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The intestinal epithelium is structured in crypt-villus units which are responsible for its continuous renewal. These units are organized in a dynamic scenario in which proliferating progenitor cells are generated from stem cells in the crypts and migrate along the villus axis until their extrusion as differentiated cells at the surface epithelium. The mechanisms controlling cell transition involve transcription factors that switch on and off compartment-specific genes. The Wnt cascade represents the dominant force controlling cell fate in the crypt-villus axis. Mutations in this cascade result in the development of colorectal cancer. Life-style modifications and dietary regimens are epidemiologically recognized contributing factors for intestinal tumorigenesis. Nuclear receptors are a family of transcription factors functioning as sensors of dietary and endogenous molecules, thus translating nutritional and hormonal stimuli into transcriptional modifications. This review presents the role of nuclear receptors in intestinal carcinogenesis and explores their influence in maintenance of intestinal epithelium architecture. [ABSTRACT FROM AUTHOR]

Background: Children undergoing diagnostic and interventional radiology procedures often require sedation to achieve immobility and analgesia if the procedure is painful. In the past decades, leading scientific organizations have developed evidence-based guidelines for procedural sedation and analgesia in children outside of the operating room. Their recommendations are being applied to procedural sedation in radiology. However, some questions remain open regarding specific aspects contextualized to the radiology setting, such as elective prone sedation, the urgency of the procedure, when venous access or airway protection is required, and others., Aims: To address the unresolved issues of procedural sedation and analgesia in pediatric diagnostic and interventional radiology., Methods: An expert panel of pediatricians, pediatric anesthesiologists, intensivists, and neuroradiologists selected topics representative of current controversies and formulated research questions. Statements were developed by reviewing the literature for new evidence, comparing expertise and experience, and expressing opinions. Panelists' agreement with the statements was collected anonymously using the DELPHI method., Results: Twelve evidence-based or expert opinion incorporate are presented, considering risks, benefits, and applicability., Conclusions: This consensus document, developed by a multidisciplinary panel of experts involved in the field, provides statements to improve the quality of decision-making practice in procedural sedation and analgesia in pediatric radiology., (© 2024 John Wiley & Sons Ltd.)

Background: Cerebral venous thrombosis (CVT) is a cerebrovascular disorder that accounts for 20% of perinatal strokes. CVT incidence ranges from 0.67 to 1.12 per 100,000 newborns, while the incidence of "deep medullary vein thrombosis" (DMVT), a subtype of CVT, cannot be accurately estimated. This study aims to analyze the case history of CVT in the neonatal period, with a specific focus on DMVT., Materials and Methods: Newborns diagnosed with CVT, with or without DMVT, between January 2002 and April 2023, were collected using the Italian Registry of Infantile Thrombosis (RITI). Cerebral MRIs were reviewed by an expert neuroradiologist following a standardized protocol., Results: Forty-two newborns with CVT were identified, of which 27/42 (64%) had CVT, and the remaining 15/42 (36%) had DMVT (isolated DMVT in 9/15). Symptom onset occurred in the first week of life (median 8 days, IQR 4-14) with a male prevalence of 59%. The most common risk factors for CVT were complicated delivery (38%), prematurity (40%), congenital heart diseases (48%), and infections (40%). Seizures were the predominant presenting symptom in 52% of all cases. Hemorrhagic infarction was higher in cases with isolated DMVT (77%) compared to patients with CVT without DMVT (p = 0.013). Antithrombotic treatment was initiated in 36% of patients. Neurological impairment was observed in 48% of cases at discharge, while 18 out of 31 infants (58%) presented one or more neurological deficits at long term follow up.     Conclusion: DMVT occurs in over a third of neonates with CVT. Multicentric studies are essential to establish standardized protocols for therapy, neuroimaging, and follow-up in these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Loss of function of the STRADA gene, an upstream mTOR inhibitor, causes a rare neurodevelopmental disorder characterized by polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE syndrome). Patients display a homogeneous phenotype including early-onset drug-resistant epilepsy, severe psychomotor delay, multisystemic comorbidities, and increased risk of premature death. The administration of sirolimus, an mTOR inhibitor, is helpful in controlling seizures in this syndrome. We report the electroclinical phenotype of two novel patients and the development of a yeast model to validate the pathogenicity of missense variants. Patient 1 harbored a missense STRADA variant and had a peculiar electroclinical phenotype with a relatively mild epilepsy course. Patient 2 harbored a truncating STRADA variant and showed a typical PMSE phenotype and a favorable response to early treatment with sirolimus. When we modeled the p.(Ser264Arg) STRADA change in its yeast homolog SPS1, it impaired SPS1 function. The results underlie the importance of a timely molecular diagnosis in these patients and show that yeast is a simple yet effective model to validate the pathogenicity of missense variants., Competing Interests: Declaration of competing interest Leonardo Salviati reports financial support was provided by Città della Speranza Pediatric Research Institute. The remaining authors declare that there are no conflicts of interests regarding the publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Morphometric studies on idiopathic Chiari malformation type 1 (CM1) pathogenesis have been mainly based on post-natal neuroimaging. Prenatal clues related to CM1 development are lacking. We present pre- and post-natal imaging time course in idiopathic CM1 and assess fetal skull and brain biometry to establish if clues about CM1 development are present at fetal age., Methods: Multicenter databases were screened to retrieve intrauterine magnetic resonance (iuMR) of children presenting CM1 features at post-natal scan. Syndromes interfering with skull-brain growth were excluded. Twenty-two morphometric parameters were measured at fetal (average 24.4 weeks; range 21 to 32) and post-natal (average 15.4 months; range 1 to 45) age; matched controls were included., Results: Among 7000 iuMR cases, post-natal scans were available for 925, with postnatal CM1 features reported in seven. None of the fetuses presented CM1 features. Tonsillar descent was clear at a later post-natal scan in all seven cases. Six fetal parameters resulted to be statistically different between CM1 and controls: basal angle (p = 0.006), clivo-supraoccipital angle (p = 0.044), clivus' length (p = 0.043), posterior cranial fossa (PCF) width (p = 0.009), PCF height (p = 0.045), and PCFw/BPDb (p = 0.013). Postnatally, only the clivus' length was significant between CM1 cases and controls., Conclusion: Pre- and post-natal CM1 cases did not share striking common features, making qualitative prenatal assessment not predictive; however, our preliminary results support the view that some of the pathogenetic basis of CM1 may be embedded to some extent already in intrauterine life., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The pathobiological mechanisms associated with perinatal asphyxia and hypoxic-ischemic encephalopathy are complex and poorly understood. The metabolic effects of therapeutic hypothermia have been partially explored., Methods: We conducted a single-center longitudinal study to investigate the metabolic effects of perinatal asphyxia and hypoxic-ischemic encephalopathy on the urinary metabolome of a group of 12 asphyctic infants over time compared to 22 matched healthy newborns, using untargeted metabolomics based on mass spectrometry., Findings: Over-representation pathway analysis identified the steroidogenesis pathway as being significantly disrupted, with reduced steroid levels in the first three days of life despite treatment with hypothermia. Comparison with matched healthy newborns showed that the urinary steroid content was lower in asphyctic infants before hypothermia. The lysine degradation and carnitine synthesis pathways were also significantly affected., Interpretation: Steroidogenesis is significantly disrupted in asphyctic infants compared to healthy newborns. Given how neurosteroids are involved in neuromodulation and neuroprotection, translational research is warranted on the potential role of neurosteroid-based intervention in asphyctic infants., Funding: None., Competing Interests: Declaration of interests The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: In a previous study of classifying fetuses with cortical formation abnormalities (CFA) with fetal MR, we noticed a cluster of cases with unilateral CFA and complete agenesis of the corpus callosum (ACC). In this study, we provide a detailed morphological analysis of such fetuses using fetal MR to determine if there are indicators (such as the gender of the fetus) that could be used to delineate a genetic substrate of the phenotype in order to inform future studies., Methods: We have studied 45 fetuses with the unilateral CFA/ACC phenotype and analysed through an expert consensus panel the location and fine detail of the CFA and the associated findings such as associated anomalies, head size, and sex of the fetus., Results: The frontal lobe was significantly more frequently involved by CFA when compared with other lobes (p < 0.001) but no preference for the left or right hemisphere. CFA most often consisted of excessive/dysmorphic sulcation. The CFA/ACC phenotype was overwhelmingly more frequent in male fetuses (M:F 4.5:1-p < 0.0001). The most frequent associated findings were: ventriculomegaly (16/45 fetuses) and interhemispheric cysts (12/45 cases)., Conclusions: This report highlights the specific phenotype of unilateral CFA/ACC that is much more common in male fetuses. This finding provides a starting point to study possible sex-linked genetic abnormalities that underpin the unilateral CFA/ACC phenotype., Key Points: • We collected fetuses with unilateral cortical formation abnormality and callosal agenesis. • That distinctive neuroimaging phenotype has a strong male gender prevalence (over 80%). • This observation forms the basis of studies about outcomes and genetic substrates., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Purpose: The ganglionic eminences are transient fetal brain structures that produce a range of neuron types. Ganglionic eminence anomalies have been recognized on fetal MR imaging and anecdotally found in association with a number of neurodevelopmental anomalies. The aim of this exploratory study was to describe and analyze the associations between ganglionic eminence anomalies and coexisting neurodevelopmental anomalies., Materials and Methods: This retrospective study includes cases of ganglionic eminence anomalies diagnosed on fetal MR imaging during a 20-year period from 7 centers in Italy and England. Inclusion criteria were cavitation or increased volume of ganglionic eminences on fetal MR imaging. The studies were analyzed for associated cerebral developmental anomalies: abnormal head size and ventriculomegaly, reduced opercularization or gyration, and abnormal transient layering of the developing brain mantle. The results were analyzed using χ 2 and Fisher exact tests., Results: Sixty fetuses met the inclusion criteria (21 females, 24 males, 15 sex unknown). Thirty-four had ganglionic eminence cavitations (29 bilateral and 5 unilateral), and 26 had increased volume of the ganglionic eminences (19 bilateral, 7 unilateral). Bilateral ganglionic eminence cavitations were associated with microcephaly ( P = .01), reduced opercularization, ( P < .001), reduced gyration ( P < .001), and cerebellar anomalies ( P = .01). Unilateral ganglionic eminence cavitations were not significantly associated with any particular feature. Bilateral increased volume of the ganglionic eminences showed an association with macrocephaly ( P = .03). Unilateral increased volume was associated with macrocephaly ( P = .002), abnormal transient layering ( P = .001), unilateral polymicrogyria ( P = .001), and hemimegalencephaly ( P < .001)., Conclusions: Ganglionic eminence anomalies are associated with specific neurodevelopmental anomalies with ganglionic eminence cavitations and increased ganglionic eminence volume apparently having different associated abnormalities., (© 2021 by American Journal of Neuroradiology.)

The COVID-19 epidemic has been a major global public health problem during past months in Italy and in several other Countries and on the date of publication of this article, is still a serious public health problem. The health staff, engaged in the care of the sick and in the prevention of the spread of the infection have been subjected to a further increase in psychological difficulties and work-related stress, related to the workload for the continuous influx of sick and intense and close working shifts for the viral emergency. The SAVE-9 (Stress and Anxiety to Viral Epidemics - 9 items) scale has been developed as a tool for assessing work anxiety and stress in response to the viral epidemic of health professionals working to prevent the spread of the virus and to treat infected people.

Through the analysis of "Luigi Alfredo Ricciardi" the main character of detective series by Maurizio De Giovanni, the structuring of a normal melancholic constitution, which we term the depression-prone style of personality, is reconstructed.

In this paper I'm going to illustrate my experience related to the six month narrative laboratory with the psychiatric patients of the Daily Psychiatric Center located in Rutigliano. This project originated from my own way of conceiving the concept of Psychiatric and Psychosocial Rehabilitation in terms of Therapeìa, that is in my view the regaining "sense and meaning" as the essence of rehabilitation therapy. My goal was to awaken thoughts, words, gestures, emotions in order to reconnect an interrupted dialogue with themselves and start an initial storytelling experience. By telling this new story the relationship between the Self, the Story and the Character is recreated so that freedom and life planning are generated again. In order to "gather unspoken yet deeply felt experiences" I used artworks extracted from the catalogue "tutti uguali, tutti diversi"; catalogue created during the awareness campaign and the fight against social stigma and social exclusion by Art, that the Center of Mental Health 3 - CSM 3 - in Troia (Puglia, Italy) held in 2007 in synergy with the School of Fine Art and with the Monuments and Fine Art Department.

