Betacoronaviruses genome analysis reveals evolution toward specific codons usage: Implications for SARS-CoV-2 mitigation strategies.

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly widespread worldwide becoming one of the major global public health issues of the last centuries. Currently, COVID-19 vaccine rollouts are finally upon us carrying the hope of herd immunity once a sufficient proportion of the population has been vaccinated or infected, as a new horizon. However, the emergence of SARS-CoV-2 variants brought concerns since, as the virus is exposed to environmental selection pressures, it can mutate and evolve, generating variants that may possess enhanced virulence. Codon usage analysis is a strategy to elucidate the evolutionary pressure of the viral genome suffered by different hosts, as possible cause of the emergence of new variants. Therefore, to get a better picture of the SARS-CoV-2 codon bias, we first identified the relative codon usage rate of all Betacoronaviruses lineages. Subsequently, we correlated putative cognate transfer ribonucleic acid (tRNAs) to reveal how those viruses adapt to hosts in relation to their preferred codon usage. Our analysis revealed seven preferred codons located in three different open reading frame which appear preferentially used by SARS-CoV-2. In addition, the tRNA adaptation analysis indicates a wide strategy of competition between the virus and mammalian as principal hosts highlighting the importance to reinforce the genomic monitoring to prompt identify any potential adaptation of the virus into new potential hosts which appear to be crucial to prevent and mitigate the pandemic.

Analysis of small-scale soil CO2 fluxes in an orange orchard under irrigation and soil conservative practices.

The quantification of soil carbon dioxide (CO2) flux represents an indicator of the agro-ecosystems sustainability. However, the monitoring of these fluxes is quite challenging due to their high spatially-temporally variability and dependence on environmental variables and soil management practices.In this study, soil CO2 fluxes were measured using a low-cost accumulation chamber, that was realized ad hoc for the surveys, in an orange orchard managed under different soil management (SM, bare versus mulched soils) and water regime (WR, full irrigation versus regulated deficit irrigation) strategies. In particular, the soil CO2 flux measurements were acquired in discontinuous and continuous modes, together with ancillary agrometeorological and soil-related information, and then compared to the agrosystem scale CO2 fluxes measured by the eddy covariance (EC) technique.Overall significant differences were obtained for the soil CO2 discontinuous fluxes as function of the WR (0.16 ± 0.01 and 0.14 ± 0.01 mg m-2 s-1 under full irrigation and regulated deficit irrigation, respectively). For the continuous soil CO2 measurements, the response observed for the SM factor varied from year to year, indicating for the overall reference period 2022-23 higher soil CO2 flux under the mulched soils (0.24 ± 0.01 mg m-2 s-1) than under bare soil conditions (0.15 ± 0.00 mg m-2 s-1). Inter-annual variations were also observed as function of the day-of-year (DOY), the SM and their interactions, resulting in higher soil CO2 flux under the mulched soils (0.24 ± 0.02 mg m-2 s-1) than under bare soil (0.15 ± 0.01 mg m-2 s-1) in certain periods of the years, according to the environmental conditions. Results: suggest the importance of integrating soil CO2 flux measurements with ancillary variables that explain the variability of the agrosystem and the need to conduct the measurements using different operational modalities, also providing for night-time monitoring of CO2. In addition, the study underlines that the small-scale chamber measurements can be used to estimate soil CO2 fluxes at orchard scale if fluxes are properly scaled.

Pregnancy effect on disease activity in women with multiple sclerosis treated with cladribine.

INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.

Spontaneous cervical extradural hematoma in a cutaneo-meningospinal angiomatosis (Cobb syndrome): case report.

Spontaneous spinal extradural hematoma is a rare clinical entity, commonly associated with coagulopathies, tumours or vascular malformations. They are often a neurosurgical emergency, therefore prompt diagnosis and early treatment are necessary. The Cobb syndrome is a neurocutaneous syndrome in which there are metameric vascular skin nevus and spinal arteriovenous malformation. The authors report the case of a 52-year-old woman with acute cervical myelopathy and a cervical cutaneous hemangioma on clinical examination. It is stressed the importance of clinical suspicion of cutaneo-meningospinal angiomatosis based on a spinal cord syndrome in the presence of a vascular skin nevus of the same metameric level.

