Parents of Children Diagnosed with Autism Spectrum Disorder: What Do They Expect and Experience from Preschools?

BACKGROUND: In Sweden, children diagnosed with autism spectrum disorders (ASD) as well as other children in need of special support, according to the law should be provided stimulation and support for their development in their preschools. Parents of children diagnosed with ASD have been shown to struggle to ensure the right to support for their child from society, including in preschool. This study reports parent expectations and experiences when having a child diagnosed with ASD in preschool. METHODS: A questionnaire with 12 open-ended and 9 multiple-choice questions was completed by parents of 26 children (3 girls, 23 boys, mean age 4:3 years). The children had been diagnosed with ASD within the last year. The data were analyzed using a qualitative inductive approach with a content analysis of the open-ended questions. FINDINGS AND CONCLUSIONS: This study shows that parents expect competence and knowledge about ASD among preschool staff, including the principal. They need continuous dialogue between parents and the preschool staff and expect individualized support for their child. Concerns about their child in preschool frequently occurred.

Incidence of and risk factors for medication-related osteonecrosis of the jaw in women with breast cancer with bone metastasis: a population-based study.

OBJECTIVE: The aim of this study was to prospectively determine the incidence of medication-related osteonecrosis of the jaw (MRONJ) and define risk factors in patients with metastatic breast cancer treated with zoledronic acid and/or denosumab. STUDY DESIGN: In a prospective cohort study performed in Region Skåne, Sweden, from January 1, 2012, until December 31, 2015, all patients with breast cancer who had radiographic evidence of bone metastases and were treated with zoledronic acid or denosumab were included and followed up until May 31, 2018. RESULTS: Of the 242 patients, MRONJ developed in 16 (6.6%) during the 77 months of study. The incidence of MRONJ in patients treated with zoledronic acid was 4.1%, and in patients treated with denosumab, it was 13.6%. The risk of MRONJ was higher in patients on denosumab than in those treated with zoledronic acid (P = .011). Corticosteroid use was associated with a decreased risk of MRONJ (P = .008), and diabetes was associated with an increased risk of MRONJ (P = .02). CONCLUSIONS: The incidence of MRONJ is 13.6% (>3 times higher) in denosumab-treated patients with breast cancer compared with that in patients treated with zoledronic acid (4.1%). Corticosteroid use decreased the risk of MRONJ.

Prevalence, initiating factor, and treatment outcome of medication-related osteonecrosis of the jaw-a 4-year prospective study.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) has a wide range of prevalence, and a standard therapy has not yet been established. The aim of this study was to analyze the prevalence and initiating factors of MRONJ and the outcomes of surgical therapy. STUDY DESIGN: In a prospective cohort study, all patients diagnosed with MRONJ in the Region of Skåne, in Sweden, were included. Predictor variables (comorbidity, site, stage, gender) and initiating factors (tooth extraction, periodontitis) were recorded. Surgical treatment was sequestrectomy or block resection, and the outcome variable was healing after 2 months. To estimate the prevalence, data on the use of bisphosphonate and denosumab were used. RESULTS: Fifty-five patients with MRONJ were identified. The prevalence of MRONJ was 0.043% among patients treated with oral bisphosphonates, 1.03% among those on intravenous bisphosphonates and 3.64% in those on high-dose denosumab. Periodontal disease preceded development of MRONJ in 41 patients. Fifty patients were treated surgically and followed up for at least 2 months. Remission or healing occurred in 80% of patients treated with sequestrectomy and in 92.5% of patients treated with block resection. CONCLUSIONS: The prevalence of MRONJ in Sweden is low. Periodontitis is the most common initiating factor. The outcome of treatment of MRONJ is healing in most patients treated surgically.

A 6-year follow-up of children assessed for suspected autism spectrum disorder: parents' experiences of society's support.

