Search

Change in the fundamental period of a structure during strong earthquakes (the change from the linear to nonlinear period) can be a good indicator of the damage level of the structure. Given that the incremental dynamic analysis (IDA) has played an effective role in investigating the nonlinear behavior of engineering structures, in this article, we try to use the nonlinear (fundamental) period of the structure as a damage criterion in IDA curves for multi-degree-of-freedom (MDOF) systems, which was previously introduced for single-degree-of-freedom (SDOF) systems. In this regard, the nonlinear period at different seismic intensity levels and the collapse threshold period of steel moment-resisting frame (SMRF) structures are studied by considering the spectral shape indicators of earthquake records, and the strength and stiffness deterioration parameter. For this purpose, three regular SMRF buildings with 3, 10, and 20 stories as representatives of low-, medium-, and high-rise buildings are investigated. Fast Fourier transform (FFT) is used to calculate the nonlinear period of the structures, and the eigenvalue analysis method by using the instantaneous characteristics (stiffness) of the structure is implemented to confirm it. To perform the time history analysis, the bilinear modified Ibarra-Medina-Krawinkler (IMK) model is used in modeling the structural hysteretic behavior. One of the important applications of the nonlinear period of structures is in the process of scaling records for time history analysis. This study intends to evaluate the scaling period range by computing the nonlinear period based on the records scaled to the design spectrum. The results demonstrate that the spectral shape parameters and the structural deterioration affect the nonlinear period of the case study structures in a regular manner, while the effect of the mentioned spectral parameters on the collapse threshold period does not follow a clear trend. Also, it is shown that the upper bound period (1.5 or 2 ) mode period for scaling ground motions is too conservative for structures with a special SMRF load-resisting system having a low deterioration. [ABSTRACT FROM AUTHOR]

This article describes minimally invasive treatments for managing chronic low back pain (LBP) related to lumbar spinal stenosis, facetogenic LBP, vertebrogenic LBP, or discogenic LBP. We also propose a clinical decision-making tool to guide clinicians in appropriate patient selection for various treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: The influenza virus is a global problem for humanity due to its high variability. Research is ongoing worldwide to develop a so-called universal vaccine to control this infection. Chimeric proteins are one of the platforms for the development of such a vaccine. Within this platform, the least variable proteins of the influenza virus are used so that the vaccine can protect against many strains. In this work, we investigated the possibility of enhancing the efficacy of a candidate vaccine protein by introducing an additional fragment of influenza virus into the construct. Antigen-specific antibody and T-cell immune responses in mice to vaccination were evaluated. Animals were challenged with a lethal dose of influenza viruses to assess the efficacy of the candidate vaccine proteins. It was found that the introduction of new conserved antigens into the construct affects the formation of antibodies to other vaccine antigens but does not affect the protective efficacy of the candidate protein. Conserved influenza virus proteins, such as the hemagglutinin stem domain (HA2), nucleoprotein (NP), and matrix protein (M), are the main targets in the development of universal influenza vaccines. Previously, we constructed a recombinant vaccine protein Flg-HA2-2-4M2ehs containing the extracellular domain of the M2 protein (M2e) and the aa76–130 sequence of the second HA subunit as target antigens. It demonstrated immunogenicity and broad protection against influenza A viruses after intranasal and parenteral administration. This study shows that CD8+ epitopes of NP, inserted into a flagellin-fused protein carrying M2e and HA2, affect the post-vaccination immune humoral response to virus antigens without reducing protection. No differences were found between the two proteins in their ability to stimulate the formation of follicular Th in the spleen, which may contribute to a long-lasting antigen-specific humoral response. The data obtained on Balb/c mice suggest that the insertion of CTL NP epitopes into the flagellin-fused protein carrying M2e and HA2 reduces the antibody response to M2e and A/H3N2. In C57Bl6 mice, this stimulates the formation of NP-specific CD8+ Tem and virus-specific mono- and multifunctional CD4+ and CD8+ Tem in the spleen and completely protects mice from influenza virus subtypes A/H1N1pdm09 and A/H3N2. [ABSTRACT FROM AUTHOR]

Over the past two decades, the emergency nurse practitioner (ENP) role has significantly enhanced emergency care in the United States. With the increasing complexity of emergency care, ENPs have expanded into nontraditional settings, necessitating regulatory updates to maintain patient safety. The Consensus Model for Advanced Practice Registered Nurse Regulation has influenced ENP practice, yet consistent regulatory recognition is still needed due to the marked evolution in ENP practice. Despite collaborative efforts to prepare the ENP workforce and ensure competency through standardized education, certification, and licensure, recent unethical publications and skewed statistics have threatened the specialty's progress. Addressing these challenges is crucial for advancing the ENP role and ensuring high-quality emergency care delivery. [ABSTRACT FROM AUTHOR]

