Correlated X-ray Ptychography and Fluorescence Nano-Tomography on the Fragmentation Behavior of an Individual Catalyst Particle during the Early Stages of Olefin Polymerization.

A combination of X-ray ptychography and X-ray fluorescence tomography (XRF) has been used to study the fragmentation behavior of an individual Ziegler-Natta catalyst particle, ∼40 µm in diameter, in the early stages of propylene polymerization with submicron spatial resolution. The electron density signal obtained from X-ray ptychography gives the composite phases of the Ziegler-Natta catalyst particle fragments and isotactic polypropylene, while 3-D XRF visualizes multiple isolated clusters, rich in Ti, of several microns in size. The radial distribution of Ti species throughout the polymer-catalyst composite particle shows that the continuous bisection fragmentation model is the main contributor to the fragmentation pathway of the catalyst particle as a whole. Furthermore, within the largest Ti clusters the fragmentation pathway was found to occur through both the continuous bisection and layer-by-layer models. The fragmentation behavior of polyolefin catalysts was for the first time visualized in 3-D by directly imaging and correlating the distribution of the Ti species to the polymer-catalyst composite phase.

Genesis of MgCl2 -based Ziegler-Natta Catalysts as Probed with Operando Spectroscopy.

Ziegler-Natta catalysts for olefin polymerization are intrinsically complex multi-component systems. The genesis of the active sites involves several simultaneous and sequential steps, making the individual steps and interconnections difficult to be unraveled in an unambiguous manner. In this work, we combine X-ray diffraction and spectroscopy to probe each step of the birth and life of a MgCl2 -based Ziegler-Natta catalyst, namely the formation of high surface area MgCl2 by dealcoholation of an alcoholate precursor, the TiCl4 grafting, and the subsequent activation by triethylaluminum as co-catalyst. The so-prepared catalyst was tested towards ethylene polymerization, leading to the production of mainly crystalline high-density polyethylene. The use of operando characterization techniques allowed probing the transient details that are difficult to be dissected in the aftermath, but can radically affect the overall catalytic process.

Heterogeneity in the Fragmentation of Ziegler Catalyst Particles during Ethylene Polymerization Quantified by X-ray Nanotomography.

Ziegler-type catalysts are the grand old workhorse of the polyolefin industry, yet their hierarchically complex nature complicates polymerization activity-catalyst structure relationships. In this work, the degree of catalyst framework fragmentation of a high-density polyethylene (HDPE) Ziegler-type catalyst was studied using ptychography X-ray-computed nanotomography (PXCT) in the early stages of ethylene polymerization under mild reaction conditions. An ensemble consisting of 434 fully reconstructed ethylene prepolymerized Ziegler catalyst particles prepared at a polymer yield of 3.4 g HDPE/g catalyst was imaged. This enabled a statistical route to study the heterogeneity in the degree of particle fragmentation and therefore local polymerization activity at an achieved 3-D spatial resolution of 74 nm without requiring invasive imaging tools. To study the degree of catalyst fragmentation within the ensemble, a fragmentation parameter was constructed based on a k-means clustering algorithm that relates the quantity of polyethylene formed to the average size of the spatially resolved catalyst fragments. With this classification method, we have identified particles that exhibit weak, moderate, and strong degrees of catalyst fragmentation, showing that there is a strong heterogeneity in the overall catalyst particle fragmentation and thus polymerization activity within the entire ensemble. This hints toward local mass transfer limitations or other deactivation phenomena. The methodology used here can be applied to all polyolefin catalysts, including metallocene and the Phillips catalysts to gain statistically relevant fundamental insights in the fragmentation behavior of an ensemble of catalyst particles.

Beating heart bentall procedure for late type A aortic dissection in a patient with in-situ bilateral mammary artery bypass grafts.

We report a case of a patient who had a type A aortic dissection after previous coronary bypass grafting. The in-situ right mammary artery had been anastomosed with the left anterior descending artery, the left mammary artery had been anastomosed to the obtuse marginal, and a vein graft had been used for the right coronary artery. All grafts were patent. The patients underwent a Bentall procedure on perfused heart.

Sternal reconstruction after post-sternotomy dehiscence and mediastinitis.

