68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine well-differentiated tumours.

PURPOSE: To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. METHODS: One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018-June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs' histopathological prognostic factors were evaluated using Spearman's coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters' predictive performance. RESULTS: Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). CONCLUSION: This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness.

Deep learning radiomic nomogram can predict the number of lymph node metastasis in locally advanced gastric cancer: an international multicenter study.

BACKGROUND: Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative determination method is not accurate enough. PATIENTS AND METHODS: We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis. RESULTS: The DLRN showed good discrimination of the number of LNM on all cohorts [overall C-indexes (95% confidence interval): 0.821 (0.785-0.858) in the primary cohort, 0.797 (0.771-0.823) in the external validation cohorts, and 0.822 (0.756-0.887) in the international validation cohort]. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271). CONCLUSION: A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Human V-ATPase gene can protect or predispose the host to pulmonary tuberculosis.

Patients (305 patients with pulmonary tuberculosis) and controls (290 household genetically unrelated contacts) were tested by polymerase chain reaction (PCR) for polymorphisms in the intron 15 and the 5' untranslated region of the gene coding for the a3 isoform of the human ATPase gene. Diagnosis of pulmonary tuberculosis was based on chest radiography and sputum smear examination and confirmed by PCR and bacteriological tests. Alleles (two at each site) segregated in the form of four haplotype pairs: 13, 14 (very rare), 23, and 24. The 13/24 (double heterozygous) patients were protected against tuberculosis (OR: 0.15; P: 10(-8); CI: 0.08-0.3). The 13/13 vs 13/24 and 23/23 vs 23/24 (double homozygous) patients were susceptible to the disease (OR. 5.8; P: 6 x 10(-7); CI: 2.8-11.9; OR: 4.5; P: 5 x 10(-7); CI: 2.5-8.4, respectively).

[Health promotion through physical activity: territorial models and experiences]. / Promuovere la salute attraverso l'attività motoria: modelli ed esperienze territoriali.

Scientific evidences support the preventive role of physical activity in relation to different multifactorial pathologies. Health's promotion through the spreading of lifestyles that encourage movement, does not represent just an action in contrast with "sedentary life" risk-factor, but also a priority for "quality" of life, with relevant economical and social benefits. WHO indicates physical activity as one of the priorities for an effective prevention. Besides, the EU supports the realization and the diffusion of some prevention-programs. Main pilot experiences developed in Italy and other countries are summarized. Attention is focused on the role of the competences and structures involved in an integrated approach based on availability of medical support, social services and local structures, considering recent developments in health prevention and promotion. In Italy and Europe, new opportunities to implement health promotion through physical activity are offered by the development of higher education in movement and sport sciences.

Increased expression of titin in mouse gastrocnemius muscle in response to an endurance-training program.

Titin, a sarcomeric giant protein, plays crucial roles in muscle assembly, elasticity and stability. Little is known about titin adaptation to endurance exercise. We studied the effects of endurance training on titin expression in mouse gastrocnemius muscles (MGM). Sixty-three ten-week-old male Swiss mice were divided into seven groups. Four groups were composed of untrained control animals (C0, C15, C30, C45) instead the other three included mice trained for 15 (T15), 30 (T30) and 45 (T45) days by treadmill. The training protocol was mainly aerobic, characterized by moderate-intensity, rhythmic and continuous exercises. Titin expression was determined by immunohistochemistry on MGM sections. Results revealed a significant reduction in body weight of the T45 mice and a significant increase in titin expression (% titin immunoreactivity median [range] = 41.11 [20-60] vs. 30.00 [10-50]). It is postulated that the up-regulation of titin expression is an adaptative mechanism to increase muscle elasticity and stability in response to the high number of stretch-shorten cycles during endurance training. Such a mechanism may be important for minimizing muscle energy consumption and improving performance during running.

Hypothesis III. Tourette syndrome is only one of several causes of a developmental basal ganglia syndrome.

