Efficacy of a dual task protocol on neurophysiological and clinical outcomes in migraine: a randomized control trial.

The main aim of this study was to investigate the efficacy of a dual task protocol in people with episodic migraine with respect to both active exercises only and cognitive task only treatments, concerning some neurophysiological and clinical outcomes. A randomized control trial was adopted in people with episodic migraine without aura. Some neurophysiological and clinical outcomes were collected (t0): resting motor threshold (rMT), short intracortical inhibition (SICI) and facilitation (ICF), pressure pain threshold (PPT), trail making test (TMT), frontal assessment battery (FAB), headache-related disability (MIDAS) and headache parameters. Then, participants were randomized into three groups: active exercise only (n = 10), cognitive task only (n = 10) and dual task protocol (n = 10). After 3 months of each treatment and after 1-month follow-up the same neurophysiological and clinical outcomes were revaluated. A significant time x group effect was only found for the trapezius muscle (p = 0.012, pη2 = 0.210), suggesting that PPT increased significantly only in active exercise and dual task protocol groups. A significant time effect was found for rMT (p < 0.001, pη2 = 0.473), MIDAS (p < 0.001, pη2 = 0.426), TMT (p < 0.001, pη2 = 0.338) and FAB (p < 0.001, pη2 = 0.462). A repeated measures ANOVA for SICI at 3 ms highlighted a statistically significant time effect for the dual task group (p < 0.001, pη2 = 0.629), but not for the active exercises group (p = 0.565, pη2 = 0.061), and for the cognitive training (p = 0.357, pη2 = 0.108). The dual task protocol seems to have a more evident effect on both habituation and sensitization outcomes than the two monotherapies taken alone in people with migraine.

Effect of repeated topical capsaicin gel administration on oral thermal quantitative sensory testing: A two-arm longitudinal study.

OBJECTIVES: Few studies used thermal quantitative sensory testing to assess the effects of repeated capsaicin gel administration in the oral cavity. This study aimed to investigate thermal sensory and pain thresholds before and after repeated capsaicin gel administration. SUBJECTS AND METHODS: Ten healthy females (22 ± 2 years) applied a capsaicin gel on the gingival mucosa twice daily for 14 days, and heat pain threshold, warm detection threshold, cold pain threshold, and cold detection threshold were assessed on the oral mucosa. Measurements were performed before and after the 14 days and were compared to a control sample (n = 10, all females, 23 ± 3 years). RESULTS: Capsaicin increased heat pain threshold in the anterior maxilla by 2.9°C (95% CI: 1.6-4.2) (p < 0.001) and in the anterior mandible by 2.2°C (95% CI: 1.0-3.4) (p = 0.001), similar to warm detection threshold that increased by Δ1.1°C (95% CI: 0.3-1.9) (p = 0.009). No significant changes were found in the controls. CONCLUSIONS: These findings encourage the use of thermal quantitative sensory testing in the oral cavity to assess thermal sensation, which might be useful for assessing the effects of therapies aimed at reducing pain.

Exploiting pancreatic cancer metabolism: challenges and opportunities.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and therapy resistance has gained prominence. In this review we focus on the impact of metabolic changes on the interplay among stromal, immune, and tumor cells, as glutamine and branched-chain amino acids (BCAAs) emerge as pivotal players in modulating immune cell functions and tumor growth. We also discuss ongoing clinical trials that explore metabolic modulation for PDAC, targeting mitochondrial metabolism, asparagine and glutamine addiction, and autophagy inhibition. Overcoming challenges in understanding nutrient effects on immune-stromal-tumor interactions holds promise for innovative therapeutic strategies.

Co-existing mental and somatic conditions in Swedish children with the avoidant restrictive food intake disorder phenotype.

