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OBJECTIVE: The current study elucidates the relations between alexithymia and body image in patients with binge eating disorder (BED). METHOD: One hundred one patients with BED were evaluated. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). The severity of BED was measured with the Binge Eating Scale (BES). Body concerns were assessed with the Body Shape Questionnaire-Short Version (BSQ-S), the Body Uneasiness Test (BUT), and the Body Attitude Test (BAT). Additional measures were the Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI). RESULTS: The prevalence of alexithymia in our sample was 39.6% (n = 40) and individuals with alexithymia showed higher scores on all rating scales. Higher body dissatisfaction, lower self-esteem, depressive symptoms, and the Difficulty in Identifying Feelings/Difficulty in Describing Feelings subscales of the TAS-20 were predictors of the severity of BED in the linear regression analysis. CONCLUSION: Alexithymia was associated with more severe BED. Individuals with alexithymia and BED exhibited significantly poorer appearance evaluation and body satisfaction as well as higher depressive symptoms than individuals without alexithymia. [ABSTRACT FROM AUTHOR]

Intracellular Ca 2+ signals control several physiological and pathophysiological processes. The main tool to chelate intracellular Ca 2+ is intracellular BAPTA (BAPTA i ), usually introduced into cells as a membrane-permeant acetoxymethyl ester (BAPTA-AM). Previously, we demonstrated that BAPTA i enhanced apoptosis induced by venetoclax, a BCL-2 antagonist, in diffuse large B-cell lymphoma (DLBCL). This finding implied a novel interplay between intracellular Ca 2+ signaling and anti-apoptotic BCL-2 function. Hence, we set out to identify the underlying mechanisms by which BAPTA i enhances cell death in B-cell cancers. In this study, we discovered that BAPTA i alone induced apoptosis in hematological cancer cell lines that were highly sensitive to S63845, an MCL-1 antagonist. BAPTA i provoked a rapid decline in MCL-1-protein levels by inhibiting mTORC1-driven Mcl-1 translation. These events were not a consequence of cell death, as BAX/BAK-deficient cancer cells exhibited similar downregulation of mTORC1 activity and MCL-1-protein levels. Next, we investigated how BAPTA i diminished mTORC1 activity and identified its ability to impair glycolysis by directly inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) activity, a previously unknown effect of BAPTA i . Notably, these effects were also induced by a BAPTA i analog with low affinity for Ca 2+ . Consequently, our findings uncover PFKFB3 inhibition as an Ca 2+ -independent mechanism through which BAPTA i impairs cellular metabolism and ultimately compromises the survival of MCL-1-dependent cancer cells. These findings hold two important implications. Firstly, the direct inhibition of PFKFB3 emerges as a key regulator of mTORC1 activity and a promising target in MCL-1-dependent cancers. Secondly, cellular effects caused by BAPTA i are not necessarily related to Ca 2+ signaling. Our data support the need for a reassessment of the role of Ca 2+ in cellular processes when findings were based on the use of BAPTA i ., (© 2023. The Author(s).)

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD), with growing importance also for Crohn's disease and cancer. LRRK2 is a large and complex protein possessing both GTPase and kinase activity. Moreover, LRRK2 activity and function can be influenced by its phosphorylation status. In this regard, many LRRK2 PD-associated mutants display decreased phosphorylation of the constitutive phosphorylation cluster S910/S935/S955/S973, but the role of these changes in phosphorylation status with respect to LRRK2 physiological functions remains unknown. Here, we propose that the S910/S935/S955/S973 phosphorylation sites act as key regulators of LRRK2-mediated autophagy under both basal and starvation conditions. We show that quadruple LRRK2 phosphomutant cells (4xSA; S910A/S935A/S955A/S973A) have impaired lysosomal functionality and fail to induce and proceed with autophagy during starvation. In contrast, treatment with the specific LRRK2 kinase inhibitors MLi-2 (100 nM) or PF-06447475 (150 nM), which also led to decreased LRRK2 phosphorylation of S910/S935/S955/S973, did not affect autophagy. In explanation, we demonstrate that the autophagy impairment due to the 4xSA LRRK2 phospho-dead mutant is driven by its enhanced LRRK2 kinase activity. We show mechanistically that this involves increased phosphorylation of LRRK2 downstream targets Rab8a and Rab10, as the autophagy impairment in 4xSA LRRK2 cells is counteracted by expression of phosphorylation-deficient mutants T72A Rab8a and T73A Rab10. Similarly, reduced autophagy and decreased LRRK2 phosphorylation at the constitutive sites were observed in cells expressing the pathological R1441C LRRK2 PD mutant, which also displays increased kinase activity. These data underscore the relation between LRRK2 phosphorylation at its constitutive sites and the importance of increased LRRK2 kinase activity in autophagy regulation and PD pathology., (© 2023. The Author(s).)

Anti-apoptotic B-cell lymphoma 2 (Bcl-2) regulates a wide array of cellular functions involved in cell death, cell survival and autophagy. Less known is its involvement in the differentiation of cardiomyocytes. As a consequence, mechanisms by which Bcl-2 contributes to cardiac differentiation remain to be elucidated. To address this, we used CRISPR/Cas9 to knockout (KO) BCL2 in human induced pluripotent stem cells (hiPSCs) and investigated the consequence of this KO for differentiation towards cardiomyocytes. Our results indicate that differentiation of hiPSCs to cardiomyocytes was delayed following BCL2 KO. This was not related to the canonical anti-apoptotic function of Bcl-2. This delay led to reduced expression and activity of the cardiomyocyte Ca2+ toolkit. Finally, Bcl-2 KO reduced c-Myc expression and nuclear localization in the early phase of the cardiac differentiation process, which accounts at least in part for the observed delay in the cardiac differentiation. These results suggest that there is a central role for Bcl-2 in cardiomyocyte differentiation and maturation., Competing Interests: Competing interests The authors declare no competing or financial interests, (© 2023. Published by The Company of Biologists Ltd.)

Duchenne Muscular Dystrophy (DMD) is an X-linked neuromuscular disease which to date is incurable. The major cause of death is dilated cardiomyopathy however, its pathogenesis is unclear as existing cellular and animal models do not fully recapitulate the human disease phenotypes. In this study, we generated cardiac organoids from patient-derived induced pluripotent stem cells (DMD-COs) and isogenic-corrected controls (DMD-Iso-COs) and studied if DMD-related cardiomyopathy and disease progression occur in the organoids upon long-term culture (up to 93 days). Histological analysis showed that DMD-COs lack initial proliferative capacity, displayed a progressive loss of sarcoglycan localization and high stress in endoplasmic reticulum. Additionally, cardiomyocyte deterioration, fibrosis and aberrant adipogenesis were observed in DMD-COs over time. RNA sequencing analysis confirmed a distinct transcriptomic profile in DMD-COs which was associated with functional enrichment in hypertrophy/dilated cardiomyopathy, arrhythmia, adipogenesis and fibrosis pathways. Moreover, five miRNAs were identified to be crucial in this dysregulated gene network. In conclusion, we generated patient-derived cardiac organoid model that displayed DMD-related cardiomyopathy and disease progression phenotypes in long-term culture. We envision the feasibility to develop a more complex, realistic and reliable in vitro 3D human cardiac-mimics to study DMD-related cardiomyopathies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marini, Marino, Aliberti, Giarratana, Pozzo, Duelen, Cortés Calabuig, La Rovere, Vervliet, Torella, Bultynck, Sampaolesi and Chai.)

