Nevin Manimala

J Paediatr Child Health. 2022 Jul 23. doi: 10.1111/jpc.16128. Online ahead of print.

ABSTRACT

AIM: The sepsis risk calculator (SRC) has been shown to reduce empirical antibiotic usage in neonates at risk of early-onset sepsis without increasing adverse clinical outcomes. However, its use for categorising and improving identification of at-risk neonates exposed to chorioamnionitis in the local population has not been reported. This study compares the management guided by the SRC to our unit’s clinical practice of administering empirical antibiotics to all term neonates (born ≥37 weeks gestation), symptomatic and asymptomatic, who were exposed to chorioamnionitis, and evaluates the performance of the SRC in managing asymptomatic term neonates exposed to chorioamnionitis.

METHODS: This single-centre retrospective study identified 178 eligible term neonates exposed to chorioamnionitis over a 17-month study period. Relevant demographic and clinical information on the mother-infant dyad was collected. The SRC was executed retrospectively in the study cohort. Descriptive statistics were used for reporting the findings.

RESULTS: The mean gestational age was 39 (standard deviation, SD 1) weeks, and the mean birth weight was 3472 (SD 482) g. Of the 178 neonates, 136 (76%) were asymptomatic and received empirical antibiotic therapy for 2 days (mean). Based on management recommendations from the SRC, empirical antibiotic therapy could have been avoided in 98% of asymptomatic neonates; 88% could have been managed by observation alone, avoiding mother-infant separation. No neonate died or had a positive blood culture result.

CONCLUSIONS: The SRC could reduce antibiotic exposure in asymptomatic neonates exposed to chorioamnionitis. It could assist clinicians to categorise risk in neonates exposed to chorioamnionitis.

PMID:35869737 | DOI:10.1111/jpc.16128

Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):60-63. doi: 10.14715/cmb/2022.68.2.9.

ABSTRACT

This experiment was conducted to investigate the effect of taking Baihe Gujin decoction combined with Shengmai powder on IL-1β and IL-1Ra expression in peripheral blood CD14+ monocytes from patients with pulmonary tuberculosis. For this purpose, one hundred adult patients with primary pulmonary tuberculosis were selected for the study. The age of the enrolled cases ranged from 18 to 60 years old, with a controlled male to the female sex ratio of about 1:1. The Chinese medical evidence was considered to be a qi-yin deficiency type of pulmonary consumption. The patients were randomly divided into experimental and control groups, 50 cases each. In addition, 50 cases of healthy people were selected as a healthy control group, totaling 150 cases. In the experimental group, patients were given Baihe gujin decoction and Shengmai powder based on conventional western medicine, 1 dose for 1 day, 150mL/time for 2 times. The control group was treated with conventional Western medicine. 2 mL of fasting elbow venous blood from the subjects was taken in the morning. Peripheral blood mononuclear cells were isolated by density centrifugation. Monocytes were obtained after incubation with 5 μL of CD14+ immune magnetic beads at 4°C. The relative expression of IL1β and IL1R genes were measured using real-time quantitative PCR (RT-PCR), respectively. Results showed that the relative expression of IL1β and IL1R genes was significantly lower in the experimental group after 3 months compared with the control group, and the statistical difference was highly significant (p<0.01). It was concluded that the administration of Baihe gujin decoction and Shengmai powder was closely related to the relative expression of IL1β and IL1R genes in patients’ serum, indicating that Baihe gujin decoction and Shengmai powder have an important role in improving the clinical symptoms of pulmonary tuberculosis.

PMID:35869725 | DOI:10.14715/cmb/2022.68.2.9

Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):19-25. doi: 10.14715/cmb/2022.68.2.3.

