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Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right‐handed male patient underwent neuropsychological assessment and testing on two conditional associative‐learning tasks: the motor hand conditional associative‐learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative‐learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high‐level cognitive processes. [ABSTRACT FROM AUTHOR]

Background and purpose: 'Dancing‐like' semiology is extremely rare and described in few case reports. It is characterized by rhythmic, oscillatory movements of the pelvis and/or limbs during which the subject appears to be dancing. It has been associated with both the frontal and temporal epileptic zone; however, the possible network involved in these fascinating seizures is unclear. Methods: The case of a 45‐year‐old woman suffering from drug‐resistant focal epilepsy with multi‐day seizures of bizarre semiology is described. A structural and perfusion magnetic resonance imaging study (interictal and peri‐ictal) and video‐electroencephalograms were carried out, and several home videos were employed. A vagal stimulator was implanted. Results: Home videos documented the 'dancing' semiology of seizures better than video‐ electroencephalogram recordings. The imaging study revealed a focal frontal polymicrogyria with a peri‐ictal cerebral blood flow increase at the perisylvian lesion foci. The combination of add‐on cenobamate and vagal nerve stimulation resulted in complete seizure freedom. Conclusion: The unusual and complex dancing‐like semiology observed during our patient's seizures adds to the repertoire of fascinating complex motor manifestations of frontal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array‐comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD. Methods: The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent. Results: Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array‐CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests. Conclusions: This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in‐depth care of children with autism when genetic results are analyzed also with a focus on patient management. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic underpinnings. Microarray‐based comparative genomic hybridization (aCGH) technology has been proposed as a first‐level test in the genetic diagnosis of ASD and of neurodevelopmental disorders in general. Methods: We performed aCGH on 98 Tunisian children (83 boys and 15 girls) diagnosed with ASD according to DSM‐IV criteria. Results: "Pathogenic" or "likely pathogenic" copy number variants (CNVs) were detected in 11 (11.2%) patients, CNVs of "uncertain clinical significance" in 26 (26.5%), "likely benign" or "benign" CNVs were found in 37 (37.8%) and 24 (24.5%) patients, respectively. Gene set enrichment analysis involving genes spanning rare "pathogenic," "likely pathogenic," or "uncertain clinical significance" CNVs, as well as SFARI database "autism genes" in common CNVs, detected eight neuronal Gene Ontology classes among the top 10 most significant, including synapse, neuron differentiation, synaptic signaling, neurogenesis, and others. Similar results were obtained performing g: Profiler analysis. Neither transcriptional regulation nor immune pathways reached significance. Conclusions: aCGH confirms its sizable diagnostic yield in a novel sample of autistic children from North Africa. Recruitment of additional families is under way, to verify whether genetic contributions to ASD in the Tunisian population, differently from other ethnic groups, may involve primarily neuronal genes, more than transcriptional regulation and immune‐related pathways. [ABSTRACT FROM AUTHOR]

Surgical resection of brain tumours aims at the maximal safe resection of the pathological tissue with minimal functional impairment. To achieve this objective, reliable anatomical landmarks are indispensable to navigate into the brain. The neuronavigation system can provide information to target the location of the patient's lesion, but after the craniotomy, a brain shift and relaxation mismatch with it often occur. By contrast, sulci/gyri are topological cerebral landmarks in individual patients and do shift with the brain parenchyma during lesion removal, but remain independent from brain shift in relation to the sulci/gyri. Here, we present a case report of a novel strategy based on anatomical landmarks to guide intraoperative brain tumour resection, without using a standard neuronavigation system. A preoperative brain mapping of the peri‐tumoural sulci by the MRI and surface reconstruction was followed by confirmation of the anatomical landmarks for the motor cortex using navigated transcranial magnetic stimulation. The resulting location was used as a seed for diffusion tensor imaging tractography to reconstruct the corticospinal tracts. These selected cortical landmarks (sulci/gyri) delimited the margins of the two lesions and the specific location under which the corticospinal tract courses, thus facilitating monitoring of the peri‐tumoural region during brain resection. In this case, 96% of the brain tumour from the pericentral somatomotor region was successfully removed without chronic post‐operative motor impairments. This approach is based on cortical anatomy that is fixed during surgery and does not suffer from the brain shift that could misplace the lesion according to the neuronavigation system. [ABSTRACT FROM AUTHOR]

