Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05 ± 5.7 years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FAt ), radial diffusivity (RDt ), and axial diffusivity (ADt ). Lower ratings of interindividual pain intensity correlated with higher FAt and lower RDt of the MFB. As changes in FAt and RDt may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.

Sustained onabotulinumtoxinA therapeutic benefits in patients with chronic migraine over 3 years of treatment.

BACKGROUND: Evidence on whether the therapeutic effect and good safety profile of onabotulinumtoxinA (Botox®) in chronic migraine (CM) patients is maintained over long term treatment is still limited. We herein aimed at assessing whether there is a sustained benefit and good safety with repeated onabotulinumtoxinA sessions in CM over more than three years of treatment. METHODS: We prospectively enrolled 65 CM patients, who were classified as responders after three sessions of onabotulinumtoxinA and were eligible to further continue treatment. Data documenting longitudinal changes from the trimester after the third onabotulinumtoxinA administration (T1) to the trimester after completing two years of treatment (T2) and eventually to the trimester after completing three years of treatment (T3) in (i) mean number of monthly headache days (ii) migraine severity as expressed by the mean number of days with peak headache intensity of > 4/10, and (iii) mean number of days with use of any acute headache medication, were prospectively collected from patients' headache diaries. RESULTS: A total of 56 (86.1%) of 65 patients achieved to attain onabotulinumtoxinA over three years. At T3, a significant reduction in mean monthly headache days was evident, compared to T1 (3.4 ± 1.7 vs 7.2 ± 3.8; P < 0.001) with diminished mean number of monthly days with peak headache intensity of more than 4/10 and a significant change in days using acute headache medications per month between T1 and T3 (2.8 ± 1.3 vs 4.7 ± 3.2; P < 0.001). Significant changes were also noticed in all efficacy variables from T2 to T3. Therapy was safe and well tolerated with low rates of adverse events or drop-outs. CONCLUSION: The long -term treatment with onabotulinumtoxinA proved effective, safe and well tolerated over three years. Our findings support the strategy to consistently deliver sessions of use of onabotulinumtoxinΑ over long time in CM patients (Trial registration NTC03606356, registered retrospectively, 28 July 2018).

The social brain network in 22q11.2 deletion syndrome: a diffusion tensor imaging study.

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls. RESULTS: Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis. CONCLUSIONS: Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS.

Dynamic susceptibility contrast perfusion imaging in biopsy-proved adult medulloblastoma.

PURPOSE: Medulloblastoma (MB) is a high-grade rare brain tumor in adults, with heterogeneous imaging features and variable enhancing patterns. Diffusion and spectroscopy multimodal imaging have already been described in adult MB, yet perfusion has not been explored. This study aimed to evaluate vascularity in adult classic and desmoplastic MB, using perfusion-weighted dynamic susceptibility contrast (DSC) MRI and histopathology. METHODS: Six histologically proved MB patients were classified as classic (n=3) and desmoplastic (n=3). DSC perfusion MRI was performed in three centers and retrospectively evaluated. Postprocessing included automatic arterial input function, motion and contrast leakage correction. Region of interest (ROI) delineation was performed on three perfusion slices to obtain a total of three cerebral blood volume ratios (rCBV) that were averaged to serve as the main rCBV. Permeability was evaluated on K2 maps. RESULTS: Low rCBVs were observed in all cases (mean rCBV=1.19±0.39). rCBV values were lower than 2 for classic MB and lower than 1 for desmoplastic MB. All cases showed an increase of permeability on K2 maps. CONCLUSIONS: Our preliminary results suggest that MB exhibits rCBV values close to 1 and increased permeability on DSC perfusion imaging, especially in desmoplastic cases, which could be explained by fibrous matrix. This type of perfusion pattern contrasts with those given by other enhancing subtentorial tumors such as metastasis, high-grade gliomas or hemangioblastomas.

Left ventricular myocardial work improves in response to treatment and is associated with survival among patients with light chain cardiac amyloidosis.

