Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey.

INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. METHODS: We designed a survey (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), assessing several symptoms that have been associated with Long-COVID to be administered nationwide to COVID-19 survivors; the survey also included effort perception, measured using the Borg scale. Patients receiving the survey were divided in two groups, with a 2:1 ratio: the first group included patients that received L-Arginine + Vitamin C, whereas the second group received a multivitamin combination (alternative treatment). RESULTS: 1390 patients successfully completed the survey. Following a 30-day treatment in both groups, the survey revealed that patients in the L-Arginine + Vitamin C treatment arm had significantly lower scores compared to patients who had received the multivitamin combination. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p < 0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm. CONCLUSIONS: Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception.

Epileptic seizures, movement disorders, and breathing disturbances in Rett syndrome: diagnostic relevance of video-polygraphy.

Epileptic seizures, movement disorders and breathing disturbances may be observed in Rett syndrome, and correct diagnosis is mandatory for the management. We evaluated the usefulness of video-polygraphy in the differential diagnosis between epileptic and non-epileptic paroxysmal events in eight patients with Rett syndrome. Based on video analysis, myoclonic seizures were usually misdiagnosed as movement disorders and stereotypies; the events identified by parents as generalized tonic-clonic seizures included episodes of motor activity and breathing abnormality. Myoclonic seizures aggravated by inappropriate treatment were evident in four patients; hyperventilation and apnea during wakefulness were present in all patients, while central sleep apneas were present in one patient; sinus tachycardia and cardiac arrhythmias emerged in six patients; cortical myoclonus was disclosed in five patients. In Rett syndrome, video-polygraphy is essential in characterizing the clinical features of paroxysmal events, determining autonomic dysfunctions, documenting myoclonic motor phenomena, and evaluating the responses to the treatment of epilepsy.

Solvent effect on librational dynamics of spin-labelled haemoglobin by ED- and CW-EPR.

Two-pulse, echo-detected electron paramagnetic resonance (ED-EPR) spectra and continuous-wave EPR (CW-EPR) spectra were used to investigate the solvent effect on the librational motion of human haemoglobin spin-labelled on cysteine ß93 with the nitroxide derivative of maleimide, 6-MSL. Protein samples fully hydrated in phosphate buffer solution (PBS), in a 60% v/v glycerol/water mixture and in the lyophilized form were measured at cryogenic temperature in the frozen state. The protein librational motion was characterized by the amplitude-correlation time product, <α²>τ(c), deduced from the ED-EPR spectra. The librational amplitude, <α²>τ(c), was determined independently, from the motionally averaged hyperfine splitting in the CW-EPR spectra, and the librational correlation time, τ(c), was derived from the combination of the pulsed and conventional EPR data. Rapid librational motion of small amplitude was detected in all samples. In each case, the librational dynamics was restricted up to 180 K, beyond which it increased steeply for the hydrated protein in PBS and in the presence of glycerol. In contrast, in the dehydrated protein, the librational dynamics was hindered and less dependent on temperature up to ~240 K. In all samples, <α²> deviated from small values only for T > 200 K, where a rapid increase of <α²> was evident for the hydrated samples, whereas limited temperature variation was shown in the lyophilized samples. The librational correlation time was in the sub-nanosecond regime and weakly dependent on temperature. The results evidence that solvent favours protein dynamics.

A pulsed EPR method to determine distances between paramagnetic centers with strong spectral anisotropy and radicals: the dead-time free RIDME sequence.

Methods to determine distances between paramagnetic metal centers and radicals are scarce. This is unfortunate because paramagnetic metal centers are frequent in biological systems and so far have not been employed much as distance markers. Successful pulse sequences that directly target the dipolar interactions cannot be applied to paramagnetic metal centers with fast relaxation rates and large g-anisotropy, if no echos can be detected and the excitation bandwidth is not sufficient to cover a sufficiently large part of the spectrum. The RIDME method Kulik et al. (2002) [20] circumvents this problem by making use of the T(1)-induced spin-flip of the transition-metal ion. Designed to measure distance between such a fast relaxing metal center and a radical, it suffers from a dead time problem. We show that this is severe because the anisotropy of the metal center broadens the dipolar curves, which therefore, only can be analyzed if the full curve is known. Here, we introduce five-pulse RIDME (5p-RIDME) that is intrinsically dead-time free. Proper functioning of the sequence is demonstrated on a nitroxide biradical. The distance between a low-spin Fe(III) center and a spin label in spin-labeled cytochrome f shows the complete dipolar trace of a transition-metal ion center and a spin label, yielding the distance expected from the structure.

Aggregation of transmembrane peptides studied by spin-label EPR.

