Impact of an Injectable Trace Mineral Supplement on the Immune Response and Outcome of Mannheimia haemolytica Infection in Feedlot Cattle.

The study aimed to assess the impact of injectable trace mineral ("ITM"; Multimin90; Fort Collins, CO) supplementation on bacterial infection in cattle. Angus-crossbred steers (n = 32) were organized into two blocks by initial body weight. Steers were maintained on a ryelage and dry-rolled corn-based growing diet without supplementation of Zn, Cu, Mn, and Se for the duration of the study. The steers were transported 6 h, then randomized into three treatment groups: control received sterile saline ("CON"), ITM administered 1 day after transport (6 days before infection, "ITMPRE"), and ITM administered 2 days post infection (dpi) concurrent with antibiotic treatment ("ITMPOST"). Steers were infected with Mannheimia haemolytica on day 0, and all were treated with tulathromycin at 2 dpi. Plasma levels of Zn, Cu, and Se did not differ among treatments (P ≥ 0.74). Liver Se was higher in ITMPRE at 2 dpi (P < 0.05), and both ITM groups had higher liver Se at 5 dpi (P < 0.05) compared to CON. A time × treatment interaction was detected for liver Cu (P = 0.02). Clinical scores were lower (P < 0.05) in ITMPRE on 1 and 8 dpi and ITMPOST on 8 dpi compared to CON. Thoracic ultrasonography scores were lower in ITMPRE at 2 dpi compared to CON (P < 0.05) and ITMPOST (P < 0.1). No treatment effects (P > 0.10) were observed for bacterial detection from bronchoalveolar lavage (BAL) or nasopharyngeal swabs. At 5 dpi, both ITMPRE and ITMPOST showed higher frequencies of γδ T cells and NK cells in BAL compared to CON (P < 0.05). Before infection, leukocytes from ITMPRE steers produced more IL-6 (P < 0.01) in response to stimulation with the TLR agonist, Pam3CSK4. Use of ITM may be an effective strategy for improving disease resistance in feedlot cattle facing health challenges.

Characterization of genotype V Japanese encephalitis virus isolates from Republic of Korea.

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct in vitro phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. In vivo, NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood-brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct in vitro and in vivo characteristics.

Efficacy of genotype-matched vaccine against re-emerging genotype V Japanese encephalitis virus.

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV), is a highly threatening disease with no specific treatment. Fortunately, the development of vaccines has enabled effective defense against JE. However, re-emerging genotype V (GV) JEV poses a challenge as current vaccines are genotype III (GIII)-based and provide suboptimal protection. Given the isolation of GV JEVs from Malaysia, China, and the Republic of Korea, there is a concern about the potential for a broader outbreak. Under the hypothesis that a GV-based vaccine is necessary for effective defense against GV JEV, we developed a pentameric recombinant antigen using cholera toxin B as a scaffold and mucosal adjuvant, which was conjugated with the E protein domain III of GV by genetic fusion. This GV-based vaccine antigen induced a more effective immune response in mice against GV JEV isolates compared to GIII-based antigen and efficiently protected animals from lethal challenges. Furthermore, a bivalent vaccine approach, inoculating simultaneously with GIII- and GV-based antigens, showed protective efficacy against both GIII and GV JEVs. This strategy presents a promising avenue for comprehensive protection in regions facing the threat of diverse JEV genotypes, including both prevalent GIII and GI as well as emerging GV strains.

Skin Infiltrate Composition as a Telling Measure of Responses to Checkpoint Inhibitors.

Checkpoint inhibitors treat a variety of tumor types with significant benefits. Unfortunately, these therapies come with diverse adverse events. Skin rash is observed early into treatment and might serve as an indicator of downstream responses to therapy. We studied the cellular composition of cutaneous eruptions and whether their contribution varies with the treatment applied. Skin samples from 18 patients with cancer and 11 controls were evaluated by mono- and multiplex imaging, quantification, and statistical analysis. T cells were the prime contributors to skin rash, with T cells and macrophages interacting and proliferating on site. Among T cell subsets examined, type 1 and 17 T cells were relatively increased among inflammatory skin infiltrates. A combination of increased cytotoxic T cell content and decreased macrophage abundance was associated with dual checkpoint inhibition over PD1 inhibition alone. Importantly, responders significantly separated from nonresponders by greater CD68+ macrophage and either CD11c+ antigen-presenting cell or CD4+ T cell abundance in skin rash. The microenvironment promoted epidermal proliferation and thickening as well. The combination of checkpoint inhibitors used affects the development and composition of skin infiltrates, whereas the combined abundance of two cell types in cutaneous eruptions aligns with responses to checkpoint inhibitor therapy.

