Correction: Organic azides: "energetic reagents" for the intermolecular amination of C–H bonds

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Effectiveness of Preventive Measures in Keeping Low Prevalence of SARS-CoV-2 Infection in Health Care Workers in a Referral Children’s Hospital in Southern Italy

The coronavirus disease 2019 (COVID-19) pandemic now represents a major threat to public health. Health care workers (HCW) are exposed to biological risk. Little is currently known about the risk of HCW operating in pediatric wards for SARS-CoV-2 infection. The aim is to assess the prevalence of SARS-CoV-2 infection in HCW in a third-level children’s hospital in Southern Italy. An observational cohort study of all asymptomatic HCW (physician, technicians, nurses, and logistic and support operators) was conducted. HCW were screened, on a voluntary basis, for SARS-CoV-2 by RT-PCR on nasopharyngeal swab performed during the first wave of COVID-19. The study was then repeated, with the same modalities, at a 7-month interval, during the “second wave” of the COVID-19 pandemic. At the initial screening between 7 and 24 April 2020, 525 HCW were tested. None of them tested positive. At the repeated screening, conducted between 9 and 20 November 2020, 627 HCW were tested, including 61 additional ones resulting from COVID-emergency recruitment. At this second screening, eight subjects (1.3%) tested positive, thus being diagnosed as asymptomatic carriers of SARS-CoV-2. They were one physician, five nurses, and two HCW from the logistic/support services. They were employed in eight different wards/services. In all cases, the epidemiological investigation showed convincing evidence that the infection was acquired through social contacts. The study revealed a very low circulation of SARS-CoV-2 infection in HCW tested with RT-PCR. All the infections documented in the second wave of epidemic of SARS-CoV-2 were acquired outside of the workplace, confirming that in a pediatric hospital setting, HCW education, correct use of personal protective equipment, and separation of the COVID-patient pathway and staff flow may minimize the risk derived from occupational exposure

Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis.

Ten children with the characteristic clinical and haematological features of haemophagocytic lymphohistiocytosis are reported. Four patients treated with a combination of drugs comprising etoposide, methotrexate, and steroids were in complete remission after 10 to 30 months. Natural cytotoxic mechanisms including natural killer cell activity, antibody dependent cell mediated cytotoxicity, lymphokine activated killer cell activity, and natural killer cell like activity were persistently absent or severely impaired in these four patients despite their clinical remission. Their parents and one healthy sibling also had impaired natural cytotoxic mechanisms. Constitutional impairment of natural cytotoxic mechanisms could be important in the pathogenesis of haemophagocytic lymphohistiocytosis

A2A and A3, Adenosine receptors mRNA are overexpressed in an experimental animal model of myocardial infarction

Background: Adenosine, a purine nucleoside and a "retaliatory metabolite" in ischemia, is ubiquitous in the body, and increases 100-fold during ischemia. Its biological actions are mediated by four adenosine receptors (ARs): A1 and A3, coupled to Gi/o, and the high-affinity A2A and low-affinity A2B, coupled to Gs. Because A1R and A3R are distributed mainly in myocardial cells and A2 are on coronary vascular smooth cells in the heart, adenosine may substantially modulate cardiac function as a whole. Aim: To determine possible myocardial alterations in the expression of ARs, in an experimental animal model of myocardial infarction (MI). Materials and Methods: Left ventricular (LV) tissue was collected from male adult minipigs with MI (n=5), induced by permanent surgical legation of the left anterior descending coronary artery and from 5 healthy pigs. mRNA expression of A1R, A2AR, A2BR,A3R was determined by semi-quantitative RT-PCR in tissue sampled collected from border (BZ) and remote zones (RZ) of infarcted area. Results: Transmural infarction affected about 15% of the LV wall mass. After 4 weeks, mRNA expression was higher in infarct regions than in control for A1R (controls=2.0?1.0, BZ=2.4?0.4, RZ=1.2?0.1), A2AR (controls=0.6?0.3, BZ=1.9?0.2, RZ=1.3?0.04 p=0.002, p=0.04, controls vs. BZ and RZ), A2BR (controls=1.1?0.5, BZ=1.2?0.2, RZ=0.5?0.04) and A3R (controls=0.2?0.07, BZ=2.4?0.7, RZ=0.7?0.07, p=0.006, p=0.002, controls vs. BZ and RZ). Conclusion: All adenosine receptors, and expecially A2A and A3, are overexpressed in the BZ of MI, consistently with an adaptative retaliatory anti-ischemic adenosinergic changes of post-infarcted heart