The structure and function of membrane proteins is partly determined by the interaction of these proteins with the lipids of the membrane. Peptides forming single membrane-spanning alpha-helices, such as the WALP peptide (acetyl-GWWL(AL)(n)WWA-amide), are good models for such interactions. This interaction can be studied by investigating the aggregation of peptides. If the peptides remain isolated in the membrane, the peptide-lipid interaction dominates, if the peptides aggregate, the peptide-peptide interaction is stronger. The intrinsic dynamics and the disordered nature of the system require new approaches to determine eventual aggregation. We performed electron paramagnetic resonance (EPR) on spin-labeled WALP (SL-WALP) in the gel and the liquid-crystalline phases of two different phospholipids, the saturated DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), and the unsaturated DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine). At low temperatures (120 K) where both lipids are in the gel phase, less extensive aggregation is observed for the peptide in DOPC as compared to DPPC. Together with previous data on aggregation of WALP peptides from atomic force microscopy and fluorescence spectroscopy at 294 K ( Sparr ; et al. Biochemistry 2005 , 44 , 2 -10 ), the results suggest that at 120 K WALP peptides form line aggregates in DOPC and cluster aggregates in DPPC. In the liquid-crystalline phase of both lipids, signatures of aggregation are absent, showing that in this phase the peptide can be accommodated by either lipid. It can be concluded that the lipid phase, in this case gel or liquid-crystalline, is a more important determinant for peptide aggregation than whether the lipid is saturated (DPPC) or unsaturated (DOPC). In view of the gel-phase-like behavior of some membrane phases in physiological systems the methodology should be relevant.

Central sleep apnoea in Rett syndrome.

Breathing disturbances in Rett syndrome were reported almost entirely during wakefulness, with normal respiration during sleep. We studied a case of a proven MECP2 mutation in a girl, whose videopolygraphic and polysomnographic monitoring suggested the evidence of central apnoeas not only during awake, but also during sleep. Apart from prevalent awake respiratory dysfunction, central apnoeas in Rett syndrome may be also present during sleep.

Fibrolipoma of the lip treated by diode laser surgery: a case report.

INTRODUCTION: Several neoplasms of the adipose tissue can involve the soft tissues of the head and neck region. These neoplasms are mainly treated surgically and an accurate histological examination is mandatory for a precise diagnosis. CASE PRESENTATION: We report a case of fibrolipoma involving the lower lip of a 43-year-old man, which was successfully treated by diode laser surgery. This approach allowed adequate resection of the neoplasm with minimal damage to the adjacent tissues, thus reducing post-surgical scarring. CONCLUSION: Diode laser surgery for the treatment of benign lesions of the oral mucosa appears to be a convenient alternative to conventional blade surgery and has proved to be effective for the excision of fibrolipoma of the lip. The possibility of avoiding direct suture after excision is surely helpful when aesthetic areas, such as the lip, are surgically treated. For these reasons, and also considering the lower histological alteration of the specimen obtained with diode laser surgery if adequately used, the diode laser is undoubtedly a good alternative to conventional surgery.

Morphological, histochemical, and immunocytochemical study of CO2 and Er:YAG laser effect on oral soft tissues.

OBJECTIVE: The purpose of this study was to investigate the morphological, histochemical, and immunocytochemical changes of the oral mucosa after CO(2) or Er:YAG laser irradiation. BACKGROUND DATA: There have been no comparative reports on CO(2) and Er:YAG laser effects on human oral soft tissues. MATERIALS AND METHODS: Tissue preservation was studied in 40 oral biopsies of young patients obtained by CO(2) and Er:YAG laser surgery. Hematoxylin-eosin and Giemsa stains, PAS/diastase treatment, AE1 and AE2 cytokeratins, MiB1/Ki67, and bcl-2 immunoreactions were performed on the laser cut edges on formalin fixed, paraffin embedded biopsies. RESULTS: CO(2) laser biopsies show blisters, clefts and erosions of the epithelium. Intracellular edema and lengthened nuclei were also seen. The glycogen content results decreased in CO(2) laser biopsies. Good expression for cytokeratins and cell-cycle proliferation markers were found in Er:YAG biopsies, on the contrary the apoptosis marker was better expressed in CO(2) laser biopsies. CONCLUSION: The results suggest that Er:YAG laser may be routinely used in surgery, because of its minimal damage of the epithelial tissue, its low inflammatory reaction, its quicker healing process and its lower risk of scarring.

SEM analysis of dentin treated with the Er:YAG laser: a pilot study of the consequences resulting from laser use on adhesion mechanisms.

OBJECTIVES: The purpose of this study was to compare the morphological characteristics of lased dentinal surfaces obtained by chemical etching, which was applied either before or after laser treatment. The adhesive interface after the application of an adhesive-composite system on the above mentioned dentinal surfaces was also evaluated. MATERIALS AND METHODS: Eighteen caries-free permanent molars were transversally cut to obtain the dentinal surfaces. Ten of these surfaces were divided into three main groups according to their preparation modality: laser only, laser followed by chemical etching, and chemical etching before laser. The Er:YAG laser was used with two different energy outputs: 200 and 400 mJ at 1 Hz. The eight remaining surfaces were divided into two groups and followed the same preparation as the first three groups. The only difference was a change in frequency: 4 Hz was used for treating these surfaces. An adhesive system (Scotchbond 1, 3M), a thin layer of flowable composite (Tetric Flow, Vivadent), and a regular composite (Z250, 3M) were applied to each dentinal surface and then separately light cured. In order to evaluate the dentine-restoration interface, the samples were cut longitudinally and prepared for SEM observation. RESULTS: The dentinal surfaces that were etched by the laser treatment did not demonstrate the characteristics necessary for guaranteeing a good bond with the adhesive materials. A closer observation of the dentine-restoration interface revealed some micro-fractures located just below the lased dentinal surface. CONCLUSION: The decision to use the Er:YAG laser as an alternative to conventional techniques of acid etching is currently arguable. Given that the available adhesive systems require acid conditioning, it would not be advisable to skip this operative step.