FcRγ- NK Cell Induction by Specific Cytomegalovirus and Expansion by Subclinical Viral Infections in Rhesus Macaques.

"Adaptive" NK cells, characterized by FcRγ deficiency and enhanced responsiveness to Ab-bound, virus-infected cells, have been found in certain hCMV-seropositive individuals. Because humans are exposed to numerous microbes and environmental agents, specific relationships between hCMV and FcRγ-deficient NK cells (also known as g-NK cells) have been challenging to define. Here, we show that a subgroup of rhesus CMV (RhCMV)-seropositive macaques possesses FcRγ-deficient NK cells that stably persist and display a phenotype resembling human FcRγ-deficient NK cells. Moreover, these macaque NK cells resembled human FcRγ-deficient NK cells with respect to functional characteristics, including enhanced responsiveness to RhCMV-infected target in an Ab-dependent manner and hyporesponsiveness to tumor and cytokine stimulation. These cells were not detected in specific pathogen-free (SPF) macaques free of RhCMV and six other viruses; however, experimental infection of SPF animals with RhCMV strain UCD59, but not RhCMV strain 68-1 or SIV, led to induction of FcRγ-deficient NK cells. In non-SPF macaques, coinfection by RhCMV with other common viruses was associated with higher frequencies of FcRγ-deficient NK cells. These results support a causal role for specific CMV strain(s) in the induction of FcRγ-deficient NK cells and suggest that coinfection by other viruses further expands this memory-like NK cell pool.

Lichen planus is associated with depression and anxiety: a cross-sectional study in the All of Us research program.

Lichen planus (LP) can be accompanied by psychiatric comorbidities. Studies investigating the relationship between LP and clinically diagnosed anxiety and depression are limited. We aimed to determine the association of LP with anxiety and depression by conducting a cross-sectional population study of the All of Us research database, a National Institutes of Health cohort. Patients with LP were identified through electronic health record data using codes from the International Classification of Diseases and Systematized Nomenclature of Medicine. We used multivariable logistic regression to assess associations between LP and anxiety and depression before and after controlling for relevant covariates. Among 239,552 participants, 1083 individuals with LP were identified, with an average age of 67.20 years (standard deviation, 11.79) and a female predominance (74% female). The prevalence of depression and anxiety were higher among individuals with LP than in those without (41.6% vs 27.7%, p < 0.001; 43.5% vs 29.6%, p < 0.001). LP remained significantly associated with depression (OR, 1.36; 95% CI, 1.20-1.56, p < 0.001) and anxiety (OR, 1.48; 95% CI, 1.30-1.68, p < 0.001) after controlling for age, sex, hypothyroidism, autoimmune diseases, hypertension, type II diabetes mellitus, cardiovascular disease, and hepatitis C infection. In this cross-sectional study, LP was associated with an increase in odds of having depression and anxiety in multivariable analysis. Further study is needed to better understand the relationship between mental health outcomes and LP to address the needs of patients with LP more completely.

The serotonin reuptake inhibitor fluoxetine induces human fetal membrane sterile inflammation through p38 MAPK activation.

Serotonin Reuptake Inhibitors (SRIs) are often used as first line therapy for depression and other psychiatric disorders. SRI use during pregnancy is associated with preterm premature rupture of membranes (PPROM) and subsequent preterm birth. The objective of this study was to investigate the mechanism(s) responsible for SRI-associated PPROM. Putative mechanisms underlying PPROM include fetal membrane (FM) inflammation, increased apoptosis, and/or accelerated senescence, the later which may be reversed by statins. Human FM explants from normal term deliveries without labor, infection, or antidepressant use were treated with or without the SRI, fluoxetine (FLX), either alone or in the presence of a p38 MAPK inhibitor or the statins, simvastatin or rosuvastatin. FMs were also collected from women either unexposed or exposed to FLX during pregnancy. FLX significantly increased FM p38 MAPK activity and secretion of inflammatory IL-6. Inhibition of p38 MAPK reduced FM IL-6 secretion in response to FLX. Statins did not reduce the SRI-induced FM IL-6 production. FMs from women exposed to FLX during pregnancy expressed elevated levels of p38 MAPK activity compared to matched unexposed women. FMs exposed to FLX did not exhibit signs of increased apoptosis and/or accelerated senescence. These results indicate that the SRI, FLX, may induce sterile FM inflammation during pregnancy through activation of the p38 MAPK pathway, and in the absence of apoptosis and senescence. These findings may better inform clinicians and patients as they weigh the risks and benefits of SRI antidepressant treatment during pregnancy.