Limited Additive Diagnostic Impact of Isolated Gastrointestinal Involvement for the Triage of Children with Suspected COVID-19

The strategy for the selection of patients with a suspected SARS-CoV-2 infection is relevant for the organization of a children’s hospital to provide optimal separation into COVID-19 and non-COVID-19 areas and pathways. We analyzed the proportion of children with COVID-19 presenting with gastrointestinal (GI) symptoms in 137 consecutive patients admitted between January 2020 and August 2021. GI symptoms were present as follows: diarrhea in 35 patients (26%), vomiting in 16 (12%), and both of them in five (3%); the combination of fever, respiratory symptoms, and diarrhea was observed in 16 patients (12%). Of the 676 adult patients with COVID-19 admitted to our hospital in the same time interval, 62 (9.2%) had diarrhea, 30 (4.4%) had vomiting, and 11 (1.6%) had nausea; only one patient, a 38-year-old male, presented with isolated GI symptoms at the diagnosis. Although diarrhea was observed in one quarter of cases, one-half of them had the complete triad of fever, respiratory syndrome, and diarrhea, and only five had isolated diarrhea, of which two were diagnosed with a Campylobacter infection. The occurrence of either respiratory symptoms or gastrointestinal symptoms in our patients was not related to the patient age, while younger children were more likely to have a fever. Of the 137 patients, 73 (53%) could be tested for their serum level of SARS-CoV-2 specific IgG antibodies. The observed titer ranged between 0 (n = 3) and 1729 BAU/mL (median, 425 BAU/mL). Of 137 consecutive patients with COVID-19 admitted to our referral children’s hospital, only three presented with an isolated GI manifestation. It is interesting to note that this finding turned out to be fully in keeping with what was observed on adult patients with COVID-19 in our hospital. The additive diagnostic impact of gastrointestinal involvement for the triage of children with suspected COVID-19 appears limited

Mismatch between mRNA cardiac expression of BNP and CNP in pacing-induced heart failure

Purpose: It has been recently demonstrated in an animal model of heart failure (HF) that the high-frequency pacing of the left ventricle (LV) free wall causes a dyssynchronous pattern of contraction that leads to progressive cardiac failure with pronounced differences in regional contractility. Aim of this study was to evaluate the possible variation of brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) mRNA expression in the anterior/anterior lateral region (pacing site, PS) compared with the infero-septal region (opposite site, OS) to individualize the possible association between the contraction patterns and the expression of these biomarkers. Methods: Cardiac tissue was collected from male adult minipigs without (controls, n=6) and with pacing-induced HF (n=8) from PS, and from the tissue remote from the pacing-site. mRNA expression of BNP and CNP was evaluated by semiquantitative polymerase chain reaction (PCR) by using GAPDH as housing gene. Results: A significant difference in mRNA expression of BNP in PS was observed between HF animals and controls (BNP/GAPDH: 0.65?0.11 vs. 0.35?0.04, p=0.02) whereas in OS BNP levels resulted similar to those of controls (BNP/GAPDH: 0.36?0.05). mRNA expression of CNP was higher in HF with respect to controls both in PS and in OS, although not significantly (CNP/GAPDH: controls 0.089?0.036, PS 0.29?0.23, OS 0.54?0.16). These findings are in tune with the increase of CNP tissue concentrations (controls=0.69?0.13; PS=1.56?0.19; OS=1.70?0.42 pg/mg protein; p=0.039 controls vs.OS). The higher levels of BNP mRNA expression in PS are in agreement with a reduction of contractile function in this region while the higher CNP mRNA expression in OS could suggest the presence of a major endothelial dysfunction in the remote region. Conclusions: In clinical conditions the endothelial dysfunction precedes the overt HF, so, although further investigations are necessary, these results suggest that CNP could be a early marker of HF. In this context, CNP could be a marker more relevant than BNP in early recognizing patients with HF

Myocardial infarction activates the expression of cardiometabolic biomarkers in the heart: study in a swine model.

