Nevin Manimala

Indian Pediatr. 2023 Mar 15;60(3):217-220.

ABSTRACT

OBJECTIVE: The aim of this study was to determine the availability of serum amyloid A (SAA) in the diagnosis of coronavirus disease 2019 (COVID-19), to asses disease severity and to predict hospitalization status.

METHODS: Between March, 2020 and March, 2021, a total of 80 children (40 cases with COVID-19 and 40 cases in healthy group) were included in this study. Patients were divided into two groups (mild and moderate/severe) to evaluate SAA levels in terms of clinical severity and also hospitalization status.

RESULTS: Comparisons between the two groups revealed that median SAA values were significantly higher in children with COVID-19 than in their healthy peers (21.45vs3.05 mg/L, P=0.002). There was no significant difference in the median serum SAA levels between mild and moderate/severe clinical disease (P=0.837). The SAA difference between the two groups with regards to hospitalization was not statistically significant (P=0.098).

CONCLUSIONS: Although SAA level was found to be higher in children with COVID 19 compared to healthy controls, the sensitivity of SAA for the disease was found to be low. In addition, there was no difference between the groups in terms of clinical severity.

PMID:36916361

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Mar;35(3):293-298. doi: 10.3760/cma.j.cn121430-20221214-01094.

ABSTRACT

OBJECTIVE: To explore the mechanism of gypenoside XVII against cerebral ischemia/reperfusion (I/R) through nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathway.

METHODS: Forty SPF Sprague Dawley (SD) rats were randomly divided into sham operated group, I/R model group, 25, 50 and 100 mg/kg gypenoside XVII groups (n = 8). Gypenoside XVII groups were administered 25, 50 or 100 mg/kg (0.01 mL/g) gypenoside XVII by intragastric administration for 14 days; the other two groups received the same dose of saline. Rat cerebral I/R model was established by modified line bolt method; rats in the sham operated group underwent the same procedure without producing substantial embolization. After 24 hours of reperfusion, the neurological deficit scores of the rats in each group were assessed. Rat abdominal aortic whole blood was collected and the serum reactive oxygen species (ROS), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), superoxide dismutase (SOD), quinone NADH oxidoreductase 1 (NQO1), and malondialdehyde (MDA) were detected. Then whole brain tissue was harvested and penumbra tissue was isolated from cerebral cortex, the general condition of rat brain tissue and the volume of cerebral infarction were evaluated, the histopathological changes in the brain were observed under light microscopy, the mRNA expressions of Nrf2 and Keap1 were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR), the protein expressions of Nrf2 and Keap1 were determined by Western blotting.

RESULTS: After 24 hours of reperfusion, compared with the sham operated group, the score of neurological deficit and infarct volume were significantly increased, the NQO1, SOD and γ-GCS levels in serum were significantly decreased, MDA, HO-1 and ROS levels in serum were significantly increased, the Nrf2 and Keap1 mRNA and protein expressions in the ischemic penumbra were significantly increased in rats from I/R model group. Compared with the I/R model group, the neurological deficit scores (1.50±0.53, 1.37±0.52 vs. 2.75±0.46) and brain infarct volume [(19.8±5.1)%, (21.4±6.4)% vs. (42.3±5.8)%] were significantly reduced, serum NQO1, SOD, HO-1 and γ-GCS were significantly increased [NQO1 (ng/L): 186.05±10.38, 220.75±16.22 vs. 131.36±5.95, SOD (kU/L): 63.23±5.30, 72.70±8.62 vs. 36.75±6.55, HO-1 (ng/L): 60.57±7.93, 60.35±4.72 vs. 42.72±4.95, γ-GCS (kU/L): 8.81±0.53, 8.72±0.69 vs. 6.80±0.56], serum MDA and ROS levels were significantly reduced [MDA (μmol/L): 5.94±0.66, 5.61±0.53 vs. 10.88±1.34, ROS (kU/L): 69.11±4.23, 67.12±4.52 vs. 104.43±7.54], the mRNA and protein expressions of Nrf2 and Keap1 in the ischemic penumbra were significantly increased in rats from 50 mg/kg and 100 mg/kg gypenoside XVII groups [Nrf2 mRNA (2^-ΔΔCt): 1.90±0.13, 2.13±0.18 vs. 1.48±0.11, Keap1 mRNA (2^-ΔΔCt): 1.78±0.11, 1.85±0.10 vs. 1.43±0.10, Nrf2/β-actin: 0.73±0.04, 0.79±0.03 vs. 0.60±0.03, Keap1/β-actin: 0.71±0.01, 0.76±0.03 vs. 0.61±0.01], all the comparative differences were statistically significant (all P < 0.01); 25 mg/kg gypenoside XVII had no significant effect.