AIMS: Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance. METHODS AND RESULTS: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year. Patients were stratified according to haematologic response as complete or not complete responders. A significant reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2771-1486 pg/mL; P < 0.001) and posterior wall thickness (13-12 mm; P = 0.002) and an increase in global work index (GWI) (1115-1356 mmHg%; P = 0.018) was observed at 1 year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2-12.0 mm; P = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; P for interaction = 0.045), increased global constructive work (1245-1436 mmHg%; P = 0.008), and GWI (926-1250 mmHg%, P = 0.002) compared with non-CR. Furthermore, deltaGLS (ρspearman = 0.35; P < 0.001) and deltaGWI (ρspearman = -0.32; P = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank P = 0.048 and log-rank P = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS [hazard ratio (HR) = 1.404, P = 0.046 per 1% increase] and deltaGWI (HR = 0.996, P = 0.042 per 1mmHg% increase) were independent predictors of survival. CONCLUSION: Complete haematologic response to treatment is associated with improved left ventricular myocardial work indices, and their change is associated with improved survival in AL-CA.

Brain age of rhesus macaques over the lifespan.

Through the application of machine learning algorithms to neuroimaging data the brain age methodology was shown to provide a useful individual-level biological age prediction and identify key brain regions responsible for the prediction. In this study, we present the methodology of constructing a rhesus macaque brain age model using a machine learning algorithm and discuss the key predictive brain regions in comparison to the human brain, to shed light on cross-species primate similarities and differences. Structural information of the brain (e.g., parcellated volumes) from brain magnetic resonance imaging of 43 rhesus macaques were used to develop brain atlas-based features to build a brain age model that predicts biological age. The best-performing model used 22 selected features and achieved an R2 of 0.72. We also identified interpretable predictive brain features including Right Fronto-orbital Cortex, Right Frontal Pole, Right Inferior Lateral Parietal Cortex, and Bilateral Posterior Central Operculum. Our findings provide converging evidence of the parallel and comparable brain regions responsible for both non-human primates and human biological age prediction.

Evaluation of strategies towards harmonization of FDG PET/CT studies in multicentre trials: comparison of scanner validation phantoms and data analysis procedures.

PURPOSE: PET quantification based on standardized uptake values (SUV) is hampered by several factors, in particular by variability in PET acquisition settings and data analysis methods. Quantitative PET/CT studies acquired during a multicentre trial require harmonization of imaging procedures to maximize study power. The aims of this study were to determine which phantoms are most suitable for detecting differences in image quality and quantification, and which methods for defining volumes of interest (VOI) are least sensitive to these differences. METHODS: The most common accreditation phantoms used in oncology FDG PET/CT trials were scanned on the same scanner. These phantoms were those used by the Society of Nuclear Medicine Clinical Trials Network (SNM-CTN), the European Association of Nuclear Medicine/National Electrical Manufacturers Association (EANM/NEMA) and the American College of Radiology (ACR). In addition, tumour SUVs were derived from ten oncology whole-body examinations performed on the same PET/CT system. Both phantom and clinical data were reconstructed using different numbers of iterations, subsets and time-of-flight kernel widths. Subsequently, different VOI methods (VOI(A50%), VOI(max), VOI(3Dpeak), VOI(2Dpeak)) were applied to assess the impact of changes in image reconstruction settings on SUV and recovery coefficients (RC). RESULTS: All phantoms demonstrated sensitivity for detecting changes in SUV and RC measures in response to changes in image reconstruction settings and VOI analysis methods. The SNM-CTN and EANM/NEMA phantoms showed almost equal sensitivity in detecting RC differences with changes in image characteristics. Phantom and clinical data demonstrated that the VOI analysis methods VOI(A50%) and VOI(max) gave SUV and RC values with large variability in relation to image characteristics, whereas VOI(3Dpeak) and VOI(2Dpeak) were less sensitive to these differences. CONCLUSION: All three phantoms may be used to harmonize parameters for data acquisition, processing and analysis. However, the SNM-CTN and EANM/NEMA phantoms are the most sensitive to parameter changes and are suitable for harmonizing SUV quantification based on 3D VOIs, such as VOI(A50%) and VOI(3Dpeak), and VOImax. Variability in SUV quantification after harmonization could be further minimized using VOI(3Dpeak) analysis, which was least sensitive to residual variability in image quality and quantification.

