Objective
Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome‐associated autoinflammatory syndrome ...(CANDLE/PRAAS), stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy (SAVI), and Aicardi‐Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of “points to consider” to improve diagnosis, treatment, and long‐term monitoring of patients with these rare diseases.
Methods
Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates, and an allied health care professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires, and consensus methodology, “points to consider” to guide patient management were developed.
Results
The Task Force devised consensus and evidence‐based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment, and long‐term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI, and AGS.
Conclusion
These points to consider represent state‐of‐the‐art knowledge to guide diagnostic evaluation, treatment, and management of patients with CANDLE/PRAAS, SAVI, and AGS and aim to standardize and improve care, quality of life, and disease outcomes.
Faces hold a substantial value for effective social interactions and sharing. Covering faces with masks, due to COVID-19 regulations, may lead to difficulties in using social signals, in particular, ...in individuals with neurodevelopmental conditions. Daily-life social participation of individuals who were born preterm is of immense importance for their quality of life. Here we examined face tuning in individuals (aged 12.79 ± 1.89 years) who were born preterm and exhibited signs of periventricular leukomalacia (PVL), a dominant form of brain injury in preterm birth survivors. For assessing the face sensitivity in this population, we implemented a recently developed experimental tool, a set of Face-n-Food images bordering on the style of Giuseppe Arcimboldo. The key benefit of these images is that single components do not trigger face processing. Although a coarse face schema is thought to be hardwired in the brain, former preterms exhibit substantial shortages in the face tuning not only compared with typically developing controls but also with individuals with autistic spectrum disorders. The lack of correlations between the face sensitivity and other cognitive abilities indicates that these deficits are domain-specific. This underscores impact of preterm birth sequelae for social functioning at large. Comparison of the findings with data in individuals with other neurodevelopmental and neuropsychiatric conditions provides novel insights into the origins of deficient face processing.
Cerebral palsy is a non-progressive syndrome due to a pre-, peri- or postnatal brain injury, which frequently involves an impairment of non-motor abilities. The aim of this paper was to examine ...visuospatial attention and inhibitory control of prepotent motor responses in children with cerebral palsy showing a normal IQ or mild cognitive impairment, measuring their performance in oculomotor tasks. Ten children (9-16 year-old) with spastic cerebral palsy and 13 age-matched, typically developing children participated in the study. Subjects performed a simple visually-guided saccade task and a cue-target task, in which they performed a saccade towards a peripheral target, after a non-informative visual cue was flashed 150 ms before the imperative target, either at the same (valid) or at a different (invalid) spatial position. Children with cerebral palsy showed severe executive deficits in maintaining sustained attention and complying with task instructions. Furthermore, saccadic inhibitory control appeared to be significantly impaired in presence of both stimulus-driven and goal-directed captures of attention. In fact, patients showed great difficulties in suppressing saccades not only to the cue stimuli, but also to the always-present target placeholders, which represented powerful attentional attractors that had to be covertly attended throughout the task execution. Moreover, impairment did not affect in equal manner the whole visual field, but showed a marked spatial selectivity in each individual subject. Saccade latencies in the cue-target task were faster in the valid than in the invalid condition in both child groups, indicating the preservation of low-level visuospatial attentive capabilities. Finally, this study provides evidence that these impairments of executive skills and in inhibitory control, following early brain injuries, manifest in childhood but recover to virtually normal level during adolescence.
Individuals with Down syndrome (DS) are widely believed to possess considerable socialization strengths. However, the findings on social cognition capabilities are controversial. In the present ...study, we investigated whether individuals with DS exhibit shortage in face tuning, one of the indispensable components of social cognition. For this purpose, we implemented a recently developed Face-n-Food paradigm with food-plate images composed of food ingredients such as fruits and vegetables. The key benefit of such face-like non-face images is that single elements do not facilitate face processing. In a spontaneous recognition task, 25 children with DS aged 9 to 18 years were presented with a set of Face-n-Food images bordering on the Giuseppe Arcimboldo style. The set of images was administered in a predetermined order from the least to most resembling a face. In DS individuals, thresholds for recognition of the Face-n-Food images as a face were drastically higher as compared not only with typically developing controls, but also with individuals with autistic spectrum disorders and Williams-Beuren syndrome. This outcome represents a significant step toward better conceptualization of the visual social world in DS and neurodevelopmental disorders in general.
Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during ...preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control.
Other issues related to the reproductive journey have emerged as “unmet needs”, such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper.
Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.
A
bstract
In the known examples of flux vacua with calibrated spacetime-filling sources (branes or orientifold planes), one can smear the source in order to perform a standard KK reduction and obtain ...a lower-dimensional supergravity description. Furthermore, it is expected that the smeared and localized solution preserve equal amounts of supersymmetry. In this note we point out that the AdS
7
solution discussed in
arXiv:1111.2605
and
arXiv:1309.2949
is a counterexample to this common lore. The solution is supersymmetric when the spacetime-filling D6-branes are localized but breaks supersymmetry in the smeared limit. By using the embedding tensor formalism we demonstrate that there is no gauged supergravity description for the solution, regardless of the source being smeared or not. We conjecture that for flux solutions with separation between the KK scale and AdS radius this cannot occur.
Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), ...stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases.
Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed.
The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS.
These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.
•An earlier onset of absence epilepsy implies a longer duration of antiseizure therapy.•The earlier the onset of the seizures, the more it is recommended to carry out a genetic investigation and a ...neurocognitive evaluation.•Early onset absence epilepsy positive for genetic analyses, requires therapy for longer time.•Early onset absence epilepsy which did not meet Panayiotopoulos's criteria for clinical and electroencephalographic features or comorbidities has a worse outcome and a more frequent symptomatic etiology.
The aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology.
We carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset.
Our sample is composed of 56 patients. Among the children with epilepsy onset under two years of age (11), all were still on therapy after three and six years of follow-up, and 64 % of them required polytherapy. Among patients with epilepsy onset between two and three years of age (24), 87 % were still on therapy after three years of follow-up and 68 % after six years of follow-up; 46 % of these subjects required polytherapy. Among patients with epilepsy onset between three and four years of age (21), 89 % were still on therapy after three years of follow-up and 38 % after six years of follow-up; 38 % of them required polytherapy.
We observe that patients with an earlier epilepsy onset have a worse outcome and a lower drug sensitivity. This may allow to predict in which cases it would be appropriate to maintain antiseizure therapy for a prolonged period.
Objective: To evaluate the efficacy and tolerability of anti-tumour necrosis factor α (TNFα) monoclonal antibody (infliximab) in the treatment of spondyloarthropathy (SpA) associated with active and ...inactive Crohn’s disease (CD). Methods: Twenty four patients with SpA associated with active or inactive CD (16 active, 8 quiescent) were treated with anti-TNFα monoclonal antibody (infliximab) with repeated infusions for a period of 12–18 months. The treatment aimed at ameliorating the general musculoskeletal and spinal pain, controlling peripheral arthritis and enthesitis, decreasing the BASDAI score, modifying acute phase reactants, and reducing CD activity. Results: Infliximab improved both gastrointestinal (p<0.01) and overall articular symptoms (BASDAI, p<0.01; general musculoskeletal and spinal pain, p<0.01; peripheral arthritis, p<0.01) in patients with active CD. Additionally, infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis (p<0.01) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers. Amelioration of gut and musculoskeletal involvement persisted for up to 12 months. Conclusion: Infliximab may act on the inflammation of entheses and of periarticular structures, which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA, suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD.
Cerebral visual impairment (CVI) is a brain based visual disorder associated with the maldevelopment of central visual pathways. Individuals with CVI often report difficulties finding a target of ...interest in cluttered and crowded visual scenes. However, it remains unknown how manipulating task demands and other environmental factors influence visual search performance in this population.
We developed a novel and naturalistic virtual reality (VR) based static visual search task combined with eye tracking called the “virtual toy box” to objectively assess visual search performance in CVI.
A total of 38 individuals with CVI (mean age 13.18 years ± 3.58 SD) and 53 controls with neurotypical development (mean age 15.25 years ± 5.72 SD) participated in the study. In a first experiment, study subjects were instructed to search for a preselected toy presented among a varying number of surrounding distractor toys (set size ranging from 1 to 36 items). In a second experiment, we assessed the effects of manipulating item spacing and the size of the visual area explored (field of view; FOV).
Behavioral outcomes collected were success rate, reaction time, gaze error, visual search area, and off-screen percent (an index of task compliance). Compared to age-matched controls, participants with CVI showed an overall impairment with respect to all the visual search outcomes of interest. Specifically, individuals with CVI were less likely and took longer to find the target, and search patterns were less accurate and precise compared to controls. Visual search response profiles were also comparatively less efficient and were associated with a slower initial pre-search (visual orienting) response as indexed by higher slope and intercept values derived from the analysis of reaction time × set size functions. Search performance was also more negatively affected in CVI at the smallest as well as largest spacing conditions tested, while increasing FOV was associated with greater decreased gaze accuracy and precision
These results are consistent with a general profile of impaired visual search abilities in CVI as well as worsening performance with increased visual task demands and an overall sensitivity to visual clutter and crowding. The observed profile of impaired visual search performance may be associated with dysfunctions related to how visual selective attention is deployed in individuals with CVI.
•Higher order visual perceptual abilities are typically not assessed as part of a standard ophthalmological exam.•Visual search performance in CVI was characterized by using a novel virtual reality-based task combined with eye tracking.•Compared to age-matched controls, participants with CVI showed an overall impairment in performance on all visual search outcomes of interest.•The general profile observed in CVI was consistent with worsening performance with increased visual task demands and sensitivity to visual clutter and crowding.
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