Background: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder, characterized by limited variety and/or quantity of food intake impacting physical health and psychosocial functioning. Children with ARFID often present with a range of psychiatric and somatic symptoms, and therefore consult various pediatric subspecialties; large-scale studies mapping comorbidities are however lacking. To characterize health care needs of people with ARFID, we systematically investigated ARFID-related mental and somatic conditions in 616 children with ARFID and >30,000 children without ARFID. Methods: In a Swedish twin cohort, we identified the ARFID phenotype in 6-12-year-old children based on parent-reports and register data. From >1,000 diagnostic ICD-codes, we specified mental and somatic conditions within/across ICD-chapters, number of distinct per-person diagnoses, and inpatient treatment days between birth and 18th birthday (90 outcomes). Hazard ratios (HR) and incidence rate ratios (IRR) were calculated. Findings: Relative risks of neurodevelopmental, gastrointestinal, endocrine/metabolic, respiratory, neurological, and allergic disorders were substantially increased in ARFID (e.g., autism HR[CI95%]=9.7[7.5-12.5], intellectual disability 10.3[7.6-13.9], gastroesophageal reflux disease 6.7[4.6-9.9], pituitary conditions 5.6[2.7-11.3], chronic lower respiratory diseases 4.9[2.4-10.1], epilepsy 5.8[4.1-8.2]). ARFID was not associated with elevated risks of autoimmune illnesses and obsessive-compulsive disorder. Children with ARFID had a significantly higher number of distinct mental diagnoses (IRR[CI95%]=4.7[4.0-5.4]) and longer duration of hospitalizations (IRR[CI95%]=5.5[1.7-17.6]) compared with children without ARFID. Children with ARFID were diagnosed earlier with a mental condition than children without ARFID. No sex-specific differences emerged. Interpretation: This study yields the broadest and most detailed evidence of co-existing mental and somatic conditions in the largest sample of children with ARFID to date. Findings suggest a complex pattern of health needs in youth with ARFID, underscoring the critical importance of attention to the illness across all pediatric specialties. Funding: Fredrik and Ingrid Thurings Foundation, Mental Health Foundation.

Differences in musculoskeletal dysfunctions and in postural alterations between chronic migraine and chronic tension type headache: A cross-sectional study.

OBJECTIVE: The aim of present study is to assess postural alterations and musculoskeletal dysfunctions over all spine in patients with chronic migraine and chronic tension type headache, moreover to highlight the differences between these two forms of primary headache. METHODS: A Cross sectional study was adopted to evaluate the musculoskeletal profile in patients with chronic migraine and with chronic tension type headache. The Bio photogrammetric evaluation was performed using the postural assessment software PAS/SAPO, while unilateral passive accessory intervertebral motion (PAIMs) were applied for manual examinations of spine segments from C0 to L5 vertebra. The One-way Analysis of Variance (ANOVA) test was used to compare the three groups with the software GraphPad InStat 3.06. RESULTS: A total of 60 patients were recruited, 20 for chronic tension type group, 20 for chronic migraine group and 20 healthy controls. The most interesting findings was that patients with chronic primary headaches presented postural alterations in all parameters (cranio-vertebral angle and lumbar-pelvic angle) and musculoskeletal dysfunctions in all spine with respect to healthy controls. Finally, the most clinically relevant finding was that no differences were found between chronic migraine and chronic tension type headache concerning the postural alterations nor the musculoskeletal dysfunctions. CONCLUSION: The sensitization acts as a substrate or consequence of these musculoskeletal dysfunctions in chronic primary headache. Therefore, non-pharmacological treatments targeted in the musculoskeletal system may be a good option in the management of chronic primary headache, especially when these therapies integrate various techniques that involve all spine.

Instrumental assessment of pressure pain threshold over trigeminal and extra-trigeminal area in people with episodic and chronic migraine: a cross-sectional observational study.

BACKGROUND: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body. METHODS: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae). RESULTS: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group. CONCLUSIONS: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Efficacy of dual-task augmented reality rehabilitation in non-hospitalized adults with self-reported long COVID fatigue and cognitive impairment: a pilot study.

