Chronic Orofacial Pain: Burning Mouth Syndrome and Other Neuropathic Disorders

Chronic orofacial pain is a symptom associated with a wide range of neuropathic, neurovascular, idiopathic, and myofascial conditions that affect a significant proportion of the population. While the collective impact of the subset of the orofacial pain disorders involving neurogenic and idiopathic mechanisms is substantial, some of these are relatively uncommon. Hence, patients with these disorders can be vulnerable to misdiagnosis, sometimes for years, increasing the symptom burden and delaying effective treatment. This manuscript first reviews the decision tree to be followed in diagnosing any neuropathic pain condition, as well as the levels of evidence needed to make a diagnosis with each of several levels of confidence: definite, probable, or possible. It then examines the clinical literature related to the idiopathic and neurogenic conditions that can occasion chronic orofacial pain, including burning mouth syndrome, trigeminal neuralgia, glossopharyngeal neuralgia, post-herpetic neuralgia, and atypical odontalgia. Temporomandibular disorders also are examined as are other headache conditions, even though they are not neurologic conditions, because they are common and can mimic symptoms of the latter disorders. For each of these conditions, the paper reviews literature regarding incidence and prevalence, physiologic and other contributing factors, diagnostic signs and symptoms, and empirical evidence regarding treatments. Finally, in order to improve the quality and accuracy of clinical diagnosis, as well as the efficiency with which effective treatment is initiated and delivered, criteria are offered that can be instrumental in making a differential diagnosis

Pain, comorbidities, and clinical decision-making: conceptualization, development, and pilot testing of the Pain in Aging, Educational Assessment of Need instrument

IntroductionPain is highly prevalent in older adults and often contextualized by multiple clinical conditions (pain comorbidities). Pain comorbidities increase with age and this makes clinical decisions more complex. To address gaps in clinical training and geriatric pain management, we established the Pain in Aging—Educational Assessment of Need (PAEAN) project to appraise the impacts of medical and mental health conditions on clinical decision-making regarding older adults with pain. We here report development and pilot testing of the PAEAN survey instrument to assess clinician perspectives.MethodsMixed-methods approaches were used. Scoping review methodology was applied to appraise both research literature and selected Medicare-based data. A geographically and professionally diverse interprofessional advisory panel of experts in pain research, medical education, and geriatrics was formed to advise development of the list of pain comorbidities potentially impacting healthcare professional clinical decision-making. A survey instrument was developed, and pilot tested by diverse licensed healthcare practitioners from 2 institutions. Respondents were asked to rate agreement regarding clinical decision-making impact using a 5-point Likert scale. Items were scored for percent agreement.ResultsScoping reviews indicated that pain conditions and comorbidities are prevalent in older adults but not universally recognized. We found no research literature directly guiding pain educators in designing pain education modules that mirror older adult clinical complexity. The interprofessional advisory panel identified 26 common clinical conditions for inclusion in the pilot PAEAN instrument. Conditions fell into three main categories: “major medical”, i.e., cardio-vascular-pulmonary; metabolic; and neuropsychiatric/age-related. The instrument was pilot tested by surveying clinically active healthcare providers, e.g., physicians, nurse practitioners, who all responded completely. Median survey completion time was less than 3 min.ConclusionThis study, developing and pilot testing our “Pain in Aging—Educational Assessment of Need” (PAEAN) instrument, suggests that 1) many clinical conditions impact pain clinical decision-making, and 2) surveying healthcare practitioners about the impact of pain comorbidities on clinical decision-making for older adults is highly feasible. Given the challenges intrinsic to safe and effective clinical care of older adults with pain, and attendant risks, together with the paucity of existing relevant work, much more education and research are needed

Oxygenated Aromatic Compounds are Important Precursors of Secondary Organic Aerosol in Biomass Burning Emissions

Biomass burning is the largest combustion-related source of volatile organic compounds (VOCs) to the atmosphere. We describe the development of a state-of-the-science model to simulate the photochemical formation of secondary organic aerosol (SOA) from biomass-burning emissions observed in dry (RH <20%) environmental chamber experiments. The modeling is supported by (i) new oxidation chamber measurements, (ii) detailed concurrent measurements of SOA precursors in biomass-burning emissions, and (iii) development of SOA parameters for heterocyclic and oxygenated aromatic compounds based on historical chamber experiments. We find that oxygenated aromatic compounds, including phenols and methoxyphenols, account for slightly less than 60% of the SOA formed and help our model explain the variability in the organic aerosol mass (R² = 0.68) and O/C (R² = 0.69) enhancement ratios observed across 11 chamber experiments. Despite abundant emissions, heterocyclic compounds that included furans contribute to ∼20% of the total SOA. The use of pyrolysis-temperature-based or averaged emission profiles to represent SOA precursors, rather than those specific to each fire, provide similar results to within 20%. Our findings demonstrate the necessity of accounting for oxygenated aromatics from biomass-burning emissions and their SOA formation in chemical mechanisms

Optimized polyepitope neoantigen DNA vaccines elicit neoantigen-specific immune responses in preclinical models and in clinical translation

BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation. METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor. RESULTS: Our data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ub CONCLUSIONS: We have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation

GALC Deletions Increase the Risk of Primary Open-Angle Glaucoma: The Role of Mendelian Variants in Complex Disease