Factors affecting the changes in antihypertensive medications in patients with hypertension.

As frequent changes in anti-hypertensive (HTN) medications may reduce adherence to the treatments, identifying modifiable factors leading to changes in anti-HTN medications can help clinicians optimize treatment strategies for individual patients. We performed this study to explore the pattern of anti-HTN medications and to identify factors that are associated with the changes in anti-HTN medications. To this end, we used a clinical database of Seoul National University Hospital, extracted, transformed, and loaded by the observational medical outcomes partnership common data model. Demographic and all recorded clinical diagnoses, medications, and procedures data of eligible subjects were collected. Of 636 subjects who were eligible for this study, 297 subjects with a record of ≥1 anti-HTN medication changes and other 297 subjects without a record of medication change were selected for the study population. High diastolic blood pressure (adjusted odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.001-1.040, p = 0.040), arrhythmia (adjusted OR: 10.01, 95% CI: 1.86-185.57, p = 0.030), and angina pectoris with antianginal agents (adjusted OR: 4.85, CI: 1.05-23.89, p = 0.046) were associated with the changes in anti-HTN medications, indicating that any patients with these covariates require additional attention to reduce the likelihood of changing anti-HTN medications.

Surface Modification of ZrO2 Nanoparticles with TEOS to Prepare Transparent ZrO2@SiO2-PDMS Nanocomposite Films with Adjustable Refractive Indices.

Here, highly transparent nanocomposite films with an adjustable refractive index were fabricated through stable dispersion of ZrO2 (n = 2.16) nanoparticles (NPs) subjected to surface modification with SiO2 (n = 1.46) in polydimethylsiloxane (PDMS) (n = 1.42) using the Stöber method. ZrO2 NPs (13.7 nm) were synthesized using conventional hydrothermal synthesis, and their surface modification with SiO2 (ZrO2@SiO2 NPs) was controlled by varying the reaction time (3-54 h). The surface modification of the NPs was characterized using Fourier-transform infrared spectroscopy, dynamic light scattering, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, and ellipsometry. The surface modification was monitored, and the effective layer thickness of SiO2 varied from 0.1 nm to 4.2 nm. The effective refractive index of the ZrO2@SiO2 NPs at λ = 633 nm was gradually reduced from 2.16 to 1.63. The 100 nm nanocomposite film was prepared by spin-coating the dispersion of ZrO2@SiO2 NPs in PDMS on the coverslip. The nanocomposite film prepared using ZrO2@SiO2 NPs with a reaction time of 18 h (ZrO2@SiO2-18h-PDMS) exhibited excellent optical transparency (Taverage = 91.1%), close to the transparency of the coverslip (Taverage = 91.4%) in the visible range, and an adjustable refractive index (n = 1.42-1.60) as the NP content in the film increased from 0 to 50.0 wt%.

Support Models for Addiction Related Treatment (SMART) for pregnant women: Study protocol of a cluster randomized trial of two treatment models for opioid use disorder in prenatal clinics.

INTRODUCTION: The prevalence of opioid use disorder (OUD) in pregnancy increased nearly five-fold over the past decade. Despite this, obstetric providers are less likely to treat pregnant women with medication for OUD than non-obstetric providers (75% vs 91%). A major reason is many obstetricians feel unprepared to prescribe medication for opioid use disorder (MOUD). Education and support may increase prescribing and overall comfort in delivering care for pregnant women with OUD, but optimal models of education and support are yet to be determined. METHODS AND ANALYSIS: We describe the rationale and conduct of a matched-pair cluster randomized clinical trial to compare the effectiveness of two models of support for reproductive health clinicians to provide care for pregnant and postpartum women with OUD. The primary outcomes of this trial are patient treatment engagement and retention in OUD treatment. This study compares two support models: 1) a collaborative care approach, based upon the Massachusetts Office-Based-Opioid Treatment Model, that provides practice-level training and support to providers and patients through the use of care managers, versus 2) a telesupport approach based on the Project Extension for Community Healthcare Outcomes, a remote education model that provides mentorship, guided practice, and participation in a learning community, via video conferencing. DISCUSSION: This clustered randomized clinical trial aims to test the effectiveness of two approaches to support practitioners who care for pregnant women with an OUD. The results of this trial will help determine the best model to improve the capacity of obstetrical providers to deliver treatment for OUD in prenatal clinics. TRIAL REGISTRATION: Clinicaltrials.gov trial registration number: NCT0424039.

Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Therefore, we developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against RSV. The H-2Db-restricted, immunodominant peptides from RSV (M187-195 and NS161-75) were introduced to MHC-I on DC-derived exosomes to express peptide/MHC-I (pMHC-I) complexes. A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses. Ex vivo assays demonstrated that engineered exosomes carrying RSV-specific peptides can elicit interferon-gamma (IFN-γ) production by virus-specific CD8+ T cells isolated from RSV-infected C57BL/6 mice. In vivo assays demonstrated that subcutaneous administration of both M187-195 and NS161-75 engineered exosomes to mice, with or without additional adjuvant, appeared safe and well tolerated, however, did not prime antigen-specific CD8+ T cell responses. Surface engineered exosomes are immunogenic and promising for further development as a vaccine platform.

Hazardous characteristics of dust waste from metal manufacturing industries in South Korea.

The Ministry of Environment, South Korea, is involved in efforts to reduce safety-related accidents that could occur during hazardous waste disposal and minimise the environmental impacts of waste disposal. To reach such goals, new factors have been added that contribute to the hazardous characteristics of hazardous waste. The Ministry is also expanding regulations on inorganic and organic components present in hazardous waste for these factors and continues to correct the classification system to establish standards for waste components. Metallic dust, for example, is mostly generated during the operation of melting furnaces or precipitators and dangerous materials contained in this dust may cause accidents, such as explosions or fires. South Korean accident cases have confirmed that waste containing hazardous materials, such as Mg, Al and Mg-Al alloys, can cause such events. Therefore, this study analysed 28 dust samples collected from the dust accumulated in precipitators in 28 metal manufacturing facilities in South Korea. Nine samples were flammable and four samples were reactive to water. Two samples also exhibited leaching toxicities. The results applied to relevant laws in South Korea showed that the proportion of waste containing hazardous characteristics increased from 7.14% in the previous management category to 39.29% in the extended category, an overall increase of 32.15 percentage points.

Impact of delayed graft function on clinical outcomes in highly sensitized patients after deceased-donor kidney transplantation.

Background: We investigated whether the development of delayed graft function (DGF) in pre-sensitized patients affects the clinical outcomes after deceased-donor kidney transplantation (DDKT). Methods: The study included 709 kidney transplant recipients (KTRs) from three transplant centers. We divided KTRs into four subgroups (highly sensitized DGF, highly sensitized non-DGF, low-sensitized DGF, and low-sensitized non-DGF) according to panel reactive antibody level of 50%, or DGF development. We compared post-transplant clinical outcomes among the four subgroups. Results: Incidence of biopsy-proven acute rejection (BPAR) was higher in two highly sensitized subgroups than in low-sensitized subgroups. It tended to be higher in highly sensitized DGF subgroups than in the highly sensitized non-DGF subgroups. In addition, the highly sensitized DGF subgroup showed the highest risk for BPAR (hazard ratio, 3.051; P=0.005) and independently predicted BPAR. Allograft function was lower in the two DGF subgroups than in the non-DGF subgroup until one month after transplantation, but thereafter it was similar. Death-censored graft loss rates and patient mortality tended to be low when DGF developed, but it did not reach statistical significance. Conclusions: DGF development in highly sensitized patients increases the risk for BPAR in DDKT compared with patients without DGF, suggesting the need for strict monitoring and management of such cases.

Effects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Randomized Controlled Study.

BACKGROUND The decreased postural control ability of stroke patients affects their ability to balance in various postures such as sitting and standing. This study aimed to determine whether cognitive task training for stroke patients is effective in improving walking and balancing abilities. MATERIAL AND METHODS Seventeen stroke patients (10 males, 7 females) were randomized by ballot to be assigned to the cognitive task group (CBT) or the general task group (GBT). For the cognitive task training, a dual task of balance and cognition using traffic signals, a familiar form to the subjects, was applied as a program. In both groups the interventions were performed for 30 min a day, 3 times a week, for 4 weeks. The timed up and go test (TUG), the Berg balance scale (BBS), and gait ability evaluation were performed to compare the therapeutic effects. RESULTS After the intervention, the BBS showed significant differences in both groups (p<0.05). The cognitive task training group had significant improvement in all outcome scores after the intervention (p<0.05). The TUG score of the CBT group significantly decreased to 6.17 s (p<0.05), but that of the GBT showed no statistically significant change. CONCLUSIONS Cognitive task training could be used in clinical rehabilitation as a more effective intervention method to improve balance and gait ability of stroke patients.