BACKGROUND: Cognitive impairment and chronic fatigue represent common characteristics of the long COVID syndrome. Different non-pharmacological treatments have been proposed, and physiotherapy has been proposed to improve the symptoms. This study aimed to evaluate the effects of a dual-task augmented reality rehabilitation protocol in people with long COVID fatigue and cognitive impairment. METHODS AND MATERIALS: Ten non-hospitalized adults with reported fatigue and "brain fog" symptoms after COVID (7/10 females, 50 years, range 41-58) who participated in 20 sessions of a 1-h "dual-task" training, were compared to 10 long COVID individuals with similar demographics and symptoms (9/10 females, 56 years, range 43-65), who did not participate to any rehabilitation protocol. Cognitive performance was assessed with the Trail Making Test (TMT-A and -B) and Frontal Assessment Battery (FAB), and cardiovascular and muscular fatigue were assessed with the fatigue severity scale (FSS), six-minute walking test and handgrip endurance. Finally, transcranial magnetic stimulation (TMS) investigated cortical excitability. RESULTS: The mixed-factors analysis of variance found a significant interaction effect only in cognitive performance evaluation, suggesting TMT-B execution time decreased (- 15.9 s, 95% CI 7.6-24.1, P = 0.001) and FAB score improved (1.88, 95% CI 2.93-0.82, P = 0.002) only in the physiotherapy group. For the remaining outcomes, no interaction effect was found, and most parameters similarly improved in the two groups. CONCLUSION: The preliminary results from this study suggest that dual-task rehabilitation could be a feasible protocol to support cognitive symptoms recovery after COVID-19 and could be helpful in those individuals suffering from persisting and invalidating symptoms.

Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study.

OBJECTIVE: The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function. METHODS: A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery. RESULTS: Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles ( P < 0.001), lower resting motor threshold (-10.5% of the stimulator output, 95% CI: -16.8 to -4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (-1.1, 95% CI: -1.7 to -0.5, P = 0.001, Cohen d = 0.915). CONCLUSIONS: Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.

Efficacy of manual therapy and pelvic floor exercises for pain reduction in primary dysmenorrhea: A prospective observational study.

BACKGROUND: Primary dysmenorrhea represents one of the most common causes of pelvic and low back pain. Pharmacological treatment can present some side effects, and non-pharmacological treatments should be considered to improve the symptoms of primary dysmenorrhea. The aim of this study was to evaluate the efficacy of manual therapy (MT), pelvic floor exercises (PFE), and their combination (MT + PFE) to improve clinical outcomes and pain sensitivity in women with primary dysmenorrhea. METHODS: A prospective observational study was conducted. Thirty females (age 25.0 ± 6.1 y) with history of primary dysmenorrhea participated to 8 sessions of 60 min of either MT, PFE or MT + PFE, twice per week. They participated to the different treatments according to the different services offered by the school of physiotherapy. A 0-10 numeric rating scale (NRS) was administered to assess subjective pain, while short-form 36 (SF-36) was used to evaluate quality of life. The pressure pain threshold (PPT) was assessed with a portable algometer on different pelvic and lumbar areas. RESULTS: Independently from the treatment, significant improvements were reported for general pain NRS (p < 0.001; pη2 = 0.511), as well as most the domains of the SF-36, although the general health domain did not reach statistical significance (p = 0.613; pη2 = 0.010). PPT revealed a general improvement in all tested body areas, although on the quadratus lumborum, the PFE treatment did not induce a significant improvement compared to the MT and MT + PFE protocols (p = 0.039). CONCLUSIONS: These findings highlight the importance of proposing physiotherapy treatments to females with primary dysmenorrhea to improve symptoms, with manual therapy combined with active pelvic floor exercise providing the best outcomes including an improvement of lumbar pain thresholds.

Shoulder tensiomyography and isometric strength in swimmers before and after a fatiguing protocol.