DNA copy number variants (CNVs) have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG) is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC). This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1.) (p = 0.017, fisher's exact test). It was validated with array comparative genomic hybridization (arrayCGH) and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio) = 3.5, 95% CI −1.1–12.0). Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6–16.4). Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P &lt; 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P &lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Disease concepts and treatment by tribal healers of an Amazonian forest culture

<p>Abstract</p> <p>Background</p> <p>The extensive medicinal plant knowledge of Amazonian tribal peoples is widely recognized in the scientific literature and celebrated in popular lore. Despite this broad interest, the ethnomedical systems and knowledge of disease which guide indigenous utilization of botanical diversity for healing remain poorly characterized and understood. No study, to our knowledge, has attempted to directly examine patterns of actual disease recognition and treatment by healers of an Amazonian indigenous culture.</p> <p>Methods</p> <p>The establishment of traditional medicine clinics, operated and directed by elder tribal shamans in two remote Trio villages of the Suriname rainforest, presented a unique investigational opportunity. Quantitative analysis of clinic records from both villages permitted examination of diseases treated over a continuous period of four years. Cross-cultural comparative translations were articulated of recorded disease conditions through ethnographic interviews of elder Trio shamans and a comprehensive atlas of indigenous anatomical nomenclature was developed.</p> <p>Results</p> <p>20,337 patient visits within the period 2000 to 2004 were analyzed. 75 disease conditions and 127 anatomical terms are presented. Trio concepts of disease and medical practices are broadly examined within the present and historical state of their culture.</p> <p>Conclusion</p> <p>The findings of this investigation support the presence of a comprehensive and highly formalized ethnomedical institution within Trio culture with attendant health policy and conservation implications.</p

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

A View of Tropical Cyclones from Above: The Tropical Cyclone Intensity Experiment

Tropical cyclone (TC) outflow and its relationship to TC intensity change and structure were investigated in the Office of Naval Research Tropical Cyclone Intensity (TCI) field program during 2015 using dropsondes deployed from the innovative new High-Definition Sounding System (HDSS) and remotely sensed observations from the Hurricane Imaging Radiometer (HIRAD), both on board the NASA WB-57 that flew in the lower stratosphere. Three noteworthy hurricanes were intensively observed with unprecedented horizontal resolution: Joaquin in the Atlantic and Marty and Patricia in the eastern North Pacific. Nearly 800 dropsondes were deployed from the WB-57 flight level of ∼60,000 ft (∼18 km), recording atmospheric conditions from the lower stratosphere to the surface, while HIRAD measured the surface winds in a 50-km-wide swath with a horizontal resolution of 2 km. Dropsonde transects with 4–10-km spacing through the inner cores of Hurricanes Patricia, Joaquin, and Marty depict the large horizontal and vertical gradients in winds and thermodynamic properties. An innovative technique utilizing GPS positions of the HDSS reveals the vortex tilt in detail not possible before. In four TCI flights over Joaquin, systematic measurements of a major hurricane’s outflow layer were made at high spatial resolution for the first time. Dropsondes deployed at 4-km intervals as the WB-57 flew over the center of Hurricane Patricia reveal in unprecedented detail the inner-core structure and upper-tropospheric outflow associated with this historic hurricane. Analyses and numerical modeling studies are in progress to understand and predict the complex factors that influenced Joaquin’s and Patricia’s unusual intensity changes

Harmful algal blooms and eutrophication : examining linkages from selected coastal regions of the United States

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Harmful Algae 8 (2008): 39-53, doi:10.1016/j.hal.2008.08.017.Coastal waters of the United States (U.S.) are subject to many of the major harmful algal bloom (HAB) poisoning syndromes and impacts. These include paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), ciguatera fish poisoning (CFP) and various other HAB phenomena such as fish kills, loss of submerged vegetation, shellfish mortalities, and widespread marine mammal mortalities. Here, the occurrences of selected HABs in a selected set of regions are described in terms of their relationship to eutrophication, illustrating a range of responses. Evidence suggestive of changes in the frequency, extent or magnitude of HABs in these areas is explored in the context of the nutrient sources underlying those blooms, both natural and anthropogenic. In some regions of the U.S., the linkages between HABs and eutrophication are clear and well documented, whereas in others, information is limited, thereby highlighting important areas for further research.Support was provided through the Woods Hole Center for Oceans and Human Health (to DMA), National Science Foundation (NSF) grants OCE-9808173 and OCE-0430724 (to DMA), OCE-0234587 (to WPC), OCE04-32479 (to MLP), OCE-0138544 (to RMK), OCE-9981617 (to PMG); National Institute of Environmental Health Sciences (NIEHS) grants P50ES012742-01 (to DMA) and P50ES012740 (to MLP); NOAA Grants NA96OP0099 (to DMA), NA16OP1450 (to VLT), NA96P00084 (to GAV and CAH), NA160C2936 and NA108H-C (to RMK), NA860P0493 and NA04NOS4780241 (to PMG), NA04NOS4780239-02 (to RMK), NA06NOS4780245 (to DWT). Support was also provided from the West Coast Center for Oceans and Human Health (to VLT and WPC), USEPA Grant CR826792-01-0 (to GAV and CAH), and the State of Florida Grant S7701617826 (to GAV and CAH)