Effects of laser photobiomodulation in the management of oral lichen planus: a literature review.

Objectives: This review aims to understand whether Photobio-modulation (PBM) therapy is a valid aid in the management of Oral Lichen Planus (OLP) and its symptoms. Moreover, an analysis to determine whether it is a valid replacement for conventional therapies and whether standardized protocols can be used in PBM sessions or whether these should be changed depending on the type of injury has been made. Finally, an evaluation to determine whether PBM may induce transformation of dysplastic oral keratinocytes into squamous cell carcinoma has been made. Materials and Methods: Searches were conducted on two search databases for relevant publications released between 1992 and 2019. The databases used were: Pubmed "Medline", and Google Scholar. Forty-four articles complied with the inclusion criteria and were included for quality assessment and data extraction. Results: All the studies reported positive effects of PBM; how-ever, there was wide heterogeneity in the laser parameters used in the management of the OLP. The effective dose ranges from 2 to 3 J/cm2, in order to see the desired biological effects. Conclusions: PBM is useful in controlling algal sensation and can be used in cases of OLP lesions that are not responsive to conventional therapies or when corticosteroid doses are too high for the patient, resulting in possible side effects. Standardized biostimulation protocols with further scientific insights are therefore required.

Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes.

BACKGROUND: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients. METHODS: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score >14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1month, compared to TSMs. RESULTS: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1month). CONCLUSIONS: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype.

Current and emerging approaches for evaluating platelet disorders.

Platelets play a central role in physiological hemostasis and also in pathological thrombosis. It is well established that congenital or acquired abnormalities of platelet function are associated with a heightened risk of bleeding of variable severity and excessive hemorrhage after surgery or trauma. Several kinds of different platelet function tests have been developed over the years to identify or diagnose platelet function disorders. The use of these tests for the assessment of thrombotic risk or for monitoring the effects of drugs inhibiting platelet function is not well established. Light transmission aggregometry (LTA) is the gold standard for the study of patients with defects of platelet function. Its results are affected by several pre-analytical and analytical variables. The Subcommittee on Platelet Physiology of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published official guidelines for the standardization of the variables affecting LTA, which should be followed to harmonize the procedures across different laboratories worldwide. The lumi-aggregometer, a modification of LTA that measures platelet secretion in parallel with aggregation, is preferable to LTA for diagnosing inherited defects of platelet function, because it is more sensitive to the most common disorders, which are characterized by abnormalities of platelet secretion. LTA (or lumi-aggregometry) is useful as a first screening test of patients with the clinical suspicion of defects of platelet function, because it helps to provide an interim diagnostic hypothesis, which can then be confirmed or discounted using appropriate and specific tests.

Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

Cognitive dysfunction and negative symptoms of schizophrenia remain an unmet clinical need. Therefore, it is essential that new treatments and approaches are developed to recover the cognitive and social impairments that are seen in patients with schizophrenia. These may only be discovered through the use of carefully validated, aetiologically relevant and translational animal models. With recent renewed interest in the neurodevelopmental hypothesis of schizophrenia, postnatal administration of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) has been proposed as a model that can mimic aspects of schizophrenia pathophysiology. The purpose of the current review is to examine the validity of this model and compare it with the adult subchronic PCP model. We review the ability of postnatal PCP administration to produce behaviours (specifically cognitive deficits) and neuropathology of relevance to schizophrenia and their subsequent reversal by pharmacological treatments. We review studies investigating effects of postnatal PCP on cognitive domains in schizophrenia in rats. Morris water maze and delayed spontaneous alternation tasks have been used for working memory, attentional set-shifting for executive function, social novelty discrimination for selective attention and prepulse inhibition of acoustic startle for sensorimotor gating. In addition, we review studies on locomotor activity and neuropathology. We also include two studies using dual hit models incorporating postnatal PCP and two studies on social behaviour deficits following postnatal PCP. Overall, the evidence we provide supports the use of postnatal PCP to model cognitive and neuropathological disturbances of relevance to schizophrenia. To date, there is a lack of evidence to support a significant advantage of postnatal PCP over the adult subchronic PCP model and full advantage has not been taken of its neurodevelopmental component. When thoroughly characterised, it is likely that it will provide a useful neurodevelopmental model to complement other models such as maternal immune activation, particularly when combined with other manipulations to produce dual or triple hit models. However, the developmental trajectory of behavioural and neuropathological changes induced by postnatal PCP and their relevance to schizophrenia must be carefully mapped out. Overall, we support further development of dual (or triple) hit models incorporating genetic, neurodevelopmental and appropriate environmental elements in the search for more aetiologically valid animal models of schizophrenia and neurodevelopmental disorders (NDDs).

Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency.

Arachidonic acid (AA), when cleaved from phospholipids by cytosolic phospholipase A2 alpha (cPLA2a), generates eicosanoids, with pro-hemostatic, pro-inflammatory, vasoactive and gastro-protective functions. We describe a patient (27-year-old man) and his twin-sister with early-onset bleeding diathesis and recurrent gastro-intestinal (GI) ulcers. Platelet aggregation/δ-granules secretion by collagen was impaired, but normal by AA; serum levels of thromboxane (Tx) B2 and 12-hydroxyeicosatetraenoic acid, and urinary levels of 11-dehydro-TxB2 were extremely low. Patients were homozygous for 1723G>C transition in PLA2G4A gene, which changed the codon for Asp575 to His. GI ulcers affected 5/14 heterozygous (< 40 years) and 1/16 wild-type homozygous (> 60 years) family members; none had bleeding diathesis. The proband, his sister and mother also had mildly reduced factor XI levels. Platelet messenger RNA expression did not differ among subjects with different PLA2G4A genotypes. Conversely, platelet cPLA2a was undetectable by Western Blotting in the proband and his sister, and decreased in 1723G>C heterozygous subjects, suggesting that the variant is transcribed, but not translated or translated into an unstable protein. We described a syndromic form of deficiency of cPLA2a , characterised by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. Unlike other reported patients with cPLA2a deficiency, these patients had extremely low levels of platelet TxA2 biosynthesis.

Longitudinal analysis of heart and liver iron in thalassemia major patients according to chelation treatment.

Iron chelators and nuclear magnetic resonance imaging (MRI) techniques for assessing iron loading in liver and heart have greatly improved survival of thalassemic patients suffering iron overload-associated cardiomyopathy. However, the correlation between liver iron concentration and myocardial siderosis is ambiguous. Using an objective metric of time delay, scientists have demonstrated a lag in the loading and unloading of cardiac iron with respect to that of the liver. In the present study, we further tested this hypothesis with different chelation treatments. We analyzed the effect of three chelating treatment approaches on liver and cardiac iron content in 24 highly compliant patients who underwent 3 or more MRIs under each chelation treatment. Of the 84 MRIs considered, 32 were performed on deferoxamine (DFO - 8 patients), 24 on deferiprone (DFP - 7 patients), and 28 on combined therapy (DFO+DFP - 9 patients). In patients treated with DFO, changes in cardiac iron significantly lagged changes in liver iron but the opposite pattern was observed in patients treated with DFP (p=0.005), while combined therapy showed a pattern in-between DFO and DFP. We conclude that the temporality of changes of cardiac and liver iron is chelator-dependent, so that chelation therapy can be tailored to balance iron elimination from the liver and the heart.

Molecular detection of virulence factors and antibiotic resistance pattern in clinical Enterococcus faecalis strains in Sardinia.

In this study, the antibiotic resistance pattern and the presence of genes encoding several virulence factors in 91 Enterococcus faecalis strains isolated from different human clinical sources in Sardinia were investigated. Genotypic determination of virulence genes (gelE, esp, agg, ace, cylA,B,M,L(L),L(S), efaA, fsrB) was carried out by PCR. The production of gelatinase and haemolytic activity were also determined. Antimicrobial susceptibility tests were performed by an automated microdilution test (Vitek). The strains examined in this study contained at least one and up to as many as all virulence genes investigated. Examining the distribution of these factors in the different groups of clinical strains, we found that all but one virulence determinant were detected more frequently among urinary isolates. The detection of some factors by PCR did not always correlate with its phenotypic expression. Antibiotic susceptibilities among the Enterococcus faecalis strains investigated in our study were typical for the species, with expected levels of acquired resistance. Faecal isolates had the highest percentage of resistance, especially to high level-gentamicin, ciprofloxacin and norfloxacin. In summary, a wide variety of genes encoding virulence factors have been detected among our clinical Enterococcus faecalis strains, and those isolated from UTI were characterized by a higher virulence potency compared with strains from other clinical sources. Silent virulence genes (cyl or gelE) were frequently detected, therefore both the genotypic and phenotypic assays seem necessary for a better characterization of the strains. Our results may serve as a basis for additional surveillance studies of infections caused by this microorganism.

