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Resistance trend in bacteria isolated from corneal ulcers: A retrospective analysis from Pakistan

Objective The purpose of this study is to isolate and characterize bacteria from corneal ulcers and screen them for multiple antibiotic resistance, contributing to understanding patterns of resistance and identifying effective treatment strategies. Design A retrospective study was conducted between January 2024 to August 2024 Subjects, participants and/or controls The study involved the isolation of pathogenic bacterial strains from 15 corneal ulcer samples. Methods, intervention, or testing We isolated and characterized bacterial strains from corneal ulcer samples, which were routinely collected at an ophthalmology clinic for suspected infectious corneal ulcers and examined their resistance to twenty-six routinely prescribed antibiotics. The bacterial species included methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and E. coli among others. Antibiotic resistance patterns were assessed, with a focus on commonly used antibiotics such as ciprofloxacin, gentamycin, and vancomycin. Main outcome measures The study measured the healing rates of corneal ulcer patients, antibiotic resistance levels across bacterial strains, and specific treatment responses to various antibiotics. Results Thirteen out of fifteen corneal ulcer patients healed completely, while two patients developed full corneal opacity due to infection with P. aeruginosa. Significant differences in resistance were observed among the bacterial strains. MRSA exhibited the highest resistance levels, particularly to multiple antibiotics. Ciprofloxacin and gentamycin were less effective against the isolated strains, while vancomycin showed reduced resistance, against Gram-positive bacteria. Both ciprofloxacin and co-trimoxazole exhibited strong connections with multiple bacterial strains, indicating high resistance. Conclusion This study underscores the need for ongoing surveillance of antibiotic resistance patterns to guide treatment approaches and slow the spread of resistant bacteria. It also highlights the importance of developing new antibiotics and alternative therapies, with an emphasis on understanding the molecular mechanisms behind resistance to combat the global health posed by antibiotic-resistant infections.

Multidimensional performance enablers of Ethiopian community-based health extension program: A scoping review

Introduction Ethiopian Health Extension Program (HEP) aims to improve access to primary care, yet suboptimal health outcomes persist, indicating the need to optimize HEP implementation. This scoping review aims is to identify and synthesize evidence on the enabling factors that influence the Ethiopian HEP and Health Extension Workers (HEWs) performance. Methods A comprehensive search strategy was employed across multiple databases, including PubMed, EMBASE, Web of Science, and institutional websites. The review included studies published since January 2003, encompassing quantitative, qualitative, and mixed-methods researchs. The PRISMA flow diagram guideline was utilized for reporting of a review process and JBI methodology guideline was used for data extraction. Data extraction was conducted using Atlas.ti software, capturing verbatim excerpts and applying thematic coding to illustrate key findings. Results This review identified key multidimensional enablers of the Ethiopian HEP that collectively enhance the program’s performance. Motivational factors for HEWs play a critical role, encompassing intrinsic desires and extrinsic factors including opportunities for career growth and fair compensation. Additionally, the review identified the importance of continuous capacity building to enhance the skills of HEWs and program performance. The review also highlights the positive impact of diversifying HEP services including customizing the HEP services to the varied contexts and integrating male HEWs to enhance program reach and acceptance. Engaging communities through organized campaigns, stakeholder coordination, and leveraging local structures enable and strengthen the program’s effectiveness. Finally, the availability of essential resources is crucial for HEWs to provide timely and appropriate care. These multidimensional enabling factors form pathways for HEWs and HEP to create supportive environment and capability that significantly enhances HEP performance. Conclusions Intrinsic and extrinsic motivations, community engagement, clinical nurse inclusion, male HEWs participation, mentorship and improving living conditions of HEWs enhances the HEWs’ effectiveness and program performance.

