Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia.

BACKGROUND: West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease. METHODS: Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis. RESULTS: Statistically different bacterial signatures (P<0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of Veillonella and Streptococcus, with a moderate number of Capnocytophaga. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (Selenomonas, Eubacterium, Dialister). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease. CONCLUSIONS: Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia.

Caregivers of people with neurodegenerative diseases: profile and unmet needs from a population-based survey in South Australia.

INTRODUCTION: Neurodegenerative diseases (NDD) are characterized by progressive decline and loss of function, requiring considerable third-party care. NDD carers report low quality of life and high caregiver burden. Despite this, little information is available about the unmet needs of NDD caregivers. METHODS: Data from a cross-sectional, whole of population study conducted in South Australia were analyzed to determine the profile and unmet care needs of people who identify as having provided care for a person who died an expected death from NDDs including motor neurone disease and multiple sclerosis. Bivariate analyses using chi(2) were complemented with a regression analysis. RESULTS: Two hundred and thirty respondents had a person close to them die from an NDD in the 5 years before responding. NDD caregivers were more likely to have provided care for more than 2 years and were more able to move on after the death than caregivers of people with other disorders such as cancer. The NDD caregivers accessed palliative care services at the same rate as other caregivers at the end of life, however people with an NDD were almost twice as likely to die in the community (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.30 to 3.01) controlling for relevant caregiver factors. NDD caregivers reported significantly more unmet needs in emotional, spiritual, and bereavement support. CONCLUSION: This study is the first step in better understanding across the whole population the consequences of an expected death from an NDD. Assessments need to occur while in the role of caregiver and in the subsequent bereavement phase.

Trade-offs between cancer and other diseases: do they exist and influence longevity?

Relationships between aging, disease risks, and longevity are not yet well understood. For example, joint increases in cancer risk and total survival observed in many human populations and some experimental aging studies may be linked to a trade-off between cancer and aging as well as to the trade-off(s) between cancer and other diseases, and their relative impact is not clear. While the former trade-off (between cancer and aging) received broad attention in aging research, the latter one lacks respective studies, although its understanding is important for developing optimal strategies of increasing both longevity and healthy life span. In this paper, we explore the possibility of trade-offs between risks of cancer and selected major disorders. First, we review current literature suggesting that the trade-offs between cancer and other diseases may exist and be linked to the differential intensity of apoptosis. Then we select relevant disorders for the analysis (acute coronary heart disease [ACHD], stroke, asthma, and Alzheimer disease [AD]) and calculate the risk of cancer among individuals with each of these disorders, and vice versa, using the Framingham Study (5209 individuals) and the National Long Term Care Survey (NLTCS) (38,214 individuals) data. We found a reduction in cancer risk among old (80+) men with stroke and in risk of ACHD among men (50+) with cancer in the Framingham Study. We also found an increase in ACHD and stroke among individuals with cancer, and a reduction in cancer risk among women with AD in the NLTCS. The manifestation of trade-offs between risks of cancer and other diseases thus depended on sex, age, and study population. We discuss factors modulating the potential trade-offs between major disorders in populations, e.g., disease treatments. Further study is needed to clarify possible impact of such trade-offs on longevity.

Alternative splicing in multiple sclerosis and other autoimmune diseases.

Alternative splicing is a general mechanism for regulating gene expression that affects the RNA products of more than 90% of human genes. Not surprisingly, alternative splicing is observed among gene products of metazoan immune systems, which have evolved to efficiently recognize pathogens and discriminate between "self" and "non-self", and thus need to be both diverse and flexible. In this review we focus on the specific interface between alternative splicing and autoimmune diseases, which result from a malfunctioning of the immune system and are characterized by the inappropriate reaction to self-antigens. Despite the widespread recognition of alternative splicing as one of the major regulators of gene expression, the connections between alternative splicing and autoimmunity have not been apparent. We summarize recent findings connecting splicing and autoimmune disease, and attempt to find common patterns of splicing regulation that may advance our understanding of autoimmune diseases and open new avenues for therapy.

Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.

Final report of the Lyme disease review panel of the Infectious Diseases Society of America.

In April 2008, the Infectious Diseases Society of America (IDSA) entered into an agreement with Connecticut Attorney General Richard Blumenthal to voluntarily undertake a special review of its 2006 Lyme disease guidelines. This agreement ended the Attorney General's investigation into the process by which the guidelines were developed. The IDSA agreed to convene an independent panel to conduct a one-time review of the guidelines. The Review Panel members, vetted by an ombudsman for potential conflicts of interest, reviewed the entirety of the 2006 guidelines, with particular attention to the recommendations devoted to post-Lyme disease syndromes. After multiple meetings, a public hearing, and extensive review of research and other information, the Review Panel concluded that the recommendations contained in the 2006 guidelines were medically and scientifically justified on the basis of all of the available evidence and that no changes to the guidelines were necessary.

The genomic analysis of erythrocyte microRNA expression in sickle cell diseases.

BACKGROUND: Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). METHODS AND FINDINGS: Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. CONCLUSIONS: In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases.

The increasing impact of human immunodeficiency virus infections, sexually transmitted diseases, and viral hepatitis in Durham County, North Carolina: a call for coordinated and integrated services.