Phelan‐McDermid syndrome (PMS, OMIM #606232), also known as chromosome 22q13 deletion syndrome, is a rare genetic disorder characterized by intellectual disability, hypotonia, delayed or absent speech, motor impairment, autism spectrum disorder, behavioral anomalies, and minor aspecific dysmorphic features. Haploinsufficiency of SHANK3, due to intragenic deletions or point mutations, is sufficient to cause many neurobehavioral features of PMS. However, several additional genes located within larger 22q13 deletions can contribute to the great interindividual variability observed in the PMS phenotype. This review summarizes the phenotypic contributions predicted for 213 genes distributed along the largest 22q13.2‐q13.33 terminal deletion detected in our sample of 63 PMS patients by array‐CGH analysis, spanning 9.08 Mb. Genes have been grouped into four categories: (1) genes causing human diseases with an autosomal dominant mechanism, or (2) with an autosomal recessive mechanism; (3) morphogenetically relevant genes, either involved in human diseases with additive co‐dominant, polygenic, and/or multifactorial mechanisms, or implicated in animal models but not yet documented in human pathology; (4) protein coding genes either functionally nonrelevant, with unknown function, or pathogenic through mechanisms other than haploinsufficiency; piRNAs, noncoding RNAs, miRNAs, novel transcripts and pseudogenes. Our aim is to understand genotype–phenotype correlations in PMS patients and to provide clinicians with a conceptual framework to promote evidence‐based genetic work‐ups, clinical assessments, and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background and purpose: CLOCK and PER2 genes have been implicated in sleep–wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. Methods: Sixty‐eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow‐up every 2 years for a mean time of 10 years were included. Subjects who developed AD (SCD‐c and MCI‐c) and non‐converters (SCD‐nc, MCI‐nc) were considered. Results: CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P = 0.049), fewer years of education (P = 0.007) and a lower frequency of family history of AD (P = 0.04) than G non‐carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow‐up, two SCD and 15 MCI subjects progressed to AD: both of the SCD‐c subjects presented the PER2 G allele, while none of the SCD PER2 G non‐carriers converted to AD (P = 0.003). Conclusion: PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical effects of health care reorganization because of COVID‐19, in a non‐red zone Italian referral department of Otorhinolaryngology. Materials and Methods: We retrospectively reviewed the statistics of admissions to the Emergency Department (ED) of the Careggi University Hospital, Florence, from January 1, 2020, to May 17, 2020. Data regarding elective and urgent head and neck disorders were reviewed and the most challenging cases were discussed. Results: During the lockdown period, outpatient otolaryngological consultations and elective procedures decreased by 78% and 75% respectively, while emergency/urgency surgery increased by 128%. The five most emblematic clinical cases were thoroughly analyzed. Conclusion: Our analysis shows how the profound rearrangement of clinical and surgical activities, along with the citizens' fear to seek medical care has probably exacerbated the management of many routine head and neck conditions. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Foam formation in porous media is a topic of growing scientific and industrial interest due to its range of applications, from daily life consumer products to oil recovery. Despite the work done so far on foams flowing through complex structures, such as rigid porous media, this subject still needs to be fully elucidated. An additional complexity to the problem arises when the porous medium is deformable, a situation which has only been faced, to our knowledge, from a modelling point of view. In this work, the investigation of foam formation in deformable porous media is carried out by using commercial sponges as a deformable porous media system, with special emphasis on the effect of confinement on foam bubble size distribution. Foam is formed by wetting the sponge with an aqueous surfactant solution and then squeezing the sponge either between two glass cover slides or between a plastic net and a cover slide. Our experimental data reveal that the latter system allows the formation of drier foams (ie, with lower liquid fraction, fL < 0.3), more similar to the ones obtained in dish‐washing applications. Moreover, the effect of sponge type, in terms of material and microstructure, on final foam is presented. Our results are of potential interest for the optimization of foams in complex structures, such as in deformable porous media. [ABSTRACT FROM AUTHOR]