ABSTRACT

The aetiology of oral lichen planus (OLP) is multifactorial, having variable triggers. A role for vitamin D related to the immune system has been established. Vitamin D modulating effect is on the adaptive and innate immune responses. Our study aimed to compare serum levels of vitamin D in patients having different clinical symptoms of OLP (symptomatic or asymptomatic) with healthy individuals. Also, in this study, for further evaluation, the expression level of interleukin-17A and interleukin-6 (IL-17A and IL-6) was evaluated because the presence of active vitamin D reduces the expression of these pro-inflammatory factors. This study was included three groups with 30 volunteers in each. The first group included asymptomatic oral lichen planus patients (reticular or plaque-like lesions). The second group consisted of symptomatic oral lichen planus patients (atrophic or bullous-erosive lesions). In contrast, the third group consisted of healthy control subjects. The serum 25-hydroxyvitamin D was measured between the three groups and then correlated with clinical manifestation of oral lichen planus, either symptomatic or non-symptomatic. The Real-Time PCR technique was used to evaluate the expression of IL-17A and IL-6. Patients with symptomatic OLP (second group) had statistically significantly lower Vitamin D levels than asymptomatic OLP patients (first group). Healthy Controls (third group) exhibited statistically significantly higher vitamin D levels than OLP groups. The results of IL-17A and IL-6 genes expression showed that the presence of vitamin D had a statistically significant effect on reducing the expression of these two pro-inflammatory cytokines among symptomatic and asymptomatic OLP patients. Also, the results showed that there was a statistically significant difference between OLP patients (group I and II) and the control group (group III). In general, the current study results showed that lack of vitamin D had an important role in initiating or increasing the OLP’s severity.

PMID:35869723 | DOI:10.14715/cmb/2022.68.2.3

Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):48-53. doi: 10.14715/cmb/2022.68.2.7.

ABSTRACT

This work was developed to investigate the activation of silent information regulator 1 (SIRT1) to regulate hypoxia-induced oxidative stress in cardiomyocytes through the PI3K/MTOR signaling pathway. For this purpose, 30 SD healthy rats were selected, and 10 of them were randomly selected as the control group. The remaining 20 rats were established as acute myocardial infarction model rats, and randomly divided into model group and activated SIRT1 group. Interventions were performed on rats in each of the 3 groups. ROS staining, inflammatory factors [IL-6, IL-1β levels], H9c2 cell viability, Caspase3 and Caspase8 activity, antioxidant enzyme indexes [SOD, CAT, MDA levels], SIRT1, PI3K, MTOR, HIF-1α, HO-1, GLUT1 mRNA expression were compared between groups. Results showed that IL-6 and IL-1β levels were abnormally elevated in the model group compared with the control group (P<0.05). IL-6 and IL-1β levels decreased in the activated SIRT1 group compared with the model group (P<0. 05). H9c2 cell viability decreased and Caspase3 and Caspase8 activities increased in the model group compared with the control group(P <0.05). H9c2 cell viability increased and Caspase3 and Caspase8 activities decreased in the activated SIRT1 group compared with the model group (P<0.05). SOD and CAT levels were abnormally decreased and MDA levels were abnormally increased in the model group compared with the control group (P<0.05). SOD and CAT levels were abnormally increased and MDA levels were decreased in the activated SIRT1 group compared with the model group (P<0.05). PI3K and SIRT1 expression decreased and MTOR expression increased in the model group compared with the control group (P < 0. 05). PI3K and SIRT1 expression increased and MTOR expression decreased in the activated SIRT1 group compared with the model group(P<0.05). The expression of HIF-1α, HO-1 and GLUT1 mRNA increased in the model group compared with the control group, and the difference was statistically significant (P <0.05). The expression of HIF-1α, HO-1, and GLUT1 mRNA decreased in the activated SIRT1 group compared with the model group, and the difference was statistically significant (P<0.05). It was concluded that the activation of SIRT1 can regulate PI3K/MTOR signaling pathway, thus reducing hypoxia-induced oxidative stress in cardiomyocytes, inflammatory conditions and enhancing cardiomyocyte viability, with better intervention effects.

PMID:35869722 | DOI:10.14715/cmb/2022.68.2.7

Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):178-182. doi: 10.14715/cmb/2022.68.2.25.