Purpose. Inflammation, extra-cellular matrix (ECM) remodeling and adipokine system activation represent essential processes of molecular response to cardiac injury. The aim of this study was to evaluate the cardiac expression of biomarkers involved in the inflammation, ECM remodeling and adiponectin system in an experimental animal model of myocardial infarction (AMI). Methods. Left ventricular (LV) tissue was collected from male adult pigs with AMI (n=6), induced by permanent surgical ligation of the left anterior descending coronary artery and from 6 healthy pigs. mRNA expression was determined by RT-PCR in tissue samples collected from border (BZ) and remote zones (RZ) of infarcted area. Proinflammatory cytokines (IL-6, TNF-&#945;), matrix metalloproteinases (MMP)-2, -9, their tissue inhibitors (TIMP)-1, -2 and collagen (COL3&#945;) were evaluated. In addition, adiponectin and its receptors, adipo-R1 and adipo-R2, were evaluated, owing its anti-inflammatory actions. Results. This surgical approach resulted in a permanent transmural infarction affecting 10-15% of the LV wall mass and after 4 weeks the mRNA expression of biomarkers, normalized on the respective GAPDH, was significantly higher in infarcted regions than in controls (MMP-9: 7.09?4.31; 1.18?0.28; 0.72?0.11, respectively for BZ, RZ and controls, p<0.05 BZ vs. RZ and controls; TIMP-1: 2.41?1.20; 0.28?0.04; 0.33?0.05, p=0.01; TIMP-2: 2.75?1.51; 0.53?0.04; 0.38?0.03, p<0.05; COL3&#945;: 4.28?1.11; 0.87?0.13; 0.61?0.18, p<0.0004). Inflammatory indices were increased in AMI, both BZ and RZ. Adiponectin was significantly increased with respect to controls (BZ: 2.95?1.69; RZ: 0.93?0.33; controls: 0.52?0.12, p<0.05 BZ vs controls) as well as the Adipo-R1 (BZ: 1.40?0.31, RZ: 1.26?0.20, controls: 0.63?0.07; p<0.05 BZ and RZ vs controls). Conclusions. The inflammatory and ECM remodelling processes are activated after myocardial injury together with the system of adiponectin, confirming its involvement in the process of cardiac remodelling/repair. The knowledge of the interaction between the various mediators of the complex response to cardiac damage could represent an important target for new therapies. Reference. Shibata R et al, Cardiovasc Res. 2007 Jun 1;74(3):471-9

Plasma adiponectin is a marker of severity in heart failure

Purpose. Adiponectin, a 247 aminoacid protein produced mainly by adipose tissue, beside its effects on glucose metabolism, plays important protective function against cardiovascular disease. Adiponectin is inversely correlated with an increased cardiovascular risk and hypo-adiponectinemia is considered an independent cardiovascular risk factor. On the contrary, the role of adiponectin in heart failure (HF) is not fully known. In order to evaluate the prognostic value of circulating adiponectin, we measured total adiponectin plasma levels in patients with HF of different severity. Methods. Total adiponectin, leptin and interleukin(IL)-6 levels were measured in plasma samples of 159 no diabetic patients with different etiology HF (17 in NYHA class I, 82 in NYHA class II, 46 in NYHA class III and 14 in NYHA class IV, age 62?14 yrs, LEVF% 32.5?0.79, mean?sem) and in 31 healthy subjects as control, by dedicated ELISA (Linco Res-US, DRG Diagnostics-Germany, Diaclone Research-France, respectively). In the same group brain natriuretic peptide (BNP) levels were determined by IRMA (Shionogi, Osaka, Japan). Results. Our findings indicated that total adiponectin levels increased significantly as a function of disease severity (7.1?0.61 mg/ml vs 10.9?1.4 in NYHA class I vs 12.8?0.95 in NYHA class II vs 15.7?1.3 in NYHA III vs 16.7?1.8 in NYHA class IV; p<0.001 NYHA II, III and IV vs controls) and they correlated negatively with LVEF% (p=0.0009), positively with cardiac function (BNP levels) (p<0.0001) and inflammation (IL-6 levels) (p<0.0001). We did not observe any correlation with metabolism (BMI) in patients with HF, while a significant correlation was found between leptin and BMI (p<0.0001). Conclusion. Circulating adiponectin is associated with cardiovascular function and inflammation in HF patients. The increased adiponectin plasma levels in HF is a marker of disease severity, indipendent of metabolism

