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Association between serum secretory phospholipase A2 and risk of ischemic stroke

Eur J Neurol. 2021 Jul 3. doi: 10.1111/ene.15004. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Previous literature has demonstrated an association between high serum levels of type-II secretory phospholipase A2 (sPLA2) concentration and an increased risk of coronary artery disease. However, such association has not been established in terms of ischemic stroke risk. We aimed to evaluate the association between both sPLA2 concentration and activity as continuous variables with risk of future ischemic stroke.

METHODS: We conducted a nested case-control study using data from the European Prospective Investigation into Cancer – Norfolk study. Cases (n=145) in the current study were participants who developed ischemic stroke during follow-up, with controls (n=290) matched in a 2:1 ratio based on age and sex. Statistical analyses were performed using SPSS (version 25.0, Chicago, Ill) software. Logistic regression was used to determine odds ratios (OR) and corresponding 95% confidence intervals (95% CIs) for ischemic stroke.

RESULTS: After adjusting for a wide array of cardiovascular confounders, sPLA2 activity was found to be associated with an increased risk of ischemic stroke using both multiple imputations with chained equations and complete case analysis: OR 1.20 (95% CI: 1.01-1.43) and OR 1.23 (95% CI: 1.01 -1.49), respectively. However, sPLA2 concentration was not found to be associated with increased risk of ischemic stroke.

CONCLUSIONS: The activity of sPLA2, but not sPLA2 concentration, is associated with an increased risk of future ischemic stroke. This finding may be significant in risk group stratification, allowing targeted prophylactic treatment, or the development of novel therapeutic agents.

PMID:34216520 | DOI:10.1111/ene.15004

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Epidemiologic, immunologic, and virus characteristics in patients with paired SARS-CoV-2 serology and reverse transcription polymerase chain reaction testing

J Infect Dis. 2021 Jul 3:jiab349. doi: 10.1093/infdis/jiab349. Online ahead of print.

ABSTRACT

BACKGROUND: The natural history and clinical progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can be better understood using combined serological and reverse transcription polymerase chain reaction (RT-PCR) testing.

METHODS: Nasopharyngeal swabs and serum were collected at a single time-point from patients at an urban, public hospital August – November 2020 and tested for SARS-CoV-2 using RT-PCR, viral culture, and anti-Spike pan-Ig antibody testing. Participant demographics and symptoms were collected through interview. Chi-squared and Fisher’s exact tests were used to identify associations between RT-PCR and serology results with presence of viable virus and frequency of symptoms.

RESULTS: Among 592 participants, 129 (21.8%) had evidence of SARS-CoV-2 infection by RT-PCR or serology. Presence of SARS-CoV-2 antibodies was strongly associated with lack of viable virus (p-value=0.016). COVID-19 symptom frequency was similar for patients testing RT-PCR positive/seronegative and patients testing RT-PCR positive/seropositive. Patients testing RT-PCR positive/seronegative reported headaches, fatigue, diarrhea and vomiting at rates not statistically significantly different from those testing RT-PCR negative/seropositive.

CONCLUSIONS: While patients testing SARS-CoV-2 seropositive were unlikely to test positive for viable virus and were therefore low-risk for forward transmission, COVID-19 symptoms were common. Paired SARS-CoV-2 RT-PCR and antibody testing provides more nuanced understanding of patients’ COVID-19 status.

PMID:34216468 | DOI:10.1093/infdis/jiab349

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Follow-up genotoxicity assessment of Ames-positive/equivocal chemicals using the improved thymidine kinase gene mutation assay in DNA repair-deficient human TK6 cells

Mutagenesis. 2021 Jul 3:geab025. doi: 10.1093/mutage/geab025. Online ahead of print.