Objectives: This study assessed the use and perceptions of physician associates/assistants (PAs) and NPs at liver transplant centers and sought to determine their financial effect. Methods: Leaders of liver transplant programs performing 25 or more transplants in 2020 were contacted to complete an 11-question survey about the role and effect of PAs and NPs in liver transplant. A single-center retrospective analysis compared length of stay (LOS) and readmission rates for primary liver transplants and simultaneous liver-kidney transplants before and after a dedicated PA team was established. Chi-square and t-test analyses were performed. Results: The survey achieved a 77% response rate, and 98% of institutions reported using PAs and NPs. The single-center study found the mean LOS post-transplant was significantly shorter in the post-PA cohort (P = .0005). No significant difference was found in 30-day readmission rates. Conclusions: PAs and NPs are used broadly across the postliver transplant care continuum. Using LOS as a surrogate financial marker suggests that a dedicated PA and NP team may contribute to cost savings. [ABSTRACT FROM AUTHOR]

Current influenza vaccines mainly induce neutralizing antibodies against the highly variable surface antigen hemagglutinin and require annual manufacturing and immunization. Different from surface antigens, intracellular nucleoprotein (NP) is highly conserved and has been an attractive target to develop universal T cell vaccines against influenza. Yet, influenza NP protein mainly induces humoral immune responses and lacks the ability to induce potent cytotoxic T lymphocyte (CTL) responses, key for the success of universal T cell vaccines. This study compared CpG 1018 and AddaVax to enhance recombinant NP-induced CTL responses and protection in murine models. CpG 1018 was explored to boost intradermal NP immunization, while AddaVax was explored to boost intramuscular NP immunization due to the high risk of AddaVax adjuvant to induce significant local reactions following intradermal delivery. We found CpG 1018 was highly effective to enhance NP-induced humoral and cellular immune responses superior to AddaVax adjuvant. Furthermore, CpG 1018 potentiated Th1-biased antibody responses, while AddaVax enhanced Th1/Th2-balanced antibody responses. CpG 1018 significantly enhanced IFNγ-secreting Th1 cells, while AddaVax adjuvant significantly increased IL4-secreting Th2 cells. Influenza NP immunization in the presence of CpG 1018 induced significant protection against lethal viral challenges, while influenza NP immunization in the presence of AddaVax failed to elicit significant protection. Our data validated CpG 1018 as an effective adjuvant to enhance influenza NP-induced CTL responses and protection.

Engineered nanoparticles (NPs) composed of elements such as silica and titanium, smaller than 100 nm in diameter and their aggregates, are found in consumer products such as cosmetics, food, antimicrobials and drug delivery systems, and oral health products such as toothpaste and dental materials. They may also interact accidently with epithelial tissues in the intestines and oral cavity, where they can aggregate into larger particles and induce inflammation through pathways such as inflammasome activation. Persistent inflammation can lead to precancerous lesions. Both the particles and lesions are difficult to detect in biopsies, especially in clinical settings that screen large numbers of patients. As diagnosis of early stages of disease can be lifesaving, there is growing interest in better understanding interactions between NPs and epithelium and developing rapid imaging techniques that could detect foreign particles and markers of inflammation in epithelial tissues. NPs can be labelled with fluorescence or radioactive isotopes, but it is challenging to detect unlabeled NPs with conventional imaging techniques. Different current imaging techniques such as synchrotron radiation X-ray fluorescence spectroscopy are discussed here. Improvements in imaging techniques, coupled with the use of machine learning tools, are needed before diagnosis of particles in biopsies by automated imaging could move usefully into the clinic.

For quadratic word equations, there exists an algorithm based on rewriting rules which generates a directed graph describing all solutions to the equation. For regular word equations – those for which each variable occurs at most once on each side of the equation – we investigate the properties of this graph, such as bounds on its diameter, size, and DAG-width, as well as providing some insights into symmetries in its structure. As a consequence, we obtain a combinatorial proof that the problem of deciding whether a regular word equation has a solution is in NP. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cellmediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development. [ABSTRACT FROM AUTHOR]

Copyright of Eurasian Journal of Ecology is the property of Al-Farabi Kazakh National University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In our prior investigations, we elucidated the role of the tryptophan-to-tyrosine substitution at the 61st position in the nonstructural protein NSsW61Y in diminishing the interaction between nonstructural proteins (NSs) and nucleoprotein (NP), impeding viral replication. In this study, we focused on the involvement of NSs in replication via the modulation of autophagosomes. Initially, we examined the impact of NP expression levels, a marker for replication, upon the infection of HeLa cells with severe fever thrombocytopenia syndrome virus (SFTSV), with or without the inhibition of NP binding. Western blot analysis revealed a reduction in NP levels in NSsW61Y-expressing conditions. Furthermore, the expression levels of the canonical autophagosome markers p62 and LC3 decreased in HeLa cells expressing NSsW61Y, revealing the involvement of individual viral proteins on autophagy. Subsequent experiments confirmed that NSsW61Y perturbs autophagy flux, as evidenced by reduced levels of LC3B and p62 upon treatment with chloroquine, an inhibitor of autophagosome–lysosome fusion. LysoTracker staining demonstrated a decrease in lysosomes in cells expressing the NS mutant compared to those expressing wild-type NS. We further explored the mTOR-associated regulatory pathway, a key regulator affected by NS mutant expression. The observed inhibition of replication could be linked to conformational changes in the NSs, impairing their binding to NP and altering mTOR regulation, a crucial upstream signaling component in autophagy. These findings illuminate the intricate interplay between NSsW61Y and the suppression of host autophagy machinery, which is crucial for the generation of autophagosomes to facilitate viral replication. [ABSTRACT FROM AUTHOR]

