Omeprazole activates aryl hydrocarbon receptor to reduce hyperoxia-induced oxidative stress in the peripheral blood mononuclear cells from premature infants.

OBJECTIVE: To investigate the correlation between the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) of premature infants, to demonstrate the protective role of AhR against hyperoxia-induced oxidative stress in premature infants and to provide a rational basis for the use of omeprazole (OM) as a new treatment for bronchopulmonary dysplasia (BPD). METHODS: From January 2021 to June 2021, 1-3 ml of discarded peripheral blood was collected from premature infants of gestational age less than 32 weeks who were not taking inhaled oxygen and were admitted to the Department of Neonatology of the Affiliated Hospital of Southwest Medical University. Using a random number table, the PBMCs were randomly assigned to each of the following groups: the control group, air + OM group, hyperoxia group, and hyperoxia + OM group. After 48 h of in vitro modeling and culture, PBMCs and the culture medium of each group were collected. Immunofluorescence analysis was used to examine ROS levels in PBMCs. A full-spectrum spectrophotometer was used to examine malondialdehyde (MDA) levels in the culture medium. Enzyme-linked immunosorbent assay (ELISA) was used to examine monocyte chemotactic protein 1 (MCP-1) levels in culture medium. Immunofluorescence analysis was used to examine the intracellular localization of AhR. Western blotting was used to examine the expression level of AhR in PBMCs. RESULTS: Compared with those in the control group, the levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR in the air + OM group did not change significantly (p > 0.05), but the expression level of AhR increased significantly (p < 0.05). The levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR significantly increased in the hyperoxia group (p < 0.05), and the expression level of AhR was significantly reduced (p < 0.05). Compared with those in the hyperoxia group, the levels of ROS, MDA, and MCP-1 in the hyperoxia + OM group were significantly reduced (p < 0.05), and the cytoplasm-nuclear translocation rate of AhR and the expression level of AhR were significantly increased (p < 0.05), but did not reach the level of the control group (p < 0.05). CONCLUSION: OM can activate AhR to inhibit hyperoxia-induced oxidative stress in the PBMCs from premature infants.

Corrigendum to "Image fusion of multi-vision system with one high resolution image for the measurement of long distance" [Heliyon 9(3) (March 2023) e14433].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14433.].

Effects of self-management interventions for cancer patients with pain: A systematic review of randomised controlled trials.

AIMS: To evaluate the effects of self-management interventions targeting individuals with cancer-related pain on pain intensity, self-efficacy, quality of life (QoL), pain medication adherence, and pain-related knowledge and provide recommendations for the content and format of self-management interventions based on the existing evidence. DESIGN: A systematic review of randomised controlled trials (RCTs) and narrative synthesis. DATA SOURCES: A search of six electronic databases, including Medline, PsycINFO, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus. REVIEW METHODS: This systematic review followed the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published from January 2011 to March 2022 in English were retrieved. The Cochrane Risk of Bias Tool was used to assess quality. Data were summarised using narrative synthesis. RESULTS: This systematic review included six RCTs involving 748 patients with cancer-related pain. The results support the effectiveness of the intervention on QoL and pain-related knowledge. Mixed results were observed in the effectiveness on pain intensity, self-efficacy and medication adherence. Overall, the quality of the evidence was low. The content of self-management interventions varied across studies but with similar formats (face-to-face coaching and telephone follow-up). CONCLUSION: The existing evidence supports the effectiveness of self-management interventions on pain-related knowledge and QoL. Further high-quality RCTs are needed to determine the most effective interventions. RELEVANCE TO CLINICAL PRACTICE: Self-management is recommended to improve cancer patients' pain awareness, self-management behaviour and adaptability. Components for self-management of cancer pain, including patient attitude and knowledge assessment, nurse coaching and counselling, reinforcement during follow-up period, and provision of supplementary materials on pain management and medication adherence, could be covered in the intervention. In the future, it is worthwhile exploring an effective intervention using Internet-based information technology, for example WeChat, to aid the delivery of self-management intervention. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review does not necessarily involve patients or public members in this work.

Image fusion of multi-vision system with one high resolution image for the measurement of long distance.

