Stress granule formation helps to mitigate neurodegeneration.

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and rodent neurons, reducing stress granule formation with nsP3 had modest impacts on lifespan even in the setting of serial stress pathway induction. In contrast, reducing stress granule formation in models of ataxia, amyotrophic lateral sclerosis and frontotemporal dementia largely exacerbated disease phenotypes. These data support a model whereby stress granules mitigate, rather than promote, neurodegenerative cascades.

Stress granule formation helps to mitigate neurodegeneration.

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP (rin in Drosophila) and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and rodent neurons, reducing stress granule formation with nsP3 had modest impacts on lifespan even in the setting of serial stress pathway induction. In contrast, reducing stress granule formation in models of ataxia, amyotrophic lateral sclerosis and frontotemporal dementia largely exacerbated disease phenotypes. These data support a model whereby stress granules mitigate, rather than promote, neurodegenerative cascades.

Influence of increased patient age on longitudinal outcomes of root canal treatment: a systematic review.

OBJECTIVES: To conduct a systematic review of longitudinal endodontic outcomes in elders. BACKGROUND: Negative opinions about the prognosis of non-surgical root canal treatment (NSRCT) in elders affect decisions made by patients and dentists. Patient, caregiver and dentist attitudes and behaviours may interact to decrease the provision of NSRCT. Critical examination of the available evidence through systematic review could provide objective data to assist patients, caregivers, healthcare providers and third-party payers in making decisions about the efficacy of NSRCT in elders and provide a robust foundation for the health promotion of NSRCT in elders. METHODS: Inclusion/exclusion criteria were used for defined searches in MEDLINE and Cochrane CENTRAL. Title lists were scanned, and abstracts read to determine utility; articles meeting inclusion/exclusion criteria were analysed. Data were extracted and compiled into a table of evidence. RESULTS: Defined searching produced 3605 titles; 24 articles were included, nine prospective and 15 retrospective. Overall study quality was good. Patient samples mostly represented modern populations from countries with very high human development indices. Over 17 430 teeth were included. Meta-analysis was not attempted due to heterogeneity in reporting. All 24 included papers demonstrated that increased patient age did not decrease the success or survival rates of NSRCT. CONCLUSIONS: This systematic review of longitudinal NSRCT outcomes demonstrated that increased patient age did not decrease the success of NSRCT. Patient age is not a prognostic factor for NSRCT. Age should not be considered by dentists or patients when making NSRCT decisions.

Prevalence of root canal treatment and periapical radiolucency in elders: a systematic review.

INTRODUCTION: Neither the prevalence of periapical radiolucency (PARL), a surrogate for disease, nor the prevalence of non-surgical root canal treatment (NSRCT) in elders have been subjected to systematic review. The purpose of this study was to conduct systematic review and meta-analysis of the prevalence of PARL and NSRCT in elders. METHODS: Inclusion/exclusion criteria were used for defined searches in MEDLINE and Cochrane CENTRAL. Title lists were scanned and abstracts read to determine utility; articles meeting the criteria were analyzed. Weighted mean percentages were calculated for prevalence of PARL, NSRCT, and PARL in both teeth with and without NSRCT. RESULTS: Defined searching produced 3576 titles; 29 prevalence articles were included. Patient samples mostly represented modern populations from countries with very high human development indices. Meta-analyses were performed on up to 74 000 elders' teeth. For those aged 65+, the prevalence of all teeth with NSRCT was extremely high, 21%; the prevalence of all teeth with PARL was quite high, 7%; the prevalence of PARL in NSRCT teeth was high, 25%; and the prevalence of PARL in untreated teeth was surprisingly high, 4%. In elders, the prevalence of NSRCT and PARL separately increased with age; whereas, PARL in NSRCT teeth decreased with age. CONCLUSIONS: In comparison to general adult populations, elders had: a much higher prevalence of NSRCT, a higher prevalence of PARL, a lower prevalence of PARL in NSRCT teeth, and a higher prevalence of PARL in untreated teeth. Teeth saved through NSRCT were preferentially retained by elders.

Prevalence of periapical radiolucency and root canal treatment: a systematic review of cross-sectional studies.

INTRODUCTION: Cross-sectional studies describe the health status of a population and measure the prevalence of disease or treatment. Neither the prevalence of periapical radiolucency, a surrogate for disease, nor the prevalence of root canal treatment have been subjected to a systematic review, which is the highest level of clinical evidence. The purpose of this study was to conduct a systematic review and meta-analysis of the prevalence of periapical radiolucency and nonsurgical root canal treatment. METHODS: Inclusion/exclusion criteria were used for defined searches in MEDLINE and EMBASE. Title lists were scanned and abstracts were read to determine utility. Articles meeting the inclusion/exclusion criteria were analyzed for heterogeneity. Weighted mean percentages were calculated for the prevalence of overall periapical radiolucency, root canal treatment, and apical radiolucency in both treated and untreated teeth. RESULTS: Defined searching produced 11,491 titles. Thirty-three articles were included. Most patient samples represented modern populations from countries with high or very high human development indices. Meta-analysis was performed on 300,861 teeth. Of these, 5% had periapical radiolucencies, and 10% were endodontically treated. Of the 28,881 endodontically treated teeth, 36% had periapical radiolucencies; however, cross-sectional studies cannot distinguish between healing and failing cases. Of the 271,980 untreated teeth, 2% had periapical radiolucencies. The technical quality of root canal treatment was decried by most authors of the included studies. CONCLUSIONS: The prevalence of periapical radiolucency was very high, broadly equivalent to 1 radiolucency per patient. The prevalence of teeth with root canal treatment was very high, broadly equivalent to 2 treatments per patient. Billions of teeth are retained through root canal treatment.

Pain prevalence and severity before, during, and after root canal treatment: a systematic review.

INTRODUCTION: Anticipation and experience of root canal associated pain is a major source of fear for patients and a very important concern of dentists. Pretreatment, treatment, and posttreatment pain is anticipated, experienced, remembered, and shared by patients. The purpose was to determine the influence of root canal treatment on pain prevalence and severity and estimate the prevalence and severity of pretreatment, treatment, and posttreatment pain in patients receiving root canal treatment. METHODS: Defined searching of MEDLINE, Embase, Cochrane, and PsycINFO databases identified 5,517 articles. Systematic review, including title scanning, abstract scanning, full-text review, and quality rating, provided 72 studies for meta-analysis. L'Abbe plots were used to evaluate the influence of root canal treatment on pain prevalence and severity. Pretreatment, treatment, and posttreatment pain prevalence and severity data were analyzed. RESULTS: L'Abbe plots revealed that pain prevalence and severity decreased substantially after treatment. Mean pretreatment, 24-hour posttreatment, and 1-week posttreatment pain prevalences with associated standard deviations were 81 (28%), 40 (24%), and 11 (14%), respectively. Pretreatment, 24-hour posttreatment, and 1-week posttreatment pain severities, on a 100-point scale, were 54 (24%), 24 (12%), and 5 (5%), respectively. Supplemental injections were frequently required (60 [24%]). CONCLUSIONS: Pretreatment root canal-associated pain prevalence was high but dropped moderately within 1 day and substantially to minimal levels in 7 days. Pretreatment root canal-associated pain severity was moderate, dropped substantially within 1 day of treatment, and continued to drop to minimal levels in 7 days. Supplemental anesthesia was often required.