In this paper, we continue the investigation of graph-based reaction systems. We extend the notion by input and output states as well as admitted context sequences to model explicitly input–output relations and decision problems on the inputs. Moreover, we combine extended graph-based reaction systems into families to cover infinite input–output relations and decision problems on infinite sets of graphs. This is used to model NP-problems on graphs and reductions between them as well as to prove their correctness. [ABSTRACT FROM AUTHOR]

Objective: To analyze the expression levels of serum brain-derived neurotrophic factor (BDNF) and Toll receptor 4 (TLR4) in patients with different types of neuropathic pain (NP) and their diagnostic value. Methods: A total of 80 NP patients and 100healthy subjects admitted to our hospital from May 2021 to May 2022 were selected as the study subjects. NP patients were included in the NP group, and healthy subjects were included in the control group. The neuropathic pain scale (NPS) was used to distinguish the nature of pain in the NP group (20 cases of dull pain, 28 cases of discomfort, 17 cases of deep pain, and 15 cases of body surface pain) . The expression levels of serum BDNF and TLR4 in the two groups of patients and patients with different types of pain in the NP group were detected. Bivariate Spearman correlation was used to test the correlation between serum BDNF, TLR4 and different types of pain in NP.At the same time, a multivariate Logistic model was established to analyze the influencing factors of different types of pain in NP and compare their diagnostic efficacy. Results: Compared with the control group, the expression level of serum BDNF in NP group was lower,and the expression level of TLR4 was higher (P＜0.05) . There were significant differences in the expression levels of serum BDNF and TLR4 in NP dull pain, discomfort, deep pain and body surface pain (P＜0.05) . Serum BDNF was negatively correlated with NP dull pain,discomfort, deep pain and body surface pain, while serum TLR4 was positively correlated with NP dull pain, discomfort, deep pain and body surface pain (P＜0.05) . Logistic multivariate analysis showed that BDNF and TLR4 were independent risk factors for NP dull pain,discomfort, deep pain and body surface pain (P＜0.05) . The ACU of serum BDNF, TLR4 and BDNF + TLR4 for NP dull pain, discomfort,deep pain and body surface pain were all＞0.70. Conclusion: Serum BDNF and TLR4 are associated with NP of blunt pain, discomfort,deep pain, and body surface pain. They have high sensitivity and specificity in the diagnosis of different NP properties, which is beneficial to provide reference for clinical treatment. [ABSTRACT FROM AUTHOR]

We consider the vertex proper coloring problem for highly restricted instances of geometric intersection graphs of line segments embedded in the plane. Provided a graph in the class UNIT-PURE-k-DIR, corresponding to intersection graphs of unit length segments lying in at most k directions with all parallel segments disjoint, and provided explicit coordinates for segments whose intersections induce the graph, we show for k = 4 that it is NP-complete to decide if a proper 3-coloring exists, and moreover, # P -complete under many-one counting reductions to determine the number of such colorings. In addition, under the more relaxed constraint that segments have at most two distinct lengths, we show these same hardness results hold for finding and counting proper k - 1 -colorings for every k ≥ 5 . More generally, we establish that the problem of proper 3-coloring an arbitrary graph with m edges can be reduced in O m 2 time to the problem of proper 3-coloring a UNIT-PURE-4-DIR graph. This can then be shown to imply that no 2 o n time algorithm can exist for proper 3-coloring PURE-4-DIR graphs under the Exponential Time Hypothesis (ETH), and by a slightly more elaborate construction, that no 2 o n time algorithm can exist for counting the such colorings under the Counting Exponential Time Hypothesis (#ETH). Finally, we prove an NP-hardness result for the optimization problem of finding a maximum order proper 3-colorable induced subgraph of a UNIT-PURE-4-DIR graph. [ABSTRACT FROM AUTHOR]

