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The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

Abstract Background The purpose of this work is to describe the objectives and design of cardiovascular magnetic resonance (CMR) imaging in the single center, prospective, population-based Hamburg City Health study (HCHS). The HCHS aims at improving risk stratification for coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF). Methods The HCHS will finally include 45,000 inhabitants of the city of Hamburg (Germany) between 45 and 74 years who undergo an extensive cardiovascular evaluation and collection of biomaterials. Risk-scores for CAD, AF and HF are used to create enriched subpopulations who are invited for CMR. A total number of approximately 12,362 subjects will undergo CMR and incident CAD, AF and HF will be assessed after 6 years follow-up. The standard CMR protocol includes cine-CMR, T1 and T2 mapping, aortic/mitral valve flow measurements, Late gadolinium enhancement, angiographies and measurements of aortic distensibility. A stress-perfusion scan is added in individuals at risk for CAD. The workflow of CMR data acquisition and analyses was evaluated in a pilot cohort of 200 unselected subjects. Results The obtained CMR findings in the pilot cohort agree with current reference values and demonstrate the ability of the established workflow to accomplish the objectives of HCHS. Conclusions CMR in HCHS promises novel insights into major cardiovascular diseases, their subclinical precursors and the prognostic value of novel imaging biomarkers. The HCHS database will facilitate combined analyses of imaging, clinical and molecular data (“Radiomics”).

Elucidating protein rigidity offers insights about protein conformational changes. An understanding of protein motion can help speed drug development, and provide general insights into the dynamic behaviors of biomolecules. Existing rigidity analysis techniques employ fine-grained, all-atom modeling, which has a costly run-time, particularly for proteins made up of more than 500 residues. In this work, we introduce coarse-grained rigidity analysis, and showcase that it provides flexibility information about a protein that is similar in accuracy to an all-atom modeling approach. We assess the accuracy of the coarse-grained method relative to an all-atom approach via a comparison metric that reasons about the largest rigid clusters of the two methods. The apparent symmetry between the all-atom and coarse-grained methods yields very similar results, but the coarse-grained method routinely exhibits 40% reduced run-times. The CGRAP web server outputs rigid cluster information, and provides data visualization capabilities, including a interactive protein visualizer.

MicroRNAs regulate gene expression of transcriptional factors, which influence Th17/Treg (regulatory T cells) balance, establishing the molecular mechanism of genetic and epigenetic regulation of Treg and Th17 cells is crucial for understanding rheumatoid arthritis (RA) pathogenesis. The study goal was to understand the potential impact of the selected microRNAs expression profiles on Treg/Th17 cells frequency, RA phenotype, the expression profile of selected microRNAs, and their correlation with the expression profiles of selected transcriptional factors: SOCS1, SMAD3, SMAD4, STAT3, STAT5 in RA; we used osteoarthritis (OA) and healthy controls (HCs) as controls. The study was conducted on 14 RA and 11 OA patients, and 15 HCs. Treg/Th17 frequency was established by flow cytometry. Gene expression analysis was estimated by qPCR. We noticed correlations in RA Th17 cells between miR-26 and SMAD3, STAT3, SOCS1; and miR-155 and STAT3—and in RA Treg cells between miR-26 and SOCS1; miR-31, -155 and SMAD3; and miR-155 and SMAD4. In RA Tregs, we found a negative correlation between miR-26, -126 and STAT5a. The expression level of miR-31 in Th17 cells from RA patients with DAS28 ≤ 5.1 is higher and that for miR-24 is greater in Tregs from patients with DAS28 > 5.1. MiR-146a in Tregs is higher in rheumatoid factor (RF) positive RA patients.