ABSTRACT

Endodontic treatment of immature permanent teeth has various problems. Today, the primary goal in the treatment of such teeth is to preserve the life of the pulp so that roots can develop entirely and naturally. If vital pulp therapy can treat these teeth, the treatment will be simpler and less expensive. Therefore, this study compared vital pulp therapy (including calcium-enriched mixture (CEM) cement and MTA methods) and root canal therapy (RCT) in symptomatic immature permanent molars. Also, the expression of TLR-2 and TLR-4 was evaluated in the gingival tissue of patients for further evaluation. In this clinical trial study, 615 patients randomly received three treatments: pulpotomy with CEM (205 cases), pulpotomy with MTA (207 cases), and root canal therapy (203 cases). The presence of periapical lesion was evaluated radiographically at three-time points: start, six months, and 12 months after treatment. The expression of TLR-2 and TLR-4 was also evaluated in the gingival tissue of patients by the Real-time PCR technique. The one-year follow-up of the periapical index shows that the presence of periapical lesion at six-month follow-up in the three groups of MTA, CEM, and RCT equals 14 cases (8%), 7 cases (4%), and 40 cases (22%). The one-year follow-up equals 12 cases (7%), 9 cases (5%), and 33 cases (18%), respectively. The TLR-2 and TLR-4 gene expression results showed no statistical difference between the three groups (CEM, MTA, and RCT). Still, one year after treatment, there was a statistically different between vital pulp therapy (CEM and MTA) and root canal therapy (P<0.05). Also, the results showed no statistical difference between CEM and MTA treatment in terms of TLR-2 and TLR-4 gene expression before and one year after treatment. In general, the results showed that pulpotomy treatment using two biomaterials, CEM and MTA, is more successful than RCT treatment.

PMID:35869721 | DOI:10.14715/cmb/2022.68.2.25

Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):87-93. doi: 10.14715/cmb/2022.68.2.13.

ABSTRACT

The purpose of this study was to investigate the effects of propofol anesthesia combined with remifentanil on inflammation, stress response, and immune function in children undergoing tonsil and adenoid surgery. For this aim, 126 children admitted to our hospital for elective temperature-controlled radio-frequency of tonsils and adenoids from October 2020 to September 2021 were randomly divided into an observation group (n=63) and a control group (n=63). The observation group was anesthetized with propofol in combination with remifentanil, while the control group underwent propofol combined with ketamine. The mean arterial pressure (MAP), heart rate, serum C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), epinephrine, cortisol (Cor), CD3+ T lymphocytes, CD4+ helper T lymphocytes, CD8+ suppressor T lymphocytes and CD4+/CD8+ ratio were compared between the two groups before induction of anaesthesia (T1), upon intubation (T2), at the beginning of surgery (T3), at the end of surgery (T4) and 5 min after extubation (T5). -(TNF-α). The recovery time from anaesthesia and adverse reactions after extubation were observed in the two groups. Results showed that the MAP and heart rate in both groups increased significantly at T2 compared to T1, but the observation group had lower values than the control group after the maintenance of anaesthesia (P<0.05). Serum CRP, IL-6 and TNF-α levels increased with time in both groups, and the increase was considered significant (P<0.05). In addition, serum epinephrine and Cor levels gradually rose from T1 to T4 in both groups, and then decreased at T5. The difference was statistically significant (P<0.05) between any two-time points. CRP, IL-6, TNF-α, epinephrine and Cor in the observation group were significantly lower than those in the control group from T3 to T5 (P<0.05). CD3+, CD4+ and CD4+/CD8+ ratio decreased whereas CD8+ went up in both groups at T4 and T5, and which were considered statistically significant when compared with data from T1 to T3 (P<0.05). However, CD3+, CD4+, CD8+ and CD4+/CD8+ ratios did not differ statistically significantly between the two groups at each time point (P>0.05). In the observation group, the time to recovery of spontaneous respiration, the time to resumption of limb movements and the span from discontinuation of anaesthetic to extubation were all significantly shorter than those in the control group, and the incidence of agitation during the awakening period was lower than that in the control group (P<0.05). Then propofol combined with remifentanil is more effective in inflammation, stress response and immune function in anesthetizing children undergoing tonsil and adenoid surgery. The observation group presented more stable hemodynamics, lower levels of inflammation and stress reactions, rapid awakening and fewer adverse effects, so the combination therapy was worthy of clinical promotion in pediatric surgery requiring general anesthesia.

PMID:35869719 | DOI:10.14715/cmb/2022.68.2.13

Mutagenesis. 2022 Jul 23:geac012. doi: 10.1093/mutage/geac012. Online ahead of print.