BACKGROUND: Early support and interventions are suggested to be important for children with autism spectrum disorder (ASD) and other developmental problems and their families. Parents are described to have a burdensome life situation where the child's problems have a great impact on the family's well-being. AIM: To obtain increased knowledge of parents' experiences of support and interventions 6 years after their child was assessed for ASD. METHODS AND PROCEDURES: A semi-structured questionnaire was sent to all parents (n=101) whose preschool children (<4 years of age) had been assessed for ASD about 6 years prior in Gothenburg, Sweden. The open-ended questions were analyzed thematically using a hermeneutic phenomenological approach. OUTCOMES AND RESULTS: Parents of 56 children answered 30 questions about their experiences concerning support from society after the neuropsychiatric assessment. From the eight open-ended questions, three themes were identified: parental responsibility, resources and competence among actors in society, and inequality. The parents experienced that they had to take responsibility for meeting the needs of and securing support for their child. They found that the support given was unequal, uncoordinated, and with great variations between both geographical areas and professionals. Parents' own resources were described as impacting the possibility to secure adequate interventions, resulting in unequal treatment of families depending on socioeconomic status. Several parents also expressed experiencing a lack of individualization of services and interventions. All children had received some kind of action from society, but not to the degree they had wished for when the children got their ASD diagnosis. CONCLUSION AND IMPLICATIONS: The essence of parents' comments was the experience of authorities and societal actors trying to push the responsibility onto someone else. The study indicates a need for continuous longitudinal support for children identified with neurodevelopmental problems before the age of 3 years. This requires collaboration and coordination between different societal bodies.

Bacterial diversity in medication-related osteonecrosis of the jaw.

OBJECTIVE: The aim was to study the association between microflora and medication-related osteonecrosis of the jaw (MRONJ) by using culture-independent molecular techniques to detect bacteria in necrotic bone lesions. STUDY DESIGN: Included were 18 consecutive patients with MRONJ, 10 with osteoporosis and 8 cancer patients. Bone biopsies were retrieved from the center of the necrotic bone and from visually healthy bone, and 16 S rRNA gene fragments from bacterial DNA were amplified with polymerase chain reaction. RESULTS: The study revealed a diversity of bacteria represented by 16 S rRNA sequences in all the necrotic bone samples and in 60% of the visually healthy bone. Eight dominating taxa groups were identified at the genus level: Porphyromonas, Lactobacillus, Tannerella, Prevotella, Actinomyces, Treponema, Streptococcus, and Fusobacterium. CONCLUSIONS: The necrotic bone lesions contained mainly anaerobic bacteria, representative of periodontal microflora, suggesting that a periodontal infection in combination with antiresorptive treatment could initiate osteonecrosis.

Characterisation of de novo mutations in the C-terminal domain of proprotein convertase subtilisin/kexin type 9.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the hepatic low-density lipoprotein receptor (LDL-R) and is therefore a prominent therapeutic target for reducing LDL-cholesterol. The C-terminal domain of PCSK9 is unlikely to be involved in a direct extracellular interaction with the LDL-R. We probed the importance of the C-terminus for the degradation of the LDL-R by designing seven de novo mutants of PCSK9 that fill potential druggable cavities. The mutants were tested for their ability to diminish LDL uptake in human HepG2 cells and for affinity towards a calcium independent mutant of the EGF(A) domain of the human LDL-R. The later was done by a newly developed surface plasmon resonance-based assay format. We identified three mutant proteins (G517R, V610R and V644R) with decreased ability to block LDL uptake into HepG2 cells. These mutations define areas outside the direct interaction area between PCSK9 and the LDL-R that could be targeted to inhibit the PCSK9 triggered degradation of the LDL-R. We also describe the mechanistic rationalisation of the affinity changes seen with the natural occurring human D374Y (gain of function) mutation causing severe hypercholesterolaemia. The action of this mutant is due to a significantly decreased dissociation rate constant, whereas the mutation does not affect the association rate constant.

Preschoolers assessed for autism: parent and teacher experiences of the diagnostic process.

Many parents of young children with autism spectrum disorder (ASD) have often been recommended to "wait and see" when they have first expressed concerns. This comparative, descriptive, partly longitudinal questionnaire study aimed to evaluate parent/preschool teacher experiences as regards time of first concern about the child and about the diagnostic process at a specialized Child Neuropsychiatry Clinic. Participants were parents and teachers of 34 preschool children with suspected ASD (26 boys, 8 girls, mean age 37 months) drawn from a general population cohort. Most of the parents, and the teachers, had their first concern about the child's development before the child's second birthday. Generally, they were satisfied with the diagnostic process and did not regret their participation in it.

Osteonecrosis of the jaw in patients treated with oral and intravenous bisphosphonates: experience in Sweden.