Impact of machine log-files uncertainties on the quality assurance of proton pencil beam scanning treatment delivery.

Irradiation log-files store useful information about the plan delivery, and together with independent Monte Carlo dose engine calculations can be used to reduce the time needed for patient-specific quality assurance (PSQA). Nonetheless, machine log-files carry an uncertainty associated to the measurement of the spot position and intensity that can influence the correct evaluation of the quality of the treatment delivery. This work addresses the problem of the inclusion of these uncertainties for the final verification of the treatment delivery. Dedicated measurements performed in an IBA Proteus Plus gantry with a pencil beam scanning (PBS) dedicated nozzle have been carried out to build a 'room-dependent' model of the spot position uncertainties. The model has been obtained through interpolation of the look-up tables describing the systematic and random uncertainties, and it has been tested for a clinical case of a brain cancer patient irradiated in a dry-run. The delivered dose has been compared with the planned dose with the inclusion of the errors obtained applying the model. Our results suggest that the accuracy of the treatment delivery is higher than the spot position uncertainties obtained from the log-file records. The comparison in terms of DVHs shows that the log-reconstructed dose is compatible with the planned dose within the 95% confidence interval obtained applying our model. The initial mean dose difference between the calculated dose to the patient based on the plan and recorded data is around 1%. The difference is essentially due to the log-file uncertainties and it can be removed with a correct treatment of these errors. In conclusion our new PSQA protocol allows for a fast verification of the dose delivered after every treatment fraction through the use of machine log-files and an independent Monte Carlo dose engine. Moreover, the inclusion of log-file uncertainties in the dose calculation allows for a correct evaluation of the quality of the treatment plan delivery.

Lippia graveolens photochemopreventive effect against UVB radiation-induced skin carcinogenesis.

Lippia graveolens HBK (Mexican oregano) is a species that is regularly used as a condiment in Mexican cuisine. In traditional medicine, it is used for the treatment of respiratory and digestive illnesses, headaches, rheumatism and inflammation-related disorders. The main chemical components reported in this species include the following: terpenoids, iridoids and flavonoids. The aim of this study was to determine the potential photochemopreventive effect of the methanolic extract of Lippia graveolens (MELG) against ultraviolet B (UVB)-induced skin cancer in SKH-1 mice. The phenolic content, radical scavenger activity, penetration and genotoxicity of the MELG were also evaluated. The MELG exhibited scavenging activity against 1,1-diphenyl-2-picrylhydrazyl, superoxide and hydroxyl radicals, and it did not exhibit genotoxic activity in the micronucleus test. In addition, the MELG absorbed UVB (280nm) electromagnetic radiation. The main components detected in the plant extract were naringenin and galangin, and pinocembrin was also isolated and identified through spectroscopic analysis. The MELG demonstrated a photoprotective effect against UVB-induced cell death in Escherichia coli. In chronic challenge experiments, the MELG protected against UVB-induced skin cancer in SKH-1 mice. The MELG penetrated the skin of mice. Topical administration of the MELG protected against chronic UVB-induced damage in mouse SKH-1 skin. Our results suggest that the MELG has photochemopreventive activity and may potentially prevent photo-tumorigenesis.

Changes in intracardiac atrial cardioversion threshold at rest and during exercise.