[Phenotypic and molecular characterization of Candida species in ICU]. / Caratterizzazione fenotipica e molecolare di Candida isolate in un reparto di Terapia Intensiva.

Two hundred sixty three Candida isolates were obtained from specimens of patients hospitalized in a Intensive Care Unit. Candida albicans was the predominant species, followed by C. tropicalis, C. krusei, C. glabrata e C. parapsilosis. For C. albicans isolates, amphotericin B was the more efficient antifungal (2.3% of resistant strains), while voriconazole was the more efficient for C. krusei and C. glabrata, known for their lower susceptibility to fluconazole. RAPD-PCR technique with CDU primer was used for the molecular characterization of 48 C. albicans strains isolated from 10 patients. Genetic similarity at 90% level was observed for some Candida strains isolated from the same patient, indicating a possible colonization from the original strain. Moreover the high similarity coefficient observed between isolates from different patients may indicate an exogenous colonization originating from hospital-endemic strains or inadequate manipulation by health care workers.

3D entropy and moments prediction of enzyme classes and experimental-theoretic study of peptide fingerprints in Leishmania parasites.

The number of protein 3D structures without function annotation in Protein Data Bank (PDB) has been steadily increased. This fact has led in turn to an increment of demand for theoretical models to give a quick characterization of these proteins. In this work, we present a new and fast Markov chain model (MCM) to predict the enzyme classification (EC) number. We used both linear discriminant analysis (LDA) and/or artificial neural networks (ANN) in order to compare linear vs. non-linear classifiers. The LDA model found is very simple (three variables) and at the same time is able to predict the first EC number with an overall accuracy of 79% for a data set of 4755 proteins (859 enzymes and 3896 non-enzymes) divided into both training and external validation series. In addition, the best non-linear ANN model is notably more complex but has an overall accuracy of 98.85%. It is important to emphasize that this method may help us to predict not only new enzyme proteins but also to select peptide candidates found on the peptide mass fingerprints (PMFs) of new proteins that may improve enzyme activity. In order to illustrate the use of the model in this regard, we first report the 2D electrophoresis (2DE) and MADLI-TOF mass spectra characterization of the PMF of a new possible malate dehydrogenase sequence from Leishmania infantum. Next, we used the models to predict the contribution to a specific enzyme action of 30 peptides found in the PMF of the new protein. We implemented the present model in a server at portal Bio-AIMS (http://miaja.tic.udc.es/Bio-AIMS/EnzClassPred.php). This free on-line tool is based on PHP/HTML/Python and MARCH-INSIDE routines. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts as well as other superior organisms, which may be of interest in drug development or target identification.

Prevalence of Candida species in different hospital wards and their susceptibility to antifungal agents: results of a three year survey.

Over a three years period, 472 Candida isolates were obtained from specimens of patients hospitalized either in "at risk", Bone Marrow Transplant Unit and Intensive Care Unit, or in conventional wards, Pneumological Divisions of the "Binaghi" Hospital of Cagliari (Italy). Antifungal susceptibility profile to amphotericin B, voriconazole, fluconazole and ketoconazole was determined. Candida albicans was the predominant species while Candida krusei was the most frequent non-albicans species. C. krusei was significantly more common among Bone Marrow Transplant Unit and Intensive Care Unit than Pneumological Divisions patients (17.9% and 14.1% vs. 6.0%; p < 0.05). No significant differences were observed when the same distribution was analysed with regard to the other Candida species or when Bone Marrow Transplant Unit and Intensive Care Unit were compared. The profiles of susceptibility to the antifungal drugs among isolates from the different hospital wards showed no significant differences, even though most of MIC values were higher for Intensive Care Unit isolates compared to those for Bone Marrow Transplant Unit and Pneumological Divisions. For C. albicans isolates, amphotericin B was the more efficient antifungal (97.7% S), while fluconazole (6.1% R [Resistant] and 2.6% SDD [Susceptible Dose Dependent]) and ketoconazole (4.1% R and 3.2% SDD) showed the lowest activity. Voriconazole was the more efficient antimycotic for C. krusei (96.7% S) and Candida glabrata (100% S [Sensible]) isolates. This study has shown a significantly higher presence of non-albicans Candida in at risk wards as well as a decreased susceptibility to the older azoles (ketoconazole and fluconazole) among C. albicans isolates.