Anti-apoptotic Bcl-2-family members not only act at mitochondria but also at the endoplasmic reticulum, where they impact Ca 2+ dynamics by controlling IP 3 receptor (IP 3 R) function. Current models propose distinct roles for Bcl-2 vs. Bcl-xL, with Bcl-2 inhibiting IP 3 Rs and preventing pro-apoptotic Ca 2+ release and Bcl-xL sensitizing IP 3 Rs to low [IP 3 ] and promoting pro-survival Ca 2+ oscillations. We here demonstrate that Bcl-xL too inhibits IP 3 R-mediated Ca 2+ release by interacting with the same IP 3 R regions as Bcl-2. Via in silico superposition, we previously found that the residue K87 of Bcl-xL spatially resembled K17 of Bcl-2, a residue critical for Bcl-2's IP 3 R-inhibitory properties. Mutagenesis of K87 in Bcl-xL impaired its binding to IP 3 R and abrogated Bcl-xL's inhibitory effect on IP 3 Rs. Single-channel recordings demonstrate that purified Bcl-xL, but not Bcl-xL K87D , suppressed IP 3 R single-channel openings stimulated by sub-maximal and threshold [IP 3 ]. Moreover, we demonstrate that Bcl-xL-mediated inhibition of IP 3 Rs contributes to its anti-apoptotic properties against Ca 2+ -driven apoptosis. Staurosporine (STS) elicits long-lasting Ca 2+ elevations in wild-type but not in IP 3 R-knockout HeLa cells, sensitizing the former to STS treatment. Overexpression of Bcl-xL in wild-type HeLa cells suppressed STS-induced Ca 2+ signals and cell death, while Bcl-xL K87D was much less effective in doing so. In the absence of IP 3 Rs, Bcl-xL and Bcl-xL K87D were equally effective in suppressing STS-induced cell death. Finally, we demonstrate that endogenous Bcl-xL also suppress IP 3 R activity in MDA-MB-231 breast cancer cells, whereby Bcl-xL knockdown augmented IP 3 R-mediated Ca 2+ release and increased the sensitivity towards STS, without altering the ER Ca 2+ content. Hence, this study challenges the current paradigm of divergent functions for Bcl-2 and Bcl-xL in Ca 2+ -signaling modulation and reveals that, similarly to Bcl-2, Bcl-xL inhibits IP 3 R-mediated Ca 2+ release and IP 3 R-driven cell death. Our work further underpins that IP 3 R inhibition is an integral part of Bcl-xL's anti-apoptotic function., (© 2021. The Author(s).)

Anti-apoptotic Bcl-2 critically controls cell death by neutralizing pro-apoptotic Bcl-2-family members at the mitochondria. Bcl-2 proteins also act at the endoplasmic reticulum, the main intracellular Ca 2+ -storage organelle, where they inhibit IP 3 receptors (IP 3 R) and prevent pro-apoptotic Ca 2+ -signaling events. IP 3 R channels are targeted by the BH4 domain of Bcl-2. Some cancer types rely on the IP 3 R-Bcl-2 interaction for survival. We previously developed a cell-permeable, BH4-domain-targeting peptide that can abrogate Bcl-2's inhibitory action on IP 3 Rs, named Bcl-2 IP 3 receptor disrupter-2 (BIRD-2). This peptide kills several Bcl-2-dependent cancer cell types, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukaemia (CLL) cells, by eliciting intracellular Ca 2+ signalling. However, the exact mechanisms by which these excessive Ca 2+ signals triggered by BIRD-2 provoke cancer cell death remain elusive. Here, we demonstrate in DLBCL that although BIRD-2 activates caspase 3/7 and provokes cell death in a caspase-dependent manner, the cell death is independent of pro-apoptotic Bcl-2-family members, Bim, Bax and Bak. Instead, BIRD-2 provokes mitochondrial Ca 2+ overload that is rapidly followed by opening of the mitochondrial permeability transition pore (mPTP). Inhibiting mitochondrial Ca 2+ overload using Ru265, an inhibitor of the mitochondrial Ca 2+ uniporter complex counteracts BIRD-2-induced cancer cell death. Finally, we validated our findings in primary CLL patient samples where BIRD-2 provoked mitochondrial Ca 2+ overload and Ru265 counteracted BIRD-2-induced cell death. Overall, this work reveals the mechanisms by which BIRD-2 provokes cell death, which occurs via mitochondrial Ca 2+ overload but acts independently of pro-apoptotic Bcl-2-family members., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson's disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5 -knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5 -knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.