Metastatic Merkel cell carcinoma (MCC) of pancreas and breast: a unique case.

Merkel cell carcinoma (MCC) is a rare potentially fatal skin tumor affecting older and immunosuppressed individuals. It is highly malignant with high rates of metastasis and poor survival.We present a case of a 67-year-old woman with a palpable mass in the upper abdomen. An abdominal CT revealed a mass in the tail of the pancreas. Two weeks before, lumpectomy of a 3.5 cm tumor of the left breast had been performed. Histology showed a primary neuroendocrine carcinoma of the mammary gland. The patient's medical history was significant for a 0.7 × 0.9 cm MCC removed from her left forearm 2.5 years ago. There was no evidence of vascular involvement or peritoneal disease and by all criteria was resectable. A somatostatin receptor scintigraphy showed an enhanced uptake in the pancreatic tail region. The tumor was immunohistochemically strong staining for synaptophysin and CD56. The diagnosis of a metastatic-MCC in the tail of the pancreas was made. Further histological investigation of the prior removed neuroendocrine breast tumor and the MCC of the left forearm confirmed neuroendocrine origin and identical histology to the previously resected MCC of the left forearm. In this article, we aim to highlight that MCC has the potential to spread even in unusual organs, such as pancreas or breast, and therefore a diligent follow-up should be applied in patients with MCC.

Radiologic findings of osteonecrosis, osteoradionecrosis, osteomyelitis and jaw metastatic disease with cone beam CT.

PURPOSE: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions. METHODS: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed. RESULTS: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001). CONCLUSIONS: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis.

Cardiovascular Toxicity of Proteasome Inhibitors: Underlying Mechanisms and Management Strategies: JACC: CardioOncology State-of-the-Art Review.

Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström's macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.

Cognitive and personality predictors of school performance from preschool to secondary school: An overarching model.

In this article, existing research investigating how school performance relates to cognitive, self-awareness, language, and personality processes is reviewed. We outline the architecture of the mind, involving a general factor, g, that underlies distinct mental processes (i.e., executive, reasoning, language, cognizance, and personality processes). From preschool to adolescence, g shifts from executive to reasoning and cognizance processes; personality also changes, consolidating in adolescence. There are three major trends in the existing literature: (a) All processes are highly predictive of school achievement if measured alone, each accounting for ∼20% of its variance; (b) when measured together, cognitive processes (executive functions and representational awareness in preschool and fluid intelligence after late primary school) dominate as predictors (over ∼50%), drastically absorbing self-concepts and personality dispositions that drop to ∼3%-5%; and (c) predictive power changes according to the processes forming g at successive levels: attention control and representational awareness in preschool (∼85%); fluid intelligence, language, and working memory in primary school (∼53%); fluid intelligence, language, self-evaluation, and school-specific self-concepts in secondary school (∼70%). Stability and plasticity of personality emerge as predictors in secondary school. A theory of educational priorities is proposed, arguing that (a) executive and awareness processes; (b) information management; and (c) reasoning, self-evaluation, and flexibility in knowledge building must dominate in preschool, primary, and secondary school, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Individual Differences on Wellbeing Indices during the COVID-19 Quarantine in Greece: A National Study.

The impact of COVID-19 and the associated lockdown measures on people's physical and mental wellbeing, as well as their daily lives and functioning, has been extensively studied. This study takes the approach of investigating the consequences of COVID-19 on a national scale, considering sociodemographic factors. The main objective is to make a contribution to ongoing research by specifically examining how age, gender, and marital status influence the overall impact of COVID-19 and wellbeing indicators during the second lockdown period that was implemented in response to the COVID-19 pandemic in the Greek population. The study involved a sample of 16,906 individuals of all age groups in Greece who completed an online questionnaire encompassing measurements related to personal wellbeing, the presence and search for meaning in life, positive relationships, as well as symptoms of depression, anxiety, and stress. Additionally, to gauge the levels of the perceived COVID-19-related impact, a valid and reliable scale was developed. The results reveal that a higher perception of COVID-19 consequences is positively associated with psychological symptoms and the search for meaning in life, while being negatively correlated with personal wellbeing and the sense of meaning in life. In terms of individual differences, the findings indicate that unmarried individuals, young adults, and females tend to report higher levels of psychological symptoms, a greater search for meaning in life, and a heightened perception of COVID-19-related impact. These findings are analyzed in depth, and suggestions for potential directions for future research are put forth.

