T‐cell immunoglobulin (Ig) and mucin domain‐containing 1 (Tim‐1) and Tim‐4 are two members of the Tim family. In mammals, Tim‐1 and Tim‐4 are proteins mainly expressed in immune cells and are ...associated with immune response. In the present study, medaka Oryzias latipes' Tim‐1 (OlTim‐1) and OlTim‐4 were identified and characterized using bioinformatics analyses. With the use of reverse‐transcription polymerase chain reaction, the expression profiles of OlTim‐1 and OlTim‐4 were examined in embryos and adult fish and in immune tissues following the intraperitoneal injection of stimulants. The results revealed that OlTim‐1 possesses a cytoplasmic region, a transmembrane region, a mucin domain, and an Ig‐like domain, while OlTim‐4 is composed of two Ig‐like domains and a mucin domain, but without the transmembrane region and cytoplasmic region. OlTim‐1 and OlTim‐4 expressions are detectable from the gastrula stage on, indicating that they are zygotic genes. Furthermore, OlTim‐1 and OlTim‐4 are expressed ubiquitously in the adult. Administration of immune stimulants, namely lipopolysaccharides and polyinosinic:polycytidylic acid, significantly increased the expression levels of OlTim‐1 and OlTim‐4 in the liver and intestine within 1 day and in the head, kidney, and spleen within 3 to 4 days postinjection. These results suggest that OlTim‐1 and OlTim‐4 are possibly involved in both innate and adaptive immunities.
Tim‐1 and Tim‐4 are expressed in medaka embryos from the gastrula stage onwards. In adult medaka, both genes are ubiquitously detected. Medaka Tim‐1 and Tim‐4 significantly respond to immune stimulants such as lipopolysaccharides and polyinosinic:polycytidylic acid. These findings suggest that both Tim‐1 and Tim‐4 are zygotic genes and possibly involved in immunity.
Research Highlights
1.
OlTim‐1 and OlTim‐4 exist ubiquitously in adult tissues and are zygotic genes in embryos of medaka.
2.
OlTim‐1 and OlTim‐4 respond to lipopolysaccharides and polyinosinic:polycytidylic acid.
It remains unclear whether type 2 diabetes and the complication of arthritis are causally related to the PM
pollutant. Therefore, we aimed to investigate the associations of long-term PM
exposure ...with type 2 diabetes and with arthritis in type 2 diabetes patients.
This study used data from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011-2018. The associations were analyzed by Cox proportional hazards regression models, and the population-attributable fraction (PAF) was calculated to assess the burden of type 2 diabetes and arthritis-attributable to PM
.
A total of 21,075 participants were finally included, with 19,121 analyzed for PM
and type 2 diabetes risk and 12,427 analyzed for PM
and arthritis risk, of which 1,382 with newly-diagnosed type 2 diabetes and 1,328 with arthritis during the follow-up. Overall, each 10 μg/m
increment in PM
concentration was significantly associated with an increase in the risk of type 2 diabetes (HR = 1.26, 95 %CI1.22 to 1.31), and the PAF of type 2 diabetes attributable to PM
was 13.54 %. In type 2 diabetes patients, each 10 μg/m
increment in PM
exposure was associated with an increase in arthritis (HR = 1.42, 95 %CI: 1.28 to 1.57), and the association was significantly greater than that (H = 1.23, 95 %CI: 1.19 to 1.28) in adults without type 2 diabetes. The PAFs of arthritis-attributable to PM
in participants with and without type 2 diabetes were 18.54 % and 10.69 %, respectively.
Long-term exposure to PM
may increase the risk of type 2 diabetes and make type 2 diabetes patients susceptible to arthritis.
To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of ...Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans.
Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch.
The procedures led to successful reperfusion in all the cases (Thrombolysis in Cerebral Infarction Grade 2b-3). Eleven patients (91.7%) had significantly decreased National Institute of Health Stroke scale (NIHSS) score at discharge.AmRS score of ≤2 at 90 days was achieved in 8 of the 12 patients (66.7%).
The mismatch between ASPECTS assessed based on ASL
Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different ...between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24
+0
and 31
+6
weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR aOR: 1.10; 95% CI: 0.41–2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82–1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31–4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16–2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval CI: 1.20–3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17–1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.
Conclusion
: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR.
What is Known:
• CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR.
• NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process.
What is New:
• CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC.
• Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.
Objectives:
The aim of the study is to assess clinical characteristics of individuals with nonsyndromic sensorineural hearing loss (NSSNHL) with genetic mutations in GJB2 and/or GJB6. We describe and ...compare one group with biallelic mutations against a group of heterozygote mutation carriers.
Methods:
A total of 350 patients between the ages of 3 months and 80 years referred to a tertiary care outpatient otology practice for NSSNHL were screened for genetic mutations. Direct sequencing of GJB2 and polymerase chain reaction analysis of GJB6 was performed and clinical data from history and physical, audiologic testing and radiographic studies were reviewed.
Results:
Thirty‐two patients were found to have biallelic mutations (incidence of 9.1%). Twenty‐five patients were found to have only one GJB2 mutation (incidence of 7.1%). Severe to profound hearing loss occurred in 85% of the homozygote group and 38% of the heterozygote group. Both groups similarly had a propensity toward bilateral, symmetric, nonprogressive hearing loss with rare inner ear malformations on radiologic imaging.