IFN-γ signaling is required for the efficient replication of murine hepatitis virus (MHV) strain JHM in the brains of infected mice

Neurotropic viruses are a major public health concern as they can cause encephalitis and other severe brain diseases. Many of these viruses, including flaviviruses, herpesviruses, rhabdoviruses and alphaviruses enter the brain through the olfactory neuroepithelium (ONE) in the olfactory bulbs (OB). Due to the low percentage of encephalitis that occurs following these infections, it’s thought that OBs have specialized innate immune responses to eliminate viruses. Murine hepatitis virus strain JHM (JHMV) is a model coronavirus that causes severe encephalitis and can access the brain through olfactory sensory neurons. We’ve shown that a JHMV Mac1-mutant virus, N1347A, has decreased replication and disease in the brains of mice. Here we further show that this virus replicates poorly in the OB. However, it is unknown which innate immune factors restrict N1347A replication in the OB. RNA-seq analysis of infected olfactory bulbs showed that IFNγ was upregulated in the OB while IFN-β was barely detectable at 5 days post-infection. To determine if IFN-γ restricts JHMV N1347A replication, we utilized IFN-γ and IFN-γ receptor (IFN-γR) knockout (KO) mice. Surprisingly we found that JHMV WT and N1347A replicated very poorly in the OB and whole brains of both IFN-γ and IFN-γR KO mice following intranasal infection, though survival and weight loss were unaltered. Furthermore, we determined that microglia, macrophages, and CD4 + T cells were the primary cells producing IFN-γ during the early stages of this infection. We conclude that IFN-γ is required for the efficient replication of JHMV in the brains of infected mice.

Correction: DNA Barcode, chemical analysis, and antioxidant activity of Psidium guineense from Ecuador

Clinical profile and treatment outcomes of acute lymphoblastic leukemia among children attending at the University of Gondar comprehensive specialized hospital and Tikur Anbessa Specialized Hospital in Ethiopia

Background Acute lymphoblastic leukemia (ALL) is a common childhood cancer characterized by the uncontrolled proliferation of immature white blood cells. While advancements in treatment have significantly improved outcomes in developed countries, significant challenges remain in resource-limited settings, such as Ethiopia. This study aimed to assess the clinical profiles and treatment outcomes of ALL patients at the University of Gondar Comprehensive Specialized Hospital (UoGCSH) and Tikur Anbessa Specialized Hospital (TASH) in Ethiopia. A prospective longitudinal study was conducted among 179 ALL patients receiving treatment at the outpatient department and pediatric oncology centers of the UoGCSH and TASH between December 25, 2022, and August 30, 2024. Sociodemographic and clinical data were collected using a structured questionnaire. The data were entered and analyzed using SPSS version 25. Descriptive statistics were employed to summarize patient characteristics, while overall survival was evaluated using Kaplan-Meier analysis. Additionally, both univariate and multivariate Cox proportional hazards regression analyses were performed, with statistical significance set at a P-value of < 0.05. Results Among the 179 patients, 81 (45.3%) died during the course of treatment. Of these, 33 (18%) died before initiating induction therapy, while 48 (27.4%) died primarily due to treatment abandonment during various phases of therapy. The event-free survival rate was 75 (41.9%). Mortality rates were significantly higher in patients with certain variables identified through Cox regression analysis, including age, sepsis, and relapse, which nearly doubled the risk of death. Elevated LDH levels, malaria infection, and T-cell ALL were associated with approximately six-fold, three-fold, and seven-fold increases in the risk of death, respectively. Only 22 out of 179 patients (12.29%) achieved remission. Among these patients, hematotoxicities observed during the maintenance phase included anemia in 19/22 (86.4%), grade 3–4 neutropenia in 12/22 (52.2%), and thrombocytopenia in 17/22 (77.3%). Conclusion A high mortality rate was observed among children with ALL, with significant risk factors including relapse, age over 10 years, elevated LDH levels, sepsis, low platelet counts, T-cell ALL, malaria infection, and induction failure. To improve survival rates, it is essential to address these factors by optimizing treatment regimens and minimizing delays in diagnosis and care delivery.

Rivalry between pitch and timbre in auditory stream segregation

Two rapidly alternating tones with different pitches may be perceived as one integrated stream when the pitch differences are small or two separated streams when the pitch differences are large. Likewise, timbre differences between two tones may also cause such sequential stream segregation. Moreover, the effects of pitch and timbre on stream segregation may cancel each other out, which is called a trade-off. However, how timbre differences caused by specific patterns of spectral shapes interact with pitch differences and affect stream segregation has been largely unexplored. Therefore, we used stripe tones, in which stripe-like spectral patterns of harmonic complex tones were realized by grouping harmonic components into several bands based on harmonic numbers and removing harmonic components in every other band. Here, we show that 2- and 4-band stimuli elicited distinctive stream segregation against pitch proximity. By contrast, pitch separations dominated stream segregation for 16-band stimuli. The results for 8-band stimuli most clearly showed the trade-off between pitch and timbre on stream segregation. These results suggest that the stimuli with a small number (≤4) of bands elicit strong stream segregation due to sharp timbral contrasts between stripe-like spectral patterns, and that the auditory system looks to be limited in integrating blocks of frequency components dispersed over frequency and time.