Crimean‐Congo hemorrhagic fever virus (CCHFV) is classified among top 10 priority pathogens by World Health Organization. CCHFV belongs to Bunyaviridae family and negative sense ssRNA genome composed of three RNA segments: L, M, and S. RNA viruses show higher mutation rate as compared to DNA viruses. To gain deeper understanding of impact of point mutations in CCHFV M and S segment, mutation profiling, homology modeling, and molecular dynamic (MD) simulation were performed. Structural glycoproteins (glycoprotein C [Gc] and glycoprotein N [Gn]) of CCHFV are important for host–virus interaction and genome packaging, whereas CCHFV nucleoprotein (NP) is crucial for viral replication. Hence, current study is focused on evaluation of eight mutations in structural glycoproteins (Gc: 7 and Gn: 1) of M segment and seven mutations in NP of S segment. All these mutations were highly frequent, with mutation frequency between 0.81 and 1.0 and found to be persistent in the recent strains of CCHFV. Solubility analysis predicted that selected point mutations reduce solubility of Gc protein and increase solubility of Gn and NP proteins. MD simulation study deciphered that A1046V and G1158E in Gc protein, I778T in Gn protein, and H195R in NP protein displayed large deviation and fluctuation, and affected intramolecular interactions. In conclusion, we observed that point mutations could impact structure, stability, and host–virus interaction of protein, and might lead to evolution of new strains for better survival and drug resistance. [ABSTRACT FROM AUTHOR]

Host factors play important roles in influenza A virus (IAV) replication. In order to identify novel host factors involved in IAV replication, we compared the differentially expressed genes in A549 cells after IAV infection. We found that lncRNA lnc-RPS6P3 was up-regulated upon viral infection and poly(I:C) and IFN-β treatment, indicating it was an interferon-stimulated gene. Functional analysis demonstrated that overexpression of lnc-RPS6P3 inhibited IAV replication while knockdown of lnc-RPS6P3 promoted viral infection in A549 cells. Lnc-RPS6P3 inhibited both transcription and replication of IAV. Further study showed that lnc-RPS6P3 interacted with viral NP and interfered with NP self-oligomerization and, consequently, inhibited vRNP activity. In addition, lnc-RPS6P3 interacted with viral NS1 and reduced the interaction of NS1 and RIG-I; it also attenuated the inhibitory effect of NS1 on IFN-β stimulation. In conclusion, we revealed that lnc-RPS6P3 is an interferon-stimulated gene that inhibits IAV replication and attenuates the inhibitory effect of NS1 on innate immune response. [ABSTRACT FROM AUTHOR]

Influenza A viruses (IAVs) possess a segmented genome consisting of eight viral RNAs (vRNAs) associated with multiple copies of viral nucleoprotein (NP) and a viral polymerase complex. Despite the crucial role of RNA structure in IAV replication, the impact of NP binding on vRNA structure is not well understood. In this study, we employed SHAPE chemical probing to compare the structure of NS and M vRNAs of WSN IAV in various states: before the addition of NP, in complex with NP, and after the removal of NP. Comparison of the RNA structures before the addition of NP and after its removal reveals that NP, while introducing limited changes, remodels local structures in both vRNAs and long-range interactions in the NS vRNA, suggesting a potentially biologically relevant RNA chaperone activity. In contrast, NP significantly alters the structure of vRNAs in vRNA/NP complexes, though incorporating experimental data into RNA secondary structure prediction proved challenging. Finally, our results suggest that NP not only binds single-stranded RNA but also helices with interruptions, such as bulges or small internal loops, with a preference for G-poor and C/U-rich regions. [ABSTRACT FROM AUTHOR]

The research examines how silica aerogel and paraffin behaved as phase-change materials in thermal energy storage systems using CuO nanoparticles. The significance is in meeting the need for effective energy storage techniques in response to increasing air pollution levels and rising conventional fuel expenses. The study used molecular dynamics simulations to examine the atomic and thermal properties of a silica aerogel/paraffin/CuO nanostructure within a cylindrical duct. This modeling setup allows for a comprehensive exploration of the interactions among different materials within the thermal energy storage system, offering insights into their combined effects on thermal performance and efficiency. Key results include a nanostructure reaching a maximum (Max) velocity (Velo), temperature (Temp), and density of 0.0096 Å/fs, 626 K, and 0.1365 atom/Å3. The thermal performance represented a sample exhibiting a thermal conductivity and heat flux of 1.74 W/m.K and 66.43 W/m2. The significance of this study utilizing the proposed model lied in its potential to advance our understanding of thermal energy storage systems and their applications. Through an examination of the atomic and thermal behavior of silica aerogel/PCM when CuO nanoparticles were present in a cylinder duct, this study made a valuable contribution to the advancement of energy storage solutions that were both more efficient and effective. The findings of this study may serve as a potential for innovative developments in thermal energy storage and aid in the creation of more environmentally friendly and functional energy solutions.

