Cardiovascular Risk Score and Pulmonary Gas Exchange in COVID-19 Patients Show No Correlation.

BACKGROUND: COVID-19 induces robust systemic inflammation. Patients with cardiovascular disease (CVD) are at an increased risk of death. However, much effort is being spent to identify possible predictors of negative outcomes in order to have a more specific clinical setting. CVD scores are a useful tool in evaluating risk of cardiovascular events. AIM: We evaluated oxygenation and characteristics in COVID-19 patients according to cardiovascular risk stratification performed using the Framingham risk score (FRS) for cardiovascular disease. MATERIALS AND METHODS: We evaluated 155 COVID-19 patients (110 males and 45 females, aged 67.43 ± 14.72 years). All patients underwent a complete physical examination, chest imaging, laboratory tests and blood gas analysis at the time of diagnosis. Seventeen patients died (10 males and 7 females, aged 74.71 ± 7.23 years) while the remaining 138 patients (100 males and 38 females, aged 66.07 ± 15.16 years) were alive at discharge. RESULTS: Deceased patients have an increased FRS compared to those that survived (27.37 ± 5.03 vs. 21.33 ± 9.49, p < 0.05). Compared to survivors, the deceased group presents with a significant increase in white blood cells (p < 0.05) and D-dimers (p < 0.05). There was no difference in pCO2, SO2, and in alveolar arteriolar oxygen difference (A-aDO2). On the contrary, in deceased patients there was an increased pO2 (p < 0.05) and a decreased ratio between oxygen inspired and pO2 (P/F; p < 0.05). FRS shows a negative correlation to P/F (r = 0.42, p < 0.05) in the deceased while no correlation was found in the survivors. No other correlation has been found with blood gas parameters or in the inflammation parameters evaluated in the two groups. DISCUSSION: CVD may be considered as a major risk factor for death in COVID-19 patients. The increased risk relates to a reduced lung capacity but it is not related to blood gas values. Similarly, CV risk score results are independent from the inflammatory status of the patients.

Electrochemotherapy as palliative treatment in patients with recurrent and/or metastatic head and neck tumours: features analysis for an early determination of the partial responsive patients.

OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies. PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR. RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%. CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.

Stress induced cardiomyopathy presenting as acute coronary syndrome: Tako-Tsubo in Mercogliano, Southern Italy.

BACKGROUND: Tako-tsubo syndrome (TTS) in its typical (apical) and atypical (non-apical) forms is being increasingly recognized in the West owing to early systematic coronary angiography in acute coronary syndromes (ACS). AIM OF THE STUDY: To assess the incidence, the clinical characteristics and the outcome of TTS in a single high volume cath lab in Southern Italy over the last 6 years. METHODS: Among 1674 consecutive patients (pts) referred to our coronary care units in the last 6 years (2001-2006) for ACS we selected 6 (0.5%) pts (6 women; age 57 +/- 6 years) who fulfilled the following 4 criteria: 1) transient left ventricular wall motion abnormalities resulting in ballooning at contrast ventricolographic or echocardiographic evaluation; 2) normal coronary artery on coronary angiography performed 5 +/- 9 hours from hospitalization; 3) new electrocardiographic ischemic-like abnormalities (either ST-segment elevation or T-wave inversion) and 4) emotional or physical trigger event. RESULTS: At admission all pts had presumptive diagnosis of ACS and ECG revealed ST elevation in 3 (50%) and T wave inversion with QT elongation in 3 (50%). In the acute phase cardiogenic shock occurred in 2 (33%) and heart failure in 1(16%). Presenting symptoms were chest pain in 6 (100%), dyspnoea in 2 (33%) and lipotimia in 1 (16%). At echocardiographic-ventricolographic assessment, the mechanical dysfunction (ballooning) was apical in all 6 pts ("classic" TTS). In all patients wall motion abnormalities completely reversed within 4.5 +/- 1.5 days. The region of initial recovery was the anterior and lateral wall in 4 cases and the lateral wall in 2 cases. Ejection fraction was 35 +/- 8% in the acute phase and increased progressively at discharge (55 +/- 6%) and at 41 +/- 20 months follow-up (60 +/- 4%, p < 0.001 vs. baseline). All patients remained asymptomatic with minimal (aspirin, beta blockers, antihypertensive and antidislipidemic therapy) treatment. CONCLUSION: Classic TTS is a frequent serendipitous diagnosis after coronary angiography showed "surprisingly" normal findings in a clinical setting mimicking an ACS. Despite its long-term good prognosis life threatening complications in the acute phase can occur.