Contractile myofiber units are mainly composed of thick myosin and thin actin (F-actin) filaments. F-Actin interacts with Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 2 (MICAL2). Indeed, MICAL2 modifies actin subunits and promotes actin filament turnover by severing them and preventing repolymerization. In this study, we found that MICAL2 increases during myogenic differentiation of adult and pluripotent stem cells (PSCs) towards skeletal, smooth and cardiac muscle cells and localizes in the nucleus of acute and chronic regenerating muscle fibers. In vivo delivery of Cas9-Mical2 guide RNA complexes results in muscle actin defects and demonstrates that MICAL2 is essential for skeletal muscle homeostasis and functionality. Conversely, MICAL2 upregulation shows a positive impact on skeletal and cardiac muscle commitments. Taken together these data demonstrate that modulations of MICAL2 have an impact on muscle filament dynamics and its fine-tuned balance is essential for the regeneration of muscle tissues.

Objective: Amongst psychiatric disorders, major depressive disorder (MDD) is the most prevalent, by affecting approximately 15-17% of the population and showing a high suicide risk rate equivalent to around 15%. The present comprehensive overview aims at evaluating main research studies in the field of MDD at suicide risk, by proposing as well as a schematic suicide risk stratification and useful flow-chart for planning suicide preventive and therapeutic interventions for clinicians., Methods: A broad and comprehensive overview has been here conducted by using PubMed/Medline, combining the search strategy of free text terms and exploded MESH headings for the topics of 'Major Depressive Disorder' and 'Suicide' as following: ((suicide [Title/Abstract]) AND (major depressive disorder [Title/Abstract])). All articles published in English through May 31, 2019 were summarized in a comprehensive way., Results: Despite possible pathophysiological factors which may explain the complexity of suicide in MDD, scientific evidence supposed the synergic role of genetics, exogenous and endogenous stressors (i.e., interpersonal, professional, financial, as well as psychiatric disorders), epigenetic, the hypothalamic-pituitary-adrenal stress-response system, the involvement of the monoaminergic neurotransmitter systems, particularly the serotonergic ones, the lipid profile, neuro-immunological biomarkers, the Brain-derived neurotrophic factor and other neuromodulators., Conclusion: The present overview reported that suicide is a highly complex and multifaceted phenomenon in which a large plethora of mechanisms could be variable implicated, particularly amongst MDD subjects. Beyond these consideration, modern psychiatry needs a better interpretation of suicide risk with a more careful assessment of suicide risk stratification and planning of clinical and treatment interventions.

B-cell lymphoma 2 (Bcl-2) protein is the archetype apoptosis suppressor protein. The N-terminal Bcl-2-homology 4 (BH4) domain of Bcl-2 is required for the antiapoptotic function of this protein at the mitochondria and endoplasmic reticulum (ER). The involvement of the BH4 domain in Bcl-2's antiapoptotic functions has been proposed based on Gly-based substitutions of the Ile14/Val15 amino acids, two hydrophobic residues located in the center of Bcl-2's BH4 domain. Following this strategy, we recently showed that a BH4-domain-derived peptide in which Ile14 and Val15 have been replaced by Gly residues, was unable to dampen proapoptotic Ca 2+ -release events from the ER. Here, we investigated the impact of these mutations on the overall structure, stability, and function of full-length Bcl-2 as a regulator of Ca 2+ signaling and cell death. Our results indicate that full-length Bcl-2 Ile14Gly/Val15Gly, in contrast to wild-type Bcl-2, (a) displayed severely reduced structural stability and a shortened protein half-life; (b) failed to interact with Bcl-2-associated X protein (BAX), to inhibit the inositol 1,4,5-trisphosphate receptor (IP 3 R) and to protect against Ca 2+ -mediated apoptosis. We conclude that the hydrophobic face of Bcl-2's BH4 domain (Ile14, Val15) is an important structural regulatory element by affecting protein stability and turnover, thereby likely reducing Bcl-2's ability to modulate the function of its targets, like IP 3 R and BAX. Therefore, Bcl-2 structure/function studies require pre-emptive and reliable determination of protein stability upon introduction of point mutations at the level of the BH4 domain., (© 2017 Federation of European Biochemical Societies.)

