PRICKLE1-related early onset epileptic encephalopathy

The PRICKLE1 (Prickle Planar Cell Polarity Protein 1-MIM 608500) gene is involved in different phases of human development. The related diseases include autosomal recessive progressive myoclonus epilepsy - ataxia syndrome, neural tube defects associated with heterozygous mutations, agenesis of corpus callosum, polymicrogyria, and autistic spectrum disorder. Reported here is a young boy with a new variant (NM_153026.2:c.820G>A, p.Ala274Thr) presenting with an early infantile epileptic encephalopathy with developmental arrest

Adherence to Mediterranean diet, physical activity level, and severity of periodontitis: Results from a university-based cross-sectional study

Background: The aim of this study was to evaluate the association between adherence to Mediterranean diet (MD) and physical activity (PA) level with the periodontal status of a University-based cohort of individuals. Methods: A total of 235 individuals were included in the study. MD adherence and PA level were registered through validated questionnaires, together with a full periodontal examination. Crude and adjusted odds ratios (ORs) [95% confidence interval] were calculated to evaluate the association between MD adherence, PA level, and periodontitis severity. A final logistic multivariate regression model was built to evaluate the impact of the combination between low MD adherence and low PA level on the prevalence of Stage III/IV periodontitis. Results: The adjusted ORs for Stage III/IV periodontitis were 1.65 [0.84 to 3.28; P = 0.42] for low PA and 5.63 [3.21 to 9.84; P = 0.00] for low MD adherence. The final logistic multivariate regression model resulted in OR = 10.23 [4.01, 26.09; P = 0.00] of having Stage III/IV periodontitis in individuals with low MD adherence and low PA. Conclusions: Individuals conducting a lifestyle characterized by the combination of low MD adherence and lack of regular exercise had 10 times the odds to have severe forms of periodontitis. © 2022 The Author

GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

Expanding the genetic and phenotypic spectrum of CHD2-related disease: From early neurodevelopmental disorders to adult-onset epilepsy

CHD2 encodes the chromodomain helicase DNA-binding protein 2, an ATP-dependent enzyme that acts as a chromatin remodeler. CHD2 pathogenic variants have been associated with various early onset phenotypes including developmental and epileptic encephalopathy, self-limiting or pharmacoresponsive epilepsies and neurodevelopmental disorders without epilepsy. We reviewed 84 previously reported patients carrying 76 different CHD2 pathogenic or likely pathogenic variants and describe 18 unreported patients carrying 12 novel pathogenic or likely pathogenic variants, two recurrent likely pathogenic variants (in two patients each), three previously reported pathogenic variants, one gross deletion. We also describe a novel phenotype of adult-onset pharmacoresistant epilepsy, associated with a novel CHD2 missense likely pathogenic variant, located in an interdomain region. A combined review of previously published and our own observations indicates that although most patients (72.5%) carry truncating CHD2 pathogenic variants, CHD2-related phenotypes encompass a wide spectrum of conditions with developmental delay/intellectual disability (ID), including prominent language impairment, attention deficit hyperactivity disorder and autistic spectrum disorder. Epilepsy is present in 92% of patients with a median age at seizure onset of 2 years and 6 months. Generalized epilepsy types are prevalent and account for 75.5% of all epilepsies, with photosensitivity being a common feature and adult-onset nonsyndromic epilepsy a rare presentation. No clear genotype-phenotype correlation has emerged

Deep-Manager: a versatile tool for optimal feature selection in live-cell imaging analysis

One of the major problems in bioimaging, often highly underestimated, is whether features extracted for a discrimination or regression task will remain valid for a broader set of similar experiments or in the presence of unpredictable perturbations during the image acquisition process. Such an issue is even more important when it is addressed in the context of deep learning features due to the lack of a priori known relationship between the black-box descriptors (deep features) and the phenotypic properties of the biological entities under study. In this regard, the widespread use of descriptors, such as those coming from pre-trained Convolutional Neural Networks (CNNs), is hindered by the fact that they are devoid of apparent physical meaning and strongly subjected to unspecific biases, i.e., features that do not depend on the cell phenotypes, but rather on acquisition artifacts, such as brightness or texture changes, focus shifts, autofluorescence or photobleaching. The proposed Deep-Manager software platform offers the possibility to efficiently select those features having lower sensitivity to unspecific disturbances and, at the same time, a high discriminating power. Deep-Manager can be used in the context of both handcrafted and deep features. The unprecedented performances of the method are proven using five different case studies, ranging from selecting handcrafted green fluorescence protein intensity features in chemotherapy-related breast cancer cell death investigation to addressing problems related to the context of Deep Transfer Learning. Deep-Manager, freely available at https://github.com/BEEuniroma2/Deep-Manager, is suitable for use in many fields of bioimaging and is conceived to be constantly upgraded with novel image acquisition perturbations and modalities

Functional implant prosthodontic score of a one-year prospective study on three different connections for single-implant restorations