Usefulness of PFA-100 testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time.

BACKGROUND: Global tests of hemostasis that are used to screen patients with clinical suspicion of bleeding disorders should help the physician to identify the phase of the hemostatic system that is abnormal and guide further diagnostic workup. PATIENTS AND METHODS: We compared the performance of Platelet Function Analyzer-100 (PFA-100) closure time (CT) with bleeding time (BT), both of which are screening tests for primary hemostasis, in the diagnostic workup of 128 consecutive patients who were screened for bleeding disorders. The sensitivities of BT and PFA-100 CT for known defects of hemostasis were evaluated; in addition, we calculated their correlation with the levels of severity of the bleeding symptoms, which were recorded using a standardized questionnaire. RESULTS: The sensitivity of PFA-100 testing was 71% for von Willebrand disease (VWD) [with both collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI) cartridges]; 58% (C-EPI) and 8% (C-ADP) for platelet function disorders (PFDs); and the sensitivity of BT was 29% (VWD) and 33% (PFD). C-EPI CT was also prolonged in about 20% of patients with abnormalities of coagulation or fibrinolysis. Only the C-EPI CT was significantly associated with the levels of severity of the patients' bleeding scores. CONCLUSIONS: BT and C-EPI are insufficiently sensitive to be recommended as hemostasis screening tests. The C-ADP cartridge, which is sensitive to VWD only, might prove useful in further diagnostic workup of defects of primary hemostasis. The association of C-EPI CT with the severity of bleeding symptoms as a useful predictor of risk of bleeding in clinical practise should be tested in properly designed studies.

New approaches for measuring coagulation.

Although specific assays of coagulation factors are essential for diagnostic purposes they only give partial information about an individual's haemostatic state. This can be better assessed by various global tests, and recent developments and evaluations of five such tests are described in this symposium: the PFA-100; waveform analysis; thrombin generation; overall haemostasis potential; thrombelastography. Each test has advantages in various applications, but the thrombin generation test and waveform analysis have been found most useful in haemophilia, whilst the PFA-100 is helpful in von Willebrand's disease.

Analysis of red cell parameters on the Sysmex XE 2100 and ADVIA 120 in iron deficiency and in uraemic chronic disease.

OBJECTIVE: The percentage measurement of hypochromic red cells (HYPO) and reticulocyte haemoglobin content (CHr) using the ADVIA system has recently been validated as a useful tool in indicating iron deficiency, also in cases of chronic diseases such as renal failure. The aim of this study was to evaluate the extent to which the red cell parameters, RBC-Y and RET-Y, provided by Sysmex XE 2100, correlate with HYPO and CHr. MATERIAL AND METHODS: The laboratory markers of iron status were evaluated together with HYPO, CHr, RBC-Y and RET-Y in 92 healthy subjects (C), 42 iron-deficient patients (ID) and 88 uraemic patients receiving regular dialysis treatment (RDT). RESULTS: In ID patients, increased HYPO and decreased RBC-Y, CHr and RET-Y values, with no overlapping with reference values, were found and a significant correlation was present between ADVIA 120 and Sysmex indices (p<0.001 for each correlation). In RDT patients, HYPO median values were increased with a wide distribution of values (95 % reference range = 0.7-27.5 % and 0.7-22.6 % in men and women, respectively). In contrast, RBC-Y was normal/increased (95 % reference range = 169.4-191.1 and 168.7-190.5 in men and women, respectively), even though there was a significant correlation between them (p<0.001). CHr and RET-Y values were within the reference range; moreover, in these patients mean cell volume of red cells and of reticulocytes (MCV and MCVr) median values were increased. CONCLUSIONS: This study confirmed the validity of RBC-Y in the management of ID, but not in RDT, where the diagnostic power of RBC-Y as an index of cell hypochromia is limited owing to high MCV values.

[Percutaneous neurolysis of the celiac plexus under CT guidance in the invasive treatment of visceral pain caused by cancer]. / Neurolisi percutanea del plesso celiaco sotto guida TC nel trattamento invasivo del dolore viscerale da cancro.