The mutual restriction between angle detection accuracy and spatial resolution of image will restrict the detection of long distance by multi-vision system. One higher resolution image of a multi-vision system can be used to improve the resolution of the images of each camera. In present paper, a new fusion method with the help of one higher resolution image is proposed and analytically studied. As an example, an image fusion for the images captured by the combining optical system of camera arrays and the synthetic aperture is studied. Both of the simulation and experiment shows that the proposed method is simple and accuracy.

Red blood cell transfusions post diagnosis of necrotizing enterocolitis and the deterioration of necrotizing enterocolitis in full-term and near-term infants: a propensity score adjustment retrospective cohort study.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of serious gastrointestinal inflammatory diseases in newborn infants, with a high morbidity and mortality. Red blood cell transfusion (RBCT) plays a controversial and doubtful role in the treatment of NEC. In present study, we aim to analyze the association between RBCT and the deterioration of NEC. METHODS: This was a retrospective cohort study of near-term and full-term infants with a confirmed diagnosis of Bell's stage II NEC between Jan 1, 2010 and Jan 31, 2020. The maternal and infant baseline characteristics, treatment information and laboratory test for each case were collected. The eligible subjects were divided into two groups based on receiving RBCT post NEC diagnosis or not. The propensity score was used to eliminate potential bias and baseline differences. A multivariate logistic regression model was used to adjust the propensity score and calculate the odds ratio (OR) and 95% confidential interval (CI) of RBCT for the deterioration of NEC. RESULTS: A total of 242 infants were included in this study, 60 infants had a history of RBCT post NEC diagnosis, and 40 infants deteriorated from Bell's stage II to stage III. By adjusting the propensity score, RBCT post NEC diagnosis was associated with an increased risk for NEC deteriorating from stage II to III (adjusted OR 6.06, 95%CI 2.94-12.50, P = 0.000). CONCLUSIONS: NEC infants who required RBCT post NEC diagnosis were more likely to deteriorate from stage II to III in full-term and near-term infants.

Risk factors and clinical analysis of peripherally inserted central catheter-related fungal colonization in premature infants.

We aimed to analyze the risk factors of positive peripherally inserted central catheter (PICC)-related fungal colonization in preterm infants. This retrospective study collected data from 2018 to 2020. The enrolled infants who underwent PICC insertion were born at < 32 weeks' gestation or birth weight < 1500 g. The demographics, PICC-related characteristics, and treatment information were collected. Univariate and multivariate analyses were performed to investigate risk factors for PICC-related fungal colonization. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values for the duration of antibiotics and parenteral nutrition. In total, 124 premature infants underwent PICC insertion. Among them, 19 patients had positive results of fungi on the PICC tips. The duration of antibiotics (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.02-1.31), parenteral nutrition infusion (OR 1.27, 95% CI 1.05-1.54), and postnatal glucocorticoid exposure (OR 9.48, 95% CI 1.06-84.98) were independent risk factors for fungal colonization in PICCs. The ROC curves showed that the risk increased after 15 days of antibiotic use and 28 days of parenteral nutrition infusion. Appropriate clinical management should be used to prevent fungal colonization and fungemia.

Role of the SENP1-SIRT1 pathway in hyperoxia-induced alveolar epithelial cell injury.

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, and its main pathogenesis partly involves oxidative stress. A large number of studies have shown that silent information regulator 1 (SIRT1) plays a protective role in oxidative stress. SUMO-specific protease 1 (SENP1) is vital in the nucleoplasmic distribution of SIRT1 under stress. However, whether the SENP1-SIRT1 pathway is involved in the hyperoxic lung injury is unknown. Therefore, this study aimed to explore the role and related mechanisms of the SENP1-SIRT1 pathway in hyperoxic lung injury. Peripheral blood mononuclear cells (PBMCs) from infants with BPD and SENP1-silenced alveolar epithelial cells were used as research models. PBMCs were isolated from the peripheral blood of premature infants. Next, the SENP1-silenced human alveolar epithelial cells were used to verify the role of the SENP1-SIRT1 pathway in vitro. The results indicated that the ROS level and the mRNA and protein expression of SENP1 increased in PBMCs of infants with BPD, but the expression of SIRT1 decreased in the nucleus and increased in the cytoplasm, and then the expression of acetyl-p53 (Ac-p53) increased. In the hyperoxic alveolar epithelial cell injury model, it seemed that hyperoxia could induce the same variation trend in the SENP1-SIRT1 pathway as in infants with BPD and then increased the expression of Ac-p53 and BAX, and cell apoptosis. Furthermore, silencing SENP1 could alleviate these hyperoxia-induced changes. These results suggested that SENP1 played an important role in hyperoxia-induced lung injury. It could regulate the expression and nucleoplasmic distribution of SIRT1 to inhibit its deacetylase activity, and then promoted cell apoptosis. Hence, SENP1 may become a potential intervention target of BPD in the future.