Optimization of Z-shaped assembled mortise and tenon joint box culvert connection and structural characteristics

This paper proposes a new type of Z-shaped prefabricated mortise and tenon joint box culvert designed to enhance the longitudinal connection stability of highway prefabricated box culverts. Using actual engineering parameters and material properties, finite element simulation software was employed to analyze the culvert. The results indicated that maximum deformation and stress concentration occurred at the ends and armpits of the groove joint, specifically at the junction of the two culverts. The deformation of the middle section of the single culvert section is 75.86% higher than that of the end section. The deformation at the maximum deformation of the side wall of the single culvert section is 980% higher than that at the end. Under identical soil filling conditions, the mechanical properties of the integral box culvert and the prefabricated box culvert exhibited the greatest differences at their joint. The deformation and stress values at other locations showed minimal differences. Based on the stress and deformation characteristics of the culvert body, various box culvert designs with different joint heights and lengths were developed and simulated. The findings indicate that the mechanical properties of the joint culvert are most significantly enhanced with a joint height of 1.8 m and a joint length of 0.5 m. By integrating the advantages of the mortise and tenon joint structure—such as limiting joint displacement, preventing misalignment and uneven settlement, and facilitating smooth load transfer—the mortise and tenon joint is incorporated into the assembled box culvert joint. Ultimately, a Z-shaped prefabricated mortise and tenon joint box culvert, featuring a well-designed structure and a 1.25 m long mortise and tenon joint, was selected. Following optimization, the mechanical properties of the assembled box culvert joints have significantly improved. The connection performance is excellent, meeting the required bearing capacity, and demonstrating strong compressive shear and deformation resistance. Additionally, the yield and failure limits under identical uneven loads have been considerably enhanced, while maintaining economic and prefabrication rationality. This study provides valuable insights for the practical engineering of similar assembled box culverts.

Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3

Complex water networks visualized by cryogenic electron microscopy of RNA

Abstract The stability and function of biomolecules are directly influenced by their myriad interactions with water1–16. Here we investigated water through cryogenic electron microscopy (cryo-EM) on a highly solvated molecule: the Tetrahymena ribozyme. By using segmentation-guided water and ion modelling (SWIM)17,18, an approach combining resolvability and chemical parameters, we automatically modelled and cross-validated water molecules and Mg2+ ions in the ribozyme core, revealing the extensive involvement of water in mediating RNA non-canonical interactions. Unexpectedly, in regions where SWIM does not model ordered water, we observed highly similar densities in both cryo-EM maps. In many of these regions, the cryo-EM densities superimpose with complex water networks predicted by molecular dynamics, supporting their assignment as water and suggesting a biophysical explanation for their elusiveness to conventional atomic coordinate modelling. Our study demonstrates an approach to unveil both rigid and flexible waters that surround biomolecules through cryo-EM map densities, statistical and chemical metrics, and molecular dynamics simulations.

Misophonia impact questionnaire (MIQ), tinnitus impact questionnaire (TIQ), and hyperacusis impact questionnaire (HIQ): Factor analysis, test-retest reliability, and minimum detectable change using a non-clinical population