OBJECTIVE: To describe the prevalence, inciting factors, and treatment outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) during the 2003-2010 period in southern Sweden (population, approximately 1.2 million people). STUDY DESIGN: Patient records were searched for inflammatory conditions including unspecified inflammation, osteomyelitis, osteonecrosis due to drugs, and other osteonecrosis. Data on underlying disease, type of bisphosphonate (BP), inciting factor, location, stage, treatment, and treatment outcomes were collected. RESULTS: Of the 341 patients identified, 55 had been diagnosed with BRONJ. Those with a malignant disease were treated with intravenous BPs, and those with osteoporosis were treated with oral BPs. All but 5 were treated with antibiotics and 47 with local resection. Healing was recorded in 79% of patients with osteoporosis and in 26% of patients with malignant disease. CONCLUSIONS: Healing in patients with osteoporosis occurred more frequently than in patients with a malignant disease treated with intravenous BPs (P = .00009).

High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma - 5-year follow up of a population-based study.

CONCLUSION: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. OBJECTIVES: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. METHODS: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000-2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. RESULTS: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.

Autism in preschoolers: does individual clinician's first visit diagnosis agree with final comprehensive diagnosis?

Comprehensive clinical diagnosis based on all available information is considered the "gold standard" in autism spectrum disorders (ASD). We examined agreement across independent assessments (clinical judgment) of 34 young children (age 24-46 months) with suspected ASD, assessed by a multidisciplinary team, and final comprehensive clinical diagnosis. Agreement across settings and between each clinician's assessment and final diagnosis was moderate. The poorest fit was found at assessment in connection with psychological evaluation and the best with preschool observation and parent interview. Some individual clinicians had good and others had poor fit with final diagnosis. Disagreement across assessments was pronounced for girls. The findings suggest that multidisciplinary assessments remain important and that comprehensive clinical diagnosis should still be regarded as the gold standard in ASD.

Autism in toddlers: can observation in preschool yield the same information as autism assessment in a specialised clinic?

We wanted to know whether preschool observation of children suspected of suffering from autism can provide the same information about core autism symptoms as the Autism Diagnostic Observation Schedule (ADOS) performed in a clinic. Forty 2-4-year-old children (9 girls, 31 boys), referred for assessment of suspected autism spectrum disorder participated in the study. The symptom areas covered by the ADOS algorithm were scored by an education specialist after free-field observation of each child in the preschool without using the prescribed ADOS materials. The ADOS was then completed in a clinic setting by examiners blind to the preschool results. Excellent agreement across results obtained at the two different types/settings of observations was found. The only significant difference found was with regard to spontaneous initiation of joint attention. The present study does not address the issue of whether or not one of the methods used is superior to the other when it comes to determining the "true" level of "autism problems" in these children. However, it is of interest that free-field preschool observation of children with suspected autism using a structured checklist yields very similar information as that obtained at ADOS assessment performed in a clinic setting.

Pre-school children with suspected autism spectrum disorders: do girls and boys have the same profiles?

The male to female ratio is raised in autism spectrum disorders (ASD). Previous studies have suggested that girls with ASD have more problems with communication than boys, but boys show more repetitive behaviours than girls. In this study, 20 girls, 1.8-3.9 years of age were matched for chronological and developmental age with 20 boys with suspected ASD. All the children were recruited after population screening and referral by Child Health Care Services to a specialised neuropsychiatry clinic, where they underwent comprehensive neuropsychiatric assessments. Comparisons were made with regard to diagnosis, developmental profiles and global disability. No significant gender differences were found. There were strong correlations between results obtained in different developmental areas. The results suggest that either (1) previous studies finding clear gender differences may have overrated discrepancies between girls and boys in ASD, or that (2) there may be girls, who will not be identified in the early years with our current screening instruments. More research with a much larger population representative study samples is required.

Periosteal expansion before local bone reconstruction using a new technique for measuring soft tissue profile stability: a clinical study.