CONCLUSIONS: Gypenoside XVII (50 mg/kg and 100 mg/kg) may play a role in anti-cerebral I/R injury by regulating NQO1, SOD, HO-1, γ-GCS, ROS and MDA through Nrf2/ARE signaling pathway.

PMID:36916343 | DOI:10.3760/cma.j.cn121430-20221214-01094

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Mar;35(3):287-292. doi: 10.3760/cma.j.cn121430-20220705-00632.

ABSTRACT

OBJECTIVE: To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2, 6-diphosphatase 3 (PFKFB3).

METHODS: Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups (n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α (TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na⁺-K⁺-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting.

RESULTS: Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na⁺-K⁺-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na⁺-K⁺-ATPase activity was further decreased (mmol×L^-1×h^-1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na⁺-K⁺-ATPase activity was increased (mmol×L^-1×h^-1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved.

CONCLUSIONS: Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

PMID:36916342 | DOI:10.3760/cma.j.cn121430-20220705-00632

J Child Health Care. 2023 Mar 14:13674935231163362. doi: 10.1177/13674935231163362. Online ahead of print.

ABSTRACT

We surveyed pediatric primary care clinicians working in Federally Qualified Health Centers about their perceptions of children’s social-emotional wellbeing. We identified clinician’s current methods for assessing social-emotional wellbeing in practices, perceived implementation barriers to providing behavioral health care, and interest in adopting a validated, low-burden developmentally sensitive parent-report instrument for screening for social-emotional wellbeing in young children. We surveyed 72 PCCs working in FQHCs from 9 US states. Analyses included examining central tendencies, correlations, analysis of variance, and group differences via t-tests. Average PCC perceptions of social-emotional wellbeing importance for overall health were statistically significantly higher than their confidence in providing care for common social-emotional wellbeing concerns (mean difference = 1.31, 95% CI = 1.13-1.49). PCCs expressed low satisfaction with currently available screening measures for identifying concerns in social-emotional wellbeing. Fewer than half of clinicians reported using any standardized parent-reported measure for identifying concerns in social-emotional wellbeing. Assessment methods and decision tools that improve clinician confidence concerning risk indications are needed, particularly at the critical early childhood period. Policymakers and payers ought to facilitate funding mechanisms that support pediatric PCCs in identifying early concerns in social-emotional wellbeing and providing referral guidance to evidence-based interventions to support parents and caregivers.

PMID:36916317 | DOI:10.1177/13674935231163362

J Sch Nurs. 2023 Mar 14:10598405231160249. doi: 10.1177/10598405231160249. Online ahead of print.

ABSTRACT

Evidence-based practices in concussion management (CM) have been codified into legislation. However, legislation is varied, and implementation is narrowly evaluated. School nurses hold a unique position to assess the implementation of health policies. The implementation of concussion management policies across Massachusetts high schools was evaluated by the school nurse. A cross-sectional survey was sent to school nurses (N = 304), and responses (n = 201; 68.1% response rate) were tallied whereby higher scores indicated more practices being implemented. One open-text question was included to encourage nurses to provide context regarding implementation in their school. Descriptive statistics and thematic analysis were used to assess current implementation and nursing perspectives. Findings indicate that the degree of implementation varies, and some nurses reported difficulty with mobilizing clinical uptake of concussion management practices in their schools. Further implementation research is needed, and school nurses are an important stakeholder to include when assessing the clinical uptake of concussion management policies in schools.

PMID:36916285 | DOI:10.1177/10598405231160249

Stroke. 2023 Mar 14. doi: 10.1161/STROKEAHA.122.040759. Online ahead of print.

ABSTRACT

BACKGROUND: Multidelay arterial spin labeling (ASL) is a novel perfusion method of ASL, with arterial transit time (ATT) calculated by multiple postlabeling delays to correct cerebral blood flow (CBF). We verify the accuracy of multidelay ASL in evaluating the ischemic penumbra and perfusion levels in patients with acute ischemic stroke, compared with computed tomography perfusion (CTP).