Supplementing a Saccharomyces cerevisiae fermentation product modulates innate immune function and ameliorates bovine respiratory syncytial virus infection in neonatal calves.

The objectives of this study were to determine the effects of oral supplementation with Saccharomyces cerevisiae fermentation products (SCFP; SmartCare and NutriTek; Diamond V, Cedar Rapids, IA) on immune function and bovine respiratory syncytial virus (BRSV) infection in preweaned dairy calves. Twenty-four Holstein × Angus, 1- to 2-d-old calves (38.46 ± 0.91 kg initial body weight [BW]) were assigned two treatment groups: control or SCFP treated, milk replacer with 1 g/d SCFP (SmartCare) and calf starter top-dressed with 5 g/d SCFP (NutriTek). The study consisted of one 31-d period. On days 19 to 21 of the supplementation period, calves were challenged via aerosol inoculation with BRSV strain 375. Calves were monitored twice daily for clinical signs, including rectal temperature, cough, nasal and ocular discharge, respiration effort, and lung auscultation. Calves were euthanized on day 10 postinfection (days 29 to 31 of the supplementation period) to evaluate gross lung pathology and pathogen load. Supplementation with SCFP did not affect BW (P = 0.762) or average daily gain (P = 0.750), percentages of circulating white blood cells (P < 0.05), phagocytic (P = 0.427 for neutrophils and P = 0.460 for monocytes) or respiratory burst (P = 0.119 for neutrophils and P = 0.414 for monocytes) activity by circulating leukocytes either before or following BRSV infection, or serum cortisol concentrations (P = 0.321) after BRSV infection. Calves receiving SCFP had reduced clinical disease scores compared with control calves (P = 0.030), reduced airway neutrophil recruitment (P < 0.002), reduced lung pathology (P = 0.031), and a reduced incidence of secondary bacterial infection. Calves receiving SCFP shed reduced virus compared with control calves (P = 0.049) and tended toward lower viral loads in the lungs (P = 0.051). Immune cells from the peripheral blood of SCFP-treated calves produced increased (P < 0.05) quantities of interleukin (IL)-6 and tumor necrosis factor-alpha in response to toll-like receptor stimulation, while cells from the bronchoalveolar lavage (BAL) of SCFP-treated calves secreted less (P < 0.05) proinflammatory cytokines in response to the same stimuli. Treatment with SCFP had no effect on virus-specific T cell responses in the blood but resulted in reduced (P = 0.045) virus-specific IL-17 secretion by T cells in the BAL. Supplementing with SCFP modulates both systemic and mucosal immune responses and may improve the outcome of an acute respiratory viral infection in preweaned dairy calves.

Digital sextortion: Internet predators and pediatric interventions.

PURPOSE OF REVIEW: Sextortion is defined as the act of coercing people into sending explicit images of themselves and subsequently blackmailing victims with the public release of said images. Prosecutions of sextortion cases involving minors have increased almost two-fold in the past 5 years. The purpose of this review is to explore the literature regarding the behavior of both victims and perpetrators, the effects on victims, and the support resources available for clinicians, victims, and parents. RECENT FINDINGS: Sextortion begins as an unassuming request for personal pictures and quickly escalates. Minors targeted by predators fear both punishment by guardians and the social consequences that follow the release of their explicit pictures. This cycle of victimization endangers minors and may lead to mental health problems, such as anxiety and depression. Recently, sextortion cases have risen to the forefront of national attention through the mainstream media with celebrities revealed as both perpetrators and victims. This higher visibility of sextortion highlights the importance of reviewing recent research regarding minors and their online behavior and the tactics of perpetrators. SUMMARY: Sextortion, an extreme form of cyber abuse, endangers minors and may lead to anxiety and depression. Pediatricians should be familiar with the concept of sextortion and discuss its dangers and available resources with parents and minors.

Profuse and acute hemorrhagic gastroesophageal injury after cryotherapy in a cardiac surgery patient.

Upper gastrointestinal injury associated with cryoablation and under placement of transesophageal echocardiography (TEE) during cardiac surgery is a rare complication but potentially fatal. During the cryoablation for the treatment of atrial fibrillation, delivered cryoenergy can adversely affect the esophagus, resulting in gastroesophageal ulceration. The TEE probe itself also can induce adverse effects like esophageal ulceration or perforation. In this case report, we describe a case of emergent gastroesophageal injury with massive bleeding that occurred after manipulation of a TEE probe during cryoablation therapy in a cardiac surgery patient.