Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Resting-state fMRI functional connectome of C9orf72 mutation status.

OBJECTIVE: The resting-state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status. METHODS: Here we studied the network-to-network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72-), and 19 ALS-mimic patients (ALSm) well-matched for demographic and clinical variables. RESULTS: When compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole-connectome showed greater node degree (P < 0.001), while sensorimotor cortices resulted isolated in C9orf72+. INTERPRETATION: Our results suggest a crucial involvement of extra-motor functions in ALS spectrum disease. In particular, alterations of the visual cortex may have a pathogenic role in C9orf72-related ALS. The prominent feature of these patients would be increased visual system connectivity with the networks responsible of the functional balance between internal and external attention.

C9orf72 ALS mutation carriers show extensive cortical and subcortical damage compared to matched wild-type ALS patients.

OBJECTIVE: C9orf72 mutation carriers with different neurological phenotypes show cortical and subcortical atrophy in multiple different brain regions, even in pre-symptomatic phases. Despite there is a substantial amount of knowledge, small sample sizes, clinical heterogeneity, as well as different choices of image analysis may hide anatomical abnormalities that are unique to amyotrophic lateral sclerosis (ALS) patients with this genotype or that are indicative of the C9orf72-specific trait overlain in fronto-temporal dementia patients. METHODS: Brain structural and resting state functional magnetic imaging was obtained in 24 C9orf72 positive (ALSC9+) ALS patients paired for burden disease with 24 C9orf72 negative (ALSC9-) ALS patients. A comprehensive structural evaluation of cortical thickness and subcortical volumes between ALSC9+ and ALSC9- patients was performed while a region of interest (ROI)-ROI analysis of functional connectivity was implemented to assess functional alterations among abnormal cortical and subcortical regions. Results were corrected for multiple comparisons. RESULTS: Compared to ALSC9- patients, ALSC9+ patients exhibited extensive disease-specific patterns of thalamo-cortico-striatal atrophy, supported by functional alterations of the identified abnormal regions. Cortical thinning was most pronounced in posterior areas and extended to frontal regions. Bilateral atrophy of the mediodorsal and pulvinar nuclei was observed, emphasizing a focal rather than global thalamus atrophy. Volume loss in a large portion of bilateral caudate and left putamen was reported. The marked reduction of functional connectivity observed between the left posterior thalamus and almost all the atrophic cortical regions support the central role of the thalamus in the pathogenic mechanism of C9orf72-mediated disease. CONCLUSIONS: These findings constitute a coherent and robust picture of ALS patients with C9orf72-mediated disease, unveiling a specific structural and functional characterization of thalamo-cortico-striatal circuit alteration. Our study introduces new evidence in the characterization of the pathogenic mechanisms of C9orf72 mutation.

Alteration of the Functional Connectivity of the Cortical Areas Characterized by the Presence of Von Economo Neurons in Schizophrenia, a Pilot Study.

Von Economo neurons (VENs) are rod, stick, or corkscrew cells mostly located in layer V of the frontoinsular and anterior cingulate cortices. VENs are projection neurons related to human-like social cognitive abilities. Post-mortem histological studies found VEN alterations in several neuropsychiatric disorders, including schizophrenia (SZ). This pilot study aimed to evaluate the role of VEN-containing areas in shaping patterns of resting-state brain activation in patients with SZ (n = 20) compared to healthy controls (HCs; n = 20). We performed a functional connectivity analysis seeded in the cortical areas with the highest density of VENs followed by fuzzy clustering. The alterations found in the SZ group were correlated with psychopathological, cognitive, and functioning variables. We found a frontotemporal network that was shared by four clusters overlapping with the salience, superior-frontal, orbitofrontal, and central executive networks. Differences between the HC and SZ groups emerged only in the salience network. The functional connectivity of the right anterior insula and ventral tegmental area within this network were negatively correlated with experiential negative symptoms and positively correlated with functioning. This study provides some evidence to show that in vivo, VEN-enriched cortical areas are associated with an altered resting-state brain activity in people with SZ.

Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-ß inhibition.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor characterized by an intensive desmoplastic reaction due to the exaggerated presence of the extracellular (ECM) matrix components. Liver fibroblasts close to the tumor, activated by transforming growth factor (TGF)-ß1 and expressing high levels of α-smooth muscle actin (α-SMA), become cancer-associated fibroblasts (CAFs). CAFs are deputed to produce and secrete ECM components and crosstalk with cancer cells favoring tumor progression and resistance to therapy. Overexpression of Notch signaling is implicated in CCA development and growth. The study aimed to determine the effectiveness of the Notch inhibitor, Crenigacestat, on the surrounding microenvironment of iCCA. METHODS: We investigated Crenigacestat's effectiveness in a PDX model of iCCA and human primary culture of CAFs isolated from patients with iCCA. RESULTS: In silico analysis of transcriptomic profiling from PDX iCCA tissues treated with Crenigacestat highlighted "liver fibrosis" as one of the most modulated pathways. In the iCCA PDX model, Crenigacestat treatment significantly (p < 0.001) reduced peritumoral liver fibrosis. Similar results were obtained in a hydrodynamic model of iCCA. Bioinformatic prediction of the upstream regulators related to liver fibrosis in the iCCA PDX treated with Crenigacestat revealed the involvement of the TGF-ß1 pathway as a master regulator gene showing a robust connection between TGF-ß1 and Notch pathways. Consistently, drug treatment significantly (p < 0.05) reduced TGF-ß1 mRNA and protein levels in tumoral tissue. In PDX tissues, Crenigacestat remarkably inhibited TGF-ß signaling and extracellular matrix protein gene expression and reduced α-SMA expression. Furthermore, Crenigacestat synergistically increased Gemcitabine effectiveness in the iCCA PDX model. In 31 iCCA patients, TGF-ß1 and α-SMA were upregulated in the tumoral compared with peritumoral tissues. In freshly isolated CAFs from patients with iCCA, Crenigacestat significantly (p < 0.001) inhibited Notch signaling, TGF-ß1 secretion, and Smad-2 activation. Consequently, Crenigacestat also inactivated CAFs reducing (p < 0.001) α-SMA expression. Finally, CAFs treated with Crenigacestat produced less (p < 005) ECM components such as fibronectin, collagen 1A1, and collagen 1A2. CONCLUSIONS: Notch signaling inhibition reduces the peritumoral desmoplastic reaction in iCCA, blocking the TGF-ß1 canonical pathway.

A 35-Year-Old Man With Fever, Cough, and Erythematous-Erosive Mucous Membrane Lesions Accompanied by a Generalized Cutaneous Rash.

CASE PRESENTATION: A 35-year-old man presented to the ED with a 7-day history of fever, asthenia, and cough. He had previously received a 3-day course of amoxicillin and clavulanic acid (1 g tid po) and then ceftriaxone (1 g IM once per day) prescribed by his general practitioner with no substantial benefit. He was an active smoker (11.2 pack/y), without known allergy-related syndromes and any important reports in his medical history.

Magnetic Resonance Imaging for Cerebral Micro-embolizations During Minimally Invasive Mitral Valve Surgery.

The role of aortic clamping techniques on the occurrence of neurological complications after right mini-thoracotomy mitral valve surgery is still debated. Brain injuries can occur also as silent cerebral micro-embolizations (SCM), which have been linked to significant deficits in physical and cognitive functions. Aims of this study are to evaluate the overall rate of SCM and to compare endoaortic clamp (EAC) with trans-thoracic clamp (TTC). Patients enrolled underwent a pre-operative, a post-operative, and a follow-up MRI. Forty-three patients were enrolled; EAC was adopted in 21 patients, TTC in 22 patients. Post-operative SCM were reported in 12 cases (27.9%). No differences between the 2 groups were highlighted (23.8% SCM in the EAC group versus 31.8% in the TTC). MRI analysis showed post-operative SCM in nearly 30% of selected patients after right mini-thoracotomy mitral valve surgery. Subgroup analysis on different types of aortic clamping showed comparable results. CLINICAL RELEVANCE: The rate of SCM reported in the present study on patients undergoing minimally invasive MVS and RAP is consistent with data in the literature on patients undergoing cardiac surgery through median sternotomy and antegrade arterial perfusion. Moreover, no differences were reported between EAC and TTC: both the aortic clamping techniques are safe, and the choice of the surgical setting to adopt can be really done according to the patient's characteristics.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

How Interpersonal Psychotherapy Changes the Brain: A Study of fMRI in Borderline Personality Disorder.