Introduction Compared to the public sector, not-for-profits are less focused on cross-agency data linkage. Technical capacity is often secondary to addressing caseloads and protecting clients. Clients’ privacy is paramount and can be perceived as a barrier to collaboration between agencies. However, collaboration could streamline referrals and better assist vulnerable populations. Objectives and Approach Six not-for-profit agencies in Calgary, Canada participated in a data sharing project to measure various aspects of poverty and link data to determine cross-agency service usage. With this goal in mind, agencies examined their consent and data sharing practices to assess barriers to data sharing. There was a thorough exploration of client consent and how a client’s context can enable or limit data sharing. Cross-agency program usage was assessed among participating agencies using a privacy-preserving record linkage (PPRL) methodology. Results Amongst the six participating agencies, four were deemed to have adequate technical capacity to share data. A contributing factor to the willingness of agencies to share data was the development of LinkWise: a PPRL software created and developed by PolicyWise. Linkage rates amongst three agencies were compared. Rates ranged from 47.8% to 0.23%. A higher linkage rate between two agencies indicated a small community based agency which provided many referrals to a larger agency, such as a food bank. Lower linkage rates on client intake may indicate an agency with many clients. It may also indicate differing socio-economic brackets for their clients’ catchment area. Conclusion/Implications While capacity, caseloads, and privacy protection restrict data sharing, not-for-profit agencies would benefit from a data sharing strategy. Linking data represent opportunities for collaboration within a significantly resource constrained sector. Moreover, it could more effectively address issues of vulnerable populations, streamline referrals for services, and facilitate quality improvement.

Introduction Poor mental health among post-secondary students has been on the rise, and as such, has become a growing concern for the Alberta government. Alberta’s major post-secondary institutions have emphasized the need for evidence that would improve mental health supports for students troubled by mental health issues. Objectives and Approach Responding to the need for evidence, the Child and Youth Data Laboratory profiled the socio-demographic characteristics (sex, socio-economic status, etc) of students who used mental health services between 2005/06 and 2010/11. In addition, using linked administrative data from a range of government programs, the profiles provide new data on the program involvement of post-secondary students who used mental health services, including educational achievement in high school, high cost health service use, the presence of chronic conditions, injury diagnoses, disability status, justice system involvement, income support, and type of mental health condition. Results Over the study period, 7% (~6,000) of post-secondary students received mental health services. Of those, between 11 and 13% were high cost health service users, ~20% received an injury diagnosis, and ~15% had a chronic condition. These proportions were higher compared to the proportions among students who did not receive mental health services. Rates of income support service use, corrections involvement, and students with disabilities were higher compared to students not receiving mental health services. A greater proportion of Canadian students (between 6.5% and 7.1%) compared to non-Canadian students (between 3.4% and 4.1%) received mental health services. In 2010/11, a greater proportion of part-time compared to full-time students were diagnosed with an anxiety disorder (3.4%, part-time; 2.3% full-time) or depression (4.0% part-time; 2.3% full-time). Conclusion/Implications Evidence produced from linked administrative data offers a unique understanding of students who use mental health services, particularly in terms of their government program involvement. This new evidence can be used, for example, to determine if mental health service needs are different for Canadian versus non-Canadian students, or for full-time versus part-time students.

Introduction This study uses linked administrative data to identify Albertan children and youth (aged 0 to 25 years) with Autism Spectrum Disorder (ASD), Cerebral Palsy (CP) or Fetal Alcohol Spectrum Disorder (FASD), and to examine their government service use patterns from 2005/06 to 2010/11. Objectives and Approach The analysis looks at whether children with ASD, CP and FASD have similar government service use patterns and how their service use patterns changed over time. Six Government of Alberta ministries’ data were linked (Health, Justice, Education, Advanced Education, Children’s Services and Community and Social Services). Individuals were defined as having ASD, CP or FASD if, at any point during the study period, they had a diagnostic code for one of three conditions (ASD, CP or FASD) from a health service (i.e., physician visits, or emergency room visits, or hospitalizations), or accessed disability support programs for ASD, CP or FASD. Results The results showed different service use patterns for the three conditions: (1) a higher proportion of children with ASD were students with special needs compared to children with FASD and CP; (2) a lower proportion of children with FASD received FSCD services compared to children with ASD and CP; (3) a higher proportion of children with FASD were involved in the Child Intervention system and were Income Support recipients compared to children with ASD and CP. Moreover, the study showed that there was a decrease in accessing services and programming from Persons with Development Disabilities (PDD) for young Albertans with ASD, CP and FASD from 2005/06 to 2010/11. In contrast, the use of another adult disability program that provides only financial assistance, Assured Income for Severely Handicapped, increased over time. Conclusion/Implications The use of population-based linked administrative data allows a comprehensive and comparative study for government service use patterns. The findings have implications for cross-ministry policy and program development, resource allocation, and service coordination and delivery to young Albertans with ASD, CP and FASD.