CONTEXT.: Shoulder muscles are active during front crawl swimming to provide propulsion and stabilize the glenohumeral and scapulothoracic joints. It has been proposed that fatigue might contribute to altered activation of these muscles and represent a risk factor for injuries. Tensiomyography (TMG) might represent a non-invasive tool to detect exercise-induced neuromuscular fatigue changes in contractile parameters of the skeletal muscles, and it has never been used in the shoulder muscles in swimmers. OBJECTIVE.: The aim of this study was to assess the effects of a fatiguing swimming protocol on shoulder muscles TMG parameters and isometric strength in competitive swimmers. DESIGN.: A cross-sectional study. SETTING.: A swimming pool facility. PATIENTS OR OTHER PARTICIPANTS.: Sixteen young front crawl competitive swimmers were invited to participate in the study, and 14 of them (21 y, range 17-26, 11 males 3 females) completed all the assessments before and after a 30-min high-intensity swimming training. MAIN OUTCOME MEASURE(S).: The main outcome included the TMG assessment which was performed on seven muscles of the shoulder according to front crawl biomechanics and applicability of the technique, in order to obtain data such as time to contraction and muscle belly radial displacement (Dm), whereas isometric strength was assessed with a digital dynamometer during shoulder flexion, extension, external rotation and internal rotation. RESULTS.: Fatigue induced a smaller Dm (-0.5 mm, 95% CI: -0.7 - -0.3, p< 0.001, pη2= 0.692), mostly observable in latissimus dorsi and pectoralis major muscles. Only shoulder extension showed a significant isometric strength reduction after the fatiguing protocol (-0.03 N/kg, 95% CI: -0.05 - -0.01, p= 0.045, pη2= 0.275). CONCLUSIONS.: This study provides preliminary evidence for the usefulness of TMG to detect fatigue-induced changes in contractile properties of the shoulder muscles in swimmers, in particular the latissimus dorsi, pectoralis major and lower trapezius.

Inertial Sensors and Pressure Pain Threshold to Evaluate People with Primary Adhesive Capsulitis: Comparison with Healthy Controls and Effects of a Physiotherapy Protocol.

Inertial sensors (IMUs) have been recently widely used in exercise and rehabilitation science as they can provide reliable quantitative measures of range of motion (RoM). Moreover, the pressure pain threshold (PPT) evaluation provides an objective measure of pain sensation in different body areas. The aim of this study was to evaluate the efficacy of physiotherapy treatment in people with adhesive capsulitis in terms of RoM and pain improvement measured by IMUs and the PPT. A combined prospective cohort/cross-sectional study was conducted. Nineteen individuals with adhesive capsulitis (10/19 females, 54 ± 8 years) and nineteen healthy controls (10/19 females, 51 ± 6 years) were evaluated for active glenohumeral joint RoM and PPT on shoulder body areas. Then, individuals with adhesive capsulitis were invited to 20 sessions of a physiotherapy protocol, and the assessments were repeated within 1 week from the last session. The range of motion in the flexion (p = 0.001) and abduction (p < 0.001) of the shoulder increased significantly after the physiotherapy protocol. Similarly, the PPT was found to increase significantly in all the assessed shoulder body areas, leading to no significant differences compared to the healthy controls. IMU and PPT assessments could be used to evaluate the efficacy of physical therapy in people with adhesive capsulitis.

Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study.

Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53-1.58] to 2.65 [ ≥ 4 adversities; 1.98-3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59-1.84] to 1.37 [1.30-1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

Trunk muscles' characteristics in adolescent gymnasts with low back pain: a pilot study on the effects of a physiotherapy intervention including a postural reeducation program.

BACKGROUND: Trunk muscles' function and characteristics are of great importance for both static and dynamic tasks in different sports, and abnormalities of trunk flexors and extensors might be associated with low back pain (LBP). The aim of this study was to provide a comprehensive evaluation of the functional, morphological and contractile properties in trunk flexors and extensors of young gymnasts with and without LBP. METHODS: Young gymnasts (14/25 females, 14-18 y) were screened for the presence of chronic LBP. Abdominal and lumbar muscles were tested for function (McGill's endurance tests), thickness (ultrasound), and contractile responses (tensiomyography). An 8-sessions physiotherapy intervention including postural reeducation was performed by a subsample of 10 subjects with LBP. RESULTS: LBP was found to be associated to higher flexors-to-extensors endurance ratio (OR 11.250, 95% CI: 1.647-76.849, p = 0.014), reduced mean lumbar multifidus thickness (OR 16.500, 95% CI: 2.246-121.228, p = 0.006), and reduced mean erector spinae radial displacement (OR 16.500, 95% CI: 2.246-121.228, p = 0.006). The physiotherapy intervention was found to reduce LBP symptoms and it was associated with a significant improvement in the flexors-to-extensors ratio (p < 0.001). CONCLUSIONS: This study provides preliminary evidence of functional, morphological, and contractile trunk muscles' alterations associated with chronic LBP in young gymnasts, and presents the effects of a postural reeducation program on symptoms and muscles' functional properties.