Background: Children with autism spectrum disorder (ASD) display impressive clinical heterogeneity, also involving treatment response. Genetic variants can contribute to explain this large interindividual phenotypic variability. Methods: Array‐CGH (a‐CGH) and whole genome sequencing (WGS) were performed on a multiplex family with two small children diagnosed with ASD at 17 and 18 months of age. Both brothers received the same naturalistic intervention for one year according to the Early Start Denver Model (ESDM), applied by the same therapists, yielding dramatically different treatment outcomes. Results: The older sibling came out of the autism spectrum, while the younger sibling displayed very little, in any, improvement. This boy was subsequently treated applying a structured Early Intensive Behavioral Intervention paired with Augmentative Alternative Communication, which yielded a partial response within another year. The ESDM nonresponsive child carries a novel maternally inherited 65 Kb deletion at chr. 13q32.2 spanning FARP1. Farp1 is a synaptic scaffolding protein, which plays a significant role in neural plasticity. Conclusion: These results represent a paradigmatic example of the heuristic potential of genetic markers in predicting treatment response and possibly in supporting the targeted prescription of specific early intervention approaches. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorder with a worldwide prevalence of about 5%. The disorder is characterized by inattentive, hyperactive and impulsive behavior and is often comorbid with other neuropsychiatric conditions. Array comparative genomic hybridization (array‐CGH) testing has been proved to be useful to detect chromosomal aberrations in several neuropsychiatric conditions including autism spectrum disorders (ASD) and intellectual disability (ID). The usefulness of array‐CGH in the ADHD clinics is still debated and no conclusive evidence has been reached to date. We performed array‐CGH in 98 children and adolescents divided in two similarly sized groups according to the clinical diagnosis: (a) one group diagnosed with ADHD as primary diagnosis; (b) the other group in which ADHD was co‐morbid with ASD and/or ID. We detected pathogenetic and likely pathogenetic copy number variants (CNVs) in 12% subjects in which ADHD was co‐morbid with autism and/or intellectual disability and in 8.5% subjects diagnosed with ADHD as primary diagnosis. Detection of CNVs of unknown clinical significance was similar in the two groups being 27% and 32%, respectively. Benign and likely benign CNVs accounted for 61% and 59.5% in the first and second group, respectively. Differences in the diagnostic yield were not statistically significant between the two groups (P >.05). Our data strongly suggest that array‐CGH (a) is a valuable diagnostic tool to detect clinically significant CNVs in individuals with ADHD even in the absence of comorbidity with ASD and/or ID and (b) should be implemented routinely in the ADHD clinics. [ABSTRACT FROM AUTHOR]