METHODS: Patients with acute ischemic stroke with anterior circulation large vessel occlusion received baseline CTP, multidelay ASL, and diffusion-weighted imaging (DWI) in succession. Multidelay ASL image was processed to reconstruct ATT, CBF without ATT correction, and CBF corrected by ATT. The consistency of hypoperfusion and ischemic penumbra volume calculated by CTP and multidelay ASL were quantified by intraclass correlation coefficient (ICC) in 2-way mixed effects, absolute agreement, and single measure. Wilcoxon signed-rank test was used to compare the difference in penumbra volume between CTP, corrected ASL, and uncorrected ASL.

RESULTS: Thirty patients were included. Hypoperfusion volume based on multidelay ASL with different thresholds were 117.95 (87.77-151.49) mL for corrected relative CBF<40%, 130.29 (85.99-249.37) mL for CBF corrected by ATT<20 mL·100g^-1·min^-1, no statistical difference (P>0.05) compared with the volume of CTP, and consistency was almost excellent (ICC, 0.91) and substantial consistent (ICC, 0.727). The volumes of ischemic penumbra were 91.00 (42.68-125.27) mL for corrected relative CBF<40%-DWI, 108.94 (62.03-150.86) mL for CBF corrected by ATT<20 mL·100 g^-1·min^-1-DWI, which showed no statistical difference compared with the penumbra volume of CTP (P>0.05). The consistency was excellent (ICC, 0.822) and moderate (ICC, 0.501), respectively. The volume of uncorrected relative CBF <40%-DWI was 209.57 (123.21-292.45) mL, statistically larger than corrected relative CBF <40%-DWI (P<0.001) and CTP (P<0.001). The volume of uncorrected CBF<20 mL·100g^-1·min^-1-DWI was 186.23 (86.56-298.22) mL, statistically larger than CBF corrected by ATT<20 mL·100g^-1·min^-1-DWI (P<0.001) and CTP(P<0.001).

CONCLUSIONS: The volume of ischemic penumbra determined by CBF/DWI mismatch based on multidelay ASL is consistent with CTP. The penumbra volume calculated by CBF adjusted by ATT is more accurate.

PMID:36916272 | DOI:10.1161/STROKEAHA.122.040759

Ear Nose Throat J. 2023 Mar 14:1455613231163737. doi: 10.1177/01455613231163737. Online ahead of print.

ABSTRACT

OBJECTIVES: While surgeries to correct the anatomical malformations that cause nasal airway obstruction (NAO) are generally successful, the outcomes of such procedures are often unsatisfactory. The aim of the present study was to assess the value of opening the middle meatus in patients with NAO.

METHODS: Thirty-four patients with nasal obstruction due to nasal septal deviation were included in this study. After randomization, the middle meatus was either opened or not opened during septoplasty. The patients were evaluated through pre- and postoperative rhinomanometry and acoustic rhinometry. The Visual Analog Scale (VAS) scores of subjective symptoms along with responses to the 20-item Sinonasal Outcome Test (SNOT-20) were obtained before surgery and three months after surgery.

RESULTS: The VAS scores and SNOT-20 responses improved significantly in both groups after surgery. The effective treatment rate based on the nasal congestion score (NCS) was 64.7% in the single group (septoplasty alone) and 100% in the combined group (septoplasty in conjunction with opening the middle meatus), and the difference was statistically significant (P = .018). In both groups, surgery significantly improved nasal flow, resistance, minimal cross-sectional area, cross-sectional area 6 cm (CA6) from the anterior nostril and nasal volume. Nasal volume and CA6 after surgery were statistically different between the 2 groups (P = .004 and .019, respectively).

CONCLUSIONS: Opening the middle meatus may further improve the subjective perception of patency on the basis of septoplasty.

PMID:36916238 | DOI:10.1177/01455613231163737

J Clin Psychol. 2023 Mar 14. doi: 10.1002/jclp.23504. Online ahead of print.

ABSTRACT

OBJECTIVE: There is a relatively small body of research on the cost-of-illness of personality disorders (PDs). Most studies only include borderline PD. The aim of this study was to investigate mean societal costs, including its components, (direct) health service costs and (indirect) productivity loss, among treatment-seeking patients with the broad range of all PDs according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

METHODS: Cross-sectional data from 911 patients diagnosed with at least 1 PD were retrieved from the quality register of the Norwegian Network for Personality Disorders-a collaboration of PD treatment units within specialist mental health services. The patients were referred in the time period 2017-2020. Estimation of costs was based on a bottom-up approach, using information from a structured interview covering the 6-month period before assessment, whereas unit costs were retrieved from public reports, public records, or public agencies. The human capital approach was used to calculate productivity loss. Diagnoses were determined by semi-structured diagnostic interviews (Structured Clinical Interview for DSM-5-PD [SCID-5-PD]).