Tourette syndrome (TS) is a hereditary condition characterized by the presence of chronic, multiple motor tics and is commonly associated with obessive-compulsive behavior, attentional and executive dysfunction, and aggressive behavior. A wide range of other genetic and environmental conditions that interfere with normal basal ganglia developmental processes can produce a clinical syndrome that we call the developmental basal ganglia syndrome (DBGS), and which closely resembles TS. Failure to distinguish TS from other causes of DBGS has probably hampered research efforts aimed at clarifying the neurobiological mechanisms, localizing the genetic defect, assessing therapy, and establishing accurate prevalence rates for TS.

Factors associated with incident human immunodeficiency virus-dementia.

BACKGROUND: Antecedents to human immunodeficiency virus-dementia (HIV-D) are poorly understood. OBJECTIVE: To identify risk factors for HIV-D. METHODS: Subjects who are positive for HIV who have CD4+ counts either below 200/microL or below 300/microL with evidence of cognitive impairment were enrolled in this study. Neurologic, cognitive, functional, and laboratory assessments were done semiannually for up to 30 months. Human immunodeficiency virus-dementia was diagnosed using American Academy of Neurology criteria for probable HIV-1-associated dementia complex. RESULTS: One hundred forty-six nondemented patients were enrolled, 45 of whom subsequently met criteria for incident HIV-D. In univariate analyses using the Cox proportional hazards regression model, the following variables were significantly associated with time to develop dementia: cognitive: abnormal scores on Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol tests; attention-memory, psychomotor, and executive function domain scores; and the diagnosis of minor cognitive/motor disorder; neurologic and medical: increased abnormalities on the neurologic examination, extrapyramidal signs, history of HIV-related medical symptoms; functional: higher reported role or physical function difficulties. Depression was also a strong risk factor, along with sex, hematocrit, hemoglobin, and beta2-microglobulin levels. In a multivariate model that used cognitive domain scores, covariates with significant hazard ratios included depression, executive dysfunction, and the presence of minor cognitive/motor disorder. CONCLUSION: Cognitive deficits, minor cognitive/motor disorder, and depression may be early manifestations of HIV-D.

Clinical trials in HIV-associated cognitive impairment: cognitive and functional outcomes.

Cognitive and functional outcomes are of primary interest in the design of efficacy trials in HIV-associated cognitive impairment. In a longitudinal cohort study, weak associations were found between measures of cognitive performance and commonly used measures of daily functioning (mostly self-report measures) in HIV-infected individuals. Modifications of current functional scales or new functional instruments are needed to assess the clinical relevance of cognitive changes in clinical trials of HIV-associated cognitive impairment.

The behavioral spectrum of tic disorders: a community-based study.

BACKGROUND: Tourette syndrome (TS) and related tic disorders are commonly associated with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). It has been argued, however, that any observed association between TS and these and other psychopathologies may be due to ascertainment bias in that individuals with multiple problems are more likely to be referred for medical evaluation. METHODS: In order to overcome the potential confounding by ascertainment bias, the authors conducted a community-based study of school children using direct interviews to determine the prevalence of tic disorders and any comorbid psychopathology. A standard psychiatric interview and standardized rating scales were utilized to diagnose childhood behavioral disorders. RESULTS: Of the 1,596 children interviewed, 339 were identified as having tics. The following psychopathologies were found more commonly (p < 0.05) in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. CONCLUSION: The behavioral spectrum of tic disorders includes OCD, other anxiety disorders, a mood disorder, and attention-deficit and disruptive behavior disorders.

Motion aftereffects associated with pursuit eye movements.

Contrary to an earlier report [Anstis and Gregory, Q. Jl exp. Psychol. 17, 173-174 (1965)], we find that the sustained retinal motion caused by tracking a moving target over a stationary grating does not result in a motion aftereffect (MAE) which is equivalent to that resulting from comparable retinal motion caused by actual motion of a grating. The MAE associated with tracking generally occurs in elements falling on areas not previously exposed to retinal motion. It is in the same direction as the previous retinal motion in the display and is apparently an induced MAE caused by a weak, below threshold MAE in the elements stimulating areas that were previously exposed to retinal motion. Based on an analysis of eye movement records, we do not believe that the weakness of the tracking MAE is primarily a function of the poor quality of the tracking eye movements. Other possible reasons for the weakness of the MAE are suggested.