Cardiac mechanics in response to proteasome inhibition: a prospective study.

AIM: Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans. METHODS AND RESULTS: We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < -18% or LA strain rate > 1.71 were associated with null hypertension events. CONCLUSION: Inhibition of the UPS induced global deterioration of cardiac function.

Changing priorities in the development of cognitive competence and school learning: A general theory.

This paper summarizes a theory of cognitive development and elaborates on its educational implications. The theory postulates that development occurs in cycles along multiple fronts. Cognitive competence in each cycle comprises a different profile of executive, inferential, and awareness processes, reflecting changes in developmental priorities in each cycle. Changes reflect varying needs in representing, understanding, and interacting with the world. Interaction control dominates episodic representation in infancy; attention control and perceptual awareness dominate in realistic representations in preschool; inferential control and awareness dominate rule-based representation in primary school; truth and validity control and precise self-evaluation dominate in principle-based thought in adolescence. We demonstrate that the best predictors of school learning in each cycle are the cycle's cognitive priorities. Also learning in different domains, e.g., language and mathematics, depends on an interaction between the general cognitive processes dominating in each cycle and the state of the representational systems associated with each domain. When a representational system is deficient, specific learning difficulties may emerge, e.g., dyslexia and dyscalculia. We also discuss the educational implications for evaluation and learning at school.

Patient-specific connectomic models correlate with, but do not reliably predict, outcomes in deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. To address these gaps, we performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. With this best-practices approach, no model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Thus, patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

A case of bilateral self-induced keratoconus in a patient with tourette syndrome associated with compulsive eye rubbing: case report.

BACKGROUND: Tourette syndrome is a neurologic disorder that is characterized by repetitive muscle contractions that produce stereotyped movements or sounds. Approximately 50% of individuals with TS also exhibit obsessive-compulsive behaviors including eye rubbing. We report a case of bilateral self-induced keratoconus in a patient with TS, associated with compulsive eye rubbing. CASE PRESENTATION: A 35-year-old man was first seen in our clinic as an outpatient due to rapid deterioration of vision in his right eye associated with pain and tearing, over a period of one month. Slit lamp biomicroscopy of the right eye showed a central stromal scar due to corneal hydrops. Clinical examination and corneal topography of the left eye were normal. Six months later the patient developed corneal hydrops of his left eye. During the following examinations his vision continued to deteriorate in both eyes, while a central stromal scar was forming in his left cornea. Four years after the initial examination the patient's visual acuity was no light perception in the right eye and counting fingers at 33 cm in the left eye. His right eye was phthisic. CONCLUSIONS: Our patient developed a rapidly progressing bilateral corneal ectasia and phthisis of his right eye during a time period of 4 years. This unusual pattern suggests that the patient's compulsive behavior compromised both of his corneas and led to bilateral keratoconus.

A Research Domain Criteria Approach to Gambling Disorder and Behavioral Addictions: Decision-Making, Response Inhibition, and the Role of Cannabidiol.

