ADHD Follow-Up in Adulthood among Subjects Treated for the Disorder in a Child and Adolescent Mental Health Service from 1995 to 2015

Background and Objectives: ADHD is a neurodevelopmental disorder characterized by inattention and hyperactivity/impulsivity and can persist in adulthood. The aim of this study is to deepen knowledge about adult ADHD follow-up. Materials and Methods: This observational study consists of one retrospective part aimed at collecting records of children and adolescents treated for ADHD in the Children and Adolescent Mental Health Service (CAMHS) from 1995 to 2015 and, successively, at identifying their adult follow-up in Adult Mental Health Service (AMHS); the second part consists of ADHD scale administration, Diagnostic Interview for ADHD in Adults (DIVA 2-0) and Adult Self Rating Scale (ASRSv1.1), for the subjects currently being treated at AMHS who agreed to participate in the study. Results: We observed that among the 55 patients treated at CAMHS between 1995 and 2015 for ADHD and subsequently at the AMHS, none presented a diagnosis of ADHD; instead, they were treated for Intellectual Dysfunction (33%), Borderline Personality Disorder (15%) and Anxiety Disorders (9%), and two individuals were also diagnosed with comorbid substance/alcohol abuse (4%). Of the 55 patients, only 25 (45%) were treated at AMHS during the study period. Though we asked for their informed consent to administer the questionnaires, we were able to test only seven patients. The ASRS-V1.1 score showed that 43% of patients reported symptoms of ADHD persistence in adulthood. For DIVA 2.0, 57% of individuals reported scores indicating the persistence of the ADHD inattention component, and 43% the persistence of both ADHD dimensions. Conclusions: ADHD cannot be considered a disorder confined to childhood/adolescence but instead is a chronic and complex condition that can persist into adulthood. The very small size of our final sample may account for both the high ADHD dropout rate over the long follow-up period and the difficult transition from child to adult health care in ADHD treatment. Our investigation suggests the need for specific training in the diagnosis and treatment of adult ADHD and the implementation of transition protocols between minor and adult services to improve long-term treatments

Neurological features of 14q24-q32 interstitial deletion: report of a new case

Background: Interstitial deletions of the long arm of chromosome 14 involving the 14q24-q32 region have been reported in less than 20 patients. Previous studies mainly attempted to delineate recognizable facial dysmorphisms; conversely, descriptions on neurological features are limited to the presence of cognitive and motor delay, but no better characterization exists. Case presentation: In this paper we report on a patient with a de novo interstitial deletion of 5.5 Mb at 14q24.3-q31.1. The deletion encompasses 84 genes, including fourteen Mendelian genes. He presented with dysmorphic face, developmental delay, paroxysmal non-epileptic events and, subsequently, epilepsy. Conclusions: The clinical and molecular evaluation of this patient and the review of the literature expand the phenotype of 14q23-q32 deletion syndrome to include paroxysmal non-epileptic events and infantile-onset focal seizures. © 2015 Nicita et al

Laparoscopic versus open rectal resection. a 1:2 propensity score-matched analysis of oncological adequateness, short- and long-term outcomes

Laparoscopic resections for rectal cancer are routinely performed in high-volume centres. Despite short-term advantages have been demonstrated, the oncological outcomes are still debated. The aim of this study was to compare the oncological adequateness of the surgical specimen and the long-term outcomes between open (ORR) and laparoscopic (LRR) rectal resections

Evaluation of Sheep Anticipatory Response to a Food Reward by Means of Functional Near-Infrared Spectroscopy

Anticipatory behaviour to an oncoming food reward can be triggered via classical conditioning, implies the activation of neural networks, and may serve to study the emotional state of animals. The aim of this study was to investigate how the anticipatory response to a food reward affects the cerebral cortex activity in sheep. Eight ewes from the same flock were trained to associate a neutral auditory stimulus (water bubble) to the presence of a food reward (maize grains). Once conditioned, sheep were trained to wait 15 s behind a gate before accessing a bucket with food (anticipation phase). For 6 days, sheep were submitted to two sessions of six consecutive trials each. Behavioural reaction was filmed and changes in cortical oxy- and deoxy-hemoglobin concentration ([ΔO2Hb] and [ΔHHb] respectively) following neuronal activation were recorded by functional near infrared spectroscopy (fNIRS). Compared to baseline, during the anticipation phase sheep increased their active behaviour, kept the head oriented to the gate (Wilcoxon’s signed rank test; p ≤ 0.001), and showed more asymmetric ear posture (Wilcoxon’s signed rank test; p ≤ 0.01), most likely reflecting a learnt association and an increased arousal. Results of trial-averaged [ΔO2Hb] and [ΔHHb] within individual sheep showed in almost every sheep a cortical activation during the anticipation phase (Student T-test; p ≤ 0.05). The sheep showed a greater response of the right hemisphere compared to the left hemisphere, possibly indicating a negative affective state, such as frustration. Behavioural and cortical changes observed during anticipation of a food reward reflect a learnt association and an increased arousal, but no clear emotional valence of the sheep subjective experience. Future work should take into consideration possible factors affecting the accurateness of measures, such as probe’s location and scalp vascularization