BACKGROUND: Durham County, North Carolina, faces high rates of human immunodeficiency virus (HIV) infection (with or without progression to AIDS) and sexually transmitted diseases (STDs). We explored the use of health care services and the prevalence of coinfections, among HIV-infected residents, and we recorded community perspectives on HIV-related issues. METHODS: We evaluated data on diagnostic codes, outpatient visits, and hospitalizations for individuals with HIV infection, STDs, and/or hepatitis B or C who visited Duke University Hospital System (DUHS). Viral loads for HIV-infected patients receiving care were estimated for 2009. We conducted geospatial mapping to determine disease trends and used focus groups and key informant interviews to identify barriers and solutions to improving testing and care. RESULTS: We identified substantial increases in HIV/STDs in the southern regions of the county. During the 5-year period, 1,291 adults with HIV infection, 4,245 with STDs, and 2,182 with hepatitis B or C were evaluated at DUHS. Among HIV-infected persons, 13.9% and 21.8% were coinfected with an STD or hepatitis B or C, respectively. In 2009, 65.7% of HIV-infected persons receiving care had undetectable viral loads. Barriers to testing included stigma, fear, and denial of risk, while treatment barriers included costs, transportation, and low medical literacy. LIMITATIONS: Data for health care utilization and HIV load were available from different periods. Focus groups were conducted among a convenience sample, but they represented a diverse population. CONCLUSIONS: Durham County has experienced an increase in the number of HIV-infected persons in the county, and coinfections with STDs and hepatitis B or C are common. Multiple barriers to testing/treatment exist in the community. Coordinated care models are needed to improve access to HIV care and to reduce testing and treatment barriers.

Dental microwear in live, wild-trapped Alouatta palliata from Costa Rica.

One problem with dental microwear analyses of museum material is that investigators can never be sure of the diets of the animals in question. An obvious solution to this problem is to work with live animals. Recent work with laboratory primates has shown that high resolution dental impressions can be obtained from live animals. The purpose of this study was to use similar methods to begin to document rates and patterns of dental microwear for primates in the wild. Thirty-three Alouatta palliata were captured during the wet season at Hacienda La Pacifica near Canas, Costa Rica. Dental impressions were taken and epoxy casts of the teeth were prepared using the methods of Teaford and Oyen (1989a). Scanning electron micrographs were taken of the left mandibular second molars at magnifications of 200x and 500x. Lower magnification images were used to calculate rates of wear, and higher magnification images were used to measure the size and shape of microwear features. Results indicate that, while basic patterns of dental microwear are similar in museum samples and samples of live, wild-trapped animals of the same species, ecological differences between collection locales may lead to significant intraspecific differences in dental microwear. More importantly, rates of microwear provide the first direct evidence of differences in molar use between monkeys and humans.

Dust in the wind: How climate variables and volcanic dust affect rates of tooth wear in Central American howling monkeys.

OBJECTIVES: Two factors have been considered important contributors to tooth wear: dietary abrasives in plant foods themselves and mineral particles adhering to ingested food. Each factor limits the functional life of teeth. Cross-population studies of wear rates in a single species living in different habitats may point to the relative contributions of each factor. MATERIALS AND METHODS: We examine macroscopic dental wear in populations of Alouatta palliata (Gray, 1849) from Costa Rica (115 specimens), Panama (19), and Nicaragua (56). The sites differ in mean annual precipitation, with the Panamanian sites receiving more than twice the precipitation of those in Costa Rica or Nicaragua (∼3,500 mm vs. ∼1,500 mm). Additionally, many of the Nicaraguan specimens were collected downwind of active plinian volcanoes. Molar wear is expressed as the ratio of exposed dentin area to tooth area; premolar wear was scored using a ranking system. RESULTS: Despite substantial variation in environmental variables and the added presence of ash in some environments, molar wear rates do not differ significantly among the populations. Premolar wear, however, is greater in individuals collected downwind from active volcanoes compared with those living in environments that did not experience ash-fall. DISCUSSION: Volcanic ash seems to be an important contributor to anterior tooth wear but less so in molar wear. That wear is not found uniformly across the tooth row may be related to malformation in the premolars due to fluorosis. A surge of fluoride accompanying the volcanic ash may differentially affect the premolars as the molars fully mineralize early in the life of Alouatta.

GIS-based Association Between PM10 and Allergic Diseases in Seoul: Implications for Health and Environmental Policy.

PURPOSE: The role of PM10 in the development of allergic diseases remains controversial among epidemiological studies, partly due to the inability to control for spatial variations in large-scale risk factors. This study aims to investigate spatial correspondence between the level of PM10 and allergic diseases at the sub-district level in Seoul, Korea, in order to evaluate whether the impact of PM10 is observable and spatially varies across the subdistricts. METHODS: PM10 measurements at 25 monitoring stations in the city were interpolated to 424 sub-districts where annual inpatient and outpatient count data for 3 types of allergic diseases (atopic dermatitis, asthma, and allergic rhinitis) were collected. We estimated multiple ordinary least square regression models to examine the association of the PM10 level with each of the allergic diseases, controlling for various sub-district level covariates. Geographically weighted regression (GWR) models were conducted to evaluate how the impact of PM10 varies across the sub-districts. RESULTS: PM10 was found to be a significant predictor of atopic dermatitis patient count (P<0.01), with greater association when spatially interpolated at the sub-district level. No significant effect of PM10 was observed on allergic rhinitis and asthma when socioeconomic factors were controlled for. GWR models revealed spatial variation of PM10 effects on atopic dermatitis across the sub-districts in Seoul. The relationship of PM10 levels to atopic dermatitis patient counts is found to be significant only in the Gangbuk region (P<0.01), along with other covariates including average land value, poverty rate, level of education and apartment rate (P<0.01). CONCLUSIONS: Our findings imply that PM10 effects on allergic diseases might not be consistent throughout Seoul. GIS-based spatial modeling techniques could play a role in evaluating spatial variation of air pollution impacts on allergic diseases at the sub-district level, which could provide valuable guidelines for environmental and public health policymakers.