Neurexins are presynaptic cell adhesion molecules critically involved in synaptogenesis and vesicular neurotransmitter release. They are encoded by three genes (NRXN1‐3), each yielding a longer alpha (α) and a shorter beta (β) transcript. Deletions spanning the promoter and the initial exons of the NRXN1 gene, located in chromosome 2p16.3, are associated with a variety of neurodevelopmental, psychiatric, neurological and neuropsychological phenotypes. We have performed a systematic review to define (a) the clinical phenotypes most associated with mono‐allelic exonic NRXN1 deletions, and (b) the phenotypic features of NRXN1 bi‐allelic deficiency due to compound heterozygous deletions/mutations. Clinically, three major conclusions can be drawn: (a) incomplete penetrance and pleiotropy do not allow reliable predictions of clinical outcome following prenatal detection of mono‐allelic exonic NRXN1 deletions. Newborn carriers should undergo periodic neuro‐behavioral observations for the timely detection of warning signs and the prescription of early behavioral intervention; (b) the presence of additional independent genetic risk factors should always be sought, as they may influence prognosis; (c) children with exonic NRXN1 deletions displaying early‐onset, severe psychomotor delay in the context of a Pitt‐Hopkins‐like syndrome 2 phenotype, should undergo DNA sequencing of the spared NRXN1 allele in search for mutations or very small insertions/deletions. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) poisoning is a leading cause of intentional and unintentional poisoning worldwide, associated with mortality and severe morbidity. Some survivors of CO poisoning develop, after a lucid interval, a potentially permanent encephalopathy in the form of cognitive impairment and movement disorders, such as Parkinsonism. One of the most frequent neuroimaging findings is a cerebral white matter damage, but so far its precise cause and specific therapy are still debated. We here report the case of a 33-year-old woman with severe carbon monoxide poisoning who, after a period of lucid interval, presented symptoms of declining motor and cognitive functions. She was treated with 40 sessions of Hyperbaric Oxygen Therapy (HBOT). The therapeutic use of oxygen at supraphysiological pressures might either increase systemic oxidative stress or cause an overproduction of oxygen free radicals as drawbacks. Concurrent use of antioxidants and anti-inflammatory drugs may prevent the side effects of oxygen therapy at supraphysiological pressure due to oxidative stress. For this reason, the patient was also treated with high-dose N-Acetylcysteine and glucocorticoids. Here, we describe the longitudinal monitoring of patient's cognitive abilities and leukoencephalopathy associated with her positive clinical outcome. [ABSTRACT FROM AUTHOR]

The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. [ABSTRACT FROM AUTHOR]

Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid- (PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of the miRNAs involved in the posttranscriptional regulation of the CFTR disease-gene of Cystic Fibrosis, and bearing suitable functionalization at its Nand C-ends aimed at improving its resistance to nucleases and cellular uptake, is able to revert the expression of the luciferase gene containing the 3'UTR of the gene in A549 human lung cancer cells, in agreement with the MD results that pointed at the formation of a stable RNA/PNA heteroduplex notwithstanding the short sequence of the latter. The here reported results widen the interest towards the use of small PNAs as effective anti-miRNA agents. [ABSTRACT FROM AUTHOR]

We present here an innovative experimental methodology for the quantitative investigation of chemotaxis in vitro by live imaging of cell movement in a reconstituted three-dimensional collagen gel. A well-defined chemoattractant gradient is generated by means of a novel direct viewing chamber having two compartments (separated by a membrane), one containing the chemoattractant solution, the other the cell-seeded collagen gel matrix. Cell migration is observed by means of a time-lapse motorized video-microscopy workstation equipped with an incubating system and quantified by image analysis techniques. Experimental results on three different cell lines (Jurkat, fibroblasts, and lymphocytes) are presented for the isotropic control case (no chemoattractant) and in presence of a concentration gradient. Cell motility data are in line with the concentration profile, both theoretically calculated from Fick's law and experimentally measured by epifluorescence microscopy. In particular, a transient peak in cell response was found, possibly due to cell membrane receptor saturation. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4025-4035, 2013 [ABSTRACT FROM AUTHOR]

JOSI is a software framework that tries to simplify the development of such kinds of applications both by providing the possibility of working on models for representing such semantic information and by offering some implementations of such models that can be easily used by software developers without any knowledge about semantic models and languages. This software library allows the representation of domain models through Java interfaces and annotations and then to use such a representation for automatically generating an implementation of domain models in different programming languages (currently Java and C++). Moreover, JOSI supports the interoperability with other applications both by automatically mapping the domain model representations into ontologies and by providing an automatic translation of each object obtained from the domain model representations in an OWL string representation. [ABSTRACT FROM AUTHOR]