The purpose of this study was to investigate the initiation of autophagy activation and apoptosis in nucleus pulposus cells under temporary compression (TC) and sustained compression (SC) to identify ideal research approaches in intervertebral disc degeneration. Various techniques were used: radiography (X-ray), magnetic resonance imaging (MRI), transmission electron microscope (TEM), H&E staining, Masson's trichrome staining, immunohistochemistry (IHC) (LC3, beclin-1, and cleaved caspase-3), and real-time polymerase chain reaction (RT-qPCR) for autophagy-related (beclin-1, LC3, and P62) and apoptosis-related (caspase-3 and PARP) gene expression analysis. X-ray and MRI revealed varying degrees of disc degeneration, ranging from moderate to severe in both groups. The severity was directly linked to compression duration, with SC resulting in notably severe central NP cell degeneration. Surprisingly, TC also caused similar, though less severe, degeneration. Elevated expression of LC3 and beclin-1 was identified after 6 weeks, but it notably declined after 12 weeks. Central NP cells in both groups exhibited increased expression of cleaved caspase-3 that was positively correlated with the duration of SC. TC showed fewer apoptotic markers compared to SC. LC3, beclin-1, and P62 mRNA expression peaked after 6 weeks and declined after 12 weeks in both groups. Cleaved caspase-3 and PARP expression peaked in SC, positively correlating with longer compression duration, while TC showed lower levels of apoptosis gene expression. Furthermore, TEM results revealed different events of the autophagic degradation process after 2 weeks of compression. TCmay be ideal for studying early triggered autophagy-mediated degeneration, while SC may be ideal for studying late or slower-triggered apoptosis-mediated degeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: Heart disease is the leading cause of death worldwide. There is a need to develop a drug delivery system that can specifically target injured hearts and deliver therapeutic agents. Nanoparticles are a promising option for targeted drug delivery in both preclinical and clinical studies. However, the current nanoparticle-based drug delivery system does not have enough specificity in targeting the cardiac tissue. In this study, we have designed cardiac targeting peptides that focus on the molecules present in the cardiomyocyte membrane. Data from cell and animal studies have shown that when nanoparticles are conjugated with these peptides, their binding affinity to cardiomyocytes significantly improves. Therefore, we are developing a targeting system that can be utilized to deliver therapeutic compounds specifically to cardiomyocytes for the treatment of heart diseases. Background: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. Methods: We created three linear peptides, each consisting of 16–24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. Results: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. Conclusions: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effect of an inpatient physician associate/assistant (PA) and NP program on consult volume, length of stay (LOS), and ED returns. Methods: A retrospective observational study of 4,118 orthopedic ED consults was conducted from January 2017 to March 2022. Univariate statistics were used to evaluate outcomes between cohorts and multivariate regression to evaluate the odds of an LOS of less than 24 hours. Results: After implementation of the PA and NP program, surgeon consults steadily declined and orthopedic consults increased markedly. Statistically significant differences were found in LOS of less than 24 hours and ED arrival-todischarge time. Adjusting for case mix, patients were 47% more likely to be discharged within 24 hours. Survey results noted that more than 80% of surgeons felt on-call workload, disruptions to clinic and surgical schedules decreased, and quality of care increased. Conclusions: Implementation of an inpatient PA and NP program reduced orthopedic surgeon consults and hospital LOS while improving surgeon satisfaction with on-call workload, schedule disruptions, and quality of care. [ABSTRACT FROM AUTHOR]

General practitioners (GPs) are the cornerstone of primary healthcare in the Netherlands. As a national strategy, physician associates/assistants (PAs) and NPs were introduced to address growing healthcare demand. In this study, four representative practices were analyzed quantitatively and qualitatively--two solo practices with a PA or NP and two group practices with a PA or NP. A reference group of GPs served as experts. The annual encounters per full-time GP averaged 6,839; for the NPs, 2,636; and the PAs, 4,926. Billable services were 70% to 100%, averaging 71% for NPs and 85% for PAs, and in three of the four practices, the employment of the NP or PA was cost-efficient. The qualitative data show that PAs and NPs contribute to general practice, easing the workload so that the GP has more time for complex patients. PA and NP employment was financially beneficial in 75% of cases. [ABSTRACT FROM AUTHOR]

Nucleoprotein (NP) and matrix protein 1 (M1) are highly conserved among influenza A viruses and have been attractive targets to develop vaccines to elicit cross-reactive cytotoxic T lymphocytes (CTLs). Yet, external antigens are often presented on major histocompatibility complex class II molecules and elicit humoral immune responses. In this study, we present a physical radiofrequency adjuvant (RFA) to assist recombinant NP and M1 to elicit potent CTL responses. We found recombinant NP/M1 immunization in the presence of RFA could elicit potent anti-NP CTLs and confer significant protection against homologous viral challenges, while NP/M1 immunization alone failed to elicit significant CTL responses or confer significant protection. Interestingly, RFA failed to elicit potent anti-M1 CTL responses or anti-NP or anti-M1 antibody responses. Different from RFA, AddaVax adjuvant was found to significantly increase NP-specific antibody responses but not CTLs. NP/M1 immunization in the presence of RFA or AddaVax similarly reduced body weight loss, while only the former significantly increased the survival. We further found NP/M1 immunization in the presence of RFA did not significantly increase serum IL-6 release (a systemic inflammatory mediator) and rather reduced serum IL-6 release after boost immunization. NP/M1 immunization in the presence of RFA did not induce significant local reactions or increase body temperature of mice. The high potency and safety strongly support further development of RFA-based recombinant NP/M1 vaccine to elicit cross-protective immunity.