The purpose of this work was to test, in vitro and in vivo, a new tissue-engineered construct constituted by porcine cortico-cancellous scaffold (Osteobiol Dual Block) (DB) and xeno-free ex vivo culture of human Periodontal Ligament Stem Cells (hPDLSCs). hPDLSCs cultured in xeno-free media formulation preserved the stem cells' morphological features, the expression of stemness and pluripotency markers, and their ability to differentiate into mesenchymal lineage. Transmission electron microscopy analysis suggested that after one week of culture, both noninduced and osteogenic differentiation induced cells joined and grew on DB secreting extracellular matrix (ECM) that in osteogenic induced samples was hierarchically assembled in fibrils. Quantitative RT-PCR (qRT-PCR) showed the upregulation of key genes involved in the bone differentiation pathway in both differentiated and undifferentiated hPDLSCs cultured with DB (hPDLSCs/DB). Functional studies revealed a significant increased response of calcium transients in the presence of DB, both in undifferentiated and differentiated cells stimulated with calcitonin and parathormone, suggesting that the biomaterial could drive the osteogenic differentiation process of hPDLSCs. These data were confirmed by the increase of gene expression of L-type voltage-dependent Ca2+ (VDCCL), subunits α1C and α2D1 in undifferentiated cells in the presence of DB. In vivo implantation of the hPDLSCs/DB living construct in the mouse calvaria evidenced a precocious osteointegration and vascularisation process. Our results suggest consideration of DB as a biocompatible, osteoinductive and osteoconductive biomaterial, making it a promising tool to regulate cell activities in biological environments and for a potential use in the development of new custom-made tissue engineering.

Obsessive-compulsive disorder (OCD) is a chronic condition characterized by obsessions or compulsions that cause distress or interfere with functioning. Selective serotonin reuptake inhibitors are the first-line strategy in the treatment of OCD, but approximately 40% to 60% of patients with OCD fail to respond to them. Several augmentation strategies have been proposed, including the use of atypical antipsychotics and antidepressant combinations. In the present paper we describe the case of a young female patient suffering from severe treatment-resistant OCD who remitted as a result of agomelatine augmentation of escitalopram therapy.

The effects of a hypobaric, hypoxic environment and exercise performed under extreme conditions, such as at high altitudes, are intriguing physiological aspects that need to be investigated directly on human climbers. Their skeletal muscle is one of the main tissues that can suffer from hypoxia and physical challenges, which will both define the muscle adaptation and the molecular signature of regenerative capacity. We investigated the muscle regenerative capacity characterizing satellite cells. Our study shows that satellite cells are altered by hypobaric, hypoxic environments and exercise performed at high altitudes. Of note, in human skeletal muscle after this 5,000 m a.s.l. expedition, SCs showed a significantly lower ability to regenerate skeletal muscle, in respect to before this high-altitude expedition. This impairment appears to be due to reduced satellite cell activity, consistent with their decreased myogenicity and fusion ability. Furthermore, at the transcriptional level several pathways, such as cell cycle, myogenesis, oxidative metabolism, proteolysis and sarcomeric protein synthesis, were found dysregulated.

Plants of cranberry (Vaccinium macrocarpon) furnish edible fruits and derivates that have been used for the prevention and treatment of urinary tract infections. In the present work we compare two commercial extracts that contain proanthocyanins (PACs) at 4 percent and 20 percent for antimicrobial, antiproliferative, antiradical and protective properties against oxidative stress on cell lines. Both extracts showed antimicrobial activity (MIC values range 3-100 microg/ml). Extract at 20 percent PACs showed higher antiproliferative activity against HepG2 and MCF7 cells, but not against C2C12 cells. Both extracts showed a dose-dependent free-radical scavenging capacity, and a protective effect on the cell damage was also revealed by reduction of intracellular active oxygen species release. Cranberry extracts confirmed antioxidative properties and efficacy in reduction of cell viability that resulted stronger against tumor cells. The pretreatment with cranberry extracts, furthermore, reveal an increase of cell resistance against oxidative stress, suggesting a potential role as a dietary supplement in preventing free-radical damage. The proanthocyanidin content is critical to determine the extract efficacy. In cellular experiments the extracts resulted clearly differentiated in their activity, and the activity was strongly influenced by PACs content. Only in DPPH test the free radical scavenging activity seemed to be directly related to proanthocyanidins content.