Introduction Linking administrative data provides valuable information about individuals using government services and can be very useful for policy-makers in improving and developing services and policies. The Child and Youth Data Laboratory (CYDL) links and analyses administrative data from Alberta Government ministries to provide evidence for policy and program development. Objectives and Approach Data from 20 programs of six Government of Alberta ministries (Advanced Education, Education, Health, Children’s Services, Community and Social Services, and Justice and Solicitor General) were linked anonymously. The data spans six years from 2005/06 to 2010/11 and consists of almost 50 million records corresponding to over 2 million unique Albertans aged 0 to 25 years. A data visualization tool called the Program Overlap Matrix summarises the overlap rates among the programs. It is comprised of a matrix of squares, where each cell represents the overlap between two programs. Results The Program Overlap Matrix is publically available at https://visualization.policywise.com/P2matrix/. It consists of overlap rates between programs in any study year (2005/06 to 2010/11), individual years, the first year vs. future years, and the last year vs. previous years which can be used to answer many policy-related questions such as: other service use (e.g., what other services do ESL students use?), over-represented programs (e.g., in what programs are Child Care Subsidy clients over-represented?), resilience (e.g., what is the proportion of Child Intervention clients in post-secondary institutions?), transitions (e.g., what types of services do students with special needs receive as they transition to adulthood?), and time trend (e.g., what types of services did Income Support clients receive in the past?) Conclusion/Implications The program overlap matrix is a powerful tool to discover relationships between programs. It is a useful instrument to inform public and policy-makers about the overlap rates between government programs. It can be used to answer a variety of policy-related questions.

Introduction The cultural revolution of data sharing is becoming a global movement. It allows for scientific replication and verification of research results, avoiding research duplication, and enabling greater transparency and knowledge mobilization with a relatively low cost. However, privacy protection and data security are critical concerns for human-subject related data sharing. Objectives and Approach In order to facilitate data sharing and engage various stakeholders to better inform policy and practice while protecting privacy, SAGE (Secondary Analysis to Generate Evidence) was established by PolicyWise for Children and Families. It is a collaborative data repository platform that connects stakeholders through secondary use of data. SAGE was built to link, manage, and share research data, community service data, and administrative data related to health and social well-being. Governance and technical processes are in place to ensure that data depositors are involved in decision-making, and data accessed by collaborators are secured and re-identification risks assessed. Results SAGE has been in operation for over a year. Through engagement with the research and non-profit communities, SAGE now offers ten data assets. Discovery is facilitated through well-documented metadata through NADA and Dataverse. Six new collaborative projects have been initiated through SAGE. SAGE is working actively with local non-profits to liberate data to generate evidence and collaborate with each other on common goals. SAGE has helped these organizations understand the legal and legislative barriers to data sharing, and build the technical capacity to further this goal. Discussions are underway with Alberta public entities on how SAGE can support the linkage and governance processes in the use of administrative data. Conclusion/Implications SAGE is putting the governance processes and security practices in place to fill a need for a facilitated data sharing model for sensitive data. SAGE is supporting the cultural shift towards data sharing and reuse by fostering trust and collaboration among researchers, non-profit and government ministries.