Gambling Disorder (GD) has been recently re-classified in the DSM-5 under the "substance-related and addictive disorders," in light of its genetic, endophenotypic, and phenotypic resemblances to substance dependence. Diminished control is a core defining concept of psychoactive substance dependence or addiction and has given rise to the concept of "behavioral" addictions, which are syndromes analogous to substance addiction, but with a behavioral focus other than ingestion of a psychoactive substance. The main symptom clusters are represented by loss of control, craving/withdrawal, and neglect of other areas of life, whereas in a Research Domain Criteria (RDoC) perspective, GD patients exhibit deficits in the domain of "Positive valence systems," particularly in the "Approach motivation" and "Reward learning" constructs, as well as in the "Cognitive systems," primarily in the "Cognitive control" construct. In the Addictions Neuroclinical Assessment (ANA), three relevant domains for addictions emerge: "Incentive salience," "Negative Emotionality," and "Executive Function." The endocannabinoid system (ECS) may largely modulate these circuits, presenting a promising pharmaceutical avenue for treating addictions. Up to now, research on cannabidiol has shown some efficacy in Attention Deficit/Hyperactivity Disorder (ADHD), whereas in behavioral addictions its role has not been fully elucidated, as well as its precise action on RDoC domains. Herein, we review available evidence on RDoC domains affected in GD and behavioral addictions and summarize insights on the use of cannabidiol in those disorders and its potential mechanisms of action on reward, decisional, and sensorimotor processes.

Clinical validation of time reduction strategy in continuous step-and-shoot mode during SPECT acquisition.

BACKGROUND: The SwiftScan solution (General Electric Healthcare) combines a new low-energy high-resolution sensitivity collimator and a tomographic step-and-shoot continuous (SSC) mode acquisition. The purpose of this study is to determine whether SSC mode can be used in clinical practice with shorter examination times, while preserving image quality and ensuring accurate semi-quantification. Twenty bone scan and 10 lung scan studies were randomly selected over a period of 2 months. Three sets of image datasets were produced: step-and-shoot (SS) acquisition, simulated 25% count reduction using the Poisson resampling method (SimSS), and SimSS continuous acquisition (SimSSC), where SimSS was summed with counts acquired during detector head rotation. Visual assessment (5-point Likert scale, 2 readers) and semi-quantitative evaluation (50 focal uptake from 10 bone studies), assessed by SUVmean, coefficient of variation (COV), and contrast-to-noise ratio (CNR), were performed using t test and Bland-Altman analysis. RESULTS: Intra-reader agreement was substantial for reader 1 (k = 0.71) and for reader 2 (k = 0.61). Inter-reader agreement was substantial for SS set (k = 0.93) and moderate for SimSSC (k = 0.52). Bland-Altman analysis showed a good interchangeability of SS and SimSSC SUV values. The mean CNR between SS and SimSSC was not significantly different: 42.9 ± 43.7 [23.7-62.1] vs. 43.1 ± 46 [22.9-63.3] (p = 0.46), respectively. COV values, assessing noise level, did not deviate significantly between SS and SimSSC: 0.20 ± 0.08 [0.18-0.23] vs. 0.21 ± 0.08, [0.18-0.23] (p = 0.15), respectively, whereas a significant difference was demonstrated between SS and SimSS: 0.20 ± 0.08 [0.18-0.23] vs. 0.23 ± 0.09 [0.20-0.25] (p < 0.0001), respectively. CONCLUSIONS: SSC mode acquisition decreases examination time by approximately 25% in bone and lung SPECT/CT studies compared to SS mode (~ 2 min per single-bed SPECT), without compromising image quality and signal quantification. This SPECT sensitivity improvement also offers the prospect of more comfortable exams, with less motion artifacts, especially in painful or dyspneic patients.

Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study.

Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) (n = 14) or Kd (n = 11). Cardiac ultrasound was performed before treatment initiation and C6D16 or at the time of treatment interruption. Patients were followed for a median of 10 months for CVAEs. The mean (± SD) age was 67.8 ± 7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline demographic characteristics (p > 0.1 for all). In the DaraKd group, we did not observe any significant change in markers of ventricular systolic function. However, these markers deteriorated in the Kd group; left ventricular (LV) ejection fraction, LV global longitudinal strain, tricuspid annular plane systolic excursion and RV free wall longitudinal strain significantly decreased from baseline to second visit (p < 0.05). A significant group interaction (p < 0.05) was observed for the abovementioned changes. CVAEs occurred more frequently in the Kd than the DaraKd group (45% vs. 28.6%). DaraKd was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd. The clinical significance and the underlying mechanisms merit further investigation.