The objectives of this study were to (1) assess if previously reported unidimensional factor structure of the Misophonia Impact Questionnaire (MIQ), Tinnitus Impact Questionnaire (TIQ), and Hyperacusis Impact Questionnaire (HIQ) can be confirmed in a nonclinical population, and (2) examine test-retest reliability and establish the minimum detectable change (MDC) for MIQ, TIQ and HIQ. 451 people completed the MIQ and HIQ sections of an online survey. A sub-sample of 173/451 who had tinnitus completed the TIQ too. 130/451 participants completed the second survey with 2 weeks interval for the MIQ and HIQ and 32/173 participants with tinnitus completed the TIQ in the second survey. All questionnaires showed excellent internal consistency, with Cronbach’s α of 0.93 for both the MIQ and TIQ and 0.91 for the HIQ. Confirmatory factor analysis (CFA) showed that the MIQ, TIQ and HIQ were all one-factor questionnaires. Based on the intra-class correlation coefficients (ICC) values, the test-retest reliability was good for MIQ and HIQ and it was excellent for TIQ. Based on the MDC values, when these questionnaires are used for repeated measurements, the minimum amount of change that constitutes a true change is ≥ 8 for the total score of MIQ, ≥ 4 for the TIQ, and ≥ 7 for the total score of HIQ. In conclusion, the MIQ, TIQ and HIQ can be used in clinical practice or research setting to measure the impact of misophonia, tinnitus and hyperacusis on the individual’s life, respectively, as one-factor questionnaires with excellent internal consistency and good to excellent test-retest reliability.

Axisymmetric adaptive upper-bound finite element limit analysis formulation based on second-order cone programming for bearing capacity of circular footing

An adaptive axisymmetric upper bound finite element limit analysis (UB-FELA) formulation has been presented for Mohr-Coulomb (M-C) materials in this paper. The computational domain is discretized using quadratic velocity elements. For the sake of computational efficiency, the axisymmetric UB finite element problem is recast into a model of second-order cone programming (SOCP). To enhance the precision of the proposed UB finite element method using a reduced element count, this study implements a mesh adaptation algorithm grounded in plastic dissipation. The collapse loads for determining the circular footings are then estimated by application of the proposed axisymmetric UB limit analysis formulas. By comparing the results to those reported in the literature, the analysis indicates that the method presented in this paper yields an accurate UB solution.

The effect of foliar spraying of silver and iron nanoparticles as fertilizers on the quantity, quality, and antimicrobial properties of Melissa officinalis L. essential oil

Melissa officinalis L. as a medicinal plant used in traditional medicine to treat headaches caused by stress, anemia, nausea, dizziness, indigestion, colic, epilepsy, hysteria, cancer, and heart failure. The present study aimed to evaluate the effect of foliar spraying of silver and iron nanoparticles as fertilizers on yield, type, chemical compounds, and antimicrobial properties of M. officinalis leaf essential oil. For this purpose, plant cultivation was conducted in May 2020 as a completely random design. After one year of establishment, foliar spraying was conducted at the beginning of flowering, the peak of flowering, and the end of flowering at the levels of 20, 40, 60, 80, and 100 mg/L, and the control of iron and silver nanoparticles. After collecting and drying the leaves, the essential oil was extracted by water distillation, and the compounds were identified by Gas chromatography–mass spectrometry. The antibacterial activity of essential oils was evaluated by using agar diffusion method, Minimum growth inhibitory concentration, and Minimum concentration of bacterial lethality. The results showed that foliar spraying with different nano iron and silver treatments had a significant effect on the yield, percentage of compounds, and antimicrobial activity of M. officinalis leaf essential oil (p ≤ 0.01). The 60 mg/L of FeNPs concentration with 1.70% (w/w) had the highest yield of M. officinalis leaf essential oil. The neral (33.5–0%), citral (28.53–0%), geranial (28.25–0%), caryophyllene (20.71–0%), caryophyllene-oxide (19.73–7.36%), and geranial acetate (5.99–11.84%) were the dominant compounds of essential oil. The results of antimicrobial test showed that the lowest MIC value belongs to the treatments of nano iron 100, nano silver 20, and nano silver 60 mg/L with a value of <62.5 μg/mL. against Pseudomonas aeruginosa, that it was one times weaker than rifampin and three times more potent than the control treatment. However, the best treatment in terms of of the essential oil efficiency was for the samples sprayed with nanoiron 60 mg/L. In terms of the essential oil componds, was for the nanoiron treatment 100 mg/L with the predominance of caryophyllene oxide and geranyl acetate, and in terms of the antimicrobial activity, was for the nano silver treatment, 60 mg/L. Therefore, they can be promising and potential natural options for the production of M. officinalis essential oil under foliar spraying with economical and environmentally friendly fertilizers for consumption in various pharmaceutical and cosmetic industries.