Inertial sensors-based assessment to detect hallmarks of chronic ankle instability during single-leg standing: Is the healthy limb "healthy"?

BACKGROUND: Chronic ankle instability can be common in sportsmen and can increase the risk of damaging the articular surfaces and result in negative consequences to joint health. Balance assessment is often used to evaluate ankle instability characteristics and guide rehabilitation protocols. This study aims to investigate balance-related parameters in people with chronic ankle instability and healthy-matched controls, using inertial sensors. METHODS: Ten young adults with a history of multiple ankle sprains (30 y, 25-34, 5 females) and ten matched healthy controls (30 y, 23-39, 5 females) were invited to participate in the study. Inertial sensors were placed on the head of the astragalus and on the chest to collect kinematic parameters during a 20-s single-leg stance performed on the leg with ankle instability (and corresponding for the healthy controls) and on the contralateral leg, randomly. Outcomes were calculated with MATLAB and subsequently analyzed. FINDINGS: A significant group effect was found only for the inversion angle (F1,15 = 12.514, p = 0.003, pη2 = 0.455), consisting of individuals with ankle instability being characterized by higher inversion angles (4.999 degrees, 95% CI: 1.987-8.011, p = 0.003) without significant side differences. No significant side x group effects were found for the assessed parameters. INTERPRETATION: Results from this study suggest that young adults with chronic ankle instability might be characterized by worse single-stance control in terms of inversion angle, and such worse performance could also be found in the contralateral leg. As such, inertial sensors could be used to assess kinematic parameters during balance tasks in people with chronic ankle instability.

Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited therapeutic options. However, metabolic adaptation to the harsh PDAC environment can expose liabilities useful for therapy. Targeting the key metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) and its downstream pathway shows efficacy only in subsets of patients but gene modifiers maximising response remain to be identified. DESIGN: Three independent cohorts of PDAC patients were studied to correlate PI3K-C2γ protein abundance with disease outcome. Mechanisms were then studied in mouse (KPC mice) and cellular models of PDAC, in presence or absence of PI3K-C2γ (WT or KO). PI3K-C2γ-dependent metabolic rewiring and its impact on mTORC1 regulation were assessed in conditions of limiting glutamine availability. Finally, effects of a combination therapy targeting mTORC1 and glutamine metabolism were studied in WT and KO PDAC cells and preclinical models. RESULTS: PI3K-C2γ expression was reduced in about 30% of PDAC cases and was associated with an aggressive phenotype. Similarly, loss of PI3K-C2γ in KPC mice enhanced tumour development and progression. The increased aggressiveness of tumours lacking PI3K-C2γ correlated with hyperactivation of mTORC1 pathway and glutamine metabolism rewiring to support lipid synthesis. PI3K-C2γ-KO tumours failed to adapt to metabolic stress induced by glutamine depletion, resulting in cell death. CONCLUSION: Loss of PI3K-C2γ prevents mTOR inactivation and triggers tumour vulnerability to RAD001 (mTOR inhibitor) and BPTES/CB-839 (glutaminase inhibitors). Therefore, these results might open the way to personalised treatments in PDAC with PI3K-C2γ loss.

Gestational Age in Autistic Children and Adolescents: Prevalence and Effects on Autism Phenotype.

Pre- and post-term children show increased autism risk. Little is known about gestational age (GA) prevalence among autistic children, and their respective autism phenotype. We compared prevalence of pre-, full- and post-term birth between a population-derived sample of N = 606 (137 females, 22.61%) autistic children and adolescents (mean age = 14.01, SD = 3.63, range 3-24) from the Netherlands Autism Register, and matched controls from the Dutch birth register. Autism phenotype and comorbid symptoms were assessed with the AQ-short and SDQ questionnaires. Using logistic regression, we found higher prevalence of pre- and post-term birth among autistic individuals but no phenotypical differences across GA groups. Autism risk was particularly elevated for post-term children, highlighting the need for closer investigation of autism on the whole GA range.