Background: Recent guidelines and systematic reviews suggest that disorder-specific psychotherapeutic interventions are the first choice in the treatment of borderline personality disorder (BPD). The aim of this study is to examine brain activity changes in BPD patients (DSM-5) who received a revised BPD-adapted interpersonal psychotherapy (IPT-BPD-R) compared with patients on the waiting list.Methods: Forty-three patients with a BPD diagnosis (DSM-5) were randomly assigned to IPT-BPD-R (n = 22 patients) or the waiting list with clinical management (n = 21 patients) for 10 months. Both groups were tested before and after treatment with the Social and Occupational Functioning Assessment Scale (SOFAS), the Clinical Global Impressions-Severity of Illness scale (CGI-S), the Borderline Personality Disorder Severity Index (BPDSI), the Barratt Impulsiveness Scale-version 11 (BIS-11), and the Autobiographical Interview. Both groups underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) testing. The fMRI task consisted of the presentation of resolved and unresolved life events compared to a neutral condition. All structural and functional images were analyzed using Statistical Parametric Mapping 12 software, which interfaces with MATLAB. Clinical data were analyzed using analysis of variance for repeated measures. Patients were recruited between September 2017 and April 2019.Results: In clinical results, for the 4 rating scales, a significant between-subject effect was found in favor of the IPT-BPD-R-treated group (CGI-S: P = .011; BPDSI: P = .009; BIS-11: P = .033; SOFAS: P = .022). In fMRI results, posttreatment versus pretreatment for the contrast unresolved life event versus neutral condition showed significantly decreased right temporoparietal junction (rTPJ: x = 45, y = -51, z = 36) (P = .043) and right anterior cingulate cortex (rACC: x = -4, y = 37, z = 8) activity (P = .021).Conclusions: IPT-BPD-R appears to be effective in treating BPD symptoms, and these clinical effects are reflected in the functional changes observed with fMRI. Brain areas that showed modulation of their activity are the rTPJ and rACC, which are involved in mentalization processes that are fundamental to BPD pathology.Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) code: ACTRN12619000078156.

[Emerging ethical issues in clinical practice: a regional survey]. / Questioni etiche emergenti nella pratica clinica: risultati di un'indagine regionale.

. Emerging ethical issues in clinical practice: a regional survey. INTRODUCTION: In 2016, the Friuli Venezia Giulia Region established the Clinical Ethics Committees in every health agency of the Region. To initiate a proactive way of "doing ethics" giving voice to those who face clinical-ethical problems, a survey was carried out in six health agencies. AIM: To identify the most relevant ethical issues. METHODS: Survey through self-administered questionnaires, which explore: a) the ethical dimension of work in health care; b) situations of potential moral conflict; c) death and dying; (d) how ethical issues are handled and the role of ethic committees. RESULTS: 2.774 questionnaires were collected. Almost all respondents (97%) consider ethics an integral dimension of the health profession; 35% report a lack of education on bioethic issues. Behaviors that generated moral suffering (lack of respect of patients as persons 43%; aggressive medical treatment 29%). End-of-life ethical issues were the most controversial wellas the discharge of not self-sufficient patients without a social network. Restraints use was a source of conflict; receive education on; 60% of health professionals did receive education on death and dying death and dying; 51% felt inadequate in dealing with these issues. Only 8% referred to use ethical advice. CONCLUSIONS: Ethical Committees could play a role in fostering debate, proposing methods for detecting, describing and analysing ethical dilemmas, to supporting professionals in difficult clinical choices.

An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

Reduced Self-Awareness Following a Combined Polar and Paramedian Bilateral Thalamic Infarction. A Possible Relationship With SARS-CoV-2 Risk of Contagion?

Reduced self-awareness is a well-known phenomenon investigated in patients with vascular disease; however, its impact on neuropsychological functions remains to be clarified. Importantly, selective vascular lesions provide an opportunity to investigate the key neuropsychological features of reduced self-awareness in neurocognitive disorders. Because of its rarity, we present an unusual case of a woman affected by a combined polar and paramedian bilateral thalamic infarction. The patient underwent an extensive neuropsychological evaluation to assess cognitive, behavioral, and functional domains, with a focus on executive functions. She was assessed clinically in the acute phase and after 6 months from the stroke, both clinically and by magnetic resonance imaging. The patient developed a cognitive impairment, characterised by prevalent executive dysfunction associated with reduced self-awareness and mood changes, in terms of apathy and depression. Such condition persisted after 6 months. In May 2020, the patient underwent the serology test in chemiluminescence to detect IgG antibodies against SARS-CoV-2. The result of the quantitative test highlighted a high probability of previous contact with the virus. We suggest that reduced self-awareness related to executive dysfunction and behavioral changes may be due to combined polar and paramedian bilateral thalamic lesion. Metacognitive-executive dysfunction affecting the instrumental abilities of everyday life might make people less able to take appropriate precautions, facilitating the risk of SARS-CoV-2 contagion.

