Tooth Loss in Appalachia and the Mississippi Delta Relative to Other Regions in the United States, 1999–2010

Objectives. We examined regional variation in tooth loss in the United States from 1999 to 2010.Methods. We used 6 waves of the Behavioral Risk Factor Surveillance System and data on county characteristics to describe regional trends in tooth loss and decompose diverging trends into the parts explained by individual and county components.Results. Appalachia and the Mississippi Delta had higher levels of tooth loss than the rest of the country in 1999. From 1999 to 2010, tooth loss declined in the United States. However, Appalachia did not converge toward the US average, and the Mississippi Delta worsened relative to the United States. Socioeconomic status explained the largest portion of differences between regions in 1999, but a smaller portion of the trends. The Mississippi Delta is aging more quickly than the rest of the country, which explains 17% of the disparity in the time trend.Conclusions. The disadvantage in tooth loss is persistent in Appalachia and growing in the Mississippi Delta. The increasing disparity is partly explained by changes in the age structure but is also associated with behavioral and environmental factors.People in Appalachia have worse oral health than other Americans.1–4 West Virginia, the only state entirely located in Appalachia, has the highest rate of people missing 6 or more teeth (65.6%) and the second highest rate of complete tooth loss (37.8%) for people aged 65 years and older.5,6 The Mississippi Delta, another economically disadvantaged region, also has poor oral health. Mississippi, which falls mostly in the Mississippi Delta, follows West Virginia with the second highest rate of people missing 6 or more teeth (58.2%) and the fourth highest rate of complete tooth loss (27.3%) among those aged 65 years and older.5,6 Of the 5 states with the highest rate of people missing 6 or more teeth, 4 fall in the Mississippi Delta or Appalachia.Numerous studies have examined the causes of poor oral health in Appalachia and the Mississippi Delta. Studies have highlighted the importance of both individual attributes and broader elements that affect Appalachian communities. Individual attributes include socioeconomic status (SES), genetics, oral bacteria, tobacco use, knowledge of health behaviors, and dental insurance.1,2,4,7–9 Broader elements include fluoride in the water supply, cultural importance placed on oral health, presence of coal mining, and number of dentists and dental hygienists per capita.1,2,4,10,11 Less research has been done on oral health in the Mississippi Delta, although this region also has high rates of tooth loss. Studies that have analyzed this region have highlighted the roles of race, private dental insurance, parental oral health, parental health behaviors, and diet.12–15Oral health in the United States has significantly improved in the past 4 decades. The number of decayed, missing, and filled teeth; prevalence of untreated caries; edentulous rate; and rate of periodontal disease have all declined.16–22 The overall improvement in oral health outcomes in the United States raises the question of whether all areas of the United States are improving equally or whether there are persistent regional disparities in oral health outcomes. Previous reports from the Centers for Disease Control and Prevention have provided raw data on tooth loss in each state,5,6 but data on regional disparities is lacking. Moreover, without microdata it is impossible to discern whether divergent regional trends are attributable to relatively innocuous differences, such as the age structure of the regions, or driven by more concerning disparities, such as poverty and access to oral health care.To address this gap, we used data from the Behavioral Risk Factor Surveillance System (BRFSS) to examine regional variation in the level and improvement in the rate of tooth loss from 1999 to 2010. Our regions of interest, Appalachia and the Mississippi Delta, are defined as groups of counties. We analyzed the association between tooth loss and individual characteristics, individual behavior, and county factors.We tested 3 hypotheses: (1) The Mississippi Delta and Appalachia will have had less improvement in oral health than the rest of the country in the past decade, (2) the age profile of the regions will explain a portion of the regional differences, and (3) individual characteristics, individual behavior, and county characteristics will explain a portion of the regional differences.     

Arylsulfatase B modulates neurite outgrowth via astrocyte chondroitin‐4‐sulfate: Dysregulation by ethanol

In utero ethanol exposure causes fetal alcohol spectrum disorders, associated with reduced brain plasticity; the mechanisms of these effects are not well understood, particularly with respect to glial involvement. Astrocytes release factors that modulate neurite outgrowth. We explored the hypothesis that ethanol inhibits neurite outgrowth by increasing the levels of inhibitory chondroitin sulfate proteoglycans (CSPGs) in astrocytes. Astrocyte treatment with ethanol inhibited the activity of arylsulfatase B (ARSB), the enzyme that removes sulfate groups from chondroitin‐4‐sulfate (C4S) and triggers the degradation of C4S, increased total sulfated glycosaminoglycans (GAGs), C4S, and neurocan core‐protein content and inhibited neurite outgrowth in neurons cocultured with ethanol‐treated astrocytes in vitro, effects reversed by treatment with recombinant ARSB. Ethanol also inhibited ARSB activity and increased sulfate GAG and neurocan levels in the developing hippocampus after in vivo ethanol exposure. ARSB silencing increased the levels of sulfated GAGs, C4S, and neurocan in astrocytes and inhibited neurite outgrowth in cocultured neurons, indicating that ARSB activity directly regulates C4S and affects neurocan expression. In summary, this study reports two major findings: ARSB modulates sulfated GAG and neurocan levels in astrocytes and astrocyte‐mediated neurite outgrowth in cocultured neurons; and ethanol inhibits the activity of ARSB, increases sulfated GAG, C4S, and neurocan levels, and thereby inhibits astrocyte‐mediated neurite outgrowth. An unscheduled increase in CSPGs in the developing brain may lead to altered brain connectivity and to premature decrease in neuronal plasticity and therefore represents a novel mechanism by which ethanol can exert its neurodevelopmental effects. GLIA 2014;62:259–271     

A commonly carried genetic variant in the delta opioid receptor gene,OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single‐nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders. Hum Brain Mapp 35:1226–1236, 2014. © 2013 Wiley Periodicals, Inc.     