Using art in psychotherapy could become an interesting instrument for the cure and the prevention of psychological and psychiatric problems. This belongs to that trend that sees the mediation of art as having big potential to go beyond the spoken word. Everybody knows that our emotions, thoughts, feelings, and so on, are living in the body and speaking through the body, in fact the symbolic dimension (art, music, dance, painting and so on) reconfigures the experience of living. In this form of therapy we use Art as a means of accessing ourselves and opening ourselves up to the world. The forms of artistic mediation that we mainly describe in the paper are the basic elements of tango and performative theatrical technique (Theatre of the Oppressed and Physical Theatre). In the final part of this paper a series of images illustrate specific cases in which the method and its outcomes are described.

Prejudice and stigma about mental illness is still present in society. Patients suffer both from the disease, and from the marginalization behavior exhibited by others towards them and their families. Psychiatric professionals may also become ill and suffer for the same reason. The authors of this international multicenter study have set themselves the question of whether there may be prejudice and/or stigma among psychiatric professionals towards their suffering colleagues, among patients towards nursing staff affected by the same disease and between patients themselves. Using two standardized questionnaires which have been tested, but have not been used before they have studied 207 mental health professionals and 407 patients, of Italian, Belgian, Hungarian and Croatian nationalities. The results show that there are in fact prejudices among Mental Health Professionals about colleagues suffering from mental illness because they responded that such persons cannot treat well patients with their own pathology. However Mental Health Professionals do not demonstrate behaviors which are not frankly marginalizing or stigmatizing towards colleagues suffering from mental illness. On the other hand, among patients the prevailing view was that psychiatric professionals who suffer from mental illness, can better understand the sick, because they are also suffering. This is in analogy with the Jungian theory of the "wounded healer" in the myth of the centaur Chiron. Patients did not demonstate rejection or marginalization behavior towards other sick patients. Finally both the professionals and the patients tend to be cautious in relating to healthy persons and tend not to disclose their suffering for fear of being misjudged or marginalized.

Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)

In thetransition from themodern to thepostmodern age, there has been a changein the Obsessive-Compulsive - Prone Style of Personality, style that can lead to OCD. In this paper we analyze, through literature and cinematographic art, some typical aspects of this style of personality and how they changed over time: the impersonality of the set of references on the basis of which to fix the variability of one's experience by providing it with definite and certain meaning, the issue of one's responsibility related to a failure in anticipation and a new aspect, called "logical complacency" by the current scientific literature, in which the need of the set of references is contemporary with the relationship with the others which embodies and personifies that reference system.

The tango brings out the true essence of the individuals, it removes every mask and stops the lies you tells yourself, forcingthe contact with yourself even before with the others. This is the essence on which we relied to propose a course of psychotherapy with basic elements of tango, as a peculiar mode of experiencing oneself. In this paper we analyze how Tango could become an interesting instrument for the cure and the prevention of psychological and physical problems.

There have been several reports of disulfiram intoxication, but little evidence of neurologic conditions resulting from disulfiram-induced brain damage combined with Wernicke encephalopathy-associated lesions. We report a rare patient with both Wernicke encephalopathy and disulfiram intoxication. This 50-year-old woman, who was taking disulfiram for chronic alcohol abuse, presented with an acute confusional state, dysarthria, nystagmus, supranuclear ophthalmoplegia, and paraparesis. Biochemical serum and cerebrospinal fluid analyses were normal. An electromyogram detected a motor polyneuropathy. Cognitive assessment revealed severe impairment of memory, attention, and logical and executive abilities. Magnetic resonance imaging with gadolinium enhancement showed brain lesions consistent with Wernicke encephalopathy, but also symmetric hyperintensities on T2-weighted images in the globus pallidus. Stopping the disulfiram and treating with hydration, high-dose thiamine supplements, and benzodiazepines significantly improved the patient's consciousness and oculomotor function. A magnetic resonance imaging scan after 1 month of treatment showed complete disappearance of the brain lesions and the hyperintensities in the globus pallidus. After a further month of intensive neurorehabilitation, the patient was able to interact with the medical staff, and her neuropsychological tests showed only mild memory impairment. Patients with alcoholism who present at emergency departments are at high risk for misdiagnosis, especially because there is no specific routine laboratory test for detecting asymptomatic disulfiram intoxication. Although uncommon, the combination of Wernicke encephalopathy and disulfiram intoxication should be suspected in patients with alcoholism. The disorder can be detected through a careful history and prompt clinical evaluation, together with characteristic magnetic resonance imaging findings.