Long-term impact and biological recovery in a deep-sea mining track

Abstract Deep-sea polymetallic nodule mining is in the exploration phase at present with some groups proposing a move towards extraction within years1. Management of this industry requires evidence of the long-term effects on deep-sea ecosystems2, but the ability of seafloor ecosystems to recover from impacts over decadal scales is poorly understood3. Here we show that, four decades after a test mining experiment that removed nodules, the biological impacts in many groups of organisms are persistent, although populations of several organisms, including sediment macrofauna, mobile deposit feeders and even large-sized sessile fauna, have begun to re-establish despite persistent physical changes at the seafloor. We also reveal that areas affected by plumes from this small-scale test have limited detectable residual sedimentation impacts with some biological assemblages similar in abundance compared to control areas after 44 years. Although some aspects of the modern collector design may cause reduced physical impact compared to this test mining experiment, our results show that mining impacts in the abyssal ocean will be persistent over at least decadal timeframes and communities will remain altered in directly disturbed areas, despite some recolonization. The long-term effects seen in our study provide critical data for effective management of mining activities, if they occur, including minimizing direct impacts and setting aside an effective network of protected areas4,5.

Exploring new lengths for q-ary quantum MDS codes with larger distance

In the past decade, the construction of quantum maximum distance separable codes (MDS for short) has been extensively studied. For the length n=q2−1m, where m is an integer that divides either q  +  1 or q − 1, a complete set of results has been available. In this paper, we dedicate to a previously unexplored cases where the length n=q2−1m, subject to the conditions that m is neither a divisor of q − 1 nor q  +  1. Ultimately, this problem can be summarized as exploring the necessary and sufficient conditions for the existence of pairs (m1,m2), where m=m1×m2m1+m2−2 is an integer, with the additional requirement that the greatest common divisor (gcd) of m with both m1 and m2, gcd(m,m1)>1 and gcd(m,m2)>1, and gcd(m1,m2)=2. The quantum MDS codes presented herein are novel and exhibit distance parameters exceeding q2.

CCR2 overexpressing gingiva mesenchymal stem cells provide high intestinal regeneration in a rat model of ulcerative colitis

Background/aims Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. Mesenchymal stem cells (MSCs) are candidates for use in inflammatory diseases with their tissue regeneration and anti-inflammatory capabilities. Chemokine receptor overexpression on MSCs is an effective strategy for the migration of MSCs into inflammatory tissue in high amounts. In this study, the anti-inflammatory and regenerative effects of genetically CCR2 overexpressed gingiva MSCs (GMSCs) on the inflamed colon in UC were studied. Materials and methods GMSCs were transduced with a lentiviral vector for CCR2 overexpression. The UC experimental model was induced with a single intrarectal administration of 4% w/w acetic acid. Colon tissues were analyzed for IFN or IL-17 secreting CD4+  T lymphocytes via flow cytometry and lymphocytic infiltration, fibrosis, and ulcers by histopathologic evaluation. Homing analysis of GMSCs was done by analyzing fluorescence intensity under the fluorescence microscope. Results GMSCs and CCR2+GMSCs equally downregulated colonic IFN-γ or IL-17 secreting CD4+ T lymphocytes ratios compared to the untreated group (p < 0.05). Fluorescence intensity of labeled cells was significantly high in colon tissues of CCR2+GMSCs administered rats (61.2 ± 13.7%) compared to GMSCs administered rats (19.6 ± 9.8%) (p < 0.05). In addition, mucosal integrity significantly increased and fibrosis and ulcers notably decreased in CCR2+GMSCs administered rats compared to GMSCs administered rats (p < 0.05). Conclusion The overexpression of CCR2 on GMSCs increases migration to the inflammatory colon tissue, which has a high regenerative effect in UC. Overexpression of CCR2 on GMSCs may be an alternative to cellular therapies in UC.

