ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations.

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1,500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations, however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESC), including a knock-out and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and Western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR), and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-Seq analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry, and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.

RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, we identified 24 individuals with neurodevelopmental delays from 18 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants showed reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicated that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 revealed that most disease-associated missense variants mapped to the catalytic domain. Additionally, SPOUT1/CENP-32 recurrent missense variants had reduced methyltransferase activity in vitro and compromised centrosome tethering to the spindle poles in human cells. Thus, SPOUT1/CENP-32 pathogenic variants cause an autosomal recessive neurodevelopmental disorder: SpADMiSS ( SPOUT1 Associated Development delay Microcephaly Seizures Short stature) underpinned by mitotic spindle organization defects and consequent chromosome segregation errors.

TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions.

Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and studies on mechanisms of disease, and new types of variants. We describe 29 additional patients from 18 independent families with biallelic variants in TRAPPC6B. We identified seven homozygous nonsense (n = 12 patients) and eight canonical splice-site variants (n = 17 patients). In addition, we identified one patient with compound heterozygous splice-site/missense variants with a milder phenotype and one patient with homozygous missense variants. Patients displayed non-progressive microcephaly, global developmental delay/intellectual disability, epilepsy and absent expressive language. Movement disorders including stereotypies, spasticity and dystonia were also observed. Brain imaging revealed reductions in cortex, cerebellum and corpus callosum size with frequent white matter hyperintensity. Volumetric measurements indicated globally diminished volume rather than specific regional losses. We identified a reduced rate of trafficking into the Golgi apparatus and Golgi fragmentation in patient-derived fibroblasts that was rescued by wild-type TRAPPC6B. Molecular studies revealed a weakened interaction between mutant TRAPPC6B (c.454C>T, p.Q152*) and its TRAPP binding partner TRAPPC3. Patient-derived fibroblasts from the TRAPPC6B (c.454C>T, p.Q152*) variant displayed reduced levels of TRAPPC6B as well as other TRAPP II complex-specific members (TRAPPC9 and TRAPPC10). Interestingly, the levels of the TRAPPC6B homologue TRAPPC6A were found to be elevated. Moreover, co-immunoprecipitation experiments showed that TRAPPC6A co-precipitates equally with TRAPP II and TRAPP III, while TRAPPC6B co-precipitates significantly more with TRAPP II, suggesting enrichment of the protein in the TRAPP II complex. This implies that variants in TRAPPC6B may preferentially affect TRAPP II functions compared to TRAPP III functions. Finally, we assessed phenotypes in a Drosophila TRAPPC6B-deficiency model. Neuronal TRAPPC6B knockdown impaired locomotion and led to wing posture defects, supporting a role for TRAPPC6B in neuromotor function. Our findings confirm the association of damaging biallelic TRAPPC6B variants with microcephaly, intellectual disability, language impairments, and epilepsy. A subset of patients also exhibited dystonia and/or spasticity with impaired ambulation. These features overlap with disorders arising from pathogenic variants in other TRAPP subunits, particularly components of the TRAPP II complex. These findings suggest that TRAPPC6B is essential for brain development and function, and TRAPP II complex activity may be particularly relevant for mediating this function.

Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder.

PURPOSE: SLC4A10 encodes a plasma membrane-bound transporter, which mediates Na+-dependent HCO3- import, thus mediating net acid extrusion. Slc4a10 knockout mice show collapsed brain ventricles, an increased seizure threshold, mild behavioral abnormalities, impaired vision, and deafness. METHODS: Utilizing exome/genome sequencing in families with undiagnosed neurodevelopmental disorders and international data sharing, 11 patients from 6 independent families with biallelic variants in SLC4A10 were identified. Clinico-radiological and dysmorphology assessments were conducted. A minigene assay, localization studies, intracellular pH recordings, and protein modeling were performed to study the possible functional consequences of the variant alleles. RESULTS: The families harbor 8 segregating ultra-rare biallelic SLC4A10 variants (7 missense and 1 splicing). Phenotypically, patients present with global developmental delay/intellectual disability and central hypotonia, accompanied by variable speech delay, microcephaly, cerebellar ataxia, facial dysmorphism, and infrequently, epilepsy. Neuroimaging features range from some non-specific to distinct neuroradiological findings, including slit ventricles and a peculiar form of bilateral curvilinear nodular heterotopia. In silico analyses showed 6 of 7 missense variants affect evolutionarily conserved residues. Functional analyses supported the pathogenicity of 4 of 7 missense variants. CONCLUSION: We provide evidence that pathogenic biallelic SLC4A10 variants can lead to neurodevelopmental disorders characterized by variable abnormalities of the central nervous system, including altered brain ventricles, thus resembling several features observed in knockout mice.