We have recently shown that the transcriptional coactivator PGC1α, a master regulator of mitochondrial biogenesis and function, is involved in the control of the intestinal epithelium cell fate. Furthermore, PGC1α protects against colon cancer formation by promoting ROS accumulation and, consequently, mitochondria-mediated apoptosis. Here we provide an additional mechanistic insight into the tumor suppressor activity of PGC1α showing that its pro-apoptotic effect is mediated by Bax. In fact, PGC1α overexpression in HCT116 Bax (-/-) colorectal cancer cells stimulates mitochondrial production and activity, but it fails to induce cell death as well as to oppose tumor growth in the xenograft model. The lack of ROS accumulation in the Bax (-/-) cells strengthens our view that the PGC1α-induced oxidative burst represents one of the main apoptosis-driving factors in colorectal cancer cells., (© 2011 Landes Bioscience)

Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a transcriptional coactivator able to up-regulate mitochondrial biogenesis, respiratory capacity, oxidative phosphorylation, and fatty acid β-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts migrate along the villus axis and differentiate into mature enterocytes, increasing their respiratory capacity and finally undergoing apoptosis. Here we show that in the intestinal epithelial surface, PGC1α drives mitochondrial biogenesis and respiration in the presence of reduced antioxidant enzyme activities, thus determining the accumulation of reactive oxygen species and fostering the fate of enterocytes toward apoptosis. Combining gain- and loss-of-function genetic approaches in human cells and mouse models of intestinal cancer, we present an intriguing scenario whereby PGC1α regulates enterocyte cell fate and protects against tumorigenesis.

Several steps of the HDL-mediated reverse cholesterol transport (RCT) are transcriptionally regulated by the nuclear receptors LXRs in the macrophages, liver, and intestine. Systemic LXR activation via synthetic ligands induces RCT but also causes increased hepatic fatty acid synthesis and steatosis, limiting the potential therapeutic use of LXR agonists. During the last few years, the participation of the intestine in the control of RCT has appeared more evident. Here we show that while hepatic-specific LXR activation does not contribute to RCT, intestinal-specific LXR activation leads to decreased intestinal cholesterol absorption, improved lipoprotein profile, and increased RCT in vivo in the absence of hepatic steatosis. These events protect against atherosclerosis in the background of the LDLR-deficient mice. Our study fully characterizes the molecular and metabolic scenario that elects the intestine as a key player in the LXR-driven protective environment against cardiovascular disease., (Copyright 2010 Elsevier Inc. All rights reserved.)

Cognitive evaluation of emotional stimuli involves a network of brain regions including the medial prefrontal cortex (mPFC). However, threatening stimuli may be perceived with differential salience in different individuals. The goal of our study was to evaluate how different personality styles are associated with differential modulation of brain activity during explicit recognition of fearful and angry facial expressions. Twenty-eight healthy subjects underwent fMRI. Based on a cognitivist model, subjects were categorized according to how they attribute salience to emotional stimuli and how they regulate their emotional activation. We compared 14 phobic prone (PP) subjects, whose identity is more centered on the inner experience ("inward") and around control of environmental threat, and 14 eating disorders prone (EDP) subjects, whose identity is more centered on external referential contexts ("outward") and much less around control of threatening stimuli. During fMRI subjects either matched the identity of one of two angry and fearful faces to that of a simultaneously presented target face or identified the expression of a target face by choosing one of two simultaneously presented linguistic labels. The fMRI results indicated that PP subjects had greater mPFC activation when compared with EDP subjects during cognitive labeling of threatening stimuli. Activity in the mPFC also correlated with personality style scores. These results demonstrate that PP subjects recruit greater neuronal resources in mPFC whose activity is associated with cognitive aspects that are closely intertwined with emotional processing. These findings are consistent with the contention that cognitive evaluation and salience of emotional stimuli are associated with different personality styles.