Influenza A viruses (IAVs) continue to cause tremendous economic losses to the global animal industry and respiratory diseases and deaths among humans. The nuclear import of the vRNP complex, composed of polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), polymerase acidic protein (PA), nucleoprotein (NP), and viral RNA, is essential for the efficient replication of IAV. Host factors involved in this process can be targeted for the development of countermeasures against IAV infection. Here, we found that Ankyrin Repeat and BTB Domain Containing 1 (ABTB1) promotes the replication of IAV, and positively regulates the nuclear import of the vRNP complex. ABTB1 did not interact directly with NP, indicating that ABTB1 plays an indirect role in facilitating the nuclear import of the vRNP complex. Immunoprecipitation and mass spectrometry revealed that Tripartite Motif Containing 4 (TRIM4) interacts with ABTB1. We found that TRIM4 relies on its E3 ubiquitin ligase activity to inhibit the replication of IAV by targeting and degrading NP within the incoming vRNP complex as well as the newly synthesized NP. ABTB1 interacted with TRIM4, leading to TRIM4 degradation through the proteasome system. Notably, ABTB1-mediated degradation of TRIM4 blocked the effect of TRIM4 on NP stability, and largely counteracted the inhibitory effect of TRIM4 on IAV replication. Our findings define a novel role for ABTB1 in aiding the nuclear import of the vRNP complex of IAV by counteracting the destabilizing effect of TRIM4 on the viral NP protein.

This study investigates a curious Adjective-Prepositional Phrase sequence (the A-PP string) found in coordination contexts. Investigations into the distribution of this A-PP string reveal that the A-PP string is possible only in coordination contexts and is restricted to cases where N undergoes across-the-board (ATB) movement. We point out that the distribution of the A-PP string is similar to that of Gapping observed in the verbal domain. Thus, we argue that the A-PP string is an instance of Gapping in the nominal domain, and that Gapping-like strings can be produced by an ATB-movement derivation. Based on this data from the nominal domain, we make an argument supporting the ATB-movement derivation of Gapping broadly. Furthermore, this study sheds new light on the nature of N-movement within DP in English. Previous studies have argued against N-movement in English. We demonstrate that the distribution of the A-PP string depends on the availability of ATB-N-movement. In other words, if N-movement is not available in English, we cannot capture the properties of the A-PP string. Thus, this study makes a new argument for N-movement within DP in English based on the distribution of the A-PP string. [ABSTRACT FROM AUTHOR]

* OBJECTIVE: We aimed to analyze the effects and dose-response relationship of the most effective exercises for improving pain and disability in people with chronic nonspecific neck pain. UDESIGN: Intervention systematic review with meta-analysis. * LITERATURE SEARCH: We searched the PubMed, PEDro, and CENTRAL databases from their inception to September 30, 2022. USTUDY SELECTION CRITERIA: We included randomized controlled trials that involved people with chronic neck pain adopting a longitudinal exercise intervention and assessed one pain and/ or disability outcome. * DATA SYNTHESIS: Restricted maximum-likelihood random-effects meta-analyses were modeled separately for resistance, mindfulness-based, and motor control exercises; standardized mean differences (Hedge's g, standardized mean difference [SMD]) were effect estimators. Meta-regressions (dependent variable: effect sizes of the interventions; independent variables: training dose and control group effects) were conducted to explore the dose-response relationship for therapy success of any exercise type. * RESULTS: We included 68 trials. Compared to true control, effects on pain and disability were significantly larger for resistance exercise (pain: SMD, -1.27; 95% confidence interval [CI]: -2.26, -0.28; I² = 96%; disability: SMD, -1.76; 95% CI: -3.16, -0.37; I² = 98%), motor control exercise (pain: SMD, -2.29; 95% CI: -3.82, -0.75; I² = 98%; disability: SMD, -2.42; 95% CI: -.38, -1.47; I² = 94%), and Yoga/Pilates/Tai Chi/Qui Gong exercise (pain: SMD, 1.91; 95% CI: -3.28, -0.55; I² = 96%; disability: SMD, -0.62; 95% CI: -0.85, -0.38; I² = 0%). Yoga/Pilates/Tai Chi/Qui Gong exercise was more effective than other exercises (SMD, -0.84; 95% CI: -1.553, -0.13; I² = 86%) for reducing pain. For disability, motor control exercise was superior to other exercises (SMD, -0.70; 95% CI: -1.23, -0.17; I² = 98%). There was no dose-response relationship for resistance exercise (R² = 0.32). Higher frequencies (estimate = -0.10) and longer durations (estimate = -0.11) of motor control exercise had larger effects on pain (R² = 0.72). Longer sessions (estimate = -0.13) of motor control exercise had larger effects on disability (R² = 0.61). UCONCLUSION: Resistance, mindfulness-based, and motor control exercises were effective for reducing neck pain (very low-- to moderate-certainty evidence). Higher frequencies and longer duration of sessions had a significant effect on pain for motor control exercise. [ABSTRACT FROM AUTHOR]

