Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir-an orally available inhibitor of the 3-chymotrypsin-like cysteine protease-has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals

Vitamin C Deficiency in Patients With Acute Myeloid Leukemia

Vitamin C has been shown to play a significant role in suppressing progression of leukemia through epigenetic mechanisms. We aimed to study the role of vitamin C in acute myeloid leukemia (AML) biology and clinical course. To this purpose, the plasma levels of vitamin C at diagnosis in 62 patients with AML (including 5 cases with acute promyelocytic leukemia, APL),7 with myelodysplastic syndrome (MDS), and in 15 healthy donors (HDs) were studied. As controls, vitamins A and E levels were analysed. Expression of the main vitamin C transporters and of the TET2 enzyme were investigated by a specific RQ-PCR while cytoplasmic vitamin C concentration and its uptake were studied in mononuclear cells (MNCs), lymphocytes and blast cells purified from AML samples, and MNCs isolated from HDs. There were no significant differences in vitamin A and E serum levels between patients and HDs. Conversely, vitamin C concentration was significantly lower in AML as compared to HDs (p<0.0001), inversely correlated with peripheral blast-counts (p=0.029), significantly increased at the time of complete remission (CR) (p=0.04) and further decreased in resistant disease (p=0.002). Expression of the main vitamin C transporters SLC23A2, SLC2A1 and SLC2A3 was also significantly reduced in AML compared to HDs. In this line, cytoplasmic vitamin C levels were also significantly lower in AML-MNCs versus HDs, and in sorted blasts compared to normal lymphocytes in individual patients. No association was found between vitamin C plasma levels and the mutation profile of AML patients, as well as when considering cytogenetics or 2017 ELN risk stratification groups. Finally, vitamin C levels did not play a predictive role for overall or relapse-free survival. In conclusion, our study shows that vitamin C levels are significantly decreased in patients with AML at the time of initial diagnosis, further decrease during disease progression and return to normal upon achievement of CR. Correspondingly, low intracellular levels may mirror increased vitamin C metabolic consumption in proliferating AML cells

Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale

© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students

Identification of a new sesquiterpene polyol ester from Celastrus paniculatus

A new sesquiterpene polyol ester characterized as 1alpha,6beta,8beta-triacetoxy-9beta-benzoyloxydihydro-beta-agarofuran (1), along with the three known compounds: 1alpha,6beta,8alpha-triacetoxy-9alpha-benzoyloxydihydro-beta-agarofuran (2), angulatueoid C (3), and 1alpha,6beta,8beta,14-tetraacetoxy-9alpha-benzoyloxydihydro-beta-agarofuran (4), was isolated from the CCl (4)-soluble fraction of Celastrus paniculatus methanolic seed extract. All four compounds produce at a concentration of 1 microg/mL a relaxant effect on the isolated rat ileum of 31.4 +/- 7.5, 24.3 +/- 9.6, 24.4 +/- 4.9, and 16.2 +/- 7.2 %, respectively

Sleep cyclic alternating pattern analysis in infants with apparent life-threatening events: a daytime polysomnographic study.

Objective: Non-REM sleep is characterized by a physiologic oscillating pattern that exhibits different levels of arousal, coded as cyclic alternating pattern. The aim of this study was to analyze the development of cyclic alternating pattern parameters in a group of infants with apparent life-threatening events. Methods: A total of 26 infants with apparent life-threatening events (14 females, mean age 3.4 months, 2.37 S. D., age range 0.5-9 months) were studied while they slept in the morning between feedings, by means of a 3-h video-electroencephalographic-polygraphic recording. Sleep was visually scored using standard criteria. The control group was composed of 36 healthy infants (16 females, mean age 3.2 months, 2.17 S. D., age range 0.5-9 months). Results: Children with apparent life-threatening events showed an increased frequency of periodic breathing, gastroesofageal reflux and of other risk conditions. They presented also an increased obstructive apnoea/hypopnea index. A full NREM sleep development was found in a significantly smaller percentage of patients, and they showed a significant reduction of the percentage of REM sleep, of cyclic alternating pattern A1 subtypes, an increased percentage of A2 and A3 subtypes and increased index of A2, A3 subtypes and arousal, compared to normal controls. Cyclic alternating pattern rate showed a significant positive correlation with age, only in controls. Conclusions: Our results show a higher level of arousal and an increased non-REM sleep discontinuity in babies with apparent life-threatening events, compared to controls. Significance: The enhanced mechanism of arousal might counteract life-threatening events and represent an important neurophysiologic distinction from future victims of sudden infant death syndrome who also experience similar events. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved

Healthcare-associated infections due to multidrug-resistant organisms: a surveillance study on extra hospital stay and direct costs

BACKGROUND: The increasing antimicrobial resistance poses a challenge for surveillance systems and raises concerns about the impact of multidrug-resistant organisms on patient safety. OBJECTIVE: To estimate extra hospital stay and economic burden of infections due to alert organisms - mostly multidrug-resistant - in a teaching hospital. METHODS: The present retrospective matched cohort study was conducted through the analysis of hospital admissions at Sant'Andrea Teaching Hospital in Rome from April to December 2015. Extra hospital stay was the difference in the length of stay between each case and control. All patients developing an infection due to an alert organism were considered cases, all others were eligible as controls. The costs of LOS were evaluated by multiplying the extra stay with hospital daily cost. RESULTS: Overall 122 patients developed an infection due to alert an organism and were all matched with controls. The attributable extra stay was 2,291 days (mean 18.8; median 19.0) with a significantly increased hospitalization in intensive care units (21.2 days), bloodstream infections (52.5 days), and infections due to Gram-negative bacteria (mean 29.2 days; median 32.6 days). Applying the single day hospital cost, the overall additional expenditure was 11,549 euro per patient. The average additional cost of antibiotic drugs for the treatment of infections was about 1,200 euro per patient. CONCLUSIONS: The present study presents an accurate mapping of the clinical and economic impact of infections attributable to alert organisms demonstrating that infections due to multidrug-resistant organisms are associated with higher mortality, longer hospital stays, and increased costs

Potent relaxant effect of a Celastrus paniculatus extract in the rat and human ileum

Ethnopharmacological importance: Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms. Aim of the study: To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001-10 μg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract. Materials and methods: The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum. Results: CPE exerted a tetrodotoxin- and ω-conotoxin-resistant inhibitory effect on rat ileum motility (IC50: 0.24 ± 0.02 μg/mL; Emax: 99.0 ± 0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC50: 0.26 ± 0.02 μg/mL; Emax: 99.1 ± 0.46%). Conclusion: It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca2+-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms. © 2009 Elsevier Ireland Ltd. All rights reserved

New sesquiterpenes with intestinal relaxant effect from Celastrus paniculatus

The seed oil obtained from Celastrus paniculatus has been used in Ayurvedic medicine for the treatment of several complaints including intestinal disorders. The muscle relaxing activity of C. paniculatus has been studied in vitro on isolated preparations of rat intestine.Three new sesquiterpenes polyol esters have been isolated from carbon tetrachloride fraction. These new metabolites, at the concentration of 1microg/mL produced a relaxant effect

Preoperative high-intensity training in frail old patients undergoing pulmonary resection for NSCLC

Thoracic surgery remains the better therapeutic option for non-small cell lung cancer patients that are diagnosed in early stage disease. Preoperative lung function assessment includes respiratory function tests (RFT) and cardio-pulmonary exercise testing (CPET). Vo2 peak, FEV1 and DLCO as well as recognition of performance status, presence of co-morbidities, frailty indexes, and age predict the potential impact of surgical resection on patient health status and survival risk. In this study we have retrospectively assessed the benefit of a high-intensity preoperative pulmonary rehabilitation program (PRP) in 14 patients with underlying lung function impairment prior to surgery. Amongst these, three patients candidate to surgical resection exhibited severe functional impairment associated with high score of frailty according CHS and SOF index, resulting in a substantial mortality risk. Our observations indicate that PRP appear to reduce the mortality and morbidity risk in frail patients with concurrent lung function impairment undergoing thoracic surgery. PRP produced improvement of VO2 peak degree and pulmonary function resulting in reduced postoperative complications in high-risk patients from our cases. Our results indicate that a preoperative training program may improve postoperative clinical outcomes in fraillung cancer patients with impaired lung function prior to surgical resection