Objective: The aim of the present study was to evaluate the prevalence of alexithymia and its relationships with psychopathological features and suicide risk in a sample of adult patients with a DSM-IV diagnosis of paranoid schizophrenia., Methods: A mixed male-female sample of 60 subjects (30 males and 30 females) was evaluated with the following rating scales: Toronto Alexithymia Scale (TAS-20), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Calgary Depression Scale for Schizophrenia (CDSS), Scale for Suicidal Ideation (SSI), State-Trait Anxiety Inventory (STAI)., Results: 22 subjects (36.7%) were categorized as alexithymic (TAS-20 scores > or =61). Alexithymics showed more severe negative and depressive symptoms and increased suicide risk than non alexithymics. However, the results of a linear regression with SSI score as dependent variable showed that Difficulty in Identifying and Describing Feelings dimensions of TAS-20 and higher CDSS scores were significantly associated with higher scores on the Scale for Suicide Ideation., Conclusions: The presence of alexithymia in schizophrenia may be related to higher risk of suicide ideation and more severe depressive symptoms, independently by the severity of positive and negative symptoms. However, results are preliminary and limitations must be considered.

The synthesis of milrinone analogues where the 4-pyridyl moiety was replaced by an ester or amide group is reported. Only amide derivatives are able to support intracellular calcium influx following chemical depolarization with 60 mM KCl in a percentage varying from 20 to 45% of differentiated H9C2 cardiomyocytes. Those cells were differentiated after chronic exposure to 10 nM retinoic acid which induces the expression of voltage-gated calcium channels. Analogues of milrinone containing an ester function did not show significant activity., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The basic aspects of bone tissue engineering include chemical composition and geometry of the scaffold design, because it is very important to improve not only cell attachment and growth but especially osteodifferentiation, bone tissue formation, and vascularization. Geistlich Bio-Oss (GBO) is a xenograft consisting of deproteinized, sterilized bovine bone, chemically and physically identical to the mineral phase of human bone. In this study, we investigated the growth behaviour and the ability to form focal adhesions on the substrate, using vinculin, a cytoskeletal protein, as a marker. Moreover, the expression of bone specific proteins and growth factors such as type I collagen, osteopontin, bone sialoprotein, bone morphogenetic protein-2 (BMP-2), BMP-7 and de novo synthesis of osteocalcin in normal human osteoblasts (NHOst) seeded on xenogenic GBO were evaluated. Our observations suggest that after four weeks of culture in differentiation medium, the NHOst showed a high affinity for the three dimensional biomaterial; in fact, cellular proliferation, migration and colonization were clearly evident. The osteogenic differentiation process, as demonstrated by morphological, histochemical, energy dispersive X-ray microanalysis and biochemical analysis was mostly obvious in the NHOst grown on three-dimensional inorganic bovine bone biomaterial. Functional studies displayed a clear and significant response to calcitonin when the cells were differentiated. In addition, the presence of the biomaterial improved the response, suggesting that it could drive the differentiation of these cells towards a more differentiated osteogenic phenotype. These results encourage us to consider GBO an adequate biocompatible three-dimensional biomaterial, indicating its potential use for the development of tissue-engineering techniques.

Aims: To explore: a) the burden of care, and the professional and social support in relatives of patients with bipolar disorders; b) the psychosocial interventions provided to patients and their families by Italian mental health centres., Methods: 342 outpatients with a bipolar disorder and their key-relatives were randomly recruited in 26 Italian mental health centres, randomly selected and stratified by geographical area and population density. Family burden was explored in relation to: a) patient's clinical status and disability; b) relatives' social and professional support; c) interventions received by patients and their families; d) geographical area., Results: In the previous two months, global functioning was moderately impaired in 36% of the patients, and severely impaired in 34% of them. Twenty-one percent of patients attended a rehabilitative programme, and 3% of their families received a psychoeducational intervention. Burden was higher when patient's symptoms and disability were more severe, the relatives had poorer psychological support and help in emergencies by the social network, and the family lived in Southern Italy. Differences in family burden in relation to geographical area disappeared when psychosocial interventions were provided., Conclusion: This study highlights the need to increase the availability of rehabilitative interventions for patients with bipolar disorders and of psychological support for their families, especially in Southern Italy.

The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.