To maximize cost-effective care and evaluate the use of physician associates/assistants (PAs) and NPs in an academic inpatient setting, we investigated the effect of streamlining care by using a common PA position between two neurosurgery groups. Trauma registry data were obtained and analyzed to gain insight into hospital length of stay (LOS) and clinical outcomes before and after implementing this new position. The average hospital LOS was reduced for less severely injured patients, and the time to initiation of venous thromboembolism prophylaxis decreased for injured neurosurgical patients. These results indicate the successful facilitation of time-sensitive, value-based healthcare for this specific clinical population at our Level 2 trauma center. [ABSTRACT FROM AUTHOR]

Information on the employment of patient-care clinicians is needed for policy planning and human resource management. The 2021 Bureau of Labor Statistics (BLS) employment data were probed for occupational settings of 698,700 physicians and surgeons, 246,690 NPs, and 139,100 physician associates/assistants (PAs). These three healthcare professionals accounted for about 1.1 million medical and surgical clinicians serving a US population of 331.5 million. Clinician demographics differ--in 2021, the median age of physicians was 45 years; NPs, 43 years; and PAs, 39 years. The largest employment location is "office of a physician" (physician, 53%; NP, 47%; PA, 51%), followed by hospitals (physician, 25%; NP, 25%; PA, 23%), and outpatient centers (physician, 4%; NP, 9%; PA, 10%). The 10-year job outlook predicts physician growth at 3%, NPs at 46%, and PAs at 28%. NP and PA employment is growing more than that of physicians because of constrained physician postgraduate education funding. Other factors influencing employment changes include medical practice mergers, the rising value of team-based care, the cost of new medical schools, and task shifting. [ABSTRACT FROM AUTHOR]

Background: The prevalence and cost of type 2 diabetes mellitus (T2DM) is rising. Diabetes care should be individualized based on patient risk factors and goals. Professional continuous glucose monitoring (CGM) is a tool for primary care providers to assist patients with diabetes management. Local Problem: Nurse practitioners at an outpatient primary care practice began using CGM in patients with T2DM in 2019 to guide treatment due to the high number of patients not reaching glucose targets. There was no policy in place to guide patient selection for CGM. Methods: This quality improvement (QI) project, conducted in an outpatient primary care clinic, evaluated the effect of retrospective CGM use in patients with T2DM through a retrospective chart review to create a policy for use. Interventions: Hemoglobin A1c (HbA1c) measurements pre-CGM and post-CGM use were compared. CGM reports were evaluated for the presence of hypoglycemia. Additionally, number of times a patient used CGM between HbA1c laboratory examinations as well as insulin status were determined by reviewing the electronic health record. Results: Patients using CGM for HbA1c higher than goal (n = 60) noted a 1.01% decrease in HbA1c (p <.01). The decrease was similar regardless of exogenous insulin status. Hypoglycemia was detected in 54.3% of patients (n = 44), including 45% (n = 27) of those with elevated HbA1c levels. Conclusions: Retrospective CGM is a cost-effective tool to individualize management of patients with T2DM in primary care. A policy was created to guide CGM use in patients not reaching glucose goals and those with concern for hypoglycemia. [ABSTRACT FROM AUTHOR]

Purpose: Postgraduate clinical training (PCT) has been available to PAs since the 1970s and to NPs since at least 2007. Some programs now enroll PAs and NPs. Although this new training model appears to be expanding, little data about integrated PA/NP programs are available. Methods: This study examined the PA/NP PCT landscape in the United States. Programs were identified from membership rosters of the Association of Postgraduate Physician Assistant Programs and the Association of Post Graduate APRN Programs. Data (program name, sponsoring institution, location, specialty, accreditation status) were identified from programs' websites. Results: We identified 106 programs at 42 sponsoring institutions. Various specialties, most commonly in emergency medicine, critical care, and surgery, were represented. Few were accredited. Conclusions: PA/NP PCT is now common, with about half of the programs accepting PAs and NPs. These programs represent a unique form of interprofessional education involving full integration of two professions in the same program and are worthy of further investigation. [ABSTRACT FROM AUTHOR]

The electrochemical behavior of neptunium in NaCl–2CsCl melt at 823–923 K was investigated by cyclic voltammetry, differential pulse voltammetry, and open-circuit chronopotentiometry after polarization. The results show that Np4+ ions are reduced to Np metal by a two-step mechanism via Np3+ ions in the NaCl–2CsCl melt. The diffusion coefficients of Np3+ and Np4+ ions were determined from cyclic voltammograms. The apparent standard potentials of Np3+/Np0 and Np4+/Np3+ redox couples have been determined to be E*(Np3+/Np0) = −3.353 + 7.67 × 10−4 T and E*(Np4+/Np3+) = −1.175 + 4.99 × 10−4 T vs. Cl2/Cl− (V), respectively. The activity coefficients of Np3+ and Np4+ ions were also determined using the reported data on the Gibbs free energy of formation for NpCl3 and NpCl4 in a supercooled liquid state.