Reconstruction of critical size bone defects represents a major challenge in orthopaedic surgery. Insufficient angiogenesis is a limiting factor for engraftment of large-scale tissue transplants. Transplantation or stimulation of local mesenchymal stem cells (MSCs) represents a potential solution to enhance angiogenesis. We recently identified angiogenic properties for the Toll-like receptor (TLR) 2/6 agonist MALP-2 and now investigated if MALP-2 could be used to stimulate MSCs in order to promote angiogenesis in vitro and in vivo.Human MSCs from the bone marrow of healthy subjects were isolated, cultured and expanded in vitro and were shown to be positive for mesenchymal stem cells markers as well as for the MALP-2 receptors TLR2 and TLR6. MALP-2 directly enhanced migration but not proliferation of human MSCs. Conditioned medium from MALP-2 stimulated MSCs significantly increased proliferation, migration and tube formation of endothelial cells. Analysis of the conditioned medium from MSCs revealed that MALP-2 stimulation enhanced the secretion of several chemokines and growth factors including vascular endothelial growth factors (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Finally, we studied MALP-2 effects on MSCs in a sheep model of tissue engineering in vivo. Therefore, MSCs were isolated from the iliac crest of black head sheep and co-cultivated with MALP-2 ex vivo. Implantation of autologous MSCs within a scaffold cylinder into the M. latissimus dorsi significantly enhanced vessel density of these constructs after 6 months.We here present the first evidence that TLR2/6-dependent stimulation of MSCs promotes angiogenesis in vitro and in vivo offering a novel strategy for therapeutic angiogenesis, e.g., for tissue engineering of bone.

In fertile women, HOXA-10 and HOXA-11 expression rises during the luteal phase, with the peak occurring during the implantation window, and stays at a high level until the end of the cycle. We evaluated the transcript and protein levels of HOXA-10 and HOXA-11 in the endometria of patients with idiopathic infertility (n = 15) and control patients (n = 10). The amounts of mRNA were determined by reverse transcription and real-time quantitative PCR. The protein levels were evaluated by Western blotting analysis. Using immunohistochemical techniques, we compared the localization of HOXA-10 and HOXA-11 proteins in the implantation window between the study and control groups. We observed statistically significantly decreased HOXA-10 and HOXA-11 transcript levels (p = 0.003, p = 0.012 respectively) in infertile patients compared to controls. There was no significant decrease in HOXA-10 protein levels between these groups (p = 0.074). However, we observed a significantly higher level of HOXA-11 protein in the endometria of infertile patients compared to controls (p = 0.015). HOXA-10 and HOXA-11 proteins were localized in the nuclei of the endometrial stromal cells. Immunohistochemical analyses did not reveal differences between amounts of HOXA-10 and HOXA-11 protein levels in infertility and control groups. Our results suggest that HOXA-10 and HOXA-11 gene expression in the endometrium during the implantation window may not be altered in patients with idiopathic infertility. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 111–118)

The geometry of cavities in the surfaces of proteins facilitates a variety of biochemical functions. To better understand the biochemical nature of protein cavities, the shape, size, chemical properties, and evolutionary nature of functional and nonfunctional surface cavities have been exhaustively surveyed in protein structures. The rigidity of surface cavities, however, is not immediately available as a characteristic of structure data, and is thus more difficult to examine. Using rigidity analysis for assessing and analyzing molecular rigidity, this paper performs the first survey of the relationships between cavity properties, such as size and residue content, and how they correspond to cavity rigidity. Our survey measured a variety of rigidity metrics on 120,323 cavities from 12,785 sequentially non-redundant protein chains. We used VASP-E, a volume-based algorithm for analyzing cavity geometry. Our results suggest that rigidity properties of protein cavities are dependent on cavity surface area.