The red blood cells (RBCs) population is characterized by a high heterogeneity in membrane area, cellular volume, and mechanical properties, mainly due to the variety of mechanical and chemical stresses that a red cell undergoes in its entire life span. Here, we provide the first simultaneous area and volume measurements of RBCs flowing in microcapillaries, by using high-speed video microscopy imaging and quantitative data processing based on image analysis techniques. Both confined and unbounded flow conditions (depending on the relative size of RBCs and microcapillary diameter) are investigated. The results are compared with micropipette experiments from the literature and data from Coulter counter routine clinical blood tests. Good agreement is found for RBC volume, especially in the case of confined flow conditions. Surface area measurements, which are lacking in the routine clinical test, are of special interest being a potential diagnostic parameter of altered cell deformability and aggregability. Overall, our results provide a novel flow methodology suitable for high-throughput measurements of RBC geometrical parameters, allowing one to overcome the limits of classical static methods, such as micropipette aspiration, which are not suitable for handling a large number of cells. © 2012 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Gonadotrophin-releasing hormone (GnRH) neurones fire spontaneous bursts of action potentials, although little is understood about the underlying mechanisms. In the present study, we report evidence for two types of bursting/oscillation driven by different mechanisms. Properties of these different types are clarified using mathematical modelling and a recently developed active-phase/silent-phase correlation technique. The first type of GnRH neurone (1-2%) exhibits slow (∼0.05 Hz) spontaneous oscillations in membrane potential. Action potential bursts are often observed during oscillation depolarisation, although some oscillations were entirely subthreshold. Oscillations persist after blockade of fast sodium channels with tetrodotoxin (TTX) and blocking receptors for ionotropic fast synaptic transmission, indicating that they are intrinsically generated. In the second type of GnRH neurone, bursts were irregular and TTX caused a stable membrane potential. The two types of bursting cells exhibited distinct active-phase/silent-phase correlation patterns, which is suggestive of distinct mechanisms underlying the rhythms. Further studies of type 1 oscillating cells revealed that the oscillation period was not affected by current or voltage steps, although amplitude was sometimes damped. Oestradiol, an important feedback regulator of GnRH neuronal activity, acutely and markedly altered oscillations, specifically depolarising the oscillation nadir and initiating or increasing firing. Blocking calcium-activated potassium channels, which are rapidly reduced by oestradiol, had a similar effect on oscillations. Kisspeptin, a potent activator of GnRH neurones, translated the oscillation to more depolarised potentials, without altering period or amplitude. These data show that there are at least two distinct types of GnRH neurone bursting patterns with different underlying mechanisms. [ABSTRACT FROM AUTHOR]

We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population from the same geographic area. Furthermore, serum MBL concentration (also after normalization to serum albumin) was significantly lower in centenarians and in octo- and nonagenarians as compared to the general population, suggesting that intermediate MBL haplotype/activity may be protective. We also demonstrated that in vitro MBL protein bound to senescent IMR90 fibroblasts thereby causing cell lysis, but not to other types of cycle-arrested cells not in senescence. This implicates a novel role of MBL in the clearance of senescent cells. [ABSTRACT FROM AUTHOR]

Cell responses are commonly heterogeneous, even within a subpopulation. In the present study, we investigate the source of heterogeneity in the Ca response of anterior pituitary lactotrophs to a Ca mobilisation agonist, thyrotrophin-releasing hormone. This response is characterised by a sharp increase of cytosolic Ca concentration as a result of mobilisation of Ca from intracellular stores, followed by a decrease to an elevated plateau level that results from Ca influx. We focus on heterogeneity of the evoked Ca spike under extracellular Ca free conditions. We introduce a method that uses the information provided by a mathematical model to characterise the source of heterogeneity. This method compares scatter plots of features of the Ca response obtained experimentally with those made from the mathematical model. The model scatter plots reflect random variation of parameters over different ranges, and matching the experimental and model scatter plots allows us to predict which parameters are most variable. We find that a large degree of variation in Ca efflux is a likely key contributor to the heterogeneity of Ca responses to thyrotrophin-releasing hormone in lactotrophs. This technique is applicable to any situation in which the heterogeneous biological response is described by a mathematical model. [ABSTRACT FROM AUTHOR]