Biallelic BORCS8 variants cause an infantile-onset neurodegenerative disorder with altered lysosome dynamics.

BLOC-one-related complex (BORC) is a multiprotein complex composed of eight subunits named BORCS1-8. BORC associates with the cytosolic face of lysosomes, where it sequentially recruits the small GTPase ARL8 and kinesin-1 and -3 microtubule motors to promote anterograde transport of lysosomes toward the peripheral cytoplasm in non-neuronal cells and the distal axon in neurons. The physiological and pathological importance of BORC in humans, however, remains to be determined. Here, we report the identification of compound heterozygous variants [missense c.85T>C (p.Ser29Pro) and frameshift c.71-75dupTGGCC (p.Asn26Trpfs*51)] and homozygous variants [missense c.196A>C (p.Thr66Pro) and c.124T>C (p.Ser42Pro)] in BORCS8 in five children with a severe early-infantile neurodegenerative disorder from three unrelated families. The children exhibit global developmental delay, severe-to-profound intellectual disability, hypotonia, limb spasticity, muscle wasting, dysmorphic facies, optic atrophy, leuko-axonopathy with hypomyelination, and neurodegenerative features with prevalent supratentorial involvement. Cellular studies using a heterologous transfection system show that the BORCS8 missense variants p.Ser29Pro, p.Ser42Pro and p.Thr66Pro are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution toward the cell periphery. The BORCS8 frameshift variant p.Asn26Trpfs*51, on the other hand, is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution toward the cell periphery. Therefore, all the BORCS8 variants are partial or total loss-of-function alleles and are thus likely pathogenic. Knockout of the orthologous borcs8 in zebrafish causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease. These findings thus identify BORCS8 as a novel genetic locus for an early-infantile neurodegenerative disorder and highlight the critical importance of BORC and lysosome dynamics for the development and function of the central nervous system.

General dentists' awareness of orthodontic treatment needs of patients and their referral practices.

Background: Since general dentists (GDs) usually act as the primary referral source for the patients in need of orthodontic treatments, having the proper knowledge and understanding of the accurate diagnosis of clinical situations is very important. The aim of this study was to assess GDs about the identification of orthodontic treatment needs and their referral practices. Materials and Methods: This descriptive and analytical cross-sectional study was carried out in Iran 2020. A questionnaire consisting of three main parts was designed and distributed electronically among GDs. The first section included 11 image and scenario-based questions meant to assess the ability of GDs to correctly diagnose the orthodontic treatment needs of the patients. The next two parts were to assess the dentists' knowledge of the necessity of referral to an orthodontist with 11 questions, and the proper timing of orthodontic treatments with 8 questions. Data were analyzed using SPSS 26, by conducting Mann-Whitney, Kruskal-Wallis, and correlation tests α = 0.05. Results: Among 384 participated dentists, 50.3% (193) were female. The mean score of knowledge was 17.3 ± 3.5 out of 30. The highest percentage of good knowledge (70% of range) was related to the diagnosis of orthodontic problems, while the lowest one belonged to the referring pattern. There was a weak positive correlation between the working experience and the proper timing of referral (R = 0.15, P = 0.004 (. Kruskal-Wallis test also showed a significant difference between the total knowledge scores (P = 0.04) and the knowledge of the proper timing of treatment (P = 0.04) based on the age groups of participants. Eighty-seven percentage (n = 334) reported that they would refer the patients in need of orthodontic treatment. Conclusion: The knowledge level of orthodontic treatment needs among GDs was moderate, thus emphasizing the importance of planning more educational courses for them to improve their knowledge, thus reducing the possible detriments of postponed or inaccurate treatments.

Novel homozygous variants in PRORP expand the genotypic spectrum of combined oxidative phosphorylation deficiency 54.