Botulinum toxin treatment in patients with focal dystonia and hemifacial spasm. A multicenter study of the Italian Movement Disorder Group.

In six Centers belonging to the Italian Movement Disorder Study Group, the efficacy of botulinum toxin treatment was evaluated in an open collaborative study in 251 patients with focal dystonia and hemifacial spasm. The percentage of functional improvement ranged from 66% to 81% in patients with blepharospasm, from 40% to 51% in patients with spasmodic torticollis and from 73% to 81% in those with hemifacial spasm. Good results were also obtained in patients with oromandibular dystonia, laryngeal dystonia and writer's cramp. Side effects were mild and transient. Local botulinum toxin injection is the first choice symptomatic treatment in focal dystonia and hemifacial spasm.

Antiviral activity of S-adenosylhomocysteine hydrolase inhibitors against plant viruses.

Three SAH hydrolase inhibitors, (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (isobutyl ester) [(RS)-AHPA]; (RS)-9-(2,3-dihydroxypropyl)adenine [(RS)-DHPA] and the carbocyclic analog of 3-deazaadenosine (C-c3Ado) were evaluated for their inhibitory activity against tobacco mosaic virus (TMV) and potato virus X (PVX). Using the local lesion assay and ELISA, we demonstrated that all three compounds inhibit the replication of TMV and PVX. Whereas the three compounds proved about equally active against PVX, (RS)-AHPA was the most effective against TMV. (RS)-AHPA and C-c3Ado induced chlorosis in Nicotiana tabacum leaf discs. They also caused a substantial reduction in the growth of the main root of Phaseolus vulgaris. (RS)-DHPA was less phytotoxic than its two congeners.

Cyanogen bromide cleavage at methionine residues of polypeptides containing disulfide bonds.

A method for cleaving polypeptides at their methionine residues without affecting intramolecular disulfide bonds is described. This method may be applied for cleaving recombinant heterologous hybrid polypeptides with release of the interesting peptide. The method may also be applied to assign the correct positions of disulfide bonds in protein molecules.

Expression in Escherichia coli and characterization of human growth-hormone-releasing factor.

A chemically synthesized DNA sequence, coding for the 44 amino acid residues of human growth-hormone-releasing factor (GRF) preceded by a tryptophan codon, was cloned in frame with Escherichia coli trpE gene within a pBR322-derived plasmid. GRF was expressed in E. coli as a fused polypeptide chain (TrpE-GRF) and then the GRF amino acid sequence was released from the fused protein by specific chemical cleavage at the tryptophan residue using o-iodosobenzoic acid. The thioether group of the methionine residue of GRF was converted in the sulfonium salt derivative, in order to prevent irreversible oxidation of methionine to the sulfone derivative by the o-iodosobenzoic acid reagent. GRF was purified by HPLC and characterized in terms of amino acid composition after acid hydrolysis, protein sequencing and gel electrophoretic behaviour. These data clearly established that the biosynthetic GRF was identical to the natural one, except for the lack of amidation at the carboxyl-terminal amino acid. Far-ultraviolet circular dichroism measurements established that both biosynthetic and natural GRF are devoid of secondary structure in aqueous solution at neutral pH, whereas both peptide samples achieve a high percentage of helical structure in the presence of trifluoroethanol.

Antiviral effects of dihydroxypropyladenine [RS)-DHPA) and bromovinyldeoxyuridine (BVDU) on plant viruses.

Two established antiviral agents, dihydroxypropyladenine (RS)-DHPA and bromovinyldeoxyuridine (BVDU) were evaluated for their inhibitory effects on 4 plant viruses: Tobacco mosaic virus, potato virus X (PVX), eggplant mosaic virus (EMV) and a potyvirus isolated from Solanum palinacanthum (Poty-Sp). Using the leaf disc incubation test, BVDU proved virtually inactive while (RS)-DHPA efficiently inhibited EMV and Poty-Sp when applied at concentrations as low as 5 mg/l. TMV was less susceptible to the chemical while PVX could be inhibited at drug concentrations of 100 mg/l. To achieve a similar inhibitory effect in the leaf spray test, concentrations up to 250 and 500 mg/l were required. Using these tests no phytotoxicity was observed with (RS)-DHPA at any of the concentrations used.

Convergent transcription of the Escherichia coli hisG gene cloned in Bacillus subtilis stops in the vicinity of the attenuator.