To verify the effectiveness and the incidence of complication in the transcutaneal celiac plexus block with CT-guided in the patient with intractable upper abdominal cancer, using alcoholic solutions to different concentrations (50% and 96%), previous insertion of the peridural catheter. From December 1997 to June 2002, studies were carried out on 24 patients with CT-guided percutaneous coeliac plexus neurolysis including 17 men and 7 women with inoperable abdominal malignancy and two with chronic pancreatitis. The patients were affected by very intense pain controllable only with high doses of analgesic narcotics. Before the procedure a catheter was installed in the peridurale space between L1-T12. To avoid general anesthesia, 40 mL of marcaine 0.5% was injected to relieve the back pain sometimes reported after the neurolysis, caused by the diffusion of alcohol in the coeliac plexus. This technique requires a posterior percutaneous procedural transaortic approach CT scan guided, to determine the correct position of the needle tips and the spread of neurolytic solution (40 mL of 96% + 3 mL of contrast medium) around the origin of the coeliac trunk's anatomical center of the plexus. The first 10 patients have received 40 mL of 50% ethyl alcohol + 3 mL of contrast medium. To evaluate the rate of the analgesia relief, a visual analogue pain score (VAS) was used before and 48 hours after the neurolysis. The percutaneous neurolysis of the celiac plexus is useful to relieve the pain in patients affected by cancer developing in upper abdomen. The CT-scan guide of the needle allows an omogeneous distribution of the contrast medium. The insertion of the peridural catheter made a complete analgesia and reduced the incidence of complications. Our method provided an excellent control of the pain in all patients. In our experience the pain relief was almost complete in patients treated with 96% ethyl alcohol solution (VAS from 8 before the treatment to 1, 48 hours after the treatment). The alcohol administered in elevated concentrations (96%), does not increase the incidence of complications.

Electrospray ionisation tandem mass spectrometry in the characterisation of isomeric benzofurocoumarins.

A set of aminoalkoxy-substituted, differently annullated furocoumarins, differing in the position of the aminoalkoxy chain and in the unsaturation level of the fused ring, has been subjected to electron impact and electrospray ionisation (ESI) experiments. In order to achieve a distinct characterisation of isomeric compounds, which partially failed under electron impact conditions, collision-induced dissociation experiments were performed on protonated molecules. The breakdown curves obtained by varying the tickle voltage on an ion trap ESI instrument led to the desired characterisation.

Vesicle formation from hexasubstituted cyclophosphazenic derivatives.

Hexakis[butoxytris(ethoxy)]cyclophosphazene (3a), hexakis[dodecyloxytetrakis (ethoxy)]cyclophosphazene (3b) and hexakis[hexadecyloxyeicosanekis(ethoxy)]cyclophosphazene+ ++ (3c) were synthesised and their ability to form niosomes was studied. All synthesised compounds in the presence of cholesterol were shown to form vesicles, which aggregated strongly. To prevent aggregation, dicetylphosphate was used. The capacity of the sonicated and unsonicated niosomes to encapsulate hydrophile and lipophile molecules was also studied using carboxyfluorescein and diphenylhexatriene.

Matrix-assisted laser desorption/ionization mass spectrometry in the dairy industry. 2. The protein fingerprint of ewe cheese and its application to detection of adulteration by bovine milk.

Ewe milk and ewe cheese samples were analysed by matrix-assisted laser desorption/ionization mass spectrometry and their protein profiles were compared with those obtained from bovine milk and bovine cheeses. Various mixtures of bovine and ewe cheeses in different weight ratios were analysed, leading to a reproducible calibration curve, which has been successfully employed in determining the percentage of bovine milk fraudulently added to ewe milk in the production of marketed ewe cheese.

Implant periapical lesions: clinical, histologic, and histochemical aspects. A case report.

A new entity, the "implant periapical lesion," has recently been described. The etiology of this condition could be attributed to overheating of the bone, overloading of the implant, presence of a pre-existing infection or of residual root particles and foreign bodies in the bone, implant contamination during production or during insertion, or placement of the implant in an infected maxillary sinus. In this report, a titanium plasma-sprayed implant had been inserted into the mandible of a 53-year-old patient; after 5 months a fistula developed and periapical radiography showed a large radiolucent image around the apical portion of the implant. The implant was removed, and histologic examination showed necrotic bone and an inflammatory infiltrate inside the hollow portion of the implant. The etiology of the implant failure in this instance could be related to a fracture and vascular impairment of the bone inside the implant during insertion, to external contamination of the implant, or to the poor bone quality of the implant site.