Biallelic hypomorphic variants in PRORP have been recently described as causing the autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a phenotypic spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy. Here, we report three additional families with homozygous missense PRORP variants with pleiotropic phenotypes. Each missense variant altered a highly conserved residue within the metallonuclease domain. In vitro mitochondrial tRNA processing assays with recombinant TRMT10C, SDR5C1 and PRORP indicated two COXPD54-associated PRORP variants, c.1159A>G (p.Thr387Ala) and c.1241C>T (p.Ala414Val), decreased pre-tRNAIle cleavage, consistent with both variants impacting tRNA processing. No significant decrease in tRNA processing was observed with PRORP c.1093T>C (p.Tyr365His), which was identified in an individual with leukodystrophy. These data provide independent evidence that PRORP variants are associated with COXPD54 and that the assessment of 5' leader mitochondrial tRNA processing is a valuable assay for the functional analysis and clinical interpretation of novel PRORP variants.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'.

Comparison of shear bond strength of rebonded stainless steel brackets with three different enamel surface conditioning methods.

Background: During the orthodontic bonding process, the need for repositioning or rebonding of orthodontic brackets on the enamel surface occurs frequently. The aim of this study is to compare the shear bond strength (SBS) in rebonding orthodontic stainless steel brackets with three different methods of enamel surface conditioning methods. Materials and Methods: In this in vitro study, 80 human premolars that were extracted for orthodontic purposes were randomly divided into four groups and underwent orthodontic bonding procedure (N = 20). Except for the control group, three other groups underwent debonding and rebonding process in which after removing the remaining adhesive with tungsten-carbide bur, enamel surface conditioned by three different methods including re-etching with phosphoric acid, sandblasting + acid etching, and Erbium-doped Yttrium-Aluminum-Garnet laser. Then, the SBS of the bracket to the enamel surface was compared between different groups. Scanning Electron microscopy images were also obtained from a number of samples. Statistical analysis was performed by Kruskal-Wallis and Mann-Whitney tests. Results: The highest SBS was observed in the primary bond (control group) with an average of 29,440 MPa. There was a significant difference between the studied groups (P < 0.001) and only the group that was re-etched with phosphoric acid had no significant difference with the control group (P = 0.708) ∝ =0.05. Conclusion: Rebonding of brackets using phosphoric acid for reconditioning of the enamel surface creates bond strength comparable to the primary bond. Other groups had significantly lower SBS than the control group.

Effect of sodium ascorbate on the shear bond strength of orthodontic brackets to bleached enamel using universal dental adhesive.

Background: The aim of this study was to investigate the effect of bleaching agent, sodium ascorbate as an antioxidant, and delay time on the shear bond strength (SBS) of orthodontic brackets to enamel using Transbond XT and universal adhesive. Materials and Methods: In this in vitro experimental study, 80 extracted maxillary premolars without any defect or decay were randomly divided into eight groups of 1: no bleaching + Transbond XT (NB/TX) bonding agent, 2: no bleaching + All-Bond Universal (NB/AB), 3: bleaching + Transbond XT (B/TX), 4: bleaching + All-Bond Universal (B/AB), 5: bleaching + sodium ascorbate + Transbond XT (B/SA/TX), 6: bleaching + sodium ascorbate + All-Bond Universal (B/SA/AB), 7: bleaching + Transbond XT after a 3-week delay (B/3W/TX), and 8: bleaching + All-Bond Universal after a 3-week delay (B/3W/AB). After thermocycling (1000 cycles, 5-55°C), the SBS was measured, and the adhesive remnant index scores were determined to assess the failure mode. Data were analyzed by one-way analysis of variance, Tamhane's post hoc test, Kruskal-Wallis, and Mann-Whitney U-test at the significance level of P < 0.05. Results: The mean SBS range was 5.5-29.78 MPa. The highest SBS values were related to Group 2 (NB/AB) which were significantly higher than all groups (P < 0.05) and the lowest values were observed in Group 5 (B/SA/TX) which were significantly lower than all groups except Group 3 (B/TX) (P < 0.05). Conclusion: Bleaching with 40% hydrogen peroxide significantly decreased the SBS of orthodontic brackets, and 10% sodium ascorbate could not reverse the adverse effect of bleaching on SBS. Delaying the bonding procedure by 3 weeks using Universal adhesive considerably decreased the adverse effect of bleaching on SBS and increased the SBS to a clinically acceptable level for orthodontic treatment.

Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: Report of three families.

Bi-allelic variants affecting one of the four genes encoding the AP4 subunits are responsible for the "AP4 deficiency syndrome." Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936). We report on three patients with core features from three unrelated consanguineous families originating from the Middle East. Exome sequencing identified the same homozygous nonsense variant: NM_004722.4(AP4M1):c.1012C>T p.Arg338* (rs146262009). So far, four patients from three other families carrying this homozygous variant have been reported worldwide. We describe their phenotype and compare it to the phenotype of patients with other variants in AP4M1. We construct a shared single-nucleotide polymorphism (SNP) haplotype around AP4M1 in four families and suggest a probable founder effect of Arg338* AP4M1 variant with a common ancestor most likely of Turkish origin.