A new method for aflatoxin B (AFB) determination is proposed. The AFB determination is based on acetylcholinesterase (AChE) inhibition, and the AChE residual activity is determined using the colorimetric method (Ellman's method). Cholinesterases (ChEs) from various sources were tested using AFB1 as reference aflatoxin. AChE from electric eel has shown the highest sensitivity to AFB1, and it was chosen for the rest of the work. To select and optimize the analytical procedures, an investigation on the type of AChE inhibition by AFB1 was carried out. The AChE degree of inhibition by AFB1 was independent of the incubation time and the enzyme concentrations, showing the reversibility of the inhibition. This reversibility of the inhibition permits a rapid analysis of AFB1, requiring only 3 min. For the development of the AFB1 assay, the pH, the time of reaction, temperature, and substrate concentration were evaluated and optimized. The linear range of 10-60 ng mL-1 was determined. To evaluate the selectivity of this method, the cross-reactivity with other aflatoxins such as aflatoxin B2, aflatoxin G1, aflatoxin G2, and aflatoxin M1 was investigated. Finally, the suitability of the assay for AFB1 quantification in barley was evaluated. This study shows a new approach to detect aflatoxins based on enzyme inhibition and has advantages such as the ease of use, rapidity, and cost effectiveness. Thus, it could find a possible use as a screening method for this type of mycotoxins.

Tfam is a single copy nuclear gene mapping on chromosome 10 in human and mouse, 20 in rat and 12 in Presbytis cristata. It encodes for an HMG (high-mobility-group) protein showing a high affinity with the two transcriptional promoters and other mitochondrial DNA regions. It is an activator of mitochondrial transcription acting in the presence of mitochondrial RNA polymerase and of transcription factor B. Other interesting features of Tfam gene in human and rat are reported such as the existence of a smaller isoform, originated by an alternative splicing mechanism of the exon 5 (delta5 isoform) and the presence of different processed pseudogenes in addition to the active copy of the gene. In order to widen knowledge about Tfam gene and the appearance of some of its properties in the evolutionary history of primates, we have studied some aspects of this gene in different species. In particular we have determined its chromosomal localization, suggesting that its locus is highly conserved; we have searched for the presence of the delta5 isoform, demonstrating that it is present only in hominids; we have provided evidence of Tfam processed pseudogenes in the majority of the analysed genomes. Sequence data from this article have been deposited in the EMBL nucleotide database.

Background: In a previous study, improvement of antipsychotic-induced blefarospasm and involuntary oral-mandibulo movements were observed with the use of the anticonvulsant drug gabapentin among affectively ill patients who had been exposed to maintenance neuroleptics. The results reported in the present paper represent the sequel to the previous study., Methods: The purported efficacy of gabapentin in the treatment of tardive dyskinesia has been assessed in an open design 1-year follow-up study, in which 30 schizoaffective, bipolar I and schizophrenic patients from seven Italian centres were evaluated by means of AIMS. The results showed a statistically significant time-related decrease in AIMS scores. The mean percentage of improvement at AIMS was 47.5+/-18.2%. An improvement of more than 35% after 1 year in 76% of the subjects who completed the trial (n=25) and in 63.3% of the entire sample admitted to the study was revealed., Limitation: Open trial., Conclusion: The introduction of new antipsychotic drugs has probably already limited the problems related to tardive dyskinesia. However, this type of side-effect is also observed during the course of treatment with atypical neuroleptics albeit with a lesser frequency. The fact that gabapentin treatment may have further improved clinical conditions of patients in whom therapeutic protocols had already been modified, appears to suggest exertion of a possible synergic action by the new neuroleptics on tardive dyskinesia.

During the evolution of Metazoa, the mitochondrial genome has remained practically unchanged as indicated by its small size and constant gene content in each lineage, although several evolutionary processes have taken place. In contrast, the nuclear genome of Metazoa has undergone dramatic changes, as is demonstrated by some entire genomes completely sequenced so far. The expansion of gene families and the appearance of new functions and new regulatory circuits are among the most prominent features. Here, we report a description of the evolution of the p53 gene family as an example of expansion of both genetic complexity and gene expression of the nuclear genome.

Mitochondrial DNA replication and transcription are regulated from essential nucleus-encoded components that interact with the mitochondrial (mt) D-loop region. Among these there is the mitochondrial transcription factor A (mtTFA or Tfam). We have determined the sequence of the cDNA mtTFA in rat and have demonstrated that the gene has a mosaic organization with six introns whose sizes we have calculated. A differential splicing transcript lacking exon 5 has been detected in all assayed tissues and represents 9.85% of the full length transcript. Beside the gene which is homologous to the one found in man and mouse, rat nuclear genome contains at least 12 copies of this gene or genome fragments with high similarity to mtTFA. We have determined the sequence of one of these copies. This resulted to have 76.26% similarity to the active gene but to lack introns, suggesting it might be a processed pseudogene. RT-PCR experiments have demonstrated that this pseudogene (psi mtTFA) is transcribed in liver tissue.