Evaluation of techniques for assessing neurobehavioral development in children.

A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.

Association between prenatal exposure to methylmercury and developmental outcomes in Seychellois children: effect modification by social and environmental factors.

UNLABELLED: The Seychelles Child Development Study (SCDS) is testing the hypothesis that prenatal exposure to low doses of MeHg from maternal consumption of fish is associated with the child's developmental outcomes. No deleterious relationships between exposure to MeHg and cognitive functions have been identified in the primary analysis of the main cohort through 66 months of age. We performed secondary analyses to determine if effect modification (EM) from social and environmental factors was affecting associations between MeHg and outcomes. METHODS: MeHg exposure was determined by analysis of maternal hair growing during pregnancy. Children in our Main Study cohort were evaluated at 6.5 months (N = 740) for visual recognition memory and visual attention using the Fagan Infantest, at 19 months (N = 738) and 29 months (N = 736) with the Bayley Scales of Infant Development (BSID). Interactions between MeHg and Caregiver Intelligence, Family Income and Home Environment were examined by multiple regression analysis. RESULTS: The median prenatal MeHg exposure was 5.9 ppm (Range 0.5-26.7 ppm). No EM occurred for preferential looking or visual attention at 6.5 months, for the BSID Psychomotor Scale at either 19 or 29 months, or for activity level at 29 months as measured by the BSID Infant Behavior Record. Interactions between MeHg level and both caregiver intelligence and family income were statistically significant for the BSID Mental Scale at 19 months but not at 29 months. These showed enhancement of MDI scores with increasing maternal MeHg in higher caregiver IQ groups at several levels of family income. CONCLUSIONS: In Seychellois children, consistent major EM by social or environmental factors were not identified. The small EM by caregiver intelligence and social factors at 19 months is consistent with the enhanced performance we reported when this cohort was examined at 66 months.

Pursuit eye movement dysfunction in obsessive-compulsive disorder.

Disturbances in neural circuitry including the basal ganglia and prefrontal cortex have been hypothesized to be a cause of obsessive-compulsive disorder (OCD). Because eye movements are often impaired in neurologic diseases affecting these brain areas, oculomotor functioning was assessed in 17 unmedicated patients with OCD and in 25 normal controls. As compared with control subjects, patients with OCD demonstrated low-gain (slow) pursuit eye movements and an increased frequency of square wave jerk intrusions, but no increase in anticipatory saccades. In addition, several OCD patients showed an unusual pattern of intrusive, brief epochs of high-gain (fast) pursuit lasting on the order of 50 to 130 msec. These epochs of fast pursuit moved the eyes ahead of the target being tracked, and were terminated by corrective reversal saccades. Studies of eye movement abnormalities may provide an informative neurophysiologic approach for studying disturbances in basal ganglia and frontal cortical function that have been observed in functional neuroimaging and neuropsychological studies of OCD.

Neurodevelopmental and health outcomes in term infants treated with surfactant for severe respiratory failure.

OBJECTIVE: Analysis of health, neurodevelopmental, and school performance outcomes in a pilot study of term and near-term infants with respiratory failure due to pneumonia or meconium aspiration treated with surfactant. STUDY DESIGN: Retrospective review of medical records, neurodevelopmental and psychosocial evaluations, and parent and teacher surveys. RESULTS: Of the 14 patients enrolled, only one was rehospitalized, for pneumonia. Three were reported to have episodes of wheezing, two of whom required bronchodilators. One patient had unilateral hearing loss, one had a full-scale intelligence quotient that was below normal, and all but one patient for whom complete results were obtained were performing at or above grade level. CONCLUSION: Term and near-term newborns with moderately severe respiratory failure treated with surfactant can, in general, be expected to recover completely and have normal general health, neurodevelopmental outcome, and school performance.

Characteristics of children and adolescents with mental retardation and frequent outwardly directed aggressive behavior.