Medication-resistant acute focal motor seizures in a child with COVID-19 affecting the CNS

A perfectly healthy preschool girl presented with acute repetitive focal aware motor seizures, while her brain MRI showed a lesion in the left posterior cortex. After a number of investigations, her cerebrospinal fluid PCR was positive for SARS-CoV-2. Despite receiving at least four anti-seizure medications at appropriate dosages, the seizures continued, and just after administering intravenous immunoglobulin, her seizures stopped. This dramatic response to intravenous immunoglobulin may indicate a hypothetical inflammatory process in the patient's cortex caused by COVID-19.

COVID-19 Vaccine Hesitancy Among Patients With Epilepsy or Other Chronic Conditions.

OBJECTIVES: The aim of this study was to investigate the opinions of different groups of people in Iran on their willingness to receive a coronavirus disease 2019 (COVID-19) vaccine. METHODS: In this cross-sectional study, we surveyed a sample (based on consecutive referrals) of 5 groups of people in late 2020: a group of the general population from Shiraz (without a history of any chronic medical or psychiatric problems), patients with epilepsy, patients with diabetes mellitus (DM), patients with cardiac problems, and patients with psychiatric problems. The survey included 4 general questions and 3 COVID-19-specific questions. RESULTS: A total of 582 people participated. In total, 66 (11.3%) people expressed that they were not willing to receive a COVID-19 vaccine. Psychiatric disorders (odds ratio [OR]: 3.15; 95% confidence interval [CI]: 1.31-7.60; P = 0.006) and male sex (OR: 2.10; 95% CI: 1.23-3.58; P = 0.010) were significantly associated with COVID-19 vaccine hesitancy. CONCLUSION: Vaccine hesitancy is a global issue. Patients with psychiatric disorders had the highest rate of vaccine hesitancy. Previous studies have shown that depression and anxiety are associated with a reduced adherence to the recommended medical advice. Why male sex is associated with vaccine hesitancy is not clear. Researchers should investigate the rates and the factors affecting the vaccine hesitancy in their corresponding communities.

Mask Wearing Hesitancy During the COVID-19 Pandemic in South Iran.

PURPOSE: The aim of the current study was to investigate the prevalence of face mask wearing among different groups of people in south Iran. We also investigated the associations between mask wearing hesitancy and various factors. METHODS: We surveyed a sample (convenience sampling) of 5 groups of people: general population, people with epilepsy, people with diabetes mellitus (DM), people with cardiac problems, and people with psychiatric problems. The survey included 4 general questions (age, sex, education, and medical/psychiatric problem) and 4 coronavirus disease 2019 (COVID-19)-specific questions (contracting COVID-19, relatives with COVID-19, wearing a face mask while in crowded places, and the frequency of daily hand washings). RESULTS: A total of 582 people (153 people with epilepsy, 127 patients with DM, 98 people with cardiac problems, 96 patients with psychiatric disorders, and 108 healthy individuals) participated. Twenty-eight (4.8%) people expressed that they do not wear a face mask when at crowded places. A lower education and less frequent daily hand washings had associations with mask wearing hesitancy. CONCLUSIONS: Mask wearing hesitancy is a concern during a respiratory viral disease pandemic. Paying attention to personal variables, especially if they are modifiable (eg, education and hygiene), is probably productive and practical in promoting mask wearing culture.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Effect of different bleaching treatment protocols on shear bond strength of bonded orthodontic brackets with no-primer adhesive resin.