Factor XI (FXI) deficiency is a rare bleeding disorder, resulting in a wide range of bleeding manifestations, from asymptomatic bleeding to injury-related bleeding. To identify mutations in FXI-deficient patients and to establish a possible relationship between clinical phenotype and genotype, we studied two patients from Southern Italy with FXI deficiency. They were identified by presurgical or routine laboratory screening. None of them showed bleeding. Three different mutations were detected (Glu117Stop, Cys118Arg and Trp497Gly); two of them were novel (Cys118Arg and Trp497Gly). One patient (with severe FXI levels) showed a compound heterozygosity (Glu117Stop with Cys118Arg). Two novel missense mutations were highly conserved among different species. In our patients, bleeding tendency did not appear to be correlated with FXI levels or with a single mutation in heterozygosis. On the other hand, the compound heterozygosis might explain low FXI levels, but it is not associated with bleeding. Our data confirm that a severe FXI deficiency is not necessarily associated with bleeding. [ABSTRACT FROM AUTHOR]

A letter to the editor regarding factor V deficiency in of a woman with anaphylactic transfusion is presented.

Ring 17 syndrome is a rare disorder with clinical features influenced by the presence or deletion of the Miller–Dieker critical region (MDCR). Presence of the MDCR is associated with a mild phenotype, including growth delay (GD), mental retardation (MR), seizures, cafè au lait skin (CALS) spots and minor facial dysmorphisms. Previous studies have been mainly focused on this locus providing poor information about the role of other genes located on the p- and q-arms. Here, we used bacterial artificial chromosome (BAC)/P1 artificial chromosome (PAC) and fosmid clones as fluorescence in situ hybridization (FISH) probes to perform a cyto-molecular analysis of a ring 17 case and found that the breakpoints were close to the telomeric ends. METRNL is the sole gene located on the q-arm terminal end, whereas two open reading frames and the RPH3AL gene are located on the terminal p-arm. To detect possibly unrevealed small deletions involving the transcription units, we used subcloned FISH probes obtained by long-range polymerase chain reaction (PCR), which showed that the investigated regions were preserved. Comparing our findings with other reports, it emerges that different breakpoints, involving (or not) large genomic deletions, present overlapping clinical aspects. In conclusion, our data suggest that a mechanism based on gene expression control besides haploinsufficiency should be considered to explain the common phenotypic features found in the mild ring 17 syndrome. [ABSTRACT FROM AUTHOR]

Analysis of fetal DNA in maternal plasma has recently been introduced as a new method for noninvasive prenatal diagnosis. In the majority of cases, the Y chromosome–specific sequences are commonly used as a fetus-specific marker with a high risk of false-negative cases. We attempted to develop a sensitive and reliable X chromosome short tandem repeat (STR) multiplex PCR amplification system that is suitable for the amplification of short-sized templates of free fetal DNA. Because of specific characteristics of fetal DNA in maternal plasma, cell-free fetal DNA is smaller than corresponding maternal DNA, and so we selected 10 X-STR loci in which the allele size was 250 bp. In addition, fetal sex was also investigated using the amelogenin gene in the same multiplex assay. Twenty-six women were enrolled in the study. Eight of 26 total fetuses analyzed were male and 18 were female. In the whole sample, X-STRs were informative with a mean of 4.84 ± 1.43. A mean of 2.67 ± 1.28 X-STR markers per sample (range 1–5) of paternally inherited fetal alleles were detected in pregnant women carrying a female fetus. In all cases, blind determination of fetal sex by means of the identification of amelogenin and X-STR markers was confirmed by fetal karyotyping. This study showed that this noninvasive technique is a reliable and accurate tool to investigate free fetal DNA in pregnancies within the first trimester and could be widely used in clinical research and diagnosis. [ABSTRACT FROM AUTHOR]

