Dental disease is largely preventable. Many older adults, however, experience poor oral health. National data for older adults show racial/ethnic and income disparities in untreated dental disease ...and oral health-related quality of life. Persons reporting poor versus good health also report lower oral health-related quality of life. On the basis of these findings, suggested public health priorities include better integrating oral health into medical care, implementing community programs to promote healthy behaviors and improve access to preventive services, developing a comprehensive strategy to address the oral health needs of the homebound and long-term-care residents, and assessing the feasibility of ensuring a safety net that covers preventive and basic restorative services to eliminate pain and infection.
Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We ...conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 ± 15 years, and the mean time from symptom onset to presentation was 27 ± 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.
Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part ...caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB.
We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance.
We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB.
CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated.
Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.
One of the greatest challenges facing human geneticists is the identification and characterization of susceptibility genes for common complex multifactorial human diseases. This challenge is partly ...due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes and with environmental exposures. We introduce multifactor-dimensionality reduction (MDR) as a method for reducing the dimensionality of multilocus information, to improve the identification of polymorphism combinations associated with disease risk. The MDR method is nonparametric (i.e., no hypothesis about the value of a statistical parameter is made), is model-free (i.e., it assumes no particular inheritance model), and is directly applicable to case-control and discordant-sib-pair studies. Using simulated case-control data, we demonstrate that MDR has reasonable power to identify interactions among two or more loci in relatively small samples. When it was applied to a sporadic breast cancer case-control data set, in the absence of any statistically significant independent main effects, MDR identified a statistically significant high-order interaction among four polymorphisms from three different estrogen-metabolism genes. To our knowledge, this is the first report of a four-locus interaction associated with a common complex multifactorial disease.
The exact causes of Amyotrophic lateral sclerosis (ALS), a progressive and fatal neurological disorder due to loss of upper and/or lower motoneurons, remain elusive. Gene-environment interactions are ...believed to be an important factor in the development of ALS. We previously showed that in vivo exposure of mice overexpressing the human superoxide dismutase 1 (hSOD1) gene mutation (hSOD1G93A; G93A), a mouse model for ALS, to environmental neurotoxicant methylmercury (MeHg) accelerated the onset of ALS-like phenotype. Here we examined the time-course of effects of MeHg on AMPA receptor (AMPAR)-mediated currents in hypoglossal motoneurons in brainstem slices prepared from G93A, hSOD1wild-type (hWT) and non-carrier WT mice following in vivo exposure to MeHg. Mice were exposed daily to 3 ppm (approximately 0.7 mg/kg/day) MeHg via drinking water beginning at postnatal day 28 (P28) and continued until P47, 64 or 84, then acute brainstem slices were prepared, and spontaneous excitatory postsynaptic currents (sEPSCs) or AMPA-evoked currents were examined using whole cell patch-clamp recording technique. Brainstem slices of untreated littermates were prepared at the same time points to serve as control. MeHg exposure had no significant effect on either sEPSCs or AMPA-evoked currents in slices from hWT or WT mice during any of those exposure time periods under our experimental conditions. MeHg also did not cause any significant effect on sEPSCs or AMPA-currents in G93A hypoglossal motoneurons at P47 and P64. However, at P84, MeHg significantly increased amplitudes of both sEPSCs and AMPA-evoked currents in hypoglossal motineurons from G93A mice (p < 0.05), but not the sEPSC frequency, suggesting a postsynaptic action on AMPARs. MeHg exposure did not cause any significant effect on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). Therefore, MeHg exposure in vivo caused differential effects on AMPARs in hypoglossal motoneurons from mice with different genetic backgrounds. MeHg appears to preferentially stimulate the AMPAR-mediated currents in G93A hypoglossal motoneurons in an exposure time-dependent manner, which may contribute to the AMPAR-mediated motoneuron excitotoxicity, thereby facilitating development of ALS-like phenotype.
OBJECTIVES
To examine changes in tooth loss and untreated tooth decay among older low‐income and higher‐income US adults and whether disparities have persisted.
DESIGN
Sequential cross‐sectional ...study using nationally representative data.
SETTING
The 1999 to 2004 and 2011 to 2016 National Health and Nutrition Examination Survey.
PARTICIPANTS
Noninstitutionalized US adults, aged 65 years and older (N = 3539 for 1999‐2004, and N = 3514 for 2011‐2016).
MEASUREMENTS
Differences in prevalence of tooth loss (having 19 teeth or fewer, 8 teeth or fewer, and no teeth) and untreated decay and mean number of decayed and missing teeth (DMT) between low‐ and high‐income adults 65 years and older in each survey and changes between surveys. Adjusted prevalence and count outcomes were estimated with logistic and negative binomial regression models, respectively. Models controlled for sociodemographic characteristics and smoking status. Reported findings are significant at P < .05.
RESULTS
In 2011 to 2016, unadjusted prevalence of having 19 teeth or fewer, 8 teeth or fewer, no teeth, and untreated decay among low‐income adults 65 years and older was 50.6%, 42.0%, 28.6%, and 28.6%, respectively. Multivariate analyses indicated that although most tooth loss measures improved between surveys for both income groups, tooth loss among low‐income adults remained at almost twice that among higher‐income adults. The disparity in untreated decay prevalence in 2011 to 2016, 15.2 percentage points (26.1% vs 10.9% for low vs high income) was twice that in 1999 to 2004, 8.5 percentage points (22.9% vs 14.4% for low vs high income). DMT decreased for both groups, with lower‐income adults having about five more affected teeth in both surveys.
CONCLUSION
Tooth loss is decreasing, but differential access to restorative care by income appears to have increased.
To identify the growing significance of depression as a global leading cause of years lost to disability and its role as a major independent risk factor in many chronic illnesses. The distinct ...effects of depression on morbidity and mortality in cancer, diabetes, heart disease, and stroke are investigated, including behavioral factors and plausible biological mechanisms (psychoneuroimmunology of depression).
PubMed articles in English were searched from 1992 to 2012 (20-year span) using the following search criteria: psychoneuroimmunology of depression, immune-mediated inflammation, depression treatment recommendations, depression screening, years lost to disability, underserved populations and depression, chronic illnesses and depression, and selective serotonin reuptake inhibitors and immune system.
Evidence of the robust bidirectional relationship between depression and individual chronic diseases is presented and discussed. A brief overview of currently recommended psychotherapeutic and psychopharmacologic treatment approaches in regard to depression in chronic diseases is provided.
Discordance between mental health and primary care within the US public health system is a systematic problem that must be addressed. This situation leads to a potentially high hidden prevalence of underdiagnosed and undertreated depression, especially in the underserved populations.
Measures must be implemented across the communities of mental health and primary care practitioners in order to achieve a synergistic approach to depression.
E1 and E2 (E1E2), the fusion proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. ...Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Thus, HVR-1 is akin to a safety catch that prevents premature triggering of E1E2 activity. Crucially, this mechanism is turned off by host receptor interactions at the cell surface to allow entry. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies. This discovery provides an explanation for the ability of HCV to persist in the face of continual immune assault and represents a novel regulatory mechanism that is likely to be found in other viral fusion machinery.
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