The aim of the present study was to evaluate in a non-clinical sample of undergraduate women, the relationships between alexithymia, body checking and body image, identifying predictive factors associated with the possible risk of developing an Eating Disorder (ED). The Toronto Alexithymia Scale (TAS-20), Body Checking Questionnaire (BCQ), Eating Attitudes Test (EAT-26), Body Shape Questionnaire (BSQ), Interaction Anxiousness Scale (IAS), Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI) were completed by 254 undergraduate females. We found that alexithymics had more consistent body checking behaviors and higher body dissatisfaction than nonalexithymics. In addition, alexithymics also reported a higher potential risk for ED (higher scores on EAT-26) when compared to nonalexithymics. Difficulty in identifying and describing feelings subscales of TAS-20, Overall appearance and Specific Body Parts subscales of BCQ as well as lower self-esteem was associated with higher ED risk in a linear regression analysis. Thus, a combination of alexithymia, low self-esteem, body checking behaviors and body dissatisfaction may be a risk factor for symptoms of ED at least in a non-clinical sample of university women.

To elucidate the relationships between alexithymia, fear of bodily sensations, and somatosensory amplification in young patients with panic disorder (PD), authors evaluated 84 patients. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Body Sensations Questionnaire (BSQ), the Somatosensory Amplification Scale, the Agoraphobic Cognitions Questionnaire (ACQ), and the Hamilton Rating Scale for Depression. Alexithymic patients showed higher scores on all rating scales. Higher BSQ and ACQ scores, together with the Difficulty in Identifying Feelings and Difficulty in Describing Feelings subscales of the TAS-20 were predictors of severity of PD. Results of the present study do not support a direct role of somatosensory amplification in PD. Authors discuss study limitations and future research needs.

The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.

Background: To evaluate alexithymia and body image in women with Premenstrual Dysphoric Disorder and test whether alexithymic traits influence severity of Premenstrual Dysphoric Disorder or body distress., Methods: Sixty-four consecutive women with a DSM-IV diagnosis of Premenstrual Dysphoric Disorder and age range of 18-45 were recruited. Alexithymia was measured with the Italian version 20-items Toronto Alexithymia Scale. Severity of premenstrual mood symptoms was measured through the use of Visual Analogue Scales. Body concerns were assessed with the Body Uneasiness Test, Body Shape Questionnaire and Body Attitude Test. Additional measures were Rosenberg Self-Esteem Scale and Sheehan Disability Scale., Results: Prevalence of alexithymia in our sample was 31.3% (n=20). Alexithymics showed higher scores on all rating scales (p range 0.001-< 0.001). Difficulty in Identifying Feelings and Difficulty in Describing Feelings subscales of Toronto Alexithymia Scale were predictors of severity of Premenstrual Dysphoric Disorder in the multiple linear regression analysis., Conclusions: Alexithymia was associated with more severe Premenstrual Dysphoric Disorder. Alexithymic women with Premenstrual Dysphoric Disorder exhibited significantly poorer appearance evaluation and body satisfaction than non-alexithymic women.

Background: To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function in young patients with new-onset bipolar disorder., Methods: The authors studied 25 new-onset young bipolar patients. Platelet count, platelet aggregation, platelet release, and bleeding time were evaluated before beginning VPA treatment and at least after 10 months of treatment. The control group consisted of 20 sex-matched and age-matched subjects. Patients were started on VPA at a dose of 250 to 750 mg/d, given in divided doses. Mean dosage of VPA was 1137.5 +/- 241.1 mg/d. Mean VPA total plasma concentration was 61.1 +/- 20 g/mL., Results: At baseline, no significant differences were observed for platelet count and function between the bipolar group and the control subjects. After 10 months, at the second evaluation, the platelet count was significantly lower in the bipolar patients than in the control subjects: 192.7 +/- 21.4/microL versus 289.8 +/- 23.9/microL; P < 0.0001. An important observation was that platelet counts were negatively correlated with VPA dose (r = -0.47; P = 0.05) and its plasma concentration (r = -0.50; P = 0.05). In the present study, the authors observed impairment in platelet release of ATP and aggregation that correlated with both VPA dosage and plasma levels. Bleeding times were also significantly longer in patients taking VPA compared with control subjects (P < 0.0001)., Conclusion: Thrombocytopenia can appear after a few months of therapy and with plasma VPA levels within the therapeutic range.