The Italian Twin Registry: An Update at 18 Years From Its Inception

AbstractThe Italian Twin Registry (ITR), established in 2001, is a population-based registry of voluntary twins. To date, it consists of approximately 29,000 twins who gave their consent to participate in the studies proposed by the ITR research group. The database comprises 11,500 monozygotic and 16,700 dizygotic twins resident throughout the country and belonging to a wide age range (from 0 to 95 years, mean 36.8 years). This article provides an overview of the recruitment strategies along with the major phenotypes investigated during an 18 years' research period. Over the years, several self-reported questionnaire data were collected, together with saliva/blood samples and measurements taken during in-person interviews or outpatient clinical examinations. Mental and behavioral phenotypes as well as atherosclerotic traits were studied in depth across different age groups. A birth cohort of twins was established and followed up. Novel research hypotheses are also being tested in ongoing projects. The ITR is involved in international studies in collaboration with other twin registries and represents a valuable resource for national and international research initiatives regarding a broad spectrum of health-related characteristics

Adolescents self-reported sleep quality and emotional regulation: a discordant twin study

Aim. This study explores the association between sleep quality and emotional regulation, and investigates the genetic and environmental bases of this association. Methods. Three-hundred-eighty-two adolescent twins, from the Italian Twin Registry, and their parents filled the Youth Self-Report and Child Behavior Checklist questionnaires, from which the construct of Effortful Control (EC) was derived as a measure of emotional regulation. Twins were identified as “good” or “non-good” sleepers based on answers to the Sleep Disorders Questionnaire. EC levels were compared between samesex sleep discordant twins.Results. A significant association was detected between EC scores and sleep quality. When controlling for shared (fetal or early life) environmental factors and genetic background in the discordant twin analysis, this association weakened in dizygotic twins and disappeared in monozygotic twins.Conclusion. Results support the association between sleep quality and EC in adolescence; furthermore, they suggest that sleep quality and emotional regulation may depend on common genetic or environmental factors.

Internal Macroscopic Anatomy and Electrical Evaluation of the Bradypus variegatus Heart

Background: The Bradypus variegatus species presents peculiar anatomophysiological properties and many aspects of its organic systems still need to be clarified, especially regarding the cardiovascular system, given its participation in vital activities. Disorderly anthropic action has had drastic consequences in sloth populations and the need to treat sick and injured animals is increasingly common. To this end, the importance of knowing its characteristics is emphasized. Therefore, this study proposed to describe the internal macroscopic structures of the sloth's heart, as well as to measure the ventricular walls and indicate the electrical activity of the organ.Materials, Methods and Results: For the dissections, 15 Bradypus variegatus cadavers were used (1 young female, 9 adults females and 5 adult males) belonging to the Área de Anatomia of the Departamento de Morfologia e Fisiologia Animal (DMFA), Universidade Federal Rural de Pernambuco (UFRPE), Recide, PE, Brazil. After they were fixed and preserved, the specimens received a midsagittal incision in the chest, followed by soft tissue folding and removal of ribs to access the heart. The organ was derived from the cavity and sectioned sagittal medially to identify its internal anatomy. Ventricular walls and interventricular septum were measured with a steel caliper (150 mm / 0.02 mm). An electrocardiogram was performed to determine the electrical profile on 5 healthy B. variegatus sloths, living under semi-livestock conditions at the Recife Zoo, PE, Brazil. The electrodes were taken from the regions, scapular and glutes of the animals that were called hugging a keeper during the procedure, carried out in the Zoo itself, using a portable device. Based on the data obtained, sloths have cardiac chambers separated by septa, however between atria and ventricles, in both antimeres, there are atrioventricular ostia, where valves are found, consisting of 3 valves on the right and 2 on the left. The atria are practically smooth inside and have their cavity enlarged by the atria, the right being larger than the left, these having a greater amount of pectineal muscles in relation to the atria. The ventricles have trabeculae and papillary muscles, 3 on the right and 2 on the left. These muscles hold the tendinous chords that connect the valves. The existence of trabeculae marginal septum was not evidenced. The thickness of the wall of the left ventricle, as well as that of the interventricular septum, proved to be greater than the thickness of the wall of the right ventricle, regardless of the age or sex of the animals. Based on the electrocardiographic recordings, the sloths presented sinus rhythm, with a heart rate between 67 and 100 bpm. The electrical axis ranged from -60º to -90º. The P wave is smoother than the QRS complex. While the S-T segment was classified as isoelectric. The T wave was shown to be + and predominantly > or = at 25% of the S wave, which characterized an rS type QRS deflection in both females and males.Discussion: The general characteristics of the cardiac chambers in sloths are similar to those observed in other domestic and wild mammals. However, the presence of pectineal muscles associated with the atria and auricles differs from that observed in mammals such as the paca and raccoon and in birds such as the ostrich, which have trabecular structures in these cavities. The number of valves in sloths is equal to the anteater. However, it has a marginal trabeculae septum, not seen in Bradypus variegatus. According to the electrocardiographic findings, the rhythm was sinus, but much lower than that observed in the capuchin monkey, which also maintains arboreal habits. Keywords: Xenarthra, common sloth, internal anatomy, heart, electrocardiogram.Descritores: Xenarthra, preguiça-comum, anatomia interna, coração, eletrocardiograma