RESULTS: The mean societal costs were €20.260 during the 6-month period before specialized treatment. The largest cost component was productivity loss (65%), whereas health service costs constituted 35%. The main contributors to societal costs from the underlying health service cost components were inpatient treatment (20.5%) and individual outpatient treatment (10.5%).

CONCLUSION: Societal costs were substantial among treatment-seeking patients with the broad range of DSM-5 PDs, comparable to the societal costs of schizophrenia, and significantly higher than the societal costs of both depression and anxiety disorders. The cost estimates converged with recent, register-based cost-of-illness studies of different PDs but exceeded previous findings from other bottom-up studies. Furthermore, the results underscore the importance of implementing effective and specialized treatment for patients with a broad range of PDs, not only to alleviate individual suffering but also to reduce the level of societal costs. The emphasis on productivity loss as a main contributor to the overall societal costs is substantiated, hence underlining the relevance of interventions focusing on improving occupational functioning.

PMID:36916214 | DOI:10.1002/jclp.23504

Environ Mol Mutagen. 2023 Mar 14. doi: 10.1002/em.22538. Online ahead of print.

ABSTRACT

Genetic toxicology tests are used to categorize substances as genotoxic and potentially carcinogenic. In general, test results are designated as mutagenic, not mutagenic, or inconclusive and, depending on its potential use and applicable regulations, a mutagenic result can restrict or remove a substance from further development, or assign limits to its use. In these tests, mutation responses form a continuum without a clear delineation between an increase over the background, untreated, mutant frequency and a frequency that would define the test substance as a mutagen and a potential carcinogenic hazard. This situation is illustrated using the Salmonella mutagenicity (Ames) test which is the initial, and often only, test used to characterize substances as mutagenic or nonmutagenic. It has its widest use by industry and regulatory authorities to identify potential carcinogens among chemicals in development. The OECD Test Guideline No. 471 has been adopted by regulatory agencies internationally, and describes the minimum requirements for a negative response, but does not provide a specific approach for evaluating the test data. The most widely used criterion for making yes-or-no mutagenicity decisions is a 2- or 3-fold increase over the background (solvent) mutant frequency. Other approaches rely on formal statistics and/or expert judgment. These approaches and recently proposed modifications are evaluated here. Recommendations are made that are in conformity with the OECD guideline and are based on biological relevance and the biology of the mutagenic response rather than on arbitrary decision points (e.g., ≥ 2-fold increase or p ≤ .05).

PMID:36916210 | DOI:10.1002/em.22538

Intern Med J. 2023 Mar 14. doi: 10.1111/imj.16074. Online ahead of print.

ABSTRACT

BACKGROUND: In 2014, infliximab (IFX) was listed on the Australian Pharmaceutical Benefits Scheme for acute severe ulcerative colitis (ASUC) and is now the preferred option for medical salvage, superseding cyclosporin (CsA). Optimal dosing schedules for IFX remain unknown.

AIM: We aim to evaluate the effect of changing from predominantly CsA to almost exclusively IFX for the treatment of steroid refractory ASUC on colectomy rates.

METHODS: A retrospective review was performed of patients admitted with ASUC between 2012-2020. Patients were categorised into two groups according to year of presentation – either “historical treatment” cohort (2012-2014), when CsA was primarily used, or “contemporary treatment” cohort (2014-2020) when IFX was mostly prescribed, in either standard or intensive doses.

RESULTS: 139 patients were included; 37 in the historical treatment cohort and 102 in the contemporary treatment cohort. In the historical treatment cohort, 12/37 received salvage therapy, 8 (67%) with CsA. In the contemporary treatment cohort, 49/102 patents received salvage therapy, 40 (82%) with IFX, of whom 22 (53%) received intensified doses. Colectomy rates were similar at 30 days, 6 months and 12 months between historical and contemporary treatment cohorts (14% vs 12%, p = 0.77, 19% vs 18%, p >0.99; and 22% vs 18%, p = 0.63 respectively). Difference in 12-month colectomy rates between standard vs intensive IFX did not meet statistical significance (3/21 (14%) vs 9/22 (41%), respectively; p = 0.09).

CONCLUSION: There was no difference in 30-day, 6-month or 12-month colectomy rate between the historical treatment and contemporary treatment cohorts. The use of IFX, rather than CsA, even at intensified dosing has not appeared to reduce the colectomy rate observed in our patients. This article is protected by copyright. All rights reserved.

PMID:36916208 | DOI:10.1111/imj.16074