PURPOSE: To evaluate the outcome of intraoral soft tissue expansion by measuring the profile change using objective 3D metering equipment and to evaluate localized bone grafting after soft tissue expansion with regard to gain of bone and complications. MATERIALS AND METHODS: Using a prospective study design, we asked patients with an osseous and soft tissue defect on the buccal aspect of the alveolar process to participate in this study. In 10 patients (experimental group) a self-inflatable soft tissue expander was placed under the periosteum. After 2 weeks, the expander was removed and a particulated onlay bone graft was placed in the expanded area, protected by a titanium mesh covered with a collagen membrane. Ten patients (reference group) were treated with a mandibular ramus bone block graft. The soft tissue profile was registered before each surgical procedure. The vertical and lateral dimensions of the bone grafts were noted at the grafting procedure and at the implant installation. P < .05 was considered significant. RESULTS: The mean soft tissue profile change was 2.9 ± 1.1 mm after soft tissue expansion and 2.3 ± 2.1 mm at implant placement in the experimental group compared with 1.5 ± 1.4 mm at implant placement in the reference group (P = .065). Two patients had minor perforations of the soft tissue expander. In the experimental group, the mean lateral bone augmentation after soft tissue expansion was 4.5 ± 1.3 mm, and after healing, it decreased to 3.9 ± 1.4 mm (P = .063). The mean vertical augmentation was 4.1 ± 1.7 mm and had decreased at implant placement to 3.0 ± 1.4 mm (P = .041). In the reference group, the mean lateral augmentation was 3.8 ± 0.8 mm, and after healing, it reduced to 2.7 ± 0.8 mm (P = .024). The mean vertical augmentation was 2.9 ± 0.9 mm, and after healing of the bone graft at implant placement, it was reduced to 1.6 ± 0.8 mm (P = .01). When smokers were excluded, there was significantly less resorption of the bone grafts in both lateral (P = .049) and vertical (P = .012) dimensions in the experimental group compared with the reference group. CONCLUSION: Hydrogel expansion of the periosteum is an applicable method to achieve a surplus of soft tissue to cover bone grafts. More refinements to the technique may be required to minimize complications, especially in smoking patients.

The prevalence of autism spectrum disorders in toddlers: a population study of 2-year-old Swedish children.

Autism Spectrum Disorder (ASD) is more common than previously believed. ASD is increasingly diagnosed at very young ages. We report estimated ASD prevalence rates from a population study of 2-year-old children conducted in 2010 in Gothenburg, Sweden. Screening for ASD had been introduced at all child health centers at child age 21/2 years. All children with suspected ASD were referred for evaluation to one center, serving the whole city of Gothenburg. The prevalence for all 2-year-olds referred in 2010 and diagnosed with ASD was 0.80%. Corresponding rates for 2-year-olds referred to the center in 2000 and 2005 (when no population screening occurred) were 0.18 and 0.04%. Results suggest that early screening contributes to a large increase in diagnosed ASD cases.

Guided bone generation in a rabbit mandible model after periosteal expansion with an osmotic tissue expander.

OBJECTIVES: To evaluate the space-maintaining capacity of titanium mesh covered by a collagen membrane after soft tissue expansion on the lateral border of the mandible in rabbits, and to assess bone quantity and quality using autogenous particulate bone or bone-substitute (Bio-Oss(®) ), and if soft tissue ingrowth can be avoided by covering the mesh with a collagen membrane. MATERIAL AND METHODS: In 11 rabbits, a self-inflatable soft tissue expander was placed under the lateral mandibular periosteum via an extra-oral approach. After 2 weeks, the expanders were removed and a particulated onlay bone graft and deproteinized bovine bone mineral (DBBM) (Bio-Oss(®) ) were placed in the expanded area and covered by a titanium mesh. The bone and DBBM were separated in two compartments under the mesh with a collagen membrane in between. The mesh was then covered with a collagen membrane. After 3 months, the animals were sacrificed and specimens were collected for histology. RESULTS: The osmotic soft tissue expander created a subperiosteal pocket and a ridge of new bone formed at the edges of the expanded periosteum in all sites. After the healing period of 3 months, no soft tissue dehiscence was recorded. The mean bone fill was 58.1±18% in the bone grafted area and 56.9±13.7% in the DBBM area. There was no significant difference between the autologous bone graft and the DDBM under the titanium mesh with regard to the total bone area or the mineralized bone area. Scanning electron microscopy showed that new bone was growing in direct contact with the DBBM particles and the titanium mesh. There is a soft tissue ingrowth even after soft tissue expansion and protection of the titanium mesh with a collagen membrane. CONCLUSION: This study confirms that an osmotic soft tissue expander creates a surplus of periosteum and soft tissue, and that new bone can subsequently be generated under a titanium mesh with the use of an autologous bone graft or DBBM.

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS).

By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8.

Onlay bone grafting of the mandible after periosteal expansion with an osmotic tissue expander: an experimental study in rabbits.

OBJECTIVES: To evaluate the space-maintaining capacity of a titanium mesh or a bioresorbable mesh after periosteal expansion and to assess bone formation under a titanium mesh or a bioresorbable mesh on the lateral border of the mandible by qualitative and quantitative histological analysis. MATERIAL AND METHODS: In 13 rabbits, a self-inflatable soft tissue expander was placed intraorally, bilaterally under the mandibular periosteum via an extra oral approach. After 2 weeks, the expanders were removed and a particulated onlay bone graft was placed and covered by a titanium mesh or a bioresorbable mesh. After 3 months, the animals were sacrificed and specimens were collected for histology. RESULTS: The osmotic soft tissue expander created a subperiosteal pocket and a ridge of new bone had formed at the edges of the expanded periosteum in all sites. After the healing period of 3 months, soft tissue dehiscence was recorded in two of the sites with bioresorbable meshes. The mean bone fill was 65% under the titanium mesh and 85% under the bioresorbable mesh (P<0.05). There was no significant difference between the titanium mesh and the bioresorbable mesh regarding the height of the meshes, mesh area and mineralized bone area. Scanning electron microscopy shows that new bone is growing in direct contact with the resorbable mesh and the titanium mesh. CONCLUSION: This study confirms that an osmotic soft tissue expander creates a surplus of periosteum and soft tissue and that new bone can be generated under a titanium mesh or bioresorbable mesh.

Periosteal expansion of rabbit mandible with an osmotic self-inflatable expander.

We aimed to evaluate a new technique for intraoral expansion of soft tissue with a self-inflatable expander in rabbits. We placed a self-inflatable soft tissue expander bilaterally in eight rabbits under the periosteum of the mandible through an extraoral approach. The expander was left to self-inflate for two weeks, after which the animals were killed and specimens collected for histological examination. The self-inflatable soft tissue expanders expanded the periosteum. There were no dehiscences or infections. Histological observations showed no signs of any inflammatory reaction and there was no evidence of bony resorption. New bone had formed at the edges of the expanded periosteum. In the control area no new bone had formed. The osmotic soft tissue expander model for intraoral soft tissue and periosteal expansion suggests a promising way of creating a surplus of soft tissue that can be used to cover bone grafts.

Postzygotic isolation over multiple generations of hybrid descendents in a natural hybrid zone: how well do single-generation estimates reflect reproductive isolation?

Understanding speciation depends on an accurate assessment of the reproductive barriers separating newly diverged populations. In several taxonomic groups, prezygotic barriers, especially preferences for conspecific mates, are thought to play the dominant role in speciation. However, the importance of postzygotic barriers (i.e., low fitness of hybrid offspring) may be widely underestimated. In this study, we examined how well the widely used proxy of postzygotic isolation (reproductive output of F(1) hybrids) reflects the long-term fitness consequences of hybridization between two closely related species of birds. Using 40 species-specific single nucleotide polymorphism (SNP) markers, we genotyped a mixed population of collared and pied flycatchers (Ficedula albicollis and F. hypoleuca) to identify grand- and great grand-offspring from interspecific crosses to derive an accurate, multigeneration estimate of postzygotic isolation. Two independent estimates of fitness show that hybridization results in 2.4% and 2.7% of the number of descendents typical of conspecific pairing. This postzygotic isolation was considerably stronger than estimates based on F(1) hybrids. Our results demonstrate that, in nature, combined selection against hybrids and backcrossed individuals may result in almost complete postzygotic isolation between two comparatively young species. If these findings are general, postzygotic barriers separating hybridizing populations may be much stronger than previously thought.

Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.

Nitric oxide synthase (NOS) enzymes synthesize nitric oxide, a signal for vasodilatation and neurotransmission at low concentrations and a defensive cytotoxin at higher concentrations. The high active site conservation among all three NOS isozymes hinders the design of selective NOS inhibitors to treat inflammation, arthritis, stroke, septic shock and cancer. Our crystal structures and mutagenesis results identified an isozyme-specific induced-fit binding mode linking a cascade of conformational changes to a new specificity pocket. Plasticity of an isozyme-specific triad of distant second- and third-shell residues modulates conformational changes of invariant first-shell residues to determine inhibitor selectivity. To design potent and selective NOS inhibitors, we developed the anchored plasticity approach: anchor an inhibitor core in a conserved binding pocket, then extend rigid bulky substituents toward remote specificity pockets, which become accessible upon conformational changes of flexible residues. This approach exemplifies general principles for the design of selective enzyme inhibitors that overcome strong active site conservation.