ABSTRACT

Genotoxicity testing plays an important role in the safety assessment of pharmaceuticals, pesticides, and chemical substances. Among the guidelines for various genotoxicity tests, the in vitro genotoxicity test battery comprises the bacterial Ames test and mammalian cell assays. Several chemicals exhibit conflicting results for the bacterial Ames test and mammalian cell genotoxicity studies, which may stem from the differences in DNA repair capacity or metabolism, between different cell types or species. For better understanding the mechanistic implications regarding conflict outcomes between different assay systems, it is necessary to develop in vitro genotoxicity testing approaches with higher specificity towards DNA-damaging reagents. We have recently established an improved thymidine kinase (TK) gene mutation assay (TK assay) that is deficient in DNA excision repair system using human lymphoblastoid TK6 cells lacking XRCC1 and XPA (XRCC1 -/-/XPA -/-), the core factors of base excision repair and nucleotide excision repair, respectively. This DNA repair-deficient TK6 cell line is expected to specifically evaluate the genotoxic potential of chemical substances based on the DNA damage. We focused on four reagents, N-(1-naphthyl)ethylenediamine dihydrochloride (NEDA), p-phenylenediamine (PPD), auramine, and malachite green (MG) as the Ames test-positive chemicals. In our assay, assessment using XRCC1 -/-/XPA -/- cells revealed no statistically significant increase in the mutant frequencies after treatment with NEDA, PPD, and MG, suggesting the chemicals to be non-genotoxic in humans. The observations were consistent with that of the follow-up in vivo studies. In contrast, the mutant frequency was markedly increased in XRCC1 -/-/XPA -/- cells after treatment with auramine. The results suggest that auramine is the genotoxic reagent that preferentially induces DNA damages resolved by BER and/or NER in mammals. Taken together, BER/NER deficient cell-based genotoxicity testing will contribute to elucidate the mechanism of genotoxicity and therefore play a pivotal role in the accurate safety assessment of chemical substances.

PMID:34216473 | DOI:10.1093/mutage/geab025

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Comparison of the 2011 and 2019 Kampo Medicine Curricula Across All Japanese Medical Schools

Tokai J Exp Clin Med. 2021 Jul 20;46(2):75-82.

ABSTRACT

OBJECTIVE: To examine how Kampo education in Japanese medical schools changed between 2011 and 2019.

METHODS: We administered nationwide postal questionnaire surveys about current characteristics of Kampo medicine education in all 82 Japanese medical schools, directed to the persons responsible for Kampo education at each university. One survey was conducted in 2011 and one in 2019. Analysis used Welch’s t-test and a chi-squared test.

RESULTS: The average class meeting time was shorter in 2019 than in 2011. The proportion of class meetings that were about Kampo saw a statistically significant increase in the third year and a significant decrease in the fourth and sixth years of medical school. Curriculum standardisation, preparation of simple textbooks, and fostering Kampo medicine instructors were the primary problems in both years. The proportion of mainstream medical education contents focusing on traditional Japanese Kampo medicine did not change over time, nor did the percentage of those considering using standardised textbooks. Other changes were statistically nonsignificant.

CONCLUSION: In Japanese medical schools, the number of class meetings teaching Kampo medicine has increased; however, this number is not statistically significant. Persistent problems in Kampo education, including curriculum standardisation, need to be addressed.

PMID:34216479

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Relapse of Plasmodium vivax and Plasmodium ovale malaria with and without primaquine treatment in a non-endemic area

Clin Infect Dis. 2021 Jul 3:ciab610. doi: 10.1093/cid/ciab610. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of primaquine in preventing P. vivax relapses from dormant stages is well established. For P. ovale, the relapse characteristics and the use primaquine is not as well studied. We set to evaluate the relapsing properties of these two species, in relation to primaquine use among imported malaria cases in a non-endemic setting.

METHODS: We performed a nationwide retrospective study of malaria diagnosed in Sweden 1995-2019, by reviewing medical records of 3254 cases. All episodes of P. vivax (n=972) and P. ovale (n=251) were selected for analysis.

RESULTS: First time relapses were reported in 80/857 (9.3%) P. vivax and 9/220 (4.1%) P. ovale episodes, respectively (p<0.01). Without primaquine, the risk for relapse was higher in P. vivax, 20/60 (33.3%), compared to 3/30 (10.0%) in P. ovale (HR 3.5, 95% CI 1.0-12.0). In P. vivax, patients prescribed primaquine had a reduced risk of relapse compared to episodes without relapse preventing treatment, 7.1% vs 33.3%, (HR 0.2, 95%CI 0.1-0.3). In P. ovale, the effect of primaquine on the risk of relapse did not reach statistical significance, with relapses seen in 2.8% of the episodes compared to 10.0% in patients not receiving relapse preventing treatment (HR 0.3, 95% CI 0.1-1.1).

CONCLUSION: The risk of relapse was considerably lower in P. ovale than in P. vivax infections indicating different relapsing features between the two species. Primaquine was effective in preventing P. vivax relapse. In P. ovale, relapse episodes were few and the supportive evidence for primaquine remains limited.