What Happens When I Watch a Ballet and I Am Dyskinetic? A fMRI Case Report in Parkinson Disease.

BACKGROUND: The identical sets of neurons - the mirror neuron system (MNS) - can be activated by simply observing specific, specific movements, decoded behaviors and even facial expressions performed by other people. The same neurons activated during observation are those recruited during the same movements and actions. Hence the mirror system plays a central role in observing and executing movements. Little is known about MNS in a neurodegenerative motor disorder, such as Parkinson's Disease (PD) is. METHODS: We explored the neural correlates potentially involved in empathy and embodiment in PD through complex action observation of complex behaviors like the choreutical arts. An integrated multidisciplinary assessment (neurological, neuropsychiatric, and neuropsychological) was used for the selection of the PD candidate for the neuroimaging experimental acquisition. For the first time in literature the famous Calvo-Merino's paradigm was administered to a PD subject. KEY POINTS: Functional magnetic resonance imaging (fMRI) exploratory analysis shows the recruitment of the left thalamus, the right dorsolateral prefrontal cortex, and the bilateral superior precentral gyrus (one of the main hubs of the MNS). If the observed choreic movement becomes part of the observer's motor repertoire experience, mirror neurons might activate stimulating affective empathy and making the understanding of movement an own proper body experience (cognitive embodiment). MAIN LESSONS: Our study sheds light on a possible use of complex action observation to improve or slow the deterioration of motor abilities and levodopa-induced dyskinesias in PD patients. Indeed, the modulation of the neural area involved in complex action observation could be considered a promising target for neuro-rehabilitative intervention mediated by the elicitation of the MNS.

Switch from intravenous or intramuscular to subcutaneous hepatitis B immunoglobulin: effect on quality of life after liver transplantation.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) therapy is available in intravenous (IV) or intra-muscular (IM) formulations. Recently, a subcutaneous (SC) formulation was introduced. This study evaluated changes in quality of life when liver transplant (LT) recipients were switched from IV or IM HBIG to the SC formulation. METHODS: This multicentre, observational study involved adults who had undergone LT at least 1 year prior to study entry. Quality of life was evaluated using the ITaLi-Q questionnaire, assessing the impact of HBIG therapy on daily activities and patient satisfaction, and the SF-36 Health Survey. Patients completed the questionnaires prior to switching from IV or IM HBIG to SC HBIG and 6 months later. RESULTS: Eighty-six patients were enrolled; before the switch, 68.6% were receiving IM HBIG and 31.4% IV HBIG. After 6 months, significant improvements in 7 of the 8 ITaLi-Q domains were found, particularly side effects, need for support to adhere to the therapy and satisfaction with the HBIG therapy. Significant improvements in several SF-36 domains were documented, including physical functioning, physical and emotional role limitations, pain, social functioning, physical and mental summary scores. CONCLUSIONS: The SC route of administration reduces side effects and their interference with daily life, ameliorates negative feelings, and increases patient autonomy.

Pleural effusion as first extra-medullary clinical presentation of an occult multiple myeloma: The role of medical thoracoscopy.

Multiple myeloma is a malignant neoplasm of plasma cells that usually invades the bone marrow replacing normal bone marrow and producing large amounts of light chains of immunoglobulins (Ig) [1]. Clinical manifestations are related to the accumulation of these proteins in vital organs such as kidney and heart. Pleural effusion may be a sign of chest involvement that occurs in approximately 6% of patients with Known multiple myeloma [2,3]. We present the case of an 80-year- old man with pleural effusion as first extra-medullary clinical presentation of an occult multiple myeloma.

Social support modulates the neural correlates underlying social exclusion.

Ostracism threatens the human need for social interactions, with negative consequences on cognition, affect and behavior. Understanding the mechanisms that can alleviate these consequences has therefore become an important research agenda. In this study, we used behavioral and fMRI measures to advance our understanding how social support can buffer the negative effects of social exclusion. We focused on two different types of support from a friend: emotional support, conveyed by gentle touch and appraisal support, implemented as informative text messages. Seventy-one female participants underwent fMRI scanning while playing a virtual ball-tossing game in the course of which they were excluded. Two consecutive runs of the game were separated according to the participant's experimental condition (appraisal support, emotional support and no support). Results showed that the experience of social exclusion is modulated by the type of support received. Specifically, emotional support decreased negative emotions and anterior insula activity, while appraisal support increased negative emotions, with concomitant increase of subgenual anterior cingulate cortex and decrease of temporal-parietal junction activity. These divergent effects of social support point to the necessity to characterize whether and under which conditions it represents an effective and positive resource to alleviate the negative consequences of social exclusion.

Autobiographical memories, identity disturbance and brain functioning in patients with borderline personality disorder: An fMRI study.

Identity disturbance is a core feature of borderline personality disorder (BPD). Autobiographical memory is a process of reflective thinking through which we form links between elements of life and self. It can be considered as an indirect index of identity integration. The present study was aimed to investigate the differences in brain activity patterns between BPD patients with identity diffusion and healthy controls using fMRI. We enrolled 24 BPD patients and 24 healthy controls. Identity integration in patients and controls was assessed with the Identity Disturbance Questionnaire (IDQ) score and was significantly different (p = 0.001). We analysed hemodynamic response in the regions of interest during presentation of resolved and unresolved life events. With reference to the condition "resolved", increased cerebral activity in right anterior cingulate cortex (ACC), right medial prefrontal cortex (MPFC), right dorsolateral prefrontal cortex (DLPFC), and bilateral insula was registered in BPD patients compared with controls. In the condition "unresolved", increased brain activity was observed in patients in bilateral ACC, bilateral DLPFC, and right temporo-parietal junction. Hyperactivity in ACC and DLPFC in BPD patients with both conditions (resolved and unresolved contexts) may be due to an inefficient attempt to reconstruct a coherent narrative of life events (resolved or not).

Selective Emotional Dysregulation in Splenium Agenesis. A Case Report of a Patient With Normal Cognitive Profile.

Objective: Patients with lesions of the corpus callosum are rare and may present different symptoms of the disconnection syndrome. However, to-date studies on callosotomized patients have not been conclusive, likely because of the non-uniform nature of clinical features, the extent of resection, and methods used to investigate specific and related deficits. Agenesis of the corpus callosum (AgCC) may be asymptomatic and discovered incidentally or associated with very slight deficits diagnosed during neurological examinations. In this study, we reported a case of an apparently completely asymptomatic 23-year-old woman with appreciable agenesis of the splenium of the corpus callosum. Methods: She underwent a neurological evaluation, a comprehensive battery of neuropsychological tests to identify any subclinical dysfunction that may affect the functionality of the subject in the daily life. Specifically, the possible presence of emotion dysregulation was examined by using a self-report questionnaire. Results: She showed normal neuropsychological and emotional functioning, performing efficiently on tests measuring acquired brain impairment. Discussion: The present case is discussed in terms of neuroplasticity - with a focus on putative compensatory mechanisms - emphasizing the variegated clinical feature patterns of brain defects present from birth.

Diagnosis of idiopathic pulmonary fibrosis by virtual means using "IPFdatabase"- a new software.

BACKGROUND: The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) guidelines has some shortcomings. The aim of the present study was to develop a novel software, "IPFdatabase", that could readily apply the diagnostic criteria per IPF guidelines and make a 'virtual' diagnosis of IPF. METHODS: Software was developed as a step-by-step compilation of necessary information according to guidelines to enable a diagnosis of IPF. Software accuracy was validated primarily by comparing software diagnoses to those previously made at a Center for Interstitial Lung Diseases. RESULTS: Clinical validation on 98 patients (68 male, age 61.0 ±â€¯8.5 years), revealed high software accuracy for IPF diagnosis when compared to historical diagnoses (sensitivity 95.5%, specificity 96.2%; positive predictive value 95.5%, negative predictive value 96.2%). A general radiologist and a general pathologist reviewed relevant data with and without the new software: interobserver agreement increased when they used the IPFdatabase (kappa 0.18 to 0.64 for radiology, 0.13 to 0.59 for pathology). CONCLUSION: IPFdatabase is a useful diagnostic tool for typical cases of IPF, and potentially restricts the need for MDDs to atypical and complex cases. We propose this web-designed software for instant accurate diagnosis of IPF by virtual means and for educational purposes; the software is readily accessed with mobile apps, allows incorporation of updated version of guidelines, can be utilized for gathering data useful for future studies and give physicians rapid feedback in daily practice.