Nurses' experiences and support needs following workplace violence: A qualitative systematic review.

AIMS AND OBJECTIVES: To systematically identify, appraise and synthesise existing qualitative studies exploring nurses' lived experiences of workplace violence by patients, families and hospital visitors, identifying their support needs following workplace violence. BACKGROUND: Workplace violence against nurses is a significant concern globally, as it leads to serious negative consequences for nurses, patients and organisations as a whole. Having adequate support is considered significant. While numerous studies have been conducted on workplace violence, few qualitative reviews have focused on identifying nurses' support needs following episodes of workplace violence. METHODS: Four databases (MEDLINE, CINAHL, PsychINFO and Scopus) were systematically searched. Additionally, hand searching of prominent journals, grey literature and reference lists of included studies was also performed to identify additional research. The Critical Appraisal Skills Programme checklist for qualitative studies was used to assess all included articles. Thomas and Harden's three-stage approach to thematic analysis was followed, using the ENTREQ statement for reporting. RESULTS: Ten studies published in English, conducted across eight countries, met the inclusion criteria. Four analytical themes relating to nurses' experiences were identified: "inevitable and unpredictable trauma in the career" "higher tolerance and understanding of unintentional violence," "positive learning or passive adjustment" and "struggle with the role and behaviour conflict." In terms of nurses' support needs, the analysis yielded two themes: "informal support needs" and "formal support needs." CONCLUSION: Nurses experience significant and lasting psychological trauma due to workplace violence; however, the support for nurses remains seriously inadequate. Establishing an effective and robust support system based on nurses' needs must be viewed as a priority for organisations, as well as researchers. RELEVANCE TO CLINICAL PRACTICE: Institutions and managers have a duty to maintain an awareness of nurses' experiences and support needs regarding workplace violence. There is a need for further policymaking and research, based on clinical practice, in order to develop effective preventive and interventive strategies regarding workplace violence.

[Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits].

OBJECTIVE: To elucidate the pathogenic role of leukotriene B4 (LTB4) in pulmonary hyper-permeability and inflammation induced by lung-protective mechanical ventilation (LPMV) in rabbits. METHODS: Thirty-two healthy Japanese white rabbits were randomized into 4 groups for treatment with vehicle or bestatin (a leukotriene A4 hydrolase inhibitor that inhibits LTB4 production) administered intragastrically at the daily dose of 8 mg/kg for 5 days, followed by sham operation (group S and group BS, respectively, in which the rabbits were anesthetized only) or LPMV (group PM and group BPM, respectively, in which the rabbits received ventilation with 50% oxygen at a tidal volume of 8 mL/kg for 5 h). The concentrations of LTB4 and cyclic adenosine monophosphate (cAMP) in the lung tissues were analyzed by ELISA. cAMP content, protein kinase A (PKA) protein expression and the Rap1-GTP protein to total Rap1 protein ratio were determined to assess the activities of cAMP/PKA and Rap1 signaling pathways. The lung injury was evaluated by assessing lung permeability index, lung wet/dry weight ratio, polymorphonuclear leukocyte (PMN) count in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity and lung histological scores. RESULTS: None of the examined parameters differed significantly between group S and group BS. All the parameters with the exception of lung histological score increased significantly in group PM and group BPM as compared to those in group S (P < 0.05). Compared with those in PM group, the rabbits in group BPM showed significantly reduced LTB4 production in the lungs (P < 0.05), up-regulated cAMP/ PKA and Rap1 signaling pathway activities (P < 0.05), and alleviated lung hyper-permeability and inflammation (P < 0.05). CONCLUSIONS: LPMV can induce LTB4 overproduction to down-regulate cAMP/PKA and Rap1 signaling pathways in the lungs of rabbits, which results in lung hyper-permeability and inflammation. Bestatin can inhibit LTB4 production in the lungs to protect against LPMV-induced lung hyper-permeability and inflammation.

Mindfulness and Job Satisfaction Among Hospital Nurses: The Mediating Roles of Positive Affect and Resilience.

The current study aimed to explore the relationships between nurses' mindfulness and job satisfaction and the mediating roles of positive affect and resilience. A total of 1,043 Chinese hospital nurses completed self-report questionnaires from March to April 2019. Pearson's correlation analysis was used to identify the relationships among the four variables, and the bias-corrected bootstrap method was used to test the mediation hypotheses. The results revealed that nurses' mindfulness was at a medium-high level, whereas positive affect, resilience, and job satisfaction were at medium levels. The total scores and dimension scores of the four variables showed strong positive correlations, and nurses' mindfulness affected job satisfaction directly and indirectly through the intermediary roles of positive affect and resilience. Nursing managers should recognize the importance of mindfulness and incorporate mindfulness training into health promotion and employee management plans for hospital nurses. In addition, strategies should be implemented to cultivate positive affect and resilience. [Journal of Psychosocial Nursing and Mental Health Services, 58(6), 46-55.].

Attenuated SUMOylation of sirtuin 1 in premature neonates with bronchopulmonary dysplasia.

A prospective study was performed to investigate the effects of hyperoxia on the expression of small ubiquitin­related modifier (SUMO) and sirtuin 1 (SIRT1) proteins, and to examine interactions between these proteins in premature neonates with bronchopulmonary dysplasia (BPD). Peripheral blood mononuclear cells (PBMCs) were isolated from residual venous blood samples of 20 premature infants with BPD and 20 gender­matched premature infants without BPD (non­BPD group). Expression levels of SUMO and SIRT1 proteins in PBMCs were assessed by western blot analysis, and their interactions in PBMCs were detected using the immunoprecipitation assay. Based on the fraction of inspired oxygen (FiO2) administered, neonates were divided into normoxia, low­(21%

[Relationship between cytoplasmic phospholipase A2 and nuclear factor κB in one lung ventilation-induced lung injury in rabbits].

OBJECTIVE: To elucidate the mechanisms of up regulated expression of cytoplasmic phospholipase A2 (CPLA2) induced by one lung ventilation (OLV) by investigating the interactions between nuclear factor kappaB (NF-κB) and C-PLA2. METHODS: Forty-eight healthy Japanese white rabbits were randomized into control group, solvent treatment group (group S), NF-κB inhibitor (PDTC)/solvent treatment group ( group PS), C-PLA2 inhibitor (AACOCF3)/solvent treatment group (group AS), OLV group (group O), solvent treatment plus OLV group (SO group), NFκB inhibitor (PDTC)/solvent treatment plus OLV group (group PSO) and CPLA2 inhibitor (AACOCF3)/solvent treatment plus OLV group (group ASO). ELISA was used to detect arachidonic acid (AA) content in the lung tissues, and NFκB and CPLA2 expressions were detected by Western blotting and quantitative PCR. Lung injuries were assessed based on the lung histological score, and the polymorphonuclear leukocyte count in the bronchial alveolar lavage fluid, myeloperoxidase (MPO) content in the lung tissues, and lung wet/dry weight (W/D) raito were determined. RESULTS: Treatment of the rabbits with the solvent did not produce any adverse effects. OLV caused obvious lung injury in the rabbits and up regulated the expressions of CPLA2 and NFκB in the lung tissues (P<0.05). In rabbits without OLV, treatment with AACOCF3 or PDTC significantly down regulated both CPLA2 and NFκB expressions without affecting the other parameters. In rabbits with OLV, treatment with AACOCF3 or PDTC obviously lowered CPLA2 and NFκB expressions and lessened the OLV-induced lung injuries. CONCLUSION: Both C-PLA2 and NF-κB play important roles and show interactions in OLV-induced lung injury in rabbits.

Copeptin in heart failure: Review and meta-analysis.

BACKGROUND: The aim of this study was to explore the prognostic value of copeptin for predicting all-cause mortality in heart failure (HF). METHODS: PubMed, Embase and Cochrane databases were systematically searched to identify if a 2×2 contingency table could be constructed based on both the copeptin level and the all-cause mortality in patients diagnosed with HF. The characteristics of test performance were summarized using forest plots and summary receiver operating characteristic curves (SROC). Q-test and I2 index were used to evaluate heterogeneity. RESULTS: Ten prospective cohort studies comprising 4473 patients were eligible in this meta-analysis. An elevated copeptin level was associated with an increased risk of all-cause mortality in HF patients (Relative risk (RR) was 2.64 (95% CI, 2.09-3.32)). The pooled sensitivity (SEN) and specificity (SPE) of copeptin were 0.57 (95% CI, 0.50-0.63) and 0.74 (95% CI, 0.69-0.79), respectively. The positive likelihood ratio was 2.2 (95% CI, 1.90-2.60) and the negative likelihood ratio was 0.58 (95% CI, 0.52-0.66). Furthermore, the summary Diagnostic Odds Ratio (DOR) was 4.00 (95% CI, 3.00-5.00) and the AUC was 0.70 (95% CI, 0.66-0.74) similar to the AUC of NT-proBNP 0.71 (95% CI, 0.67-0.75). CONCLUSIONS: Elevated levels of copeptin are associated with all-cause mortality in HF patients. The predictive value of copeptin is comparable with NT-proBNP for all-cause mortality in HF patients. Further studies are warranted to explore the prognostic value of copeptin in conjunction with other biomarkers and to determine an optimal cut-off level.

[Decreased SIRT1 expression is related to bronchopulmonary dysplasia in premature infants after oxygen exposure].

Objective To observe silent information regulator 1 (SIRT1) expression in the peripheral blood mononuclear cells (PBMCs), and explore the relationship between SIRT1 expression and bronchopulmonary dysplasia (BPD) in premature infants after oxygen exposure. Methods Premature infants with 28 to 30 weeks' gestation were divided into three groups according to the fraction of inspiration O2 (FiO2): low-oxygen group with FiO2<30%, medium-oxygen group with FiO2 being 30%~40%, and high-oxygen group with FiO2≥40%; other premature infants with 28 to 30 weeks' gestation and without inspiration O2 served as a control group. The children's clinical data and residual blood samples obtained from the routine examination of 0, 7, 14 and 28 days of hospitalization were collected, and PBMCs were isolated and cryopreserved in -80DegreesCelsius refrigerator. Twenty children diagnosed with BPD were enrolled as a BPD group, and other sex-matched 20 children without BPD were randomly chosen as a non-BPD group. The children's clinical data were retrospectively analyzed, and SIRT1 expression in the PBMCs of each group was measured by Western blotting. Furthermore, the role of SIRT1 expression in the occurrence and development of BPD in premature infants was also analyzed. Results Compared with the control group, SIRT1 expression in the medium-oxygen group and the high-oxygen group significantly decreased with the increase of FiO2, and the expression in the low-oxygen group and the control group was almost at a similar level. Compared with the non-BPD group, SIRT1 expression in the BPD group of 14 and 28 days was significantly reduced. Conclusion There is a certain relationship between the decreased SIRT1 expression in PBMCs and the occurrence of BPD in premature infants after continuous and high-concentration oxygen exposure.

Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites.

Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.

Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride.

Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride.

LC-ESI-MS/MS determination of simotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor: application to a pharmacokinetic study.

Simotinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor. This study presented a sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method using erlotinib as internal standard for the determination of simotinib in human plasma. The method involved a simple liquid-liquid extraction using diethyl ether. The analytes were separated with isocratic gradient elution on an Agilent TC-C18 column (4.6 × 150 mm, 5 µm). Mass spectrometric detector equipped with electrospray ionization source was carried out in the mode of multiple reaction monitoring (MRM). The monitored transitions were m/z 501.2→182.1 for simotinib and m/z 394.4→278.1 for erlotinib. The calibration curve of simotinib was established over the range of 2.058-3000 µg L(-1) (r(2)=0.9924). The intra- and inter-day precisions were all less than 10%, and all the biases were not more than 7%. This validated method was then successfully applied to a pharmacokinetic study involving twelve healthy Chinese volunteers. The mean Cmax and Tmax for simotinib were 254.79±98.30 µg L(-1) and 1.71±0.48 h, respectively. Plasma concentrations declined with a t1/2 of 5.37±2.32 h. AUC0-t and AUC0→∞ values obtained were 1262.59±501.41 µg L(-1) h and 1329.95±517.42 µg L(-1) h, respectively.