Asking for help: An empirical exploration into social grammar

This paper explores the interface between linguistic form and social meaning by focusing on correlations between sentence type and the social distance between interlocutors—a central aspect of the social meaning component of politeness. We present a forced-choice experiment with four different groups of speakers (L1 British English speakers, L1 American English speakers, L2 English/German speakers, and L1 German speakers). In this experiment, we manipulated the linguistic form of asking for help along the syntactic dimension of sentence type (declaratives, interrogatives, or imperatives) and recorded the addressee our participants picked for each form (brother, coworker, or stranger). We broaden the empirical picture by going beyond highly conventionalized forms (e.g., Can you VP?) and therefore also varying the modal auxiliary verbs (e.g., Will you VP?). Based on this comprehensive picture of ways of asking for help, we identify clusters of linguistic forms depending on their felicity in different social scenarios. Our descriptive cluster analysis as well as the statistical comparisons between sentence types indicate that there are systematic correspondences between linguistic form and social meaning across different groups of speakers and languages, and we propose that our empirical data provide a potential starting point for rethinking speech act grammar in terms of ‘social grammar’.

Development and validation of a measurement instrument for student assessment of quality physical education in Chinese secondary schools

There is a growing emphasis on developing Quality Physical Education (QPE) programs. However, a research gap exists due to the lack of measurement instruments to assess QPE for students. This study aimed to develop an instrument to assess QPE implementation and its validity and reliability in China. This study comprised three phases. In Phase 1, a conceptual framework for QPE was established using grounded theory based on interviews with 22 PE teachers and 20 students. In Phase 2, using the conceptual framework from Phase 1, we developed an item pool supported by a literature review, expert evaluations, and student interviews. In Phase 3, a cross-sectional study was conducted with secondary school students (705 participants) to analyse the items and assess the instrument’s reliability and validity through exploratory and confirmatory factor analysis, as well as test-retest analysis. The final 45-item instrument, comprising four subscales (student, family, school, and community) across 10 factors, demonstrated strong validity and reliability. Model fit indices met established thresholds (e.g., CFI and TLI ≥ .90, as well as RMSEA ≤ .08). The composite reliability and average variance extracted values for each factor exceeded.7 and.5, respectively, with the test-retest reliability also exceeding.7, indicating high reliability and validity. This study addresses a critical methodological gap in QPE research by developing a culturally contextualized assessment instrument that explicitly identifies and measures students’ perceptions of QPE implementation. This instrument enables systematic monitoring of QPE practices from students’ perspectives, informing evidence-based policymaking and resource allocation. Integrating student, family, school, and community subscales supports holistic interventions to improve the quality of PE.

Phagocytic activity of blood monocytes and neutrophils in moderate COVID-19 patients and impact of immune therapy with bacterial lysates

Background Monocytes, macrophages and dendritic cells are involved in phagocytic reactions, which potentially play an important role in the pathogenesis of COVID-19. Imbalance of these cells in peripheral blood has proven to affect not only innate but also adaptive immunity. It is possible that a search for strategies to restore monocyte activity could be a major step in achieving immune control over COVID-19. The aim of this study was to investigate the relationship between phagocytic activity of peripheral-blood monocytes and neutrophils, and COVID-19 severity, to assess the effects of a bacteria-based immunostimulating agent on phagocytosis parameters in in-hospital COVID-19 patients. Materials and methods The study included 105 adult patients with moderate COVID-19, who had been hospitalized in 2020–2021 and treated in accordance with the recommendations of the Ministry of Health of the Russian Federation. All patients were divided into two groups: in Group 1 patients received standard treatment and Immunovac VP4 therapeutic vaccine, a bacteria-based immunostimulating agent as add-on therapy from Day 1 of hospitalization; in Group 2 patients did not receive any add-on treatment. The study parameters included C-reactive protein (CRP), aspartate aminotransferase (AST), SpO2, lung involvement on chest computer tomography (CT) scan, and phagocytic activity of peripheral-blood leukocytes based on the absorption activity (AA) of monocytes and neutrophilic granulocytes against S. аureus). The parameters were assessed at 1, 14 and 30 days. Results Based on a cluster analysis of the clinical findings and the results of diagnostic tests obtained on admission, the patients were divided into 2 clusters: cluster 1 including patients with a more severe disease (n = 34) and cluster 2 including patients with a less severe disease (n = 71). Cluster 1 patients had higher levels of CRP (20.1 vs. 2.2 mg/mL, p < 0.001), AST (32.9 vs. 26.2 U/L, p = 0.003), lower SpO2 (94% vs. 96%, p < 0,001) and more extensive lung involvement on chest CT scan (35% vs. 12%, p < 0,001). There was a statistically significant direct correlation between blood monocyte AA and SpO2 (p = 0.04), an inverse correlation between monocyte AA and CRP (p = 0.003) and the extent of lung involvement on CT scan (p = 0.05). In less severe COVID-19 patients (cluster 2), no statistically significant correlation was observed. In more severe COVID-19 patients (cluster 1), there was a rise in monocyte AA on day 30 of hospitalization both in the control group (from 86.6 to 92.2, p = 0.03) and the main group, who received Immunovac VP4 add-on therapy (from 87.3 to 98.3, p = 0.05). However, the patients who received the immunostimulating agent, had higher monocyte PI than the controls, without the immunostimulant (p = 0.05). Patients from cluster 1 who were given Immunovac VP4 had higher SpO2 levels (98% vs. 97%, p = 0.01) than those who had received only the standard treatment. Discussion Blood monocyte AA correlates with COVID-19 severity: patients with less severe disease have higher AA and those with more severe illness have lower AA. The standard treatment, combined with Immunovac VP4 enhances phagocytic activity of peripheral-blood monocytes, which is associated with a more marked increase in SpO2, especially in more severe patients.