Increasing evidence suggests that smoking may increase the incidence of prosthesis-related complications after total hip arthroplasty (THA). We performed a meta-analysis of cohort studies to quantitatively evaluate the association between smoking and the risk of prosthesis-related complications after THA.Relevant articles published before August 15, 2014, were identified by searching the PubMed, EMBASE and Cochrane library databases. Pooled risk ratios (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated with either a fixed- or random-effects model.Six cohort studies, involving a total of 8181 participants, were included in the meta-analysis. Compared with the patients who never smoked, smokers had a significantly increased risk of aseptic loosening of prosthesis (summary RR=3.05, 95% CI: 1.42-6.58), deep infection (summary RR=3.71, 95% CI: 1.86-7.41) and all-cause revisions (summary RR=2.58, 95% CI: 1.27-5.22). However, no significant difference in the risk of implant dislocation (summary RR= 1.27, 95% CI: 0.77-2.10) or length of hospital stay (WMD=0.03, 95% CI: -0.65-0.72) was found between smokers and nonsmokers.Smoking is associated with a significantly increased risk of aseptic loosening of prosthesis, deep infection and all-cause revisions after THA, but smoking is not correlated with a risk of implant dislocation or the length of hospital stay after surgery.

The aim of the study was to investigate the effect of cyclic mechanical strain on differentiation markers in the presence or absence of dexamethasone. Human bone marrow stromal cells (BMSC) from seven donors (32.5±6.2 years) were cultivated with (D+) or without (D-) dexamethasone. A cyclic mechanical strain with an elongation of 2% (D+2; D-2) or 8% (D+8; D-8) was applied for three days with a stimulation time of three times two hours each day. Levels of alkaline phosphatase (ALP) and osteocalcin (OC) were compared after time intervals of four and seven days. mRNA expression of Collagen I, III and Cbfa1 was investigated after one, four, and seven days. ALP levels were significantly increased in the D+8 group after four and seven days (147.1±6.3%; p

For in vitro differentiation of bone marrow-derived mesenchymal stem cells/mesenchymal stromal cells into osteoblasts by 2-dimensional cell culture a variety of protocols have been used and evaluated in the past. Especially the external phosphate source used to induce mineralization varies considerably both in respect to chemical composition and concentration. In light of the recent findings that inorganic phosphate directs gene expression of genes crucial for bone development, the need for a standardized phosphate source in in vitro differentiation becomes apparent. We show that chemical composition (inorganic versus organic phosphate origin) and concentration of phosphate supplementation exert a severe impact on the results of gene expression for the genes commonly used as markers for osteoblast formation as well as on the composition of the mineral formed. Specifically, the intensity of gene expression does not necessarily correlate with a high quality mineralized matrix. Our study demonstrates advantages of using inorganic phosphate instead of β-glycerophosphate and propose colorimetric quantification methods for calcium and phosphate ions as cost- and time-effective alternatives to X-ray diffraction and Fourier-transform infrared spectroscopy for determination of the calcium phosphate ratio and concentration of mineral matrix formed under in vitro-conditions. We critically discuss the different assays used to assess in vitro bone formation in respect to specificity and provide a detailed in vitro protocol that could help to avoid contradictory results due to variances in experimental design.

Abstract Introduction Blunt cardiac rupture is an exceedingly rare injury. Case presentation We report a case of blunt cardiac trauma in a 43-year-old Caucasian German mother with pectus excavatum who presented after a car accident in which she had been sitting in the front seat holding her two-year-old boy in her arms. The mother was awake and alert during the initial two hours after the accident but then proceeded to hemodynamically collapse. The child did not sustain any severe injuries. Intraoperatively, a combined one-cm laceration of the left atrium and right ventricle was found. Conclusion Patients with pectus excavatum have an increased risk for cardiac rupture after blunt chest trauma because of compression between the sternum and spine. Therefore, patients with pectus excavatum and blunt chest trauma should be admitted to a Level I Trauma Center with a high degree of suspicion.