Host factors play important roles in influenza A virus (IAV) replication. In order to identify novel host factors involved in IAV replication, we compared the differentially expressed genes in A549 cells after IAV infection. We found that lncRNA lnc-RPS6P3 was up-regulated upon viral infection and poly(I:C) and IFN-β treatment, indicating it was an interferon-stimulated gene. Functional analysis demonstrated that overexpression of lnc-RPS6P3 inhibited IAV replication while knockdown of lnc-RPS6P3 promoted viral infection in A549 cells. Lnc-RPS6P3 inhibited both transcription and replication of IAV. Further study showed that lnc-RPS6P3 interacted with viral NP and interfered with NP self-oligomerization and, consequently, inhibited vRNP activity. In addition, lnc-RPS6P3 interacted with viral NS1 and reduced the interaction of NS1 and RIG-I; it also attenuated the inhibitory effect of NS1 on IFN-β stimulation. In conclusion, we revealed that lnc-RPS6P3 is an interferon-stimulated gene that inhibits IAV replication and attenuates the inhibitory effect of NS1 on innate immune response.

In the last several decades, postexposure prophylaxis (PEP) with antiretroviral therapy (ART) has become an effective tool for the prevention of HIV transmission. The continuous evolution of antiretrovirals and the associated update of clinical practice guidelines create a challenge for NPs caring for patients exposed to HIV. Understanding the life cycle of HIV is of paramount importance in streamlining treatment regimens in exposed individuals. ART is a complex combination of drugs targeting different stages of the virus's life cycle within the host. NPs play an essential role in managing treatment for people exposed to HIV and following up on these patients' response and adherence to the treatment protocol. This article provides a comprehensive overview of HIV and step-by-step guidance for NPs treating patients who have been exposed. In the last several decades, postexposure prophylaxis (PEP) with antiretroviral therapy (ART) has become an effective tool for the prevention of HIV transmission. The continuous evolution of antiretrovirals and the associated update of clinical practice guidelines create a challenge for NPs caring for patients exposed to HIV. This article provides a comprehensive overview of HIV and step-by-step guidance for NPs treating patients who have been exposed. [ABSTRACT FROM AUTHOR]

Soil nutrient deficiency, alkalinity and heavy metal toxicity are the most serious constraints for soil fertility and crop productivity around industrial zone in Dukem, central Ethiopia. Integrated nutrient management is essential to resolve this problem there by increasing the productivity of the soils. Therefore, trials were run in greenhouse to evaluate the response of selected soil physicochemical properties and heavy metals to mineral NP and vermicompost fertilizer application. The three rates of (2.5, 5 and 7.5 t/ha) vermicompost with three rates of mineral NP (25, 50, and 75%), full dose of vermicompost (7.5 t/ha), recommended inorganic NP (92 and 111 t/ha) and control treatment were arranged in a randomized complete block design (RCBD) with three replications. The results revealed that integrated application of 7.5 t/ha vermicompost and 75% NP increased the exchangeable Ca, Mg, K, cation exchange capacity, organic carbon, total N and available P by 341.51, 78.71, 133.3, 26.18, 33, 54.28 and 172.38%, respectively as compared to the control. Whereas, heavy metals Cr, Pb, Cd and Ni decreased by 80.74, 81.25, 79, 44 and 46.41%, respectively and exchangeable sodium and pH were also decreased at the same treatment. However, sole mineral NP fertilizer increased heavy metal availability. Therefore, the combined application of 7.5 t/ha vermicompost and 75% NP was found to be the best for the enhancement of soil physicochemical properties and reduction of heavy metals in study area and other similar agroecologies. [ABSTRACT FROM AUTHOR]

An electrochemical sensor based on Fe-based metal-organic framework supported on highly conductive graphene (Fe-HHTP-HITP-HCG) was prepared for the determination of trace nonylphenol (NP). Double-ligand metal-organic framework (Fe-HHTP-HITP) was grown in the empty spaces of highly conductive graphene (HCG) to form Fe-HHTP-HITP-HCG, and the electrochemical sensor was then made by drop-coating to form a film. The experimental conditions, namely the type of buffer, pH value, ligand ratio, HCG ratio, cumulative potential and cumulative time were investigated. The properties of the electrodes were evaluated through the use of cyclic voltammetry (CV), field emission scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The results of the experiments showed that Fe-HHTP-HITP-HCG had high electrochemical and catalytic activity and has good response. When the coating was four layers, the detection concentration of NP ranged from 1.0x10-7 to 1.0x10-4 mol/L, and the limit of detection was 1.22x10-8 mol/L. When the sensor was applied to NP that migrated from the milk bag, the standard addition recovery rate ranged from 96.90% to 102.00%. Based on these results, a new strategy for NP-sensitive detection using metal-organic framework composites is proposed. [ABSTRACT FROM AUTHOR]