Two interrelated cross-sectional studies were conducted to expand earlier findings about correlates of outwardly directed aggressive behavior in children with mental retardation. In Study 1 we compared children with mental retardation, 27 with and 23 without aggression. Aggression was best predicted by concurrent self-injurious behavior (SIB). In Study 2 we examined the likelihood that aggression was predicted by concurrent SIB and other nondestructive maladaptive behaviors in an archival cohort of 701 children younger than 21 with IQs below 70. Self-injurious behavior significantly predicted outwardly directed aggression for all children regardless of age. Additional predictors besides SIB showed only minimal improvements in model R2 values. Results were discussed in light of recent research proposing a common basis for aggression and SIB.

Performance and fault-tolerance of neural networks for optimization.

The fault-tolerance characteristics of time-continuous, recurrent artificial neural networks (ANNs) that can be used to solve optimization problems are investigated. The performance of these networks is illustrated by using well-known model problems like the traveling salesman problem and the assignment problem. The ANNs are then subjected to up to 13 simultaneous stuck-at-1 or stuck-at-0 faults for network sizes of up to 900 neurons. The effect of these faults on the performance is demonstrated, and the cause for the observed fault-tolerance is discussed. An application is presented in which a network performs a critical task for a real-time distributed processing system by generating new task allocations during the reconfiguration of the system. The performance degradation of the ANN under the presence of faults is investigated by large-scale simulations and the potential benefits of delegating a critical task to a fault-tolerant network are discussed.

Nonverbal perceptual organization output disability and schizophrenia spectrum symptomatology.

Patients with neurodevelopmental syndromes often receive numerous psychiatric diagnoses before the true nature of their disorder becomes apparent. We present a case in which the neuropsychological evaluation played a significant role in reconceptualizing a patient who had received, at various times, diagnoses of schizotypal personality disorder, schizoaffective disorder, and schizophrenia. The identification of specific cognitive deficits in executive functioning, perceptual organization, visual-spatial problem solving, and abstraction led to: 1) a diagnosis of nonverbal perceptual-organization-output disabled; 2) the adoption of a rehabilitative treatment model; and 3) a greater understanding of the way in which the patient's social deficits represented adaptations to her cognitive impairments. Research data and theoretical models relating cognitive deficits to psychiatric symptoms are discussed, and evidence is presented that schizophrenia and certain neurodevelopmental syndromes may share commonalities of pathophysiology. Diagnostic issues arising from similarities between these disorders are discussed. It is suggested that direct comparisons between these groups can aid in clarifying the specific nature of cognitive deficit-symptom relationships, as well as leading to improvements in the understanding, diagnosis and treatment of schizophrenic and neurodevelopmental syndromes.

Increased cx43 and angiogenesis in exercised mouse hearts.

Several studies focused on the macroscopic architecture of increased cardiac wall induced by exercise training. Our goal was to evaluate myocardiocyte, interstitial and vascular component, and connexin-43 expression in endurance-trained mouse hearts. Sixty-three 10-week-old male Swiss mice were divided into four sedentary groups (C0, C15, C30 and C45) and three groups exercised respectively for 15 (T15-D; running intensity [RI]: 3.18 m/min; running duration [RD]: 75 min/first week and 150 min/second week), 30 (T30-D; RI: 3.96 m/min; RD: 150 min/third week and 225 min/fourth week) and 45 days (T45-D; RI: 3.96 m/min and 4.8 m/min, respectively for the fifth and sixth week; RD: 300 min) on a treadmill. Morphometric analyses were performed to quantify myocardiocyte size and number, and the capillary and interstitial connective tissue (ICT) area. We assessed the expression of ventricle myosin light chain-II, vimentin and connexin-43 by western blot analyses. Our results showed a hypertrophy of the interventricular septum and left ventricle in T30-D and T45-D mice that was not due to variations in myofibrillar content, myocardiocyte size and number, or ICT quantity but to a significant increase in the capillary area. The microvascular remodeling was associated with vimentin increased expression in ICT cells and connexin-43 upregulation. The first phenomenon might be related to an enhanced request of remodeling and growth factors; the second suggests a new role of connexin-43 in cardiac angiogenesis.