Abstract Background Few data are available in Afghanistan to shape national military force health practices, particularly with regard to sexually-transmitted infections (STIs). We measured prevalence and correlates of HIV, syphilis, herpes simplex 2 virus (HSV-2), and hepatitis C virus (HCV) among Afghan National Army (ANA) recruits. Methods A cross-sectional sample of male ANA recruits aged 18–35 years were randomly selected at the Kabul Military Training Center between February 2010 and January 2011. Participants completed an interviewer-administered questionnaire and serum-based rapid testing for syphilis and hepatitis C virus antibody on-site; HIV and HSV-2 screening, and confirmatory testing were performed off-site. Prevalence of each infection was calculated and logistic regression analysis performed to identify correlates. Results Of 5313 recruits approached, 4750 consented to participation. Participants had a mean age of 21.8 years (SD±3.8), 65.5% had lived outside Afghanistan, and 44.3% had no formal education. Few reported prior marijuana (16.3%), alcohol (5.3%), or opiate (3.4%) use. Of sexually active recruits (58.7%, N = 2786), 21.3% reported paying women for sex and 21.3% reported sex with males. Prevalence of HIV (0.063%, 95% CI: 0.013- 0.19), syphilis (0.65%, 95% CI: 0.44 – 0.93), and HCV (0.82%, 95% CI: 0.58 – 1.12) were quite low. Prevalence of HSV-2 was 3.03% (95% CI: 2.56 - 3.57), which was independently associated with age (Adjusted Odds Ratio (AOR) = 1.04, 95% CI: 1.00 - 1.09) and having a television (socioeconomic marker) (AOR = 1.46, 95% CI: 1.03 – 2.05). Conclusion Though prevalence of HIV, HCV, syphilis, and HSV-2 was low, sexual risk behaviors and intoxicant use were present among a substantial minority, indicating need for prevention programming. Formative work is needed to determine a culturally appropriate approach for prevention programming to reduce STI risk among Afghan National Army troops.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions 1-6 . In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s 1/2 2p 3/2  J = 2 → 1s 1/2 2s 1/2  J = 1 intrashell transition in the heaviest two-electron ion (U 90+ ) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain., (© 2024. The Author(s).)

We report on the design and performance of a wavelength-dispersive type spectrometer based on the von Hamos geometry. The spectrometer is equipped with a segmented-type crystal for x-ray diffraction and provides an energy resolution in the order of 0.25 eV and 1 eV over an energy range of 8000 eV-9600 eV. The use of a segmented crystal results in a simple and straightforward crystal preparation that allows to preserve the spectrometer resolution and spectrometer efficiency. Application of the spectrometer for time-resolved resonant inelastic x-ray scattering and single-shot x-ray emission spectroscopy is demonstrated.

The development of a wavelength-dispersive spectrometer for microfluorescence analysis at the X-ray Microscopy ID21 beamline of the European Synchrotron Radiation Facility (ESRF) is reported. The spectrometer is based on a polycapillary optic for X-ray fluorescence collection and is operated in a flat-crystal geometry. The design considerations as well as operation characteristics of the spectrometer are presented. The achieved performances, in particular the energy resolution, are compared with the results of Monte Carlo simulations. Further improvement in the energy resolution, down to approximately eV range, by employing a double-crystal geometry is examined. Finally, examples of applications requiring both spatial and spectral resolutions are presented.

The possibility for the induction of long-lasting synaptic plasticity by the potassium channel blocker tetraethylammonium (TEA) was investigated in adult rat motor cortex in vitro. Brief application of TEA (25 mM) resulted in a long-term potentiation (LTP(K)) of field potentials evoked in layer V intralaminar connections by 59+/-17%. This effect could be prevented by preincubation with nifedipine, a voltage-dependent calcium channel blocker (20 microM), but not by N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV, 100 microM). LTP(K) induction resulted in a smaller relative potentiation of a response to the second pulse of a pair (60 ms interpulse interval). These results indicate a potential of layer V horizontal connections for a NMDA receptor-independent form of persistent synaptic enhancement.