Aim The aim of this prospective clinical trial was to analyze, using the Functional Implant Prosthodontic Score (FIPS), the clinical resultsof three different abutment-implant connections (1 hexagon vs 2 conical types) single-unit restorations after one year of clinical service. Material and methods Thirty patients were restored with cement-retained crowns on soft tissue level implants (10 TTc Windmix, 10 TTk Windmix and 10 Aadva GC) in posterior sites and followed-up for 1 year. FIPS was applied for objective outcome assessment beside clinical and radiographic examinations. Five variables were defined for evaluation, resulting in a maximum score of 10 per implant restoration. The patients’ level of satisfaction was recorded and correlated with FIPS. Results All implants and connected crowns revealed survival rates of 100% without any biological or technical complications after three years of loading. The total FIPS recorded for group 1 was 44, 43 in group 2 and 42 in group 3. The mean total FIPS score was 8.6±1.1, ranging from 6 to 10. The variable “bone” revealed the highest scores (2.0; range: 2–2), as well “occlusion” (2.0; range: 2–2). Mean scores for “design” (1.7 ±0.4; range: 1–2), “mucosa” (1.6±0.5; range: 1–2), and “interproximal” (1.5±0.6; range: 1–2) were more challenging to satisfy. The patients expressed a high level of functional satisfaction (80.5±2.5; range: 65–100). No type of connection showed to be superior to the other two. No statistically significant differences were found among the three tested groups. A significant correlation was found between FIPS and the subjective patients’ perception with a coefficient of 0.80 (P < 0.0001). Conclusions The findings of the clinical trial indicated the great potential of both conical and hexagon connections and their good performance after 1 year of clinical service. FIPS showed to be an objective and reliable instrument to assess implant success

A new generation of orthodontic retainer using 3D printing technology: report of two cases

Aim In this article the fabrication and use of new type 3D printed splint of retainer after orthodontic treatments is reported. Case report Two cases, one of an adoescent female patient and the other of an adult female, are presented, describing step-by-step the clinical and laboratory procedures. The controls after 6 months are also reported. Conclusion Further randomized clinical trials are required in order to evaluate durability and efficacy and periodontal parameters in patients treated with this new type of retainer

phosphorus and potassium fertilizer effects on alfalfa and soil in a non limited soil

Fertilization strategies for high-yielding alfalfa (Medicago sativa L.) should take in account the increase in soil nutritional status that occurred during the last decades in areas with intensive agricultural use. A field study was conducted at the University of Padova, northeastern Italy, to determine the response of alfalfa yield and nutritive value to various combinations of P and K rates in a soil lacking nutrient deficiency. Alfalfa cultivar Delta was seeded in March 2005 on a silt loam soil having 38 mg kg -1 available P and 178 mg kg -1 exchangeable K. Nine treatments deriving from the combination of three P fertilization rates (0, 100, and 200 kg ha -1 P 2 O 5 ) and three K rates (0, 300, and 600 kg ha -1 K 2 O) were compared in a randomized complete block design. Plots were harvested at bud stage during three growing seasons (2005-2007) and dry matter (DM) yield, forage nutritive value, P and K contents, canopy height, and stem density were measured at each harvest. Soil samples were collected at the end of the research period for determination of available P and exchangeable K. The results demonstrated that P application had no impact on yield and did not interact with K in determining productivity, while K had a positive effect on yield. However, the 300 kg ha -1 K 2 O rate appeared sufficient to maximize yield, without adverse effects on the forage nutritive value. Data from soil analyses showed that alfalfa has a high K uptake even when it is fertilized at high rates

Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations

OBJECTIVE: To explore the prognostic value of initial clinical and mutational findings in infants with SCN1A mutations. METHODS: Combining sex, age/fever at first seizure, family history of epilepsy, EEG, and mutation type, we analyzed the accuracy of significant associations in predicting Dravet syndrome vs milder outcomes in 182 mutation carriers ascertained after seizure onset. To assess the diagnostic accuracy of all parameters, we calculated sensitivity, specificity, receiver operating characteristic (ROC) curves, diagnostic odds ratios, and positive and negative predictive values and the accuracy of combined information. We also included in the study demographic and mutational data of the healthy relatives of mutation carrier patients. RESULTS: Ninety-seven individuals (48.5%) had Dravet syndrome, 49 (23.8%) had generalized/genetic epilepsy with febrile seizures plus, 30 (14.8%) had febrile seizures, 6 (3.5%) had focal epilepsy, and 18 (8.9%) were healthy relatives. The association study indicated that age at first seizure and frameshift mutations were associated with Dravet syndrome. The risk of Dravet syndrome was 85% in the 0- to 6-month group, 51% in the 6- to 12-month range, and 0% after the 12th month. ROC analysis identified onset within the sixth month as the diagnostic cutoff for progression to Dravet syndrome (sensitivity = 83.3%, specificity = 76.6%). CONCLUSIONS: In individuals with SCN1A mutations, age at seizure onset appears to predict outcome better than mutation type. Because outcome is not predetermined by genetic factors only, early recognition and treatment that mitigates prolonged/repeated seizures in the first year of life might also limit the progression to epileptic encephalopathy