ABSTRACT

Two prototypical genotoxicants, benzo[a]pyrene (B[a]P) and colchicine (COL), were selected as model compounds to deduce their quantitative genotoxic dose-response relationship at low doses in a multi-endpoint genotoxicity assessment platform. Male Sprague-Dawley rats were treated with B[a]P (2.5-80 mg/kg bw/day) and COL (0.125-2 mg/kg bw/day) daily for 28 days. The parameters included were as follows: comet assay in the peripheral blood and liver, Pig-a gene mutation assay in the peripheral blood, and micronucleus test in the peripheral blood and bone marrow. A significant increase was observed in Pig-a mutant frequency in peripheral blood for B[a]P (started at 40 mg/kg bw/day on Day 14, started at 20 mg/kg bw/day on Day 28), whereas no statistical difference for COL was observed. Micronucleus frequency in reticulocytes of the peripheral blood and bone marrow increased significantly for B[a]P (80 mg/kg bw/day on Day 4, started at 20 mg/kg bw/day on Days 14 and 28 in the blood; started at 20 mg/kg bw/day on Day 28 in the bone marrow) and COL (started at 2 mg/kg bw/day on Day 14, 1 mg/kg bw/day on Day 28 in the blood; started at 1 mg/kg bw/day on Day 28 in the bone marrow). No statistical variation was found in indexes of comet assay at all time points for B[a]P and COL in the peripheral blood and liver. The dose-response relationships of Pig-a and micronucleus test data were analyzed for possible point of departures using three quantitative approaches, i.e., the benchmark dose, breakpoint dose, and no observed genotoxic effect level. The practical thresholds of the genotoxicity of B[a]P and COL estimated in this study were 0.122 and 0.0431 mg/kg bw/day, respectively, and our results also provided distinct genotoxic mode of action of the two chemicals.

PMID:35869703 | DOI:10.1093/mutage/geac012

Muscle Nerve. 2022 Jul 23. doi: 10.1002/mus.27681. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: We studied COVID-19 vaccination-related adverse events (ADEs) 7-days post-vaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).

METHODS: 7-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics and multivariable regression were performed.

RESULTS: 10,900 respondents [1227 IIMs; 4640 SAIDs; 5033 healthy controls (HCs), median age 42 (IQR 30-55) years, 74% female, 45% Caucasian, 69% completely vaccinated] were analysed. 76.3% IIMs patients reported minor and 4.6% major ADEs. Patients with active IIMs reported more frequent major [OR 2.7 (1.04-7.3)] and minor [OR 1.5 (1.1-2.2)] ADEs than inactive IIMs. Rashes were more frequent in IIMs [OR-2.3(1.2-4.2)] than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs [OR 1.9 (1.1-3.3), OR 2.2 (1.1-4.3)]. Overall, ADEs were less frequent in inclusion body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients DISCUSSION: 7-day post-vaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rashes in IIMs. Patients with DM, active disease may be at higher risk, and IBM patients at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, and specifically in IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines. This article is protected by copyright. All rights reserved.

PMID:35869701 | DOI:10.1002/mus.27681

Pharmacotherapy. 2022 Jul 22. doi: 10.1002/phar.2722. Online ahead of print.

ABSTRACT

BACKGROUND: Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring.

METHODS: Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- versus trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane’s Q test and I² statistics.

RESULTS: A total of 10 studies with 4,231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469 – 0.834), p=0.001; I² =25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261 – 0.863), p=0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341 – 0.894), p=0.016] but failed to find significance in the alternative definitions.

CONCLUSIONS: AUC-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.

PMID:35869689 | DOI:10.1002/phar.2722

Eur J Dent Educ. 2022 Jul 22. doi: 10.1111/eje.12837. Online ahead of print.

ABSTRACT

INTRODUCTION: Dentistry professionals may experience significantly higher occupational stress than other health professionals and dentistry academics may have specific work content and context sources of stress.

AIMS: To identify common sources of occupational stress, and how these are associated with wellbeing, in dentistry academics.

METHODS: A cross-sectional online survey with staff in Dentistry departments in Australia and New Zealand. Assessment included 23-items from five general domains of occupational stress from the NIOSH – Generic Job Stress Questionnaire, a 23-item list of sources of stress and the 22-item Psychological General Well-Being Index. Analyses used descriptive statistics and multiple linear regression.

RESULTS: 107 respondents (average age 50±11.7 years, 56.8% men) completed the survey. Leading sources of occupational stress were job future, time pressure at work, work overload, and administration demands. A multiple linear regression model significantly predicted wellbeing, F(8,77)=13.141, p=.000, adj.R² =.53, but there were no significant associations for any of the specific sources of stress.

CONCLUSION: The combination of time pressure, workload and responsibility, job dissatisfaction, low social support, and uncertain job future was inversely associated with wellbeing among these dentistry academics. Future studies should consider the development and evaluation of interventions to address these concerns.

PMID:35869687 | DOI:10.1111/eje.12837