Conclusions:
These two patient populations have similar incidences in a cohort of patients evaluated for NSSNHL, which is higher than general population heterozygote carrier rates. Heterozygote mutation carriers had less hearing impairment, but most other factors demonstrated no differences. These results support the theory of an unidentified genetic factor contributing to hearing loss in some heterozygote carriers. Therefore, genetic counseling should consider the complexity of their genetic factors and the limitations of current screening. Laryngoscope, 2011
Abstract
Objectives Some Miller-Payne 4 and N0 patients with triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) who had better survival should avoid treatment escalation. We ...aimed to identify these patients based on spatial distributions of immunophenotypes at initial diagnosis.
Methods We retrospectively analyzed 272 TNBC patients with Miller-Payne grade 4/5 and N0 for tumor-infiltrating lymphocytes (TILs) in relation to clinical survival. The spatial immunophenotypes were analyzed by multiplexed ion beam imaging by time of flight combined with proteomic. A prognostic classifier was established by the random forest algorithm.
Results The 5-year disease-free survival (DFS) was 63.8% for Miller-Payne 4 and 83.0% for Miller-Payne 5 (p=0.003), and overall survival (OS) was 71.0% and 85.5% respectively (p=0.007). High TILs were significantly associated with better DFS and OS in the Miller-Payne 4 patients (both p=0.016). Spatially, Miller-Payne 4 with good prognosis exhibited inflamed phenotype, with dominant CD8+ T cells on tumor center, few scattered CD68+ myeloid-derived cells far away from T cells, and deposit of increased lymphocyte activate molecules. Miller-Payne 4 with poor prognosis presented excluded phenotype, with few CD8+ T cells restricted to invasive margin, high density of CD14+CD68+CD11c+ myeloid cells with related molecules. These spatial immunophenotypes provided a good classifier model (AUC=0.975) to identify Miller-Payne 4 patients with different prognosis. We also observed similar signatures in Miller-Payne 5.
Conclusion Spatial immunophenotypes may indicate the prognosis in TNBC assessed as Miller-Payne 4 and N0.
Citation Format: Jianli Ma, Yuwei Deng, Dawei Chen, Xiaomei Li, Zhiyong Yu, Haibo Wang, Lei Zhong, Yingjie Li, Chengqin Wang, Xiaoping Zhou, Xiang Li, Qingyuan Zhang, Jinming Yu. Spatial immunophenotypes contribute to predict survival of triple-negative breast cancer assessed as Miller-Payne grade 4 and N0 after neoadjuvant therapy. abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5872.
The evolution of the H5N1 highly pathogenic avian influenza virus (HPAIV) has resulted in high sequence variations and diverse antigenic properties in circulating viral isolates. We investigated ...immune responses induced by HA DNA vaccines of two contemporary H5N1 HPAIV isolates, A/bar-headed goose/Qinghai/3/2005 (QH) and A/chicken/Shanxi/2/2006 (SX) respectively, against the homologous as well as the heterologous virus isolate for comparison. Characterization of antibody responses induced by immunization with QH-HA and SX-HA DNA vaccines showed that the two isolates are antigenically distinctive. Interestingly, after immunization with the QH-HA DNA vaccine, subsequent boosting with the SX-HA DNA vaccine significantly augmented antibody responses against the QH isolate but only induced low levels of antibody responses against the SX isolate. Conversely, after immunization with the SX-HA DNA vaccine, subsequent boosting with the QH-HA DNA vaccine significantly augmented antibody responses against the SX isolate but only induced low levels of antibody responses against the QH isolate. In contrast to the antibody responses, cross-reactive T cell responses are readily detected between these two isolates at similar levels. These results indicate the existence of original antigenic sin (OAS) between concurrently circulating H5N1 HPAIV strains, which may need to be taken into consideration in vaccine development against the potential H5N1 HPAIV pandemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the ...prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24–28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65–083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57–0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58–0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52–0.66), and early extubating (aOR, 0.42; 95%CI 0.37–0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results.
Conclusion
: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form.
What is Known:
• Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown.
What is New:
• The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination.
Previous studies showed that the water extract (PVW) from Spica of Prunella vulgaris Linn. (Labiatae) exerts anti-herpes simplex virus (HSV) activity. Evaluation the antiviral activity of the graded ...ethanol precipitations indicated that 30% ethanol precipitate (PVE30) was the active principle of water extract (PVW). Further activity-oriented separation of PVE30 through salting-out method revealed that the anti-HSV activity of P. vulgaris glycoconjugates (PVG) was more potent than PVE30 and PVW, 2-fold and 4-fold, respectively. UPLC-QTOF-MS/MS, FT-IR and NMR techniques identified PVG as a type of polyphenolic-protein-polysaccharides (PPPs) with an average molecular weight of 41.69 kDa. PVG was composed of dibenzylbutyrolactone lignan units, and rich in galacturonic acid, xylose, rhamnose, rhamnose, arabinose, glucose monosaccharide units, glutamic acid and aspartic acid. Further in vitro antiviral testing confirmed that PVG substantially and stably inhibited acyclovir (ACV) resistant HSV strains; its inhibitory action was even better than the positive control ACV. Overall, our findings support PVG as a potential drug resource for anti-HSV therapy.
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