcomes. MATERIALS AND METHODS: Retrospective review of electronic medical records between March 1, 2019 and March 1, 2021 at a tertiary medical center was performed to identify patients who underwent surgery for metastatic spine disease. Primary spinal tumors were excluded. Patients were separated into two groups base on their surgery date: before the COVID-19 pandemic (March 1, 2019-February 29, 2020) and during the COVID-19 pandemic (March 1, 2020-March 1, 2021). Primary outcomes included SINS and Tokuhashi scores. A variety of statistical tests were performed to compare the groups. RESULTS: Fifty-two patients who underwent surgery before the COVID-19 pandemic were compared to 41 patients who underwent surgery during the COVID-19 pandemic. There was a significant difference between the before and during groups with respect to SINS (9.31±2.39 vs . 11.00±2.74, P =0.002) and Tokuhashi scores (9.27±2.35 vs . 7.88±2.85, P =0.012). Linear regression demonstrated time of surgery (before or during COVID-19 restrictions) was a significant predictor of SINS (ß=1.55, 95% CI: 0.42-2.62, P =0.005) and Tokuhashi scores (ß=-1.41, 95% CI: -2.49 to -0.34, P =0.010). CONCLUSIONS: Patients with metastatic spinal disease who underwent surgery during the COVID-19 pandemic had higher SINS, lower Tokuhashi scores and similar Skeletal Oncology Research Group scores compared to patients who underwent surgery before the pandemic. This suggests the pandemic has impacted the instability of disease at presentation in patients with spinal metastases, but has not impacted surgical prognosis, as there were no differences in Skeletal Oncology Research Group scores and the difference in Tokuhashi scores is most likely not clinically significant.

Orientation in the European common frog Rana temporaria during the first wintering migration.

The orientation of naive animals during their first migration is extensively studied in birds and sea turtles, whereas the data for other groups such as amphibians are still scarce. To date, it is unknown whether young-of-the-year anurans perform a random or directional search for the hibernation sites, and what cues (global or local) they use. We conducted a series of field experiments to study the orientation behavior of juvenile common frogs during their first wintering migration. We captured 1614 froglets from two subpopulations with different directions of migration and assessed their orientation in large circular outdoor arenas (20 m in diameter) on the opposite sides of the river. Before the migration, froglets used local cues and moved back towards the forest (summer habitat). At the start of migration, the froglets did not move randomly: they navigated towards the river using local cues. Later, however, before approaching the hibernation site, they memorized the compass direction of migration and followed it using global cues. Orientation along a memorized compass heading begins to dominate in the hierarchy of orientation mechanisms, and this predominance is maintained even after reaching the hibernation site. Unlike in birds, no innate direction of migration was found.

Effects of electronic correlation on the high harmonic generation in helium: A time-dependent configuration interaction singles vs time-dependent full configuration interaction study.

In this paper, we investigate the effects of full electronic correlation on high harmonic generation in the helium atom subjected to laser pulses of extremely high intensity. To do this, we perform real-time propagations of helium atom wavefunction using quantum chemistry methods coupled to Gaussian basis sets. Calculations are performed within the real-time time-dependent configuration interaction framework at two levels of theory: time-dependent configuration interaction with single excitations (uncorrelated method) and time-dependent full configuration interaction (fully correlated method). The electronic wavefunction is expanded in Dunning basis sets supplemented with functions adapted to describing highly excited and continuum states. We also compare the time-dependent configuration interaction results with grid-based propagations of the helium atom within the single-active-electron approximation. Our results show that when including the dynamical electron correlation, a noticeable improvement to the description of high harmonic generation (HHG) can be achieved in terms of, e.g., a more constant intensity in the lower energy part of the harmonic plateau. However, such effects can be captured only if the basis set used suffices to reproduce the most basic features, such as the HHG cutoff position, at the uncorrelated level of theory.

Race and reactions to women's expressions of anger at work: Examining the effects of the "angry Black woman" stereotype.

Across two studies (n = 555), we examine the detrimental effects of the "angry black woman" stereotype in the workplace. Drawing on parallel-constraint-satisfaction theory, we argue that observers will be particularly sensitive to expressions of anger by black women due to widely held stereotypes. In Study 1, we examine a three-way interaction among anger, race, and gender, and find that observers are more likely to make internal attributions for expressions of anger when an individual is a black woman, which then leads to worse performance evaluations and assessments of leadership capability. In Study 2, we focus solely on women and expand our initial model by examining stereotype activation as a mechanism linking the effects of anger and race on internal attributions. We replicated findings from Study 1 and found support for stereotype activation as an underlying mechanism. We believe our work contributes to research on race, gender, and leadership, and highlights an overlooked stereotype in the management literature. Theoretical and practical implications are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A systematic construction of Gaussian basis sets for the description of laser field ionization and high-harmonic generation.