Time-course of plasma NT-proc-type natriuretic peptide in end-stage heart failure patients supported by left ventricular assist device implant

Purpose: Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) as well as the respective amino-terminal NT-proANP and NT-proBNP have now been well established as predictors of outcome in patients with heart failure (HF). C-type natriuretic peptide (CNP) and NT-proCNP are increased in HF patients as a function of disease severity, supporting a role for these peptides in the pathophysiology of HF, but their modifications during left ventricular assist device (LVAD) implant are lacking. Aim of this study was to evaluate the time-course of natriuretic peptides in end-stage HF patients undergoing LVAD implant in order to recognize new reliable predictive biomakers of cardiac recovery during LVAD. Methods: Five end-stage HF patients (NYHA class III and IV; age: 57?11 yrs; LVEF%<20) undergoing LVAD implantation were studied. Clinical hemodynamic evaluation and blood samples were obtained at admission (T1) and at 4, 24, 72 hrs and 1, 2, 4 weeks (T2-T7) after LVAD implant. NT-proANP and NT-proCNP were measured in plasma EDTA and aprotinin samples by a direct ELISA () while NT-proBNP by the Elecsys? 2010 analyzer. Results: The NT-proCNP time-course during LVAD was the following: T1=88.8?12.8 pg/ml; T2=144?29.8; T3=241.6?86.8 (p<0.05 vs T1); T4=229.7?66.4; T5=162.3?66.5; T6=175.3?47.7; T7=76.9?8 (p=ns vs T1). NT-proANP showed a similar pathway while NT-proBNP is reduced after LVAD implant (T1=4.1?2.2 ng/ml; T3=3.0?0.4), remaining lower than at baseline until 4 weeks (T7=3.1?0.9 ng/ml). NT-proCNP positively correlated with NT-proANP (p=0.03) while no correlation was found with NT-proBNP. Conclusions: This study reports for the first time original data on NT-proCNP levels after LVAD as a function of the time. The natriuretic peptides are differently modulated by LVAD, although all peptides resulted reduced after 4 weeks from implantation. The parallel determination of these effectors could allow us to obtain an integrated description of pathophysiological changes occurring during mechanical support

Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA,partial cds and 3\u27 UTR.

LOCUS HQ419060 318 bp mRNA linear PRI 24-NOV-2010 DEFINITION Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA, partial cds and 3\u27 UTR. ACCESSION HQ419060 VERSION HQ419060.1 GI:312261407 KEYWORDS . SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 318) AUTHORS Landi,S., Melaiu,O., Cabiati,M., Landi,D., Caselli,C., Prescimone,T., Giannessi,D., Gemignani,F. and Del Ry,S. TITLE Direct Submission JOURNAL Submitted (20-OCT-2010) Laboratory of Cardiovascular Biochemistry, Institute of Clinical Physiology, Via Moruzzi 1, Pisa, PI 56100, Italy FEATURES Location/Qualifiers source 1..318 /organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /cell_line="SKNBE" /PCR_primers="fwd_seq: gtcagaagaagggcgacaag, rev_seq: gcgtttaaacgcgcacgcgt" gene <1..318 /gene="NPPC" CDS <1..188 /gene="NPPC" /codon_start=3 /product="natriuretic peptide precursor type C" /protein_id="ADQ54381.1" /db_xref="GI:312261408" /translation="GDRSRLLRDLRVDTKSRAAWARLLQEHPNARKYKGANKKGLSKG CFGLKLDRIGSMSGLGC" 3\u27UTR 189..318 /gene="NPPC" ORIGIN 1 agggcgaccg gtcgcgactg ctccgggacc tgcgcgtgga caccaagtcg cgggcagcgt 61 gggctcgcct tctgcaagag caccccaacg cgcgcaaata caaaggagcc aacaagaagg 121 gcttgtccaa gggctgcttc ggcctcaagc tggaccgaat cggctccatg agcggcctgg 181 gatgttagtg cggcgccccc tggcggcggg agaagaatga ttctgacact tggggaccag 241 ccttcagtag ctacccttgg aatgcctttg ctctcttctc tcctgtctaa acaacaaaga 301 gacggagtct gaggcct