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B (CMT1B) neuropathy, one of the most diffused genetic disorders of the PNS. We previously showed that several mutations, such as the deletion of serine 63 (P0-S63del), result in misfolding and accumulation of P0 in the endoplasmic reticulum (ER), with activation of the unfolded protein response (UPR). In addition, we observed that S63del mouse nerves display the upregulation of many ER-associated degradation (ERAD) genes, suggesting a possible involvement of this pathway in the clearance of the mutant P0. In ERAD in fact, misfolded proteins are dislocated from the ER and targeted for proteasomal degradation. Taking advantage of inducible cells that express the ER retained P0, here we show that the P0-S63del glycoprotein is degraded via ERAD. Moreover, we provide strong evidence that the Schwann cell-specific ablation of the ERAD factor Derlin-2 in S63del nerves exacerbates both the myelin defects and the UPR in vivo, unveiling a protective role for ERAD in CMT1B neuropathy. We also found that lack of Derlin-2 affects adult myelin maintenance in normal nerves, without compromising their development, pinpointing ERAD as a previously unrecognized player in preserving Schwann cells homeostasis in adulthood. Finally, we provide evidence that treatment of S63del peripheral nerve cultures with N-Acetyl-D-Glucosamine (GlcNAc), known to enhance protein quality control pathways in C.elegans, ameliorates S63del nerve myelination ex vivo. Overall, our study suggests that potentiating adaptive ER quality control pathways might represent an appealing strategy to treat both conformational and age-related PNS disorders

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B (CMT1B) neuropathy, one of the most diffused genetic disorders of the PNS. We previously showed that several mutations, such as the deletion of serine 63 (P0-S63del), result in misfolding and accumulation of P0 in the endoplasmic reticulum (ER), with activation of the unfolded protein response (UPR). In addition, we observed that S63del mouse nerves display the upregulation of many ER-associated degradation (ERAD) genes, suggesting a possible involvement of this pathway in the clearance of the mutant P0. In ERAD in fact, misfolded proteins are dislocated from the ER and targeted for proteasomal degradation. Taking advantage of inducible cells that express the ER retained P0, here we show that the P0-S63del glycoprotein is degraded via ERAD. Moreover, we provide strong evidence that the Schwann cell-specific ablation of the ERAD factor Derlin-2 in S63del nerves exacerbates both the myelin defects and the UPR in vivo, unveiling a protective role for ERAD in CMT1B neuropathy. We also found that lack of Derlin-2 affects adult myelin maintenance in normal nerves, without compromising their development, pinpointing ERAD as a previously unrecognized player in preserving Schwann cells homeostasis in adulthood. Finally, we provide evidence that treatment of S63del peripheral nerve cultures with N-Acetyl-D-Glucosamine (GlcNAc), known to enhance protein quality control pathways in C.elegans, ameliorates S63del nerve myelination ex vivo. Overall, our study suggests that potentiating adaptive ER quality control pathways might represent an appealing strategy to treat both conformational and age-related PNS disorders. Author summary Charcot-Marie-Tooth neuropathies are a large family of peripheral nerve disorders, showing extensive clinical and genetic heterogeneity. Although strong advances have been made in the identification of genes and mutations involved, effective therapies are still lacking. Intracellular retention of abnormal proteins has been recently suggested as one of the pathogenetic events that might underlie several conformational neuropathies. To limit the toxic effects of accumulated mutant proteins, cells have developed efficient protein quality control systems aimed at optimizing both protein folding and degradation. Here we show that ER-associated degradation limits Schwann cells stress and myelin defects caused by the accumulation of a mutant myelin protein into the ER. In addition, we also describe for the first time the importance of Schwann cells ERAD in preserving myelin integrity in adult nerves, showing that genetic ERAD impairment leads to a late onset, motor-predominant, peripheral neuropathy in vivo. Effort in the design of strategies that potentiate ERAD and ER quality controls is therefore highly desirable