PURPOSE: Post-sternotomy dehiscence and mediastinitis remains a serious complication in cardiothoracic surgery. The aim of this work is to report our experience over a period of 8 years in the surgical treatment and risk factor analyses of post-sternotomy dehiscence and mediastinitis. METHODS: All patients treated for post-sternotomy dehiscence at our Thoracic Surgery Unit in the last 8 years were retrospectively collected. We identified 237 patients with post-sternotomy dehiscence/mediastinitis. Forty-two patients had simple fractures of the metal steel wires, 61 had an asymmetric sternotomy with multiple sternal fractures, 113 had a symmetric sternotomy with multiple sternal fractures, 14 had a failed Robicsek procedure, and 7 had sternal dehiscence with mediastinal abscess. RESULTS: Different surgical techniques and materials were used to repair the sternum. In 21 patients, the first revision failed and a second reoperation was required. At multivariate analyses, we have identified risk factors for revision failure and in-hospital mortality. Mortality rate was significantly higher in patients who underwent more than one surgical revision (8% vs 19%, p < 0.001). CONCLUSIONS: Patients with sternal dehiscence are very fragile due to multiple preoperative comorbidities as reflected by postoperative morbidity and risk factors for in-hospital mortality. A correct evaluation of the characteristics of sternal dehiscence is important to guide the most appropriate repair strategy. Patients who need repeated sternal revisions had a higher mortality. Further randomized studies are needed to evaluate different techniques and medical devices to define the gold standard procedure to reduce significantly sternal wound complications in high-risk patients as defined by well-known risk factors.

Bariatric surgery improves atherogenic LDL profile by triglyceride reduction.

BACKGROUND: Small dense low-density lipoprotein (LDL) are atherogenic particles frequently observed in obese patients. Fatty acids modulate LDL. Objective of this study was to determine the relations between plasma phospholipid fatty acid composition and the presence of small dense LDL particles in morbidly obese patients treated with laparoscopic gastric banding (LAGB). METHODS: Small dense LDL, plasma lipids, lipoproteins, apoproteins, and phospholipid fatty acid composition (a marker of dietary fatty acid intake) were quantified before and 12 months after surgery in four men and 11 women who were morbidly obese and (BMI > 40 kg/m(2)) eligible for surgery, consecutively treated with LAGB at the Department of Medical and Surgical Sciences of the University of Padova. RESULTS: BMI was 48.3 +/- 4.8 kg/m(2) before and 36.1 +/- 5.5 kg/m(2) after LAGB. Plasma triglycerides and apoprotein E levels significantly decreased, while HDL cholesterol significantly increased after LAGB. A reduction of small dense LDL with an increase of LDL relative flotation (0.34 +/- 0.04 before vs 0.38 +/- 0.03 after LAGB, p < 0.001) was also observed. These modifications were neither related to weight reduction nor to changes in phospholipid fatty acid composition, but they were associated to triglyceride reduction, which explained 76.7% of the LDL relative flotation variation. CONCLUSION: Weight loss obtained by LAGB in morbidly obese subjects was accompanied by triglyceride reduction, high-density lipoprotein increase, and an improvement of the atherogenic LDL profile. Triglyceride reduction, but not the extent of weight loss or dietary fatty acid modifications, is the determinant of modifications of LDL physical properties in these patients.

Template-Free Nanostructured Fluorine-Doped Tin Oxide Scaffolds for Photoelectrochemical Water Splitting.

The synthesis and characterization of highly stable and conductive F:SnO2 (FTO) nanopyramid arrays are investigated, and their use as scaffolds for water splitting is demonstrated. Current densities during the oxygen evolution reaction with a NiFeOx catalyst at 2 V vs reversible hydrogen electrode were increased 5-fold when substituting commercial FTO (TEC 15) by nanostructured FTO scaffolds. In addition, thin α-Fe2O3 films (∼50 nm thick) were employed as a proof of concept to show the effect of our nanostructured scaffolds during photoelectrochemical water splitting. Double-layer capacitance measurements showed a drastic increase of the relative electrochemically active surface area for the nanostructured samples, in agreement with the observed photocurrent enhancement, whereas UV-vis spectroscopy indicates full absorption of visible light at wavelengths below 600 nm.

Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study.

The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.

Restorative proctocolectomy for ulcerative colitis: impact on lipid metabolism and adipose tissue and serum fatty acids.

The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids in patients with ulcerative colitis after restorative proctocolectomy. Fifteen consecutive patients and 15 sex- and age-matched healthy controls were enrolled. Disease activity, diet, inflammatory parameters, plasma lipoprotein concentrations, and fatty acids (FA) of serum phospholipids and of the subcutaneous adipose tissue were assessed at colectomy and at ileostomy closure. In ulcerative colitis patients, total cholesterol and docosahexaenoic acid were lower than in healthy subjects (p < 0.01 and p < 0.05). The median interval between colectomy and ileostomy closure was 6 (range 2-9) months. During that interval, the inflammatory parameters improved, high-density lipoproteins (HDL) cholesterol increased (p < 0.01), and low-density (LDL) cholesterol decreased (p = 0.01). At ileostomy closure, serum arachidonic acid levels were increased (p = 0.04), whereas serum oleic acid level was decreased (p = 0.02). In this interval, no significant alteration, either in serum n-3 FA precursors or in the FA of subcutaneous adipose tissue, was observed. The increase of serum arachidonic acid after colectomy might suggest a lower utilization for inflammatory process. The reduction of LDL cholesterol is an index of malabsorption probably due to the accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.

Short-term effects on bone turnover markers of a single high dose of oral vitamin D3.

CONTEXT: Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported. OBJECTIVE: The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D3. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Twelve elderly subjects (eight women, four men; mean age 76 ± 3 yr) were given a single oral bolus of 600,000 IU vitamin D3. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D3 administration. Twenty-four subjects served as controls. MAIN OUTCOME MEASURES: Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase. RESULTS: No relevant changes in 25OHD and bone turnover markers were observed in the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 ± 17.1 ng/ml (P < 0.001) at d 3. Subsequently it slowly decreased to 35.2 ± 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 ± 5.6 ng/ml). Mean serum PTH concentration decreased by 25-50% and serum 1,25-dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60. No changes were observed in serum bone-specific alkaline phosphatase. CONCLUSIONS: Our results indicate that the use of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or prevent vitamin D deficiency.

Quantitative ultrasound criteria for risk stratification in clinical practice: a comparative assessment.

This study aimed to compare two different classifications of the risk of fracture/osteoporosis (OP) based on quantitative ultrasound (QUS). Analyses were based on data from the Epidemiological Study on the Prevalence of Osteoporosis, a cross-sectional study conducted in 2000 aimed at assessing the risk of OP in a representative sample of the Italian population. Subjects were classified into 5 groups considering the cross-classification found in previous studies; logistic regression models were defined separately for women and men to study the fracture risk attributable to groups defined by the cross-classification, adjusting for traditional risk factors. Eight-thousand six-hundred eighty-one subjects were considered in the analyses. Logistic regression models revealed that the two classifications seem to be able to identify a common core of individuals at low and at high risk of fractures, and the importance of a multidimensional assessment in older patients to evaluate clinical risk factors together with a simple, inexpensive, radiation-free device such as QUS.

Association of single measurement of estimated glomerular filtration rate and non-quantitative dipstick proteinuria with all-cause and cardiovascular mortality in the elderly. Results from the Progetto Veneto Anziani (Pro.V.A.) Study.

OBJECTIVE: To explore the independent and combined clinical validity of estimated glomerular filtration rate (eGFR) and proteinuria on predicting all-cause and cardiovascular mortality in an Italian elderly population. METHODS: Baseline eGFR and proteinuria, all-cause and cardiovascular mortality during a mean follow-up time of 4.4 years were evaluated in 3063 subjects aged 65 years and older of the Progetto Veneto Anziani (Pro.V.A.) Study. RESULTS: Subjects with eGFR<60ml/min/1.73m(2) (n=956) presented a higher prevalence of proteinuria in comparison with those with eGFR≥60ml/min/1.73m(2) (33.8% vs 25.1%, p<0.01). After multivariable adjustment including proteinuria and major diseases, eGFR<60ml/min/1.73m(2) was not associated with increased all-cause mortality. After multivariable adjustment including eGFR and major diseases, proteinuria was associated with all-cause mortality in overall subjects (HR=1.43, 95% CI 1.15-1.78, p<0.01), and in both sexes. After multivariable adjustment both eGFR<60ml/min/1.73m(2) (HR=1.68, 95% CI 1.02-2.78, p=0.04), and proteinuria (HR=2.07, 95% CI 1.31-3.27, p<0.01) were associated with increased cardiovascular mortality. Subjects with both impaired eGFR and presence of proteinuria showed a higher risk for both all-cause and cardiovascular mortality compared to those with normal eGFR and absence of proteinuria. CONCLUSION: In this general Italian elderly population proteinuria is an independent predictor of all-cause and cardiovascular mortality, while eGFR is not an independent predictor of all-cause mortality, and it is nominally significantly associated with cardiovascular mortality. However, mortality risk is higher in individuals with combined reduced eGFR and proteinuria.

Efficacy of a new oxygenator-integrated fat and leukocyte removal device.

We evaluated the effectiveness of a new oxygenator-integrated device for removing lipid particles and leukocytes from shed mediastinal blood in 20 patients undergoing elective cardiac surgery under cardiopulmonary bypass. Another 20 patients undergoing cardiac surgery without the device served as controls. After filtration with the RemoveLL device, lipid particles, leukocytes, and fats were significantly reduced compared to preoperative levels. In the control group, blood fats and lipid particles at the end of cardiopulmonary bypass were significantly increased compared to preoperative levels. Leukocyte counts at the end of bypass were significantly lower in patients who had the filtration device compared to the control group. Platelets counts and hematocrit changes were not significantly different between the 2 groups.

Metabolic syndrome and all-cause and cardiovascular mortality in an Italian elderly population: the Progetto Veneto Anziani (Pro.V.A.) Study.

OBJECTIVE: The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population. RESEARCH DESIGN AND METHODS: Metabolic syndrome, diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria, all-cause mortality, and cardiovascular mortality, was evaluated in 2,910 subjects aged > or =65 years of the Progetto Veneto Anziani (Pro.V.A.) Study during a mean follow-up time of 4.4 years. RESULTS: After multivariable adjustment, metabolic syndrome was associated with increased all-cause mortality in all subjects (hazard ratio 1.41 [95% CI 1.16-1.72], P = 0.001), among men (1.42 [1.06-1.89], P = 0.017), and among women (1.47 [1.13-1.91], P = 0.004). High glucose in all subjects (1.27 [1.02-1.59], P = 0.037) and in women (1.61 [1.16-2.24], P = 0.005) and low HDL cholesterol in women (1.48 [1.08-2.02], P = 0.014) were predictors of all-cause mortality, even independently of the interactions of different metabolic syndrome components. After multivariable adjustment, metabolic syndrome was also associated with increased cardiovascular mortality in all subjects (1.60 [1.17-2.19], P = 0.003), among men (1.66 [1.00-2.76], P = 0.051), and among women (1.60 [1.06-2.33], P = 0.025). High glucose (2.17 [1.28-3.68], P = 0.004) and low HDL cholesterol (1.78 [1.07-2.95], P = 0.026) among women predicted higher cardiovascular mortality. CONCLUSIONS: In this general Italian elderly population, among metabolic syndrome components, all-cause mortality is better predicted by high glucose in all subjects and in women and by low HDL cholesterol in women, whereas cardiovascular mortality is better predicted by high glucose and low HDL cholesterol in women.

The effects of weight changes after middle age on the rate of disability in an elderly population sample.

OBJECTIVES: To analyze the association between weight loss and weight gain after middle age and the prevalence of late disability. DESIGN: Secondary analysis of baseline data from a longitudinal population study. SETTING: Progetto Veneto Anziani Study. PARTICIPANTS: Two thousand nine hundred ten (1,187 male, 1,723 female) Italians aged 65 and older. MEASUREMENTS: Disability status (impairment in at least one activity of daily living) was analyzed according to current body mass index (BMI), BMI at age 50, and intercurrent weight changes (weight gain >10%, weight gain 5-10%, weight stable, weight loss 5-10%, weight loss >10%). RESULTS: In subjects with normal weight at aged 50, weight gain of more than 10%, weight gain of 5% to 10%, and weight loss of more than 10% were significantly associated with disability (reference stable weight). Adjustment for major chronic diseases did not affect the relationship between weight gain and disability but attenuated the association between weight loss and disability. In participants with obesity at aged 50, weight gain of more than 10% and weight gain of 5% to 10% were associated with the presence of disability; adjustment for chronic diseases did not affect these associations. In these participants, no associations were found between weight loss and disability status. CONCLUSION: Weight gain after middle age was associated with late disability, particularly in participants who were already obese. Weight loss after middle age was associated with disability only in normal-weight participants, and this association was attenuated after adjustment for chronic diseases.

Lipid and phospholipid profile after bowel resection for Crohn's disease.

BACKGROUND AND AIM: Chronic inflammation, impaired intestinal adsorption, and bowel resection may have an impact on lipid metabolism before and after intestinal surgery for Crohn's disease (CD). The aim of this prospective study was to define the impact of intestinal surgery for CD on plasma phospholipid fatty acid (FA) composition and of serum plasma lipoprotein concentrations and to investigate the role of CD recurrence on lipid parameters. MATERIALS AND METHODS: Twenty-four consecutive patients who had intestinal surgery for CD since December 2004 to March 2006 were enrolled in this prospective study. The total amount of calorie intake and the quality of the aliments, systemic inflammatory activity, and plasma lipoproteins and phospholipid fatty acid composition were determined at operation and at follow-up. Statistical analysis was performed with pair-matched tests. RESULTS: The median follow-up was 6 (4-20) months. During the follow-up, no significant modification of body mass index was observed. An increase of high-density lipoprotein (HDL) cholesterol (p=0.02) without other modifications in the plasma phospholipid FA composition were evidenced after surgery. The comparison between colectomy and ileo-colonic or ileal resection groups did not show any significant difference in the lipoprotein concentration and phospholipid FA profile. The length of resected bowel did not show any significant correlation with any relevant difference in lipid, phospholipid profile, or in inflammatory parameters. Patients who experienced a recurrence of CD reported significantly higher levels of total (p<0.01), HDL (p=0.01), and low-density lipoprotein cholesterol (p=0.01) were observed in patients in remission than in those with recurrent active disease. CONCLUSIONS: Patients who are submitted to intestinal resection for CD improve their inflammatory status as well as their lipid metabolism, and CD recurrence, but not the extent of bowel resection, is the main predictor of alteration of serum lipid concentration.

Metabolic syndrome and cardiovascular disease in the elderly: the Progetto Veneto Anziani (Pro.V.A.) study.

BACKGROUND AND AIMS: The prevalence of the metabolic syndrome increases with age, although only few data are available about its prevalence in the general elderly population. This study describes the prevalence of the metabolic syndrome in an elderly population, and its association with cardiovascular diseases. METHODS: The Progetto Veneto Anziani (Pro.V.A.) is an observational study of 3,099 subjects aged 65 and older, randomly selected from the general population of Northern Italy. Cardiovascular diseases and metabolic syndrome according to Adult Treatment Panel III were evaluated in 2,910 subjects. RESULTS: The metabolic syndrome was present in 25.6% of men and 48.1% of women. Its prevalence was mainly due to high blood pressure (93%) in both sexes, and to abdominal obesity in 73% of women. The prevalence of cardiovascular diseases was significantly higher among subjects with metabolic syndrome. Together with age and former smoking habits, the metabolic syndrome was significantly associated with cardiovascular diseases. High blood pressure and low HDL were independently associated with cardiovascular diseases in men, and with high fasting plasma glucose and waist circumference in women. CONCLUSIONS: The metabolic syndrome is frequent, and significantly but not independently associated with prevalent cardiovascular diseases in the elderly. In old people, rather than the metabolic syndrome per se, some of its components are independently associated with cardiovascular diseases.

The use of atypical antipsychotics beyond psychoses: efficacy of quetiapine in bipolar disorder.

BACKGROUND AND RATIONALE: Atypical antpsychotics have been sucessfully used in the treatment of bipolar disorder (BD), either as adjunctive or as monotherapy. Quetiapine is an atypical antipsychotic extensively used in the treatment of psychotic disorders. It has serotonergic and dopaminergic activity and it appears to be selective for the mesolimbic and mesocortical dopamine system. The aim of this paper was to review the recent literature on the use of quetiapine in the treatment of BD. METHODS: The literature databases currently available online were searched for papers on quetiapine and BD. Papers and reports published between January 1995 and June 2005 were selected and reviewed critically. RESULTS: Augmentative low dose quetiapine was found to be effective in BD partially responsive to conventional mood-stabilizers. Manic and mixed episodes have been the best studied, and quetiapine was found to be effective either as monotherapy or as adjunctive therapy in both randomized clinical trials and open-label studies. Data on the use of quetiapine in bipolar depression showed a significant efficacy and high remission rates. Maintenance data suggested a role of quetiapine as a good alternative to classical mood stabilizers in reducing recurrence rates of BD. A few studies on the efficacy in rapid cycling BD have also been published. CONCLUSIONS: Quetiapine is an effective agent for the short- and long-term treatment of BD. The mechanism of action of quetiapine as a mood stabilizer is still unknown. Some preliminary data suggest the involvement of glutamate pathways but further studies are needed to clarify this issue.