PMID:34216464 | DOI:10.1093/cid/ciab610

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Evaluation of Liposomal Bupivacaine at Split Thickness Skin Graft Donor Sites Through a Randomized, Controlled Trial

J Burn Care Res. 2021 Jul 3:irab129. doi: 10.1093/jbcr/irab129. Online ahead of print.

ABSTRACT

Split thickness skin grafts (STSG) are commonly required in reconstructive surgery but may cause significant pain. The goal of this investigator-initiated trial is to evaluate the effect of liposomal bupivacaine on donor site pain and opioid consumption. A parallel, randomized, controlled trial of adult acute burn patients with <20% total body surface area burns (TBSA) was conducted to evaluate the efficacy of liposomal bupivacaine at STSG donor sites. The control group received standard subcutaneous infiltration of dilute lidocaine solution at the STSG donor site, and the experimental group received dilute liposomal bupivacaine infiltration in a similar fashion. Donor site pain scores and opioid consumption in morphine equivalents (MEE) were evaluated. A total of 25 patients were enrolled in each group. There were no statistical differences in demographic variables, and TBSA was 4.0% in both groups (p=.94). There were no statistical differences in pain scores at any time point postoperatively (mean control range 3.1/10-4.9/10, experimental range 3.3/10-4.3/10, p=.12-.96). There were no statistical differences in opioid consumption at 24, 48, or 72 hours postoperatively between the groups (mean control MEE range 49.3-71.1, experimental MEE range 63.6-75.8, p=.34-.85). The average length of stay was 7.7 days in both groups (p=.88). No adverse events occurred in either group. There is no statistical benefit to the use of liposomal bupivacaine for infiltration at STSG donor sites compared to standard of care with respect to pain control, opioid use, or length of stay when evaluated in a randomized, controlled fashion.

PMID:34216466 | DOI:10.1093/jbcr/irab129

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Phase behaviour and crystal structures of 2′,3′-difluorinated p-terphenyl derivatives

Acta Crystallogr C Struct Chem. 2021 Jul 1;77(Pt 7):435-440. doi: 10.1107/S2053229621006367. Epub 2021 Jun 28.

ABSTRACT

The crystal structures of difluorine derivatives of p-terphenyls (nTm) have been determined by single-crystal X-ray diffraction. For the unsymmetrical substituted compounds 2′,3′-difluoro-4-methyl-p-terphenyl (1T0, C19H14F2) and 4-ethyl-2′,3′-difluoro-4”-methyl-p-terphenyl (1T2, C21H18F2), the crystal structure is disordered, with molecules statistically entering the crystal in up and down orientations, with full superposition of all the atoms, except for those of the terminal groups (H/methyl for 1T0 and methyl/ethyl for 1T2). For triclinic 2′,3′-difluoro-4,4”-dimethyl-p-terphenyl (1T1, C20H16F2), with the space group P-1, the two crystallographically independent molecules have the same conformation, which is different from monoclinic 1T0 (space group C2) and 1T2 (space group C2/c). A common feature of the conformation of the three compounds is the noncoplanar twisted arrangement of the three rings of the p-terphenyl moiety. Two-dimensional (2D) Hirshfeld fingerprint plots are consistent with H…H and C…H contacts in the crystal packing. For the three compounds, the phase behaviour has been investigated by POM (Petra/Osiris/Molinspiration) and differential scanning calorimetry (DSC) analysis. 1T2 is mesogenic, with enantiotropic nematic behaviour.

PMID:34216450 | DOI:10.1107/S2053229621006367

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Diagnosis of parotid gland tumours with Contrast-Enhanced Ultrasound: a systematic review and meta-analysis

Med Ultrason. 2021 Jul 1. doi: 10.11152/mu-3119. Online ahead of print.

ABSTRACT

AIM: Contrast-enhanced ultrasound (CEUS) appears to be a promising application for the diagnosis of parotid gland tumours. We aimed to systematically review and meta-analyse the ability of CEUS in distinguishing benign from malignant parotid gland tumours.

MATERIAL AND METHODS: PubMed was searched for relevant studies. Data on area under time intensity curve (AUC) in arbitrary unit (AU), and mean transit time (MTT) in seconds (sec) were analysed using the Cochrane Review Manager Software.

RESULTS: Nine studies met the eligibility criteria comprising a total number of 498 parotid gland tumours (benign, number (n)=423; malignant, n=75). Descriptive evaluation of parotid gland tumours following CEUS administration showed overlap characteristics in benign and malignancies. Two publications assessed AUC and MTT in 72 and 60 parotid gland tumours, respectively. AUC was significantly lower in benign compared to malignant tumours following contrast administration (AUC, mean difference (MD) -266.77 AU, 95% confidence intervals (CI) -433.22, -100.33, p=0.002). No significant different in MTT between benign and malignant tumours (p=0.12). Heterogeneity was statistically significant in AUC (p=0.04) and MTT (p<0.00001).

