Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.

Children with Autism Spectrum Disorder are often said to present a global pragmatic impairment. However, there is some observational evidence that context-based comprehension of indirect requests may be preserved in autism. In order to provide experimental confirmation to this hypothesis, indirect speech act comprehension was tested in a group of 15 children with autism between 7 and 12 years and a group of 20 typically developing children between 2:7 and 3:6 years. The aim of the study was to determine whether children with autism can display genuinely contextual understanding of indirect requests. The experiment consisted of a three-pronged semi-structured task involving Mr Potato Head. In the first phase a declarative sentence was uttered by one adult as an instruction to put a garment on a Mr Potato Head toy; in the second the same sentence was uttered as a comment on a picture by another speaker; in the third phase the same sentence was uttered as a comment on a picture by the first speaker. Children with autism complied with the indirect request in the first phase and demonstrated the capacity to inhibit the directive interpretation in phases 2 and 3. TD children had some difficulty in understanding the indirect instruction in phase 1. These results call for a more nuanced view of pragmatic dysfunction in autism.

Background: Obstructive sleep apnea syndrome (OSA) is currently recognized as an independent risk factor for hypertension, arrhythmia, coronary heart disease, stroke, and metabolic disorders (e.g. diabetes, dyslipidemia). In clinical practice, apnea-hypopnea index (AHI) is the marker used to classify disease severity and guide treatment. However, AHI alone does not sufficiently identify OSA patients at risk for cardiometabolic comorbidities. With this in mind, the aim of this retrospective study was to determine whether some polysomnographic parameters (e.g. apnea-hypopnea duration, sleep structure, nocturnal hypoxemia) are specifically associated with cardiometabolic comorbidities in OSA. Methods: In this retrospective study, 1717 patients suffering from moderate/severe OSA were included between 2013 and 2017. Data on demographics, comorbidities, and polysomnographic characteristics were collected and analyzed to identify factors associated with cardiometabolic complications. Results: The medical files of 1717 patients (68% male) were reviewed. The mean AHI was 43.1 +/− 27.7 with 57.3% of patients suffering from severe OSA, and 52% from at least one cardiovascular comorbidity (CVCo). Diabetes affected 22% of the patients and 27% exhibited dyslipidemia. Patients affected by CVCos were older, and more often women and non-smokers. These patients also had worse sleep quality, and a more marked intermittent/ global nocturnal hypoxemia. With regard to diabetes, diabetics were older, more often non-smoker, non-drinker women, and were more obese. These patients also exhibited more severe OSA, especially in non-REM (NREM) sleep, worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. Dyslipidemia was more frequent in the absence of alcohol consumption, and was associated with OSA severity, decreased sleep quality, and longer AH in REM sleep. Conclusions: This study identifies demographic and polysomnographic factors associated with cardiometabolic comorbidities. Patients (especially women) suffering from more severe OSA, longer sleep apneas and hypopneas, worse sleep quality, and marked intermittent/global nocturnal hypoxemia are more likely to develop cardiometabolic comorbidities. This should stimulate clinicians to obtain adequate treatment in this population.

Magnetic resonance imaging is widely used for different diagnostic examinations involving autistic patients. The noisy, narrow, isolating magnetic resonance imaging environment and long scan times may not be suitable for autistic individuals, given their communication challenges, sensory sensitivities and often heightened anxiety. This systematic review aims to reveal any reasonable and feasible radiography-based adjustments to facilitate magnetic resonance imaging scanning without the use of sedation or general anaesthesia. Nine electronic databases were systematically searched. Out of 4442 articles screened, 53 were deemed directly relevant; when assessed against eligibility criteria, only 21 were finally included in this systematic review. Customising communication was found to be a key adjustment, as well as scan-based optimisation and environmental adaptations. The importance of distraction techniques and use of technology for familiarisation with the processes was also highlighted. The results of this study can inform recommendations to improve magnetic resonance imaging practice and patient experience, without the use of sedation or anaesthesia, where feasible. They can also inform the basis of dedicated training for magnetic resonance imaging radiographers. Lay abstract Autistic patients often undergo magnetic resonance imaging examinations. Within this environment, it is usual to feel anxious and overwhelmed by noises, lights or other people. The narrow scanners, the loud noises and the long examination time can easily cause panic attacks. This review aims to identify any adaptations for autistic individuals to have a magnetic resonance imaging scan without sedation or anaesthesia. Out of 4442 articles screened, 53 more relevant were evaluated and 21 were finally included in this study. Customising communication, different techniques to improve the environment, using technology for familiarisation and distraction have been used in previous studies. The results of this study can be used to make suggestions on how to improve magnetic resonance imaging practice and the autistic patient experience. They can also be used to create training for the healthcare professionals using the magnetic resonance imaging scanners.

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Purpose Telemonitoring (TMg) for patients treated with continuous positive airway pressure (CPAP) is now routine care in some sleep labs. The purpose of the present study was to identify technical interventions associated with improved CPAP compliance in a real-life cohort of newly telemonitored patients with obstructive sleep apnea (OSA) during the first 6 months of treatment. Methods All patients with moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥ 15/h) who were newly treated with CPAP were included in the study and telemonitored. A group educational session was scheduled after 1 month. Technical interventions were performed at the patient's request and during scheduled visits and the impact of each intervention on CPAP therapy compliance was collected. Results Between May 2018 and Dec 2019, 349 patients newly diagnosed with OSA were hospitalized in the sleep lab for CPAP titration and 212 patients were included (mean age 54.6 ± 13.1 years, mean BMI 31.7 ± 5.8 kg/m 2 , mean AHI 42.8 ± 22.0). TMg acceptance rate was 87%. Mean 6-month compliance was 275 ± 154 min, 13% stopped CPAP, and 17% were non-compliant. Correlations were observed between BMI (r = 0.15, p = 0.029), median and 95th percentile leaks (r = −0.23 and −0.18, p = 0.016 and 0.002), and CPAP compliance.During follow-up, 92 interventions were required, mainly for mask change (n = 80). Pressure modification (n = 16) was the only intervention that increased CPAP use > 30 min/night, p = 0.021. Conclusion Pressure modification was the only adaptation that significantly increased CPAP compliance during the first 6 months. Remote TMg allows providing daily, accurate, and immediate feedback that could help clinicians to confirm that the CPAP treatment is effective.

Results illustrate the psychopathology of autism spectrum disorder suspected children referred to a specialized autism diagnostic service, doing so by providing us with specific clinical profiles.

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