Cannabis use disorder and dissociation: A report from a prospective first-episode psychosis study.

BACKGROUND: Cannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, the relationship between cannabis use and dissociative symptoms has been scarcely investigated. AIMS: To examine differences in psychotic and dissociative symptoms, and in functioning in first-episode psychotic patients (FEPp) using cannabis compared with those not using cannabis. METHODS: Between January 2014 and December 2019, seventy FEPp with cannabis use disorder (N = 35) and without it (N = 35) were recruited in psychiatric inpatient facilities in the Italian regions of Lazio and Piemonte. All subjects were assessed at FEP, after 4 and 8 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Dissociative Experiences Scale - II (DES-II). Detailed information on the pattern of cannabis and other substance use were collected. RESULTS: FEP using cannabis showed higher levels of positive symptomatology, dissociative experiences and worse functioning than their non-user counterpart, despite a comparable antipsychotic treatment. At an eight-month prospective evaluation, FEP using cannabis still showed higher levels of positive symptomatology and dissociation. Moreover, global functioning worsened over time in FEPp using cannabis, whereas it improved those not using it. DISCUSSION: Our findings suggest that a greater degree of dissociation and positive symptoms at FEPp and their persistence over time may characterise cannabis-associated psychosis. Both these factors might explain the overall functioning worsening over time that we observed in the cannabis-user group compared to the functioning improvement in the non-user group.

Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Augmenting pharmacotherapy with neuromodulation techniques for the treatment of bipolar disorder: a focus on the effects of mood stabilizers on cortical excitability.

Introduction: Mood stabilizers and antipsychotics have been demonstrated to be effective in Bipolar Disorder, with lithium as the gold standard. However, the presence of adverse events and treatment-resistance is still a relevant issue. To this respect, the use of brain stimulation techniques may be considered as an augmentation strategy, with both Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) having shown some level of efficacy in bipolar patients although clinical trials are still not sufficient to draw any conclusion. Areas covered: The authors have conducted a systematic review of the literature, in order to evaluate the role of mood stabilizers on neural activity and cortical excitability. Furthermore, the article reviews neuromodulation techniques and highlights the potential of integrating pharmacological first-line therapies with these techniques to treat BD patients. Expert opinion: The combination of neuromodulation techniques and available pharmacotherapies is a valuable opportunity which is not undermined by specific effects on cortical excitability and could improve BD patient outcome. Neurostimulation techniques may be considered safer than antidepressant treatments in BD, with a lower level of manic switches and may represent a new treatment strategy in BD depressive episodes.

ZNF687 mutations are frequently found in pagetic patients from South Italy: implication in the pathogenesis of Paget's disease of bone.

Paget's disease of bone (PDB) is a skeletal disorder whose molecular basis is not fully elucidated. However, 10% of patients show a familial PDB and 35% of them carry mutations in the SQSTM1 gene. We recently reported a founder mutation (p.Pro937Arg) in the ZNF687 gene, underlying PDB complicated by giant cell tumor (GCT/PDB) and rarely occurring in PDB patients without neoplastic degeneration. Since 80% of Italian GCT/PDB patients derive from Avellino, we hypothesized that ZNF687 mutation rate was higher in this region than elsewhere. Interestingly, our molecular analysis on 30 PDB patients showed that 33% hosted ZNF687 mutations, with the p.Pro937Arg identified in 8 familial cases. Two novel ZNF687 mutations (p.Pro665Leu and p.Gln784Glu) were detected in 2 sporadic patients. Only 2 subjects were positive for the p.Pro392Leu mutation in SQSTM1. ZNF687-mutated patients showed a severe PDB, with a remarkable number of affected sites. in vitro studies revealed that the ZNF687-mutant osteoclasts appeared as giant sized with up to 150 nuclei, never described in PDB. Finally, we also confirmed the causality of the p.Pro937Arg mutation in 4 additional GCT/PDB cases deriving from the same geographic area, indicating that PDB and GCT/PDB represent 2 sides of the same coin.

Mitotane treatment for adrenocortical carcinoma: an overview.

Adrenocortical carcinoma (ACC) is a rare aggressive endocrine neoplasm characterized by a 5-year survival of less than 50%. Due to the widespread use of imaging techniques in clinics, ACC is increasingly recognized as an incidentally discovered tumor. Mostly characterized by poor prognosis, ACC is often diagnosed at an advanced stage of disease. Early diagnosis is uncommon; when diagnosed, ACCs are usually large and have invaded adjacent organs, even if metastatic spread to distant sites can be absent. Complete surgical resection is the only potentially curative treatment for patients with localized disease; however, due to a recurrence rate of 50-70% after apparent radical surgery, there is a strong rationale for a concomitant systemic treatment. Adrenolytic therapy with mitotane (o,p>-DDD), administered alone or in combination with others antineoplastic agents, is the primary treatment for patients with advanced ACC and is increasingly used also in an adjuvant setting, even if controversy exists on this issue due to the limitations of the available literature. Despite being in use for many years, the rarity of ACC precluded the organization of randomized trials; thus, many areas of uncertainty and controversy remain regarding the role of this old drug in the clinical management of patients with ACC. The purpose of this paper is to review the current evidence on mitotane treatment in patients with advanced disease and in ACC patients after complete surgical resection as adjuvant treatment.

Electrochemical behaviour of titanium in ammine and stannous fluoride and chlorhexidine 0.2 percent mouthwashes.

Titanium (Ti) is widely used in dentistry. Fluorides at acid pH could destabilize Ti oxide and make it susceptible to corrosion. The behaviour of IV grade machined Ti disks in 5 electrolytic solutions: Fusayama artificial saliva (Fas), ammine fluoride-stannous fluoride (Am-SnF2), 0.2 percent Chlorexidine (CHX) 0.20 percent, Fas with 20 percent Am-SnF2, and Fas with 20 percent CHX, was evaluated. Open circuit potential Ecorr was determined by immersing Ti disks for 24 hours in an electrochemical cell containing the solutions, potential changes were measured until a stable value was obtained. Examination by Scanning Electronic Microscope and Energy Dispersive X-ray Analysis were then performed. One way ANOVA analysis showed a significant difference of Ecorr values regarding the 5 solutions (p less than 0.001). The highest values were observed for Fas (-37.6 mV), intermediate for Am-SnF2 (-81mV) and lowest for CHX (-87.6mV). SEM analysis of disks after polarization curve in CHX showed a marked localized corrosion, while the other solutions showed no considerable corrosive action on Ti surface. When considering corrosive potential range in oral cavity, Ti had an excellent behaviour on both antiseptics evaluated. The results obtained in this study will enable us to recommend the use of Am-SnF2 mouthwash for patients with dental implants.

Influence of amine fluoride/stannous fluoride mouthwashes with and without chlorhexidine on secretion of proinflammatory molecules by peri-implant crevicular fluid cells.

AIM: Patients with dental implants need optimal plaque control. Peri-implantitis is an inflammation of soft and hard tissues around implants characterized by bone loss mediated by proinflammatory molecules such as IL-1beta, PGE(2), vascular endothelial growth factor (VEGF). The aim of this study was to evaluate the influence of amine fluoride/stannous fluoride (AmF-SnF(2)) vs chlorhexidine 0.12% (CHX) combined with Am-SnF(2) on IL-1beta, PGE(2) and EGF secretion by cells of crevicular peri-implant fluid. METHODS: Thirty patients with dental implants were included in this study. The test group used AmF-SnF(2) rinsing for 14 days, the control group used CHX rinsing during the first 7 days and AmF-SnF(2) during the following 7 days. Crevicular samples were collected using filter paper strips and assayed for level of IL-1beta, PGE(2) and VEGF with ELISA test. Data were analyzed with paired and unpaired t test. RESULTS: IL-1beta, VEGF and PGE(2) levels were significantly lower in test compared to control group. Comparing first with second week of treatment, a greater decrease of IL-1beta and VEGF was evident in sample group during the second week. There was a lower decrease of IL-1beta and VEGF during the entire treatment in control group. Differences of PGE(2) levels after 7 days in both the groups were not significant while there was a significant difference during the second week. CONCLUSION: The following data suggest that the use of AmF-SnF(2) could decrease the production of IL-1beta, PGE(2) and VEGF by inflammatory cells.AmF-SnF(2) could be an alternative to CHX mouth rinses in plaque control of patients with implants.

Animal models in oral cancer research.

Biologically and clinically relevant animal models are essential in investigation of the progression of diseases and the elaboration of diagnostic or therapeutic protocols. The several rodent models used for in vivo evaluation for oral cancer employ chemical, transplantation and genetic (knockout and transgenic) induction methods. These models are described together with their advantages and disadvantages. Their optimization and application in future research may improve the early detection and treatment of oral cancer.

Anti-HER-2 DNA vaccine protects Syrian hamsters against squamous cell carcinomas.

This paper illustrates the efficacy of DNA vaccination through electroporation in the prevention of oral transplantable carcinoma in Syrian hamsters. At 21 and 7 days before tumour challenge, 19 hamsters were vaccinated with plasmids coding for the extracellular and transmembrane domains of rat HER-2 receptor (EC-TM plasmids), whereas 19 control hamsters were injected intramuscularly with the empty plasmid. Immediately following plasmid injection, hamsters of both groups received two square-wave 25 ms, 375 V cm(-1) electric pulses via two electrodes placed on the skin of the injection area. At day 0, all hamsters were challenged in the submucosa of the right cheek pouch with HER-2-positive HCPC I cells established in vitro from an 7,12-dimethylbenz[a]anthracene-induced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) vaccinated hamsters. In addition, the vaccinated hamsters displayed both a stronger proliferative and cytotoxic response than the controls and a significant anti-HER-2 antibody response. Most of the hamsters that rejected the challenge displayed the highest antibody titres. These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.

[Corrosion of titanium in presence of dental amalgams and fluorides]. / La corrosione del titanio in presenza di amalgami e fluoruri.

AIM: The aim of this study was to evaluate the behaviour of titanium (Ti) in precipitant condition, and more precisely the resistance against corrosion of Ti in presence of fluorides and the electrochemical interaction between Ti- amalgam couples in fluorinated solution. METHODS: The experimental test was made with the use of an electrochemical cell. The following materials were tested: commercially pure Ti and 2 types of amalgams, the Persistalloy (Prs) and the IQC. Palladium (IQC.P). The free corrosion potential of Ti and the amalgams, the polarization curves of both amalgams and the corrosion current of the Ti-amalgam couples in the measurements were performed in 3 different electrolytic solutions: Ringer solution, fluorinated neutral Ringer solution and acid fluorinated solution. The three corrosive media are described. RESULTS: The results showed that Ti could be damaged by the presence of fluorides with an acid pH: Ti potential becomes more negative in acid fluorinated solution. The corrosion currents between Ti and amalgam couples were considered: the amalgams underwent anodic oxidation in neutral Ringer, but a reversal phenomenon occurred in the fluorinated acid solution: Ti was damaged and the amalgams both Prs and IQC.P became the cathodic partner of the couple. In neutral fluorinated solution the IQC.P amalgam induced a significantly higher corrosion of Ti, when compared to the Prs one. CONCLUSION: Results clearly show the dependence of the Ti corrosion behaviour on the pH and composition of the solution and that the outcome of the damage is affected by the composition of other metals.

Effect of the single major proteic fractions of the liver perchloric extract UK101 on the development of oral tumours in Syrian hamsters.

Squamous cell carcinoma of the oral cavity continues to be a major clinical problem, with about 100,000 new deaths each year worldwide. There is therefore a need to search for new tools to aid oral cancer treatment. We tested the inhibitory activity on chemical carcinogenesis of the three principal protein fractions of about 50, 14, and 8.5 kDa of the mixture UK101 derived from goat liver. These are composed principally of a glycoprotein rich in mannose residues, a protein with analogy to the heat shock protein family, and ubiquitin, respectively. The animal model employed was dimethylbenzanthracene-induced hamster cheek pouch carcinoma. Number of tumours per animal, tumour mass per animal, and proliferating cell nuclear antigen (PCNA) in non-tumour mucosa were quantified: the 14-kDa fraction was the most active; this was also confirmed by testing its corresponding recombinant material. The 50-kDa fraction was inactive, while the ubiquitin showed only low inhibitory activity. It is possible that the technique described and the results obtained could lead to an interesting clinical approach to the treatment of oral cancer.

USS internal fixator in lumbar and thoracolumbar vertebral fractures.

The authors report their experience in the surgical treatment of lumbar and thoracolumbar vertebral fractures with the use of the USS-AO internal fixator at the Division of Orthopaedics of the Azienda Ospedaliera OO.RR. in Foggia between July 1996 and July 1998. The cases, although not numerous, confirm the effectiveness of the method of correction and its maintenance even in time.

Perchloric acid-soluble proteins from goat liver inhibit chemical carcinogenesis of Syrian hamster cheek-pouch carcinoma.

Chemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette-Guerin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.

The role of lung biopsy in children with perinatally acquired AIDS.

There is a need for a rapid and efficacious method of diagnosis of pulmonary infiltrates in perinatal HIV infection. However, controversy still exists about which method--open lung biopsy (OLB) versus bronchoscopic techniques--is the best for this population. We present our results with OLB in 24 children with HIV-related lung disease. Over a 6-year period, 27 OLBs were performed on 24 children with diagnosis of HIV infection. The procedures were performed under general anesthesia using a limited anterolateral thoracotomy. Suspicious areas were removed with the autostapler. The specimens were studied for the presence of non-infectious as well as bacterial, viral, fungal, and mycobacterial diseases. There were no operative deaths related to the procedure. Morbidity was limited to prolonged but self-resolving air leaks in two patients (8.3%). Five hospital deaths occurred between 3 and 12 weeks postoperatively and 11 late deaths between 3 months and 6.5 years. All deaths were related to AIDS. Eight patients (33.3%) are still alive 2 to 8 years postoperatively. A total of 43 pathologies were found in 27 specimens. A positive pathologic finding was obtained in all patients, with two patients having nonspecific minimal changes. This resulted in a change of therapy in all but one case. The technique of OLB in children with AIDS is safe and simple. It should be performed early in the course of the disease and, a careful selection of candidates can minimize the incidence of complications.

Calcyclin gene expression modulation by medroxyprogesterone acetate.

Calcyclin is a cell-cycle-related gene corresponding to a calcium-binding protein whose expression is mainly controlled by platelet-derived growth factor. This paper illustrates medroxyprogesterone acetate (MPA) inhibition of endogenous calcyclin RNA expression of both estrogen-dependent human mammary carcinoma cells and estrogen-independent hamster fibroblasts. Transfection of fragments of the calcyclin promoter driving the chloramphenicol-acetyl-transferase (CAT) gene into hamster fibroblasts was used to evaluate the hormone sensitivity of different promoter regions by considering calcyclin expression at both the RNA and protein level, as evaluated by the CAT assay. A 164 bp promoter fragment showed a good activity that was inhibited by MPA, thereby confirming the results of the observation of endogenous calcyclin gene: smaller fragments, however, required cotransfection of progestin receptor to show full activity, with MPA displaying a stimulatory effect. These findings show that progestin modulation of calcyclin gene expression may be independent of progestin receptors, and that MPA has opposite effects on different promoter regions.

Enhancement of calcyclin gene RNA expression in squamous cell carcinoma of the oral mucosa, but not in benign lesions.

Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

L-histidine/medroxyprogesterone acetate interaction modulates human breast cancer cell growth and progestin receptor expression in vitro.

The effect of different L-histidine concentrations on human mammary tumour cell (CG5) proliferation was studied to test the hypothesis of a role of histidine in modulating sex steroid-regulated cell proliferation. Cell growth was only possible in the 10(-5) M and 10(-2) M range, while its inhibition by medroxyprogesterone acetate was confined to the 10(-4) M and 10(-3) M range. 10(-3) M L-histidine enhanced the effect of medroxyprogesterone acetate in reducing the number of cells in the S phase. The results show also that 10(-3) M L-histidine favours progestin diffusion into cells and increases progestin receptors density. The present data are in line with previous observations of the effect of histidine on the growth of experimental animal tumours, add evidence that histidine concentration influences the control of cell proliferation by sex steroids, and suggest a possible use of histidine in association with progestational drugs in the treatment of human neoplasia.

Growth inhibition of DMBA-induced rat mammary carcinomas by UK 114.

A perchloric acid-soluble protein extracted from goat liver and designated as UK 114 is known to be expressed over the cell membrane of (some) human cancer cell lines. This protein is antigenic, and specific antibodies elicit complement-dependent cytolysis of neoplastic target cells. In this study we demonstrate that administration of UK 114, either pure or as a crude extract (designated UK 101), inhibits the growth of mammary carcinomas induced in female Sprague-Dawley rats by dimethylbenzanthracene (DMBA). The mechanism of the tumour inhibitory activity of UK 114 is probably related to induction of immunosurveillance.

Evidence for functional beta-adrenoceptor subtypes in CG-5 breast cancer cell.

beta-adrenergic receptors (beta-ARs) were identified in CG-5 breast cancer cells using a radiometric assay. The total beta-AR concentration was measured using the highly potent beta-adrenergic antagonist (-)[3H]CGP 12177, and the densities of beta-AR subtypes were discriminated in the presence of highly selective unlabelled ligands (CGP 20712A and ICI 118551). Scatchard analysis revealed good linearity (r > 0.95) and Kd values (0.05-1 nM) indicated the presence of high affinity binding sites in CG-5 cell membranes. beta 2-AR concentrations (74%) were significantly (P < 0.05) higher than beta 1-AR concentrations (36%). Displacement studies indicated that tested adrenergic agonists displaced (-) [3H]CGP 12177 from its specific binding sites in the order of potency (-)isoproterenol > (+/-)clenbuterol > (-)adrenaline > (+/-)dobutamine > > (-)noradrenaline, whereas beta-adrenergic antagonists inhibited the binding in the following order of potency: (-)propranolol > > ICI 118 551 > > CGP 20712A. The functionality of beta-ARs identified in CG-5 cell membranes was demonstrated by the significant increase in cAMP production induced by different concentrations of isoproterenol vs unstimulated cells (control). The pathophysiological role of beta-ARs in breast cancer cells is still undefined, but their presence suggests the possible adrenergic regulation of some cellular activities such as proliferation and/or differentiation.