CONCLUSION: Descriptive evaluation of parotid gland tumours showed overlap CEUS characteristics. Perfusion related CEUS parameters analysis is promising in differentiating benign parotid tumours from malignancies.

PMID:34216453 | DOI:10.11152/mu-3119

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Colour Doppler imaging of retrobulbar circulation in different severity of glaucoma optic neuropathy

Med Ultrason. 2021 Jun 14. doi: 10.11152/mu-2954. Online ahead of print.

ABSTRACT

AIMS: To compare retrobulbar hemodynamic measured by colour Doppler imaging (CDI) in patients with a different severity of glaucoma and to correlate variables CDI with the structural parameters of the retina and optic disc.

MATERIAL AND METHODS: Of 89 eyes studied, 31 had preperimetric, 29 early, 12 moderate and 17 advanced glaucoma. Peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI) in ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs) were evaluated by CDI and compared between study groups. Retinal nerve fibre layer thickness (RNFL) and optic disc parameters measured with optical coherent tomography (OCT) were correlated with the Doppler variables.

RESULTS: In eyes with advanced, moderate and early glaucoma EDV SPCAs were significantly lower as well as RI SPCAs were significantly higher compared to the eyes with preperimetric glaucoma. In eyes with advanced and moderate glaucoma RI CRA (0.74 and 0.71) were significantly higher than in eyes with preperimetric glaucoma (0.68) (p=0.014 and 0.026). In eyes with advanced glaucoma PSV OA and PSV CRA were significantly lower than in eyes with preperimetric glaucoma (32.5 vs. 40.7 cm/s p=0.034 and 8.25 vs. 9.7 cm/s p=0.022, respectively). Positive, variable correlations were found between RNFL and EDV of all measured arteries (0.21<R<0.50, p<0,05).

CONCLUSIONS: Statistically significant alterations in the Doppler parameters of retrobulbar arteries in association with thinning of the RNFL were observed in patients with glaucoma along with a greater severity of optic neuropathy.

PMID:34216458 | DOI:10.11152/mu-2954

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Identifying teamwork-related needs of the medical emergency team: Nurses’ perspectives

Nurs Crit Care. 2021 Jul 3. doi: 10.1111/nicc.12676. Online ahead of print.

ABSTRACT

BACKGROUND: The role of medical emergency team (MET) in managing deteriorating patients and enhancing patient safety is greatly affected by teamwork.

AIMS: To identify teamwork-related needs of the MET from MET nurses’ perspectives. To assess the associations between MET nurses’ perceptions of teamwork and their work experience and education.

STUDY DESIGN: A quantitative, descriptive correlational design.

METHODS: Registered intensive care unit (ICU) nurses (n = 50) who were members of the MET in an acute tertiary care hospital answered a modified version of the team assessment questionnaire in 2017. Data were analysed using descriptive statistics, the Kruskal-Wallis test, and the univariate analysis of variance method. The reporting of this study adheres to the strengthening the reporting of observational studies (STROBE) guidelines.

RESULTS: Participants showed least agreement with the items presenting leadership skills (mean = 2.6, SD = 0.68). Approximately 50% nurses disagreed that the MET had adequate resources, training, and skills. The majority of nurses (80%) felt that their responsibilities as a MET member interfered with taking care of their own ICU patients. Many nurses (64%) felt that they did not have a voice in MET’s decision-making process. Approximately 50% nurses felt that they were not recognized for their individual contribution, and they were uncertain regarding MET’s policies for dealing with conflicts. The amounts of MET nurses’ work experience and education were associated with MET skills and function, respectively.

CONCLUSION: Key teamwork elements of the MET that need improvements include decision-making and conflict resolution skills, valuing team members, and team leadership. Practicing shared mental models, implementing the TeamSTEPPS curricula at hospitals for training ICU nurses, and simulation-based team-training programmes may be beneficial in improving teamwork of MET members.

RELEVANCE TO CLINICAL PRACTICE: This study revealed key teamwork elements of the MET that need improvements. Our findings may contribute to improve teamwork, thereby optimizing MET function, and enhancing patient outcomes.

PMID:34216412 | DOI:10.1111/nicc.12676