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American Journal on Intellectual and... Jul 2024The current study examines the efficacy of an 8-week pretend play intervention targeting social-cognitive abilities in children with Prader-Willi syndrome (PWS), ages...
The current study examines the efficacy of an 8-week pretend play intervention targeting social-cognitive abilities in children with Prader-Willi syndrome (PWS), ages 6-9. PWS is a rare disorder associated with various social, emotional, and cognitive challenges linked to pretend play impairments, and for which interventions are sparse. Nineteen children were quasi-randomized to receive the intervention or be part of a waitlist control group. Participants who received the intervention (n = 10) demonstrated significant improvements in various components of pretend play, most notably in organization of play, which may generalize to broader social-cognitive gains. These findings provide evidence of the intervention's efficacy in enhancing pretend play skills and related social-cognitive abilities during this critical period of development for children with PWS.
Topics: Humans; Prader-Willi Syndrome; Male; Female; Child; Play and Playthings; Play Therapy; Social Cognition; Social Skills
PubMed: 38917995
DOI: 10.1352/1944-7558-129.4.279 -
European Neuropsychopharmacology : the... Jun 2024
PubMed: 38917769
DOI: 10.1016/j.euroneuro.2024.05.010 -
American Journal of Human Genetics Jun 2024The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A...
The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A deletion of the SNORD116 cluster, encoding small nucleolar RNAs, or frameshift mutations within MAGEL2 result in closely related phenotypes in individuals with PWS or SYS, respectively. By investigation of their subcellular localization, we observed that in contrast to a predominant cytoplasmic localization of wild-type (WT) MAGEL2, a truncated MAGEL2 mutant was evenly distributed between the cytoplasm and the nucleus. To elucidate regulatory pathways that may underlie both diseases, we identified protein interaction partners for WT or mutant MAGEL2, in particular the survival motor neuron protein (SMN), involved in spinal muscular atrophy, and the fragile-X-messenger ribonucleoprotein (FMRP), involved in autism spectrum disorders. The interactome of the non-coding RNA SNORD116 was also investigated by RNA-CoIP. We show that WT and truncated MAGEL2 were both involved in RNA metabolism, while regulation of transcription was mainly observed for WT MAGEL2. Hence, we investigated the influence of MAGEL2 mutations on the expression of genes from the PWS locus, including the SNORD116 cluster. Thereby, we provide evidence for MAGEL2 mutants decreasing the expression of SNORD116, SNORD115, and SNORD109A, as well as protein-coding genes MKRN3 and SNRPN, thus bridging the gap between PWS and SYS.
PubMed: 38908375
DOI: 10.1016/j.ajhg.2024.05.023 -
Orphanet Journal of Rare Diseases Jun 2024Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in...
BACKGROUND
Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis.
RESULTS
We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles.
CONCLUSIONS
The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study's findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS.
Topics: Humans; Prader-Willi Syndrome; Female; Male; Genotype; Phenotype; Brazil; Child, Preschool; Child; Adolescent; Adult; Uniparental Disomy; Chromosomes, Human, Pair 15; Infant; Young Adult
PubMed: 38902749
DOI: 10.1186/s13023-024-03157-2 -
Pediatrics and Neonatology Jun 2024
PubMed: 38902162
DOI: 10.1016/j.pedneo.2024.06.002 -
World Journal of Clinical Cases Jun 2024As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many...
BACKGROUND
As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes.
CASE SUMMARY
Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved.
CONCLUSION
Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.
PubMed: 38899290
DOI: 10.12998/wjcc.v12.i16.2813 -
Trials Jun 2024Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability...
Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial.
BACKGROUND
Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients.
METHODS
Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery.
DISCUSSION
The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.
Topics: Humans; Borderline Personality Disorder; Vagus Nerve Stimulation; Emotional Regulation; Single-Blind Method; Adult; Randomized Controlled Trials as Topic; Emotions; Transcutaneous Electric Nerve Stimulation; Young Adult; Female; Treatment Outcome; Male; Adolescent; Time Factors; Vagus Nerve; Middle Aged
PubMed: 38898522
DOI: 10.1186/s13063-024-08230-6 -
Journal of Clinical Medicine Jun 2024: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home...
: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home environments. PWS-specialized hostels (SH) succeed in preventing morbid obesity and in coping with behavioral disorders; however, effects of restricted living environments on quality of life (QOL) have not been described. Evidence on QOL is critical for clinicians involved in placement decisions. : We examined the impact of living in SH versus at home or in non-specialized hostels (H and NSH) on QOL, behavior, and health parameters. All 58 adults (26 males) followed-up in the National Multidisciplinary Clinic for PWS were included: 33 resided in SH, 18 lived at home, and 7 lived in NSH. Questionnaires were administered to primary caregivers to measure QOL, and data were obtained from the medical records. : The H and NSH group were compared with those for adults in SH. Despite strict diet and exercise regimens, QOL was similar for both groups. Eight-year follow-up showed that food-seeking behavior decreased in SH but increased in H and NSH. BMI, cholesterol, and triglyceride levels were lower in SH. : Our results suggest that living in SH is associated with benefits for physical health and behavior without negatively affecting QOL.
PubMed: 38893034
DOI: 10.3390/jcm13113323 -
The Journal of Biological Chemistry Jun 2024Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases...
Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PD) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PD variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PD variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PD variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.
PubMed: 38876306
DOI: 10.1016/j.jbc.2024.107460 -
Journal of Applied Research in... Jul 2024Prader-Willi syndrome (PWS) is commonly associated with intellectual disability, but also with a specific behavioural phenotype and a high predisposition to psychiatric...
BACKGROUND
Prader-Willi syndrome (PWS) is commonly associated with intellectual disability, but also with a specific behavioural phenotype and a high predisposition to psychiatric comorbidity. This study examines the psychiatric care situation of people with PWS.
METHOD
A structured online questionnaire was administered to carers of people with PWS living in Germany, asking about demographic, diagnostic and treatment parameters as well as personal experiences.
RESULTS
Of 77 people with PWS, 44.2% had at least one psychiatric comorbid diagnosis. The main reasons for seeking psychiatric care were emotional outbursts and aggressive behaviour. 34.9% reported that they were currently seeking psychiatric care without success. However, 32.5% of PWS had been treated with psychotropic medication, mainly antipsychotics.
CONCLUSIONS
Psychiatric comorbidity appears to be undertreated in PWS, especially in the ambulatory setting. Uncertainty among mental health care providers may also lead to frequent off-label use of psychotropic medications.
Topics: Humans; Prader-Willi Syndrome; Male; Female; Adult; Mental Disorders; Middle Aged; Young Adult; Germany; Comorbidity; Adolescent; Psychotropic Drugs; Mental Health Services; Patient Acceptance of Health Care
PubMed: 38863266
DOI: 10.1111/jar.13266