Impact of physical activity and psychological skills training with parental participation on cognitive, emotional, and behavioral outcomes in children with ADHD and their parents: A study protocol

Background Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by difficulties in attention, hyperactivity, and impulse control. Previous studies have suggested that engaging in moderate to vigorous physical activity (PA) and undergoing psychological therapy can help improve ADHD symptoms when combined with pharmacological treatments. This study aims to investigate the effects of parent participation in physical activities and psychological skills training (PST) on the cognitive, emotional, and behavioral outcomes of children with ADHD, as well as the emotional well-being of their parents. Methods Participants for the study will be recruited from a tertiary medical institution. The focus will be on children aged 6–12 years who have been diagnosed with ADHD and are currently receiving treatment at the hospital. Assessments will be conducted separately for the children and their parents. We will evaluate the children’s cognitive, emotional, and behavioral aspects, while for the parents, we will assess only emotional and behavioral aspects. The study will consist of three Intervention Groups (IG 1 and IG 2) and one control group. IG 1 will receive a combined intervention of PA and PST, IG 2 will participate in PA alone, and the control group will not receive any intervention. Discussion This study’s findings underscore the benefits of greater active participation when children participate in activities with their parents. It will also demonstrate the possible advantages of integrating PA with PST. The research will also explore how these interventions may influence parents, providing insights into whether their engagement enhances their psychological well-being. Trial registration This study is registered at Clinical Research Information Service (CRIS, https://cris.nih.go.kr) as KCT0010046

Variants in Lrrk2 and Snca deficiency do not alter the course of primary encephalitis due to neurotropic reovirus T3D in newborn mice

Variants at the leucine-rich repeat kinase-2 (LRRK2) and α-synuclein (SNCA) loci are associated with Parkinson’s disease (PD) risk. Viral infections have also been linked to increased risk of developing PD. In exploring a role for each of the encoded proteins in host response against brain-directed viral infections, we previously demonstrated that two Lrrk2 knock-in variants as well as Snca expression altered survival rates from viral encephalitis following intranasal inoculation of newborn mice with a double-stranded RNA virus: respiratory-enteric-orphan virus, serotype-3 strain Dearing (reovirus T3D). Here, we examined whether outcomes of direct inoculation of the brain by reovirus T3D, which invariably causes lethal encephalitis within 15 days, would also be modified by variants in Lrrk2 and Snca. When we inoculated newborn mice intracerebrally with reovirus T3D, we found that compared to wild-type littermates Lrrk2 p.G2019S kinase-hyperactive and p.D1994S kinase-inactive mutant mice did not show any significant difference in time-to-death or in viral titres in the brain, and revealed no sex difference. In parallel studies, the reduction or absence of endogenous α-synuclein did not alter the course of disease in reovirus T3D-infected mice. Together, these findings suggest that while variants in the PD-linked Lrrk2 and Snca genes influenced disease outcomes of intranasally acquired reovirus T3D encephalitis, they did not affect survival outcomes in the intracerebrally acquired reovirus T3D encephalitis model.