A 5300-bp DNA segment containing the promoter, the attenuator and the first gene (hisG) of the Escherichia coli his operon has been inserted into an interspecific E. coli-Bacillus subtilis plasmid vector, pHV14. The resulting plasmid pPV48 restores the His+ phenotype to an E. coli hisG mutant, but fails to do so to a corresponding B. subtilis mutant. Experiments aimed at localizing the block to this heterologous expression in B. subtilis have shown that the enzymatic activity of the hisG+ gene product is neither detectable nor inhibited in crude extracts of B. subtilis cells harboring pPV48. Furthermore, electron microscopic, Southern blot and S1 mapping analysis of the transcripts produced in vitro and in vivo by B. subtilis RNA polymerase indicate that the hisG+ region is transcribed, but that the transcripts initiate at sites different from the his promoter, converge towards, and terminate in the vicinity of the attenuator.

Inhibitory effect of Distamycin-A and a pyrazino-pyrazine derivative on tomato spotted wilt virus.

Distamycin-A hydrochloride, a synthetic antibiotic, and 2,3-dihydroxy-6-bromo-pyrazino (2,3-beta) pyrazine derivative, were used against tomato spotted wilt virus (TSWV) in tobacco plants. The drugs were applied to the leaves at concentrations of 200 and 400 mg/l. The results showed that both drugs delayed virus spread within the plant, retarding the appearance of systemic symptoms. A virus recovery test, carried out on primary leaves of Phaseolus vulgaris cv. Manteiga, showed that TSWV replication was markedly inhibited by the pyrazino-pyrazine derivative at concentrations of 200 and 400 mg/l and, to a lower extent, by Dystamycin-A at 400 mg/l.

[In vivo synthesis of mitochondrial RNA immediately after fertilization in Paracentrotus lividus]. / Sintesi in vivo di RNA mitocondriale immediatamente dopo la fecondazione in Paracentrotus lividus.

In the present paper the in vivo incorporation of 3H-guanosine into mitochondrial RNA and of 35S-methionine into mitochondrial ribosomal proteins of Paracentrotus lividus embryos have been studied. Mitochondrial rRNA and low molecular weight RNA are newly synthesized in vivo by Paracentrotus lividus embryos as early as at 2-cell stage. Labeled RNA but not labeled proteins have been extracted from the mitochondrial ribosomes of the Paracentrotus lividus embryos at 32-cell stage.

Effect of virazole (ribavirin) on tomato spotted wilt virus in two systemic hosts, tomato and tobacco.

Virazole (1, beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide = Ribavirin), a synthetic nucleoside analogue, has been successfully used against tomato spotted wilt virus (TSWV) in tomato and tobacco plants. In tomato, the most efficient concentration to control TSWW was 500 mg/l while in tobacco, concentrations of 100 mg/l were sufficient to control systemic infection. When the plants did not show a systemic reaction virus could not be recovered from inoculated and treated tomato and tobacco plants by means of the local lesion assay. The results point out the response of a new plant virus to Virazole and indicate a possibility of controlling TSWW systemic infection.

Inhibitory effect of virazole (ribavirin) on the replication of tomato white necrosis virus (VNBT).

Tomato plants (Lycopersicon esculentum Mill.) inoculated with tomato white necrosis virus (VNBT) and treated with Virazole (1-beta-D-ribofuranosyl--1, 2, 4-triazole-3-carboxamide) at a concentration of 500 mg/l developed systemic virus symptoms in only 40 per cent of the plants in which a remarkable reduction in virus concentration was also observed. From inoculated and Virazole-treated plants which had produced no symptoms, no virus could be recovered. This result suggests that Virazole may inhibit replication of VNBT in tomato.

[Ultrastructural aspects of Parthenocissus tricuspidata (Planch.) (Vitaceae) "callus" kept in solid cultures (author's transl)]. / Estudo preliminar da ultraestrutura de tecidos de "callus" de Parthenocissus tricuspidata (Planch), (Vitceae) mantidos em cultura.

The normal strain shows undifferentiated chloroplasts in opposition to the very well chlorophyllated "callus" which shows all the normal ultrastructural characteristics of the various organelles. The strain which has lost completely the capacity of chlorophyl synthesis shows a remarkable increase in the size and number of mitochondria. The tumor tissue shows deep lobulation in its nuclei as well as undifferentiated plastids in the cytoplasm. An increase of the smooth endoplasmic reticulum in the tumor tissue was also observed.