OBJECTIVES: We sought to analyze in patients with chronic atrial fibrillation (AF) the change in the intracardiac atrial defibrillation threshold (ADT) at rest and during exercise, to quantify the effective risk of low energy endocavitary cardioversion during the effort and to compare the ADT of chronic and reinduced AF. BACKGROUND: Low energy endocavitary cardioversion is a new alternative to transthoracic shock in patients with chronic AF. Nevertheless, patient discomfort and possible induction of ventricular arrhythmias should be further evaluated. METHODS: Sixteen patients with chronic AF were included in the study. Two 6F custom-made catheters (Electro-Catheter, Inc.) were used for shock delivery and one tetrapolar lead for ventricular synchronization. Without sedation and in a random order, patients underwent two sequences of shocks to determine the ADT at rest and during exercise. Exercise was performed isometrically by the superior limbs. Atrial fibrillation was reinduced by atrial pacing. After each shock, the patients were requested to grade their discomfort with a score from 1 to 5. The power of the study was > 90% in detecting a 25% difference in the ADT between groups. RESULTS: Patients were classified into two groups: Nine patients (group A) underwent the first cardioversion during exercise; seven patients (group B) underwent the first cardioversion at rest. In total, the mean (+/-SD) ADT was 6.70 +/- 1.54 J during exercise and 7.02 +/- 1.82 J at rest (p = 0.59). A significantly lower ADT was observed in the second shock sequence than the first one (6.32 +/- 2.09 J vs. 7.40 +/- 0.87 J, p < 0.05). The discomfort score was 3.25 +/- 0.86 at rest and 2.94 +/- 0.77 during exercise (p = 0.09). No complications occurred. CONCLUSIONS: Low energy endocavitary cardioversion is a safe and effective procedure in patients with chronic AF. Discomfort is not generally severe enough to result in procedure termination. The ADT is not influenced by exercise and is higher in chronic than in reinduced AF.

Brain metastases: surgical versus conservative treatment.

A comparative study on surgical versus conservative brain metastases treatment has been carried out. Patients have been divided in seven groups by means of treatment modalities. Follow-up, has been carried out taking into consideration mean survival time and quality life in particular, evaluated by means of Order's classes. Anaesthesiological management problems were discussed also. From data analysis, it follows that untreated patients, (group 1) had a lower mean survival time than that of the other patients. Thirty days after first evaluation, 85% of these patients had a very poor quality life. Patients who underwent surgery associated to radio and chemotherapy (group 2) have had better recovery of functional autonomy and longest mean survival time. Among these, thirty days after treatment only 3% had a very poor quality life, while 67% had the better quality life. Patients who underwent others treatment modalities had intermediate results.

Clinical, morphometric and ultrastructural aspects in a new model of spinal cord compression.

A new model of spinal cord compression is presented. Forty-two New Zealand albino rabbits weighing between 1.2 and 1.5 kg were submitted to spinal cord compression to about half of its normal diameter by vascular Sugita's clip to different compression time (sham, 5-10-20 minutes e 1-6-12 hours) and sacrified after 72 hours. The consequent neurological dysfunction size of lesion was graded by Tarlov's scale for voluntar motility. Ultrastructural and morphometrical studies were carried out to evaluate changes in shape, perimeters, axonal and myelin areas of the lateral and the posterior tract of spinal cord. A 10 minute decrease of 50% of the transverse diameter of the spinal cord causes a defined damage. The swelling of myelin is a useful index of the importance of the damage.

Clinical use of a new pharmaceutical preparation containing L-thyroxine in solution. Preliminary report.

A pharmacological preparation containing L-thyroxine in solution has been tested in man for thyroid substitution or suppression. Twenty-two women and 2 men, aged from 30 to 82 years, with primary hypothyroidism (10) or nodular goiter (14) were treated. Serial clinical and laboratory follow-up evaluations were performed, varying from 1 to 18 months. Five hypothyroid patients and 12 with goiter had not received any previous thyroid hormone medication. Clinical and laboratory euthyroidism was achieved in all 5 hypothyroid patients by a mean weekly L-T4 dose of 580 micrograms. Inhibited or blunted TSH response to TRH was obtained in the subjects with goiter by a mean weekly L-T4 dose of 683 micrograms. The remaining 7 patients (5 hypothyroid and 2 with nodular goiter) received first L-T4 in tablet and then L-T4 in solution. Four of these 7 patients (2 hypothyroid and 2 with nodular goiter), treated with equal doses of the two L-T4 preparations, showed lower basal and stimulated serum TSH concentration during administration of L-T4 in solution. No signs of hyperthyrodism were observed during the treatment. These data indicate that the tested preparation containing L-T4 in solution can be used for thyroid substitution or suppression, and agree with our previous determination of L-T4 content in the preparations indicating an excess of L-T4 in the solution.

Needle aspiration of thyroid nodule: long-term control of its efficiency in preoperative selection.

Eight years extensive use of surgery for detecting thyroid cancer in euthyroid patients with palpable nodule was compared to 8 years preoperative selection by needle aspiration techniques to the same purpose. One thousand one hundred and forty operations were performed from 1972 to 1979; 3079 patients were examined by needle aspiration from 1980 to 1987. The female to male and single to multiple palpable nodule ratios were 5.2, 2.5 in the former and 6.8, 2.7 in the latter group respectively. Postoperative histology showed that nodules were malignant in 35 subjects and benign in 1105 patients of the first group. Two hundred thirty eight patients of the 3079 patients of the second group were operated upon mainly following aspiration findings. Postoperative histology showed primary malignant tumors in 88 patients. Therefore, introduction of needle aspiration techniques reduced the number of operations from 143 per year to 30 per year and increased from 4 to 11 per year the number of malignant nodules detected without any change of the incidence of cancer (about 3% in each group).

[Early stabilization in severe cervical vertebral and spinal cord injuries]. / La stabilizzazione precoce nei gravi traumi vertebro-midollari cervicali.

In the cervical vertebral-myelic trauma a high incidence of bronchopulmonary, metabolic, thromboembolic complications and bedsores is present. The authors, in agreement with the most recent literature (Tator, 1987), affirm that adoption of the precocious stabilization, allowing an equally precocious mobilization, considerably reduces the above-said complications. Thirty patients with vertebral-myelic lesions needing operation for stabilization have been followed. Twenty-one of these, presented irreversible myelic damages and nine cases had partially or completely reversible damages. Only in five cases severe bronchopulmonary affections and bedsores occurred. Thrombo-embolic complications did not occur. The authors conclude that the precocious mobilization allowed by the stabilization realized in acute state, permits a drastic decrease in the complications typical of this kind of affections.

[Prevention of postoperative complications in vertebro-spinal cord pathology]. / Prevenzione delle complicanze post-operatorie nelle patologie vertebro-midollari.

In 352 patients, affected by vertebral-medullary pathology, we evaluated the role played by the prevention or by the treatment of postoperative complications. We also evaluated their influence on the clinical outcome and neurological recovery. In every case we recorded a scrupulous post-operative neurological monitoring of the eventual complications, on the basis of the type, gravity and duration. From our results it appears that the complications, mostly secondary to infectious diseases, have an influence on the clinical and neurological recovery. We highlight the importance of an adequate nutritive management to prevent the complications, specifically those secondary to infectious diseases and cutaneous lesions.

[Latent long QT syndrome: discription of a clinical case]. / Sindrome del QT lungo latente: descrizione di un caso clinico.

Latent forms of long QT syndrome have been already reported. We describe one case of a 27 years old female patient who experienced an episode of cardiac arrest after several puffs of salbutamole. The malignant arrhythmia causing the cardiac arrest was torsade de pointes degenerated into ventricular fibrillation. The patient ECG showed a normal QTc basal interval and the correct diagnosis was made by contemporary recording of the ECG and MAP during orciprenalina infusion. After drug infusion, we have recorded a MAP lengthening and a dispersion of MAP duration between the right ventricular apex and the right ventricular outflow tract. These modifications were concomitant with the appearance of "humps" (probably related to the presence of early afterdepolarizations), a QT interval lengthening and morphologic changes of the T and U waves.

Influence of digital and analogue cellular telephones on implanted pacemakers.

UNLABELLED: The aim of this study was to find out whether digital and analogue cellular 'phones affect patients with pacemakers. The study comprised continuous ECG monitoring of 200 pacemaker patients. During the monitoring certain conditions caused by interference created by the telephone were looked for: temporary or prolonged pacemaker inhibition; a shift to asynchronous mode caused by electromagnetic interference; an increase in ventricular pacing in dual chamber pacemakers, up to the programmed upper rate. The Global System for Mobile Communications system interfered with pacing 97 times in 43 patients (21.5%). During tests on Total Access of Communication System telephones, there were 60 cases of pacing interference in 35 patients (17.5%). There were 131 interference episodes during ringing vs 26 during the on/off phase; (P < 0.0001); 106 at maximum sensitivity level vs 51 at the 'base' value; P < 0.0001). Prolonged pacing inhibition (> 4 s) was seen at the pacemaker 'base' sensing value in six patients using the Global system but in only one patient using Total Access. CONCLUSION: Cellular 'phones may be dangerous for pacemaker patients. However, they can be used safely if patients do not carry the 'phone close to the pacemaker, which is the only place where high risk interference has been observed.

[Ventricular nodal reentry tachycardia without ventricular dilatation: diagnosis and treatment by radiofrequency catheter ablation]. / Tachicardia ventricolare da rientro branca-branca in assenza di dilatazione ventricolare: diagnosi e trattamento mediante ablazione transcatetere a radiofrequenza.

Bundle branch reentry tachycardia has been reported in patients with left ventricular dilatation, especially in those with dilated cardiomyopathy and aortic regurgitation. These patients show aspecific intraventricular conduction delay on the ECG and a prolonged H-V interval at the electrophysiologic study. We report 2 cases of bundle branch reentry tachycardia in patients without left ventricular enlargement to help the correct diagnosis of the arrhythmia. A correct diagnosis is very important because bundle branch reentry tachycardia is easily and safely treated by right bundle transcatheter radiofrequency ablation. We also report electrophysiologic characteristics we found during the study and the ablation: -contrary to the data reported in literature, at ventricular tachycardia starting, modifications of the V-V interval are not always preceded by similar variations in the H-H interval. -during right bundle radiofrequency ablation, a QRS narrowing may precede right bundle branch block appearance. This QRS normalisation should induce to continue and not to stop energy delivering.

CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade.

CD22 is a B-cell-specific adhesion molecule that modulates BCR-mediated signal transduction. Ligation of human CD22 with monoclonal antibodies (MoAbs) that block the ligand binding site triggers rapid tyrosine phosphorylation of CD22 and primary B-cell proliferation. Because extracellular signal-regulated kinases (ERKs) couple upstream signaling pathways to gene activation and are activated by B-cell antigen receptor (BCR) signaling, we examined whether CD22 ligation also activated ERKs and/or modified BCR-induced ERK activation. Ligation of CD22 on either primary B cells or B-cell lines failed to significantly activate the mitogen activated protein kinase (MAPK) ERK-2, but did activate the stress-activated protein kinases (SAPKs; c-jun NH2-terminal kinases or JNKs). In contrast, BCR ligation resulted in ERK-2 activation without significant SAPK activation. Concurrent ligation of CD22 and BCR enhanced BCR-mediated ERK-2 activation without appreciably modulating CD22-induced SAPK activation. Consistent with its induction of SAPK activity, there was a marked increase in nuclear extracts of activator protein-1 (AP-1) and c-jun levels within 2 hours of exposure of primary B cells to the CD22 MoAb. Despite their differences in ERK activation, both CD22 and BCR ligation triggered several Burkitt lymphoma cell lines to undergo apoptosis, and the 2 stimuli together induced greater cell death than either signal alone. The pro-apoptotic effects were CD22-blocking MoAb-specific and dose-dependent. Examination of expression levels of Bcl-2 protoncogene family members (Bcl-2, Bcl-x(L), Mcl-1, and Bax) showed a downregulation of Bcl-x(L) and Mcl-1 after CD22 ligation. This study provides a plausible mechanism to explain how CD22 and BCR signaling can costimulate B-cell proliferation and induce apoptosis in Burkitt lymphoma cell lines.