A precise understanding of mechanisms governing the dynamics of electrons in atoms and molecules subjected to intense laser fields has a key importance for the description of attosecond processes such as the high-harmonic generation and ionization. From the theoretical point of view, this is still a challenging task, as new approaches to solve the time-dependent Schrödinger equation with both good accuracy and efficiency are still emerging. Until recently, the purely numerical methods of real-time propagation of the wavefunction using finite grids have been frequently and successfully used to capture the electron dynamics in small one- or two-electron systems. However, as the main focus of attoscience shifts toward many-electron systems, such techniques are no longer effective and need to be replaced by more approximate but computationally efficient ones. In this paper, we explore the increasingly popular method of expanding the wavefunction of the examined system into a linear combination of atomic orbitals and present a novel systematic scheme for constructing an optimal Gaussian basis set suitable for the description of excited and continuum atomic or molecular states. We analyze the performance of the proposed basis sets by carrying out a series of time-dependent configuration interaction calculations for the hydrogen atom in fields of intensity varying from 5 × 1013 W/cm2 to 5 × 1014 W/cm2. We also compare the results with the data obtained using Gaussian basis sets proposed previously by other authors.

Incivility and creativity in teams: Examining the role of perpetrator gender.

We conduct 3 experiments to examine how the effects of incivility on team creativity through team positive affect differ depending on the gender of the incivil team member. We argue that the incivil behavior of 1 team member decreases team positive affect, thereby decreasing team creativity. We then propose that the gender of the incivil team member plays a significant role in team member reactions. We draw on role congruity theory, which posits that individuals respond positively toward those whom they perceive as adhering to societal norms, and negatively to those who do not. Accordingly, we found that team positive affect decreased significantly when a woman behaved incivilly compared with when a man behaved incivilly due to the agentic and aggressive nature of the behavior. Lower team positive affect then decreased team creativity. Interestingly, team positive affect was not affected when a man behaved incivilly. We consider the implications of our work across several different literatures and discuss interesting directions for future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Discrimination of the phase of amplitude modulation applied to different carriers: Effects of modulation rate and modulation depth for young and older subjects.

The discrimination of amplitude modulation (AM) from frequency modulation (FM) of a 1000-Hz carrier, with equally detectable AM and FM, is better for a 2-Hz than for a 10-Hz modulation rate. This might reflect greater sensitivity to temporal fine structure for low than for high rates. Alternatively, AM-FM discrimination may depend on comparing fluctuations in excitation level on the two sides of the excitation pattern, which are in phase for AM and out of phase for FM. Discrimination of the relative phase of fluctuations might worsen with increasing rate, which could account for the effect of rate on AM-FM discrimination. To test this, discrimination of the phase of AM applied to two sinusoidal carriers was assessed, with a band of noise between the two carriers to prevent use of within-channel cues. Young and older subjects with normal hearing were tested. Performance was almost constant for AM rates from 2 to 10 Hz, but worsened at 20 Hz. Performance was near chance for AM depths near the detection threshold. The results suggest that the superior AM-FM discrimination at 2 Hz cannot be explained in terms of comparison of the phase of fluctuations on the two sides of the excitation pattern.

Cellular and synaptic phenotypes lead to disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex.

Sensory hypersensitivity is a common and debilitating feature of neurodevelopmental disorders such as Fragile X Syndrome (FXS). How developmental changes in neuronal function culminate in network dysfunction that underlies sensory hypersensitivities is unknown. By systematically studying cellular and synaptic properties of layer 4 neurons combined with cellular and network simulations, we explored how the array of phenotypes in Fmr1-knockout (KO) mice produce circuit pathology during development. We show that many of the cellular and synaptic pathologies in Fmr1-KO mice are antagonistic, mitigating circuit dysfunction, and hence may be compensatory to the primary pathology. Overall, the layer 4 network in the Fmr1-KO exhibits significant alterations in spike output in response to thalamocortical input and distorted sensory encoding. This developmental loss of layer 4 sensory encoding precision would contribute to subsequent developmental alterations in layer 4-to-layer 2/3 connectivity and plasticity observed in Fmr1-KO mice, and circuit dysfunction underlying sensory hypersensitivity.