BACKGROUNDS: Bleaching procedure can be companied before, during, or after orthodontic treatments. However, the risk of compromised bond strength of brackets to bleached enamels is in debate. This study tried to evaluate the shear bond strength (SBS) of bonded metal brackets to the previously bleached enamels. MATERIALS AND METHODS: In this in vitro study, 60 extracted, sound, human premolars were mounted vertically in cylindrical molds. The samples were randomly divided into four groups (n = 15): Control (C); at-home bleached by 20% carbamide peroxide (HB); in-office bleached by 45% carbamide peroxide (OB); and in-office bleached by 40% hydrogen peroxide activated with diode laser (L-OB). Sixty stainless steel brackets were bonded by no-primer adhesive resin (OrthoCem). Then SBS of bonded brackets was measured after 5000 thermal cycles at 5°C and 55°C. Finally, the collected data were analyzed by one-way ANOVA, and Tukey HSD tests by using SPPS software at a significant level of 0.05 (α = 0.05). RESULTS: Group C showed significantly higher SBS values (all P < 0.001); however, there were no significant differences in SBS compared to other tests' groups with each other (all P > 0.05). CONCLUSION: The SBS of bonded orthodontic brackets were compromised after bleaching with 20% and 40% of carbamide peroxide. Diode laser activation may not eliminate the negative effect of bleaching agents on SBS of bonded orthodontic brackets, neither.

Effect of citric acid on force decay of orthodontic elastomeric chains.

BACKGROUND: This study aimed to assess the effect of citric acid, as a weak acid commonly used in food industry, on elastomeric chain force decay. MATERIALS AND METHODS: In this in vitro, experimental study, sixty elastomeric chains from two commercial brands of American Orthodontics and Ortho Technology (n = 30) were cut into five-piece segments. Elastomeric chains of each brand were randomly divided into two groups of control (artificial saliva) and citric acid. All elastomeric chains were incubated in artificial saliva at 37°C. Experimental samples were immersed in 10 mL of citric acid for 90 s daily and were then transferred back to the artificial saliva. The elastomeric chain force was measured at baseline (before the experiment), 1 day, 1 week, 2 weeks, and 3 weeks using an electromechanical universal testing machine. Data were analyzed using t-test, Kruskal-Wallis test, and Mann-Whitney U-test at 0.05 level of significance. RESULTS: The elastomeric chain force gradually degraded over time. The difference in this respect was not significant at 2 and 3 weeks in any group (P > 0.05). On initiation of the experiment, the force in the citric acid group experienced a greater decay than that in the control group; the difference between the citric acid and control groups in both the brands was significant at all time points until the end of the 3rd week (P < 0.05). The difference between the American Orthodontics and Ortho Technology brands in the control and citric acid groups was significant at all time points (P < 0.001). CONCLUSION: Elastomeric chains in both the citric acid and artificial saliva groups experienced force decay over time. Force decay was greater in the citric acid group. Thus, citric acid can effectively decrease the elastomeric chain force. The Ortho Technology chain force was higher than that of American Orthodontics in both the groups at all time points.

COVID-19 in a case with Kikuchi-Fujimoto disease.

The accurate diagnosis of Kikuchi-Fujimoto disease can protect children from unnecessary diagnostic procedures and treatments. Also, the co-occurrence of rare diseases with other diseases can improve or worsen the symptoms of the patients.

Is the risk of COVID-19 contraction increased in patients with epilepsy?

OBJECTIVE: The aim of the current study was to investigate the rates of contracting COVID-19 in various populations to provide evidence on the susceptibility of patients with epilepsy (PWE) to contracting symptomatic COVID-19. METHODS: We surveyed a random sample of three groups of people: patients with epilepsy, people with psychiatric problems, and a group of the general population. The survey included four general questions (age, sex, education, and medical/psychiatric problem) and four COVID-19 specific questions (contracting COVID-19, relatives with COVID-19, wearing a face mask, and frequent hand washings). RESULTS: Three hundred and fifty -eight people were surveyed (108 healthy individuals, 154 patients with epilepsy, and 96 patients with psychiatric problems). Thirty-eight (11%) people had a history of COVID-19 contraction. The only factor that had a significant association with COVID-19 contraction was a relative with COVID-19 (Odds Ratio: 5.82; 95% Confidence Interval: 2.85-11.86; p = 0.0001). Having epilepsy did not increase the risk of COVID-19 contraction. CONCLUSION: Symptomatic COVID-19 does not seem to be more likely in PWE. The single most important factor associated with contracting COVID-19 is a close relative with this infection. Isolation of people with SARS-CoV-2 infection and observation of their close contacts may reduce the risk of secondary infections.

Central nervous system manifestations in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, EMBASE, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between 1 January 2020 and 20 April 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456). RESULTS: Of 2,353 retrieved studies, we selected 64 studies with 11,687 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 was headache (8.69%, 95%CI: 6.76%-10.82%), dizziness (5.94%, 95%CI: 3.66%-8.22%), and impaired consciousness (1.90%, 95%CI: 1.0%-2.79%). CONCLUSIONS: The growing number of studies has reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes.