Dental caries experience, oral health status and treatment needs of dental patients with autism

OBJECTIVES: Autism is a lifelong neurodevelopmental disorder. The aims of this study were to investigate whether children with autism have higher caries prevalence, higher periodontal problems, or more treatment needs than children of a control group of non-autistic patients, and to provide baseline data to enable comparison and future planning of dental services to autistic children. MATERIAL AND METHODS: 61 patients with autism aged 6-16 years (45 males and 16 females) attending Dubai and Sharjah Autism Centers were selected for the study. The control group consisted of 61 non-autistic patients chosen from relatives or friends of autistic patients in an attempt to have matched age, sex and socioeconomic status. Each patient received a complete oral and periodontal examination, assessment of caries prevalence, and caries severity. Other conditions assessed were dental plaque, gingivitis, restorations and treatment needs. Chi-square and Fisher's exact test of significance were used to compare groups. RESULTS: The autism group had a male-to-female ratio of 2.8:1. Compared to controls, children with autism had significantly higher decayed, missing or filled teeth than unaffected patients and significantly needed more restorative dental treatment. The restorative index (RI) and Met Need Index (MNI) for the autistic children were 0.02 and 0.3, respectively. The majority of the autistic children either having poor 59.0% (36/61) or fair 37.8% (23/61) oral hygiene compared with healthy control subjects. Likewise, 97.0% (59/61) of the autistic children had gingivitis. CONCLUSIONS: Children with autism exhibited a higher caries prevalence, poor oral hygiene and extensive unmet needs for dental treatment than non-autistic healthy control group. Thus oral health program that emphasizes prevention should be considered of particular importance for children and young people with autism

Training adults and children with an autism spectrum disorder to be compliant with a clinical dental assessment using a TEACCH-based approach

The specific neuropsychological and sensory profile found in persons with autism spectrum disorders complicate dental procedures and as a result of this, most are treated under general anesthesia or unnecessary sedation. The main goal of the present study was to evaluate the effectiveness of a short treatment and education of autistic and related communication-handicapped children-based intervention program (five sessions) to facilitate a 10-component oral assessment in children (n = 38, aged 4¿9 years) and adults (n = 34, aged 19¿41) with autism spectrum disorder (with or without associated intellectual disability). The assessment ranges from entering into the examination room to the evaluation of the dental occlusion. There were statistically significant differences in the number of components reached and in compliance before and after the training program

mTOR Is Essential for the Proteotoxic Stress Response, HSF1 Activation and Heat Shock Protein Synthesis

The target of rapamycin (TOR) is a high molecular weight protein kinase that regulates many processes in cells in response to mitogens and variations in nutrient availability. Here we have shown that mTOR in human tissue culture cells plays a key role in responses to proteotoxic stress and that reduction in mTOR levels by RNA interference leads to increase sensitivity to heat shock. This effect was accompanied by a drastic reduction in ability to synthesize heat shock proteins (HSP), including Hsp70, Hsp90 and Hsp110. As HSP transcription is regulated by heat shock transcription factor 1 (HSF1), we examined whether mTOR could directly phosphorylate this factor. Indeed, we determined that mTOR could directly phosphorylate HSF1 on serine 326, a key residue in transcriptional activation. HSF1 was phosphorylated on S326 immediately after heat shock and was triggered by other cell stressors including proteasome inhibitors and sodium arsenite. Null mutation of S326 to alanine led to loss of ability to activate an HSF1-regulated promoter-reporter construct, indicating a direct role for mTOR and S326 in transcriptional regulation of HSP genes during stress. As mTOR is known to exist in at least two intracellular complexes, mTORC1 and mTOR2 we examined which complex might interact with HSF1. Indeed mTORC1 inhibitor rapamycin prevented HSF1-S326 phosphorylation, suggesting that this complex is involved in HSF1 regulation in stress. Our experiments therefore suggest a key role for mTORC1 in transcriptional responses to proteotoxic stress

Protein Kinase A Binds and Activates Heat Shock Factor 1

BACKGROUND. Many inducible transcription factors are regulated through batteries of posttranslational modifications that couple their activity to inducing stimuli. We have studied such regulation of Heat Shock Factor 1 (HSF1), a key protein in control of the heat shock response, and a participant in carcinogenisis, neurological health and aging. As the mechanisms involved in the intracellular regulation of HSF1 in good health and its dysregulation in disease are still incomplete we are investigating the role of posttranslational modifications in such regulation. METHODOLOGY/PRINCIPAL FINDINGS. In a proteomic study of HSF1 binding partners, we have discovered its association with the pleiotropic protein kinase A (PKA). HSF1 binds avidly to the catalytic subunit of PKA, (PKAca) and becomes phosphorylated on a novel serine phosphorylation site within its central regulatory domain (serine 320 or S320), both in vitro and in vivo. Intracellular PKAca levels and phosphorylation of HSF1 at S320 were both required for HSF1 to be localized to the nucleus, bind to response elements in the promoter of an HSF1 target gene (hsp70.1) and activate hsp70.1 after stress. Reduction in PKAca levels by small hairpin RNA led to HSF1 exclusion from the nucleus, its exodus from the hsp70.1 promoter and decreased hsp70.1 transcription. Likewise, null mutation of HSF1 at S320 by alanine substitution for serine led to an HSF1 species excluded from the nucleus and deficient in hsp70.1 activation. CONCLUSIONS. These findings of PKA regulation of HSF1 through S320 phosphorylation add to our knowledge of the signaling networks converging on this factor and may contribute to elucidating its complex roles in the stress response and understanding HSF1 dysregulation in disease.National Institutes of Health (2RO1CA047407, RO1CA077465

Consanguinity and reproductive health among Arabs

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity

Ongoing efforts to improve the management of patients with diabetes in Bangladesh and the implications

Background: Prevalence rates of patients with diabetes are growing across countries, and Bangladesh is no exception. Associated costs are also increasing, driven by costs associated with the complications of diabetes including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia as well as improve patient comfort and adherence. However, they have been appreciably more expensive reducing their affordability and use. Biosimilars offer a way forward. Consequently, there is a need to document current prescribing and dispensing rates for long-acting insulin analogues across Bangladesh, including current prices and differences, as a result of affordability and other issues. Methods: Mixed method approach including surveying prescribing practices in hospitals coupled with dispensing practices and prices among community pharmacies and drug stores across Bangladesh. This method was adopted since public hospitals only dispense insulins such as soluble insulins free-of-charge until funds run out and all long-acting insulin analogues have to be purchased from community stores. Results: There has been growing prescribing and dispensing of long-acting insulins in Bangladesh in recent years, accounting for over 80% of all insulins dispensed in a minority of stores. This has been helped by growing prescribing and dispensing of biosimilar insulin glargine at lower costs that the originator, with this trend likely to continue with envisaged growth in the number of patients. Consequently, Bangladesh can serve as an exemplar to other low- and middle-income countries struggling to fund long-acting insulins for their patients. Conclusions: It was encouraging to see continued growth in the prescribing and dispensing of long-acting insulin analogues in Bangladesh via the increasing availability of biosimilars. This is likely to continue benefitting all key stakeholder groups

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Deformation characteristics and microstructural evolution in friction stir welding of thick 5083 aluminum alloy

The microstructure development in the weld key-hole along the plate thickness was investigated through scanning electron microscope (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM) techniques. A fundamental understanding of the contact condition at the tool/workpiece interface in a TriflatTM designed friction stir welding (FSW) tool is presented. The development of grain structure for “stop-action” weld reveals that the plasticized material undergoes complex interacting flows due to the presence of threads and flats. The localized high material velocities induce a significant increase in the strain rate within thread space and thereby tune the Zener-Hollomon parameter. An interesting analogy is drawn between the evolution of the secondary shear zone (SSZ) in a typical metal cutting and the steady state FSW processes. The presence of different morphology of the material filling the thread space is linked to the local variation of the contact state variables along weld thickness. It was found that the contact state is governed by the intrinsic interface characteristics and the mechanical property of the material. It was also shown that the presence of larger particles (> 0.5 μm) is responsible for the formation of high angle boundaries (HAGBs) and random recrystallization texture within the stir zone, reflecting random grain orientation due to particle-stimulated nucleation (PSN)