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.     

A motor learning-based intervention to ameliorate freezing of gait in subjects with Parkinson’s disease

Freezing of gait (FOG) is an episodic gait disturbance that is commonly seen in Parkinson’s disease (PD). To date, treatment efficacy is limited. We tested the hypothesis that an intervention that utilizes motor learning provided through intensive cueing can alleviate this symptom. Fifteen subjects with PD suffering from FOG participated in a 6 week progressive motor learning program (three training sessions per week—open trial). A training session included FOG-provoking situations (e.g., turns). Prior to each presumed FOG provocation (e.g., just before a turn), rhythmic auditory stimulation (RAS) was elicited and the subject was trained to walk rhythmically, coordinate left–right stepping and to increase step size, utilizing the RAS cueing. Net training duration increased from week to week and secondary cognitive tasks while walking were added to increase FOG propensity. FOG symptom burden was assessed before, immediately, and 4 weeks after the training period. The mean number of FOG episodes (±SEM) per 10 m of walking in a standardized gait assessment decreased from 0.52 ± 0.29 in the pre-testing to 0.15 ± 0.04 in the post-testing (p < 0.05). The duration of FOG episodes decreased from 4.3 ± 2.1 to 2.6 ± 0.6 s (p < 0.05). Additional measures (e.g., FOG questionnaire, gait speed) varied in their responsiveness to the treatment. These effects were retained 4 weeks after the training. The results of this open label study support the possibility that a motor learning-based intervention is apparently effective in reducing FOG burden, suggesting that RAS can deliver ‘anti-FOG’ training.     

Selective peripheral denervation: comparison with pallidal stimulation and literature review

Patients with cervical dystonia who are non-responders to Botulinum toxin qualify for surgery. Selective peripheral denervation (Bertrand’s procedure, SPD) and deep brain stimulation of the globus pallidus (GPi-DBS) are available surgical options. Although peripheral denervation has potential advantages over DBS, the latter is nowadays more commonly performed. We describe the long-term outcome of selective peripheral denervation as compared with GPi-DBS, along with the findings of literature review. Twenty patients with selective peripheral denervation and 15 with GPi-DBS were included. Tsui scale, a visual analogue scale, and the global outcome score of the Toronto Western Spasmodic Torticollis Rating Scale were used to define a “combined global surgical outcome”. The “combined global surgical outcome” for patients with selective peripheral denervation or pallidal stimulation was respectively “bad” for 65 and 13.3 %, “fair-to-good” for 30 and 26.7 %, and “marked” improvement for 5 and 60 % (p < 0.001). Improvement on visual analogue scale (p < 0.002), global outcome score (p < 0.002), and Tsui score (p < 0.000) was larger for the pallidal stimulation group. Seventy-five percent of patients with selective peripheral denervation and 60 % of patients with pallidal stimulation reported side effects. Seven patients with selective peripheral denervation successively underwent GPi-DBS, with a further significant improvement in the Tsui score (?48.6 ± 17.4 %). GPi-DBS is to be preferred to selective peripheral denervation for the treatment of cervical dystonia because it produces larger benefit, even if it can have more potentially severe complications. GPi-DBS is also a valid alternative in case of failure of SPD.     

Novel Genetic Models of Osteoporosis by Overexpression of Human RANKL in Transgenic Mice

Receptor activator of NF‐κB ligand (RANKL) plays a key role in osteoclast‐induced bone resorption across a range of degenerative bone diseases, and its specific inhibition has been recently approved as a treatment for women with postmenopausal osteoporosis at high or increased risk of fracture in the United States and globally. In the present study, we generated transgenic mice (TghuRANKL) carrying the human RANKL (huRANKL) genomic region and achieved a physiologically relevant pattern of RANKL overexpression in order to establish novel genetic models for assessing skeletal and extraskeletal pathologies associated with excessive RANKL and for testing clinical therapeutic candidates that inhibit human RANKL. TghuRANKL mice of both sexes developed early‐onset bone loss, and the levels of huRANKL expression were correlated with bone resorption and disease severity. Low copy Tg5516 mice expressing huRANKL at low levels displayed a mild osteoporotic phenotype as shown by trabecular bone loss and reduced biomechanical properties. Notably, overexpression of huRANKL, in the medium copy Tg5519 line, resulted in severe early‐onset osteoporosis characterized by lack of trabecular bone, destruction of the growth plate, increased osteoclastogenesis, bone marrow adiposity, increased bone remodeling, and severe cortical bone porosity accompanied by decreased bone strength. An even more severe skeletal phenotype developed in the high copy Tg5520 founder with extensive soft tissue calcification. Model validation was further established by evidence that denosumab, an antibody that inhibits human but not murine RANKL, fully corrected the hyper‐resorptive and osteoporotic phenotypes of Tg5519 mice. Furthermore, overexpression of huRANKL rescued osteopetrotic phenotypes of RANKL‐defective mice. These novel huRANKL transgenic models of osteoporosis represent an important advance for understanding the pathogenesis and treatment of high‐turnover bone diseases and other disease states caused by excessive RANKL. © 2014 American Society for Bone and Mineral Research.