This paper presents a multi-agent system called GAIN (Grid Agent Infrastructure), which can be used for the development of flexible agent-based Grid systems. The system supports users both in the development and execution of Grid applications. In particular, GAIN allows the definition of workflow applications by composing different tasks made available by the Grid nodes. Furthermore, it follows the different phases of the execution of the workflow providing transparent allocation and re-allocation of the tasks on the different nodes of the Grid. A first prototype of the system has been realized by using the JADE agent development software and it has been tested in lab trials involving a network of different JADE platforms. In these trials, tasks provided both by the agents of the system and by external legacy software systems have been composed. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We screened the whole coding region of the cystic fibrosis transmembrane regulator (CFTR) gene in 371 unrelated cystic fibrosis (CF) patients from three regions of southern Italy. Forty-three mutations detected 91.5% of CF mutated chromosomes by denaturing gradient gel electrophoresis analysis, and three intragenic CFTR polymorphisms predicted a myriad of rare mutations in uncharacterized CF chromosomes. Twelve mutations are peculiar to CF chromosomes from southern Italy: R1158X, 4016insT, L1065P and 711+1G>T are present in 6.3% of CF chromosomes in Campania; G1244E and 852del22 are present in 9.6% of CF chromosomes in Basilicata and 4382delA, 1259insA, I502T, 852del22, 4016insT, D579G, R1158X, L1077P and G1349D are frequent in Puglia (19.6% of CF alleles). Several mutations frequently found in northern Italy (e.g., R1162X, 711+5G>T) and northern Europe (e.g., G551D, I507del and 621+1G>T) are absent from the studied population. The I148T-3195del6 complex allele was present in two CF chromosomes, whereas I148T was present in both alleles (as a single mutation) in another CF patient and in five CF carriers; this could result from crossover events. The haplotype analysis of three intragenic polymorphisms (IVS8CA, IVS17bTA and IVS17bCA) compared with data from other studies revealed that several mutations (3849+10kbC>T, 1717-1G>A, E585X, 3272-26G>A, L558S, 2184insA and R347P) originated from multiple events, whereas others (R1158X and S549R) could be associated with one or more intragenic recombinant events. Given the large population migration from southern Italy, knowledge of the CF molecular epidemiology in this area is an important contribution to diagnosis, counselling and interlaboratory quality control for molecular laboratories worldwide. [ABSTRACT FROM AUTHOR]

Abstract The pars opercularis occupies the posterior part of the inferior frontal gyrus. Electrical stimulation or damage of this region interferes with language production. The present study investigated the morphology and morphometry of the pars opercularis in 108 normal adult human cerebral hemispheres by means of magnetic resonance imaging. The brain images were transformed into a standardized proportional steoreotaxic space (i.e. that of Talairach and Tournoux) in order to minimize interindividual brain size variability. There was considerable variability in the shape and location of the pars opercularis across brains and between cerebral hemispheres. There was no significant difference or correlation between left and right hemisphere grey matter volumes. There was also no significant difference between sex and side of asymmetry of the pars opercularis. A probability map of the pars opercularis was constructed by averaging its location and extent in each individual normalized brain into Talairach space to aid in localization of activity changes in functional neuroimaging studies. [ABSTRACT FROM AUTHOR]

Introduction Aim Methods Results Conclusions Implications for nursing and health policy The increasing complexity of the healthcare sector requires an evolution in nursing education to effectively manage care in complex and interdisciplinary contexts.This review aims to analyze the role of advanced practice nurse (APN) in the surgical context within hospital settings, detailing their functions and responsibilities. It also provides an overview of the main degrees and postgraduate training programs for specialization in perioperative management in major Western countries.This scoping review followed the Arksey–O'Malley framework and Joanna Briggs Institute methodology. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) was used to ensure rigorous and transparent reporting.Among the 3663 records analyzed, 20 were included in this review. The role of the APN spans across the preoperative, intraoperative, and postoperative phases, encompassing follow‐up care as leaders, mentors, and contributors to research. APNs play a pivotal role by offering direct and indirect patient care at each stage of the surgical journey. Acting as liaisons between the healthcare team and patients, APNs enhance healthcare delivery through personalized, coordinated care, while also fostering ongoing education and research in the field.APNs enhance surgical care by providing in‐depth clinical assessments, education, and support throughout the treatment process. However, the lack of standardized regulatory frameworks in some countries limits the autonomy of APNs within the healthcare system, compromising their ability to address unmet health needs and engage in international collaboration.The findings underscore the need for standardized educational pathways, roles, responsibilities, and autonomy for APNs, facilitating better international collaboration and contributing to scientific research. [ABSTRACT FROM AUTHOR]