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The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.
Methods:
Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.
Results:
Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).
Discussion:
Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.
Childhood infections have been shown to stunt growth, contribute to malnutrition and reduce cognition in early adulthood. This study aimed to assess relationships between early life infections and childhood cognition at age 11 years in the Newcastle Thousand Families Study (NTFS). The analysis included 741 members from the NTFS who had complete data for infections between birth and 5 years, and the 11-plus examinations. School records from the 11-plus examinations showed cognitive (IQ), English (EQ) and arithmetic (AQ) abilities. Housing conditions, overcrowding, birth order and social class were recorded at birth. Helicobacter pylori seropositivity was measured at age 49–51 years. Multivariable linear regression was used to examine relationships between infections and cognition. The total number of infections in the first 5 years of life was not significantly associated with IQ, EQ or AQ, nor were there significant relationships between cognitive outcomes and most infections. Tonsillitis did display a positive, significant association with IQ after adjustment for confounders (b = 6.43, 95% CI 0.92, 11.94, p = 0.022). Lower respiratory tract infections (LRTIs) showed significant negative relationships with all cognitive outcomes. H. pylori seropositivity at age 50 exhibited negative, significant relationships with EQ (p = 0.014) and AQ (p = 0.024) after adjustment for confounders. Although no significant relationship between overall infections and cognition were found, there were indications that LRTIs and gastrointestinal system infections may limit cognitive development. Given these infections remain prevalent, further research regarding severity and recurrence of infections and how they affect childhood cognition is needed.
In this paper, we investigate finite solvable tidy groups. We prove that a solvable group with order divisible by at least two primes is tidy if all of its Hall subgroups that are divisible by only two primes are tidy.
OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.
Let G be a p-group for some prime p. Recall that the Hughes subgroup of G is the subgroup generated by all of the elements of G with order not equal to p. In this paper, we prove that if the Hughes subgroup of G is cyclic, then G has exponent p or is cyclic or is dihedral. We also prove that if the Hughes subgroup of G is generalised quaternion, then G must be generalised quaternion. With these results in hand, we classify the tidy p-groups.
Morgan and Parker proved that if G is a group with ${\textbf{Z}(G)} = 1$, then the connected components of the commuting graph of G have diameter at most $10$. Parker proved that if, in addition, G is solvable, then the commuting graph of G is disconnected if and only if G is a Frobenius group or a $2$-Frobenius group, and if the commuting graph of G is connected, then its diameter is at most $8$. We prove that the hypothesis $Z (G) = 1$ in these results can be replaced with $G' \cap {\textbf{Z}(G)} = 1$. We also prove that if G is solvable and $G/{\textbf{Z}(G)}$ is either a Frobenius group or a $2$-Frobenius group, then the commuting graph of G is disconnected.
The patient experience of radiotherapy magnetic resonance (MR) simulation is unknown. This study aims to evaluate the patient experience of MR simulation in comparison to computed tomography (CT) simulation, identifying the quality of patient experience and pathway changes which could improve patient experience outcomes.
Materials and Methods:
MR simulation was acquired for 46 anal and rectal cancer patients. Patient experience questionnaires were provided directly after MR simulation. Questionnaire responses were assessed after 33 patients (cohort one). Changes to the scanning pathway were identified and implemented. The impact of changes was assessed by cohort two (13 patients).
Results:
Response rates were 85% (cohort one) and 54% (cohort two). 75% of cohort one respondents found the magnetic resonance imaging (MRI) experience to be better or similar to their CT experience. Implemented changes included routine use of blankets, earplugs and headphones, music and feet-first positioning and further MRI protocol optimisation. All cohort two respondents found the MRI experience to be better or similar to the CT experience.
Findings:
MR simulation can be a comfortable and positive experience that is comparable to that of standard radiotherapy CT simulation. Special attention is required due to the fundamental differences between CT and MRI scanning.
The paper attempts to integrate the results of chemical analyses, which are seriously underused in archaeological discourse, with other classes of information in order to try to interpret ancient metal working behaviour and knowledge within a semiotic framework, adopting the modernist premise that ancient metalworking was both rational and deliberate. A number of case studies from northern Italy is discussed. In the first it is noted that in the Copper Age Remedello culture arsenical copper was used for halberds and daggers while purer copper was used for flat axes; it is suggested that this distinction reflects deliberate choice and explanations are offered for it. The second case study regards the interpretation of the Pieve Albignola early Bronze Age axe hoard; evidence for the workshop practices of ancient bronzesmiths and for the use of axe preforms as ingots is discussed. The third case study concerns the swords and daggers of the middle and recent Bronze Age; finds context (tombs and wetlands) are discussed and it is suggested that metal analyses may indicate that sometimes these artefacts are not primarily functional.
The Kulshan caldera formed at ∼1.15 Ma on the present-day site of Mt. Baker, Washington State, northwest USA and erupted a compositionally zoned (dacite-rhyolite) magma and a correlative eruptive, the Lake Tapps tephra. This tephra has previously been described, but only from the Puget Lowland of NW Washington. Here an occurrence of a Kulshan caldera correlative tephra is described from the Quaternary Palouse loess at the Washtucna site (WA-3). Site WA-3 is located in east-central Washington, ∼340 km southeast of the Kulshan caldera and ∼300 km east-southeast of the Lake Tapps occurrence in the Puget Lowland. Major- and trace element chemistry and location of the deposit at Washtucna within reversed polarity sediments indicates that it is not correlative with the Mesa Falls, Rockland, Bishop Ash, Lava Creek B or Huckleberry Ridge tephras. Instead the Washtucna deposit is related to the Lake Tapps tephra by fractional crystallisation, but is chemically distinct, a consequence of its eruption from a compositionally zoned magma chamber. The correlation of the Washtucna occurrence to the Kulshan caldera-forming eruption indicates that it had an eruptive volume exceeding 100 km3, and that its tephra could provide a valuable early-Pleistocene chronostratigraphic marker in the Pacific Northwest.
Observational evidence suggests that increased whole grain (WG) intake reduces the risks of many non-communicable diseases, such as CVD, type 2 diabetes, obesity and certain cancers. More recently, studies have shown that WG intake lowers all-cause and cause-specific mortality. Much of the reported evidence on risk reduction is from US and Scandinavian populations, where there are tangible WG dietary recommendations. At present there is no quantity-specific WG dietary recommendation in the UK, instead we are advised to choose WG or higher fibre versions. Despite recognition of WG as an important component of a healthy diet, monitoring of WG intake in the UK has been poor, with the latest intake assessment from data collected in 2000–2001 for adults and in 1997 for children. To update this information we examined WG intake in the National Diet and Nutrition Survey rolling programme 2008–2011 after developing our database of WG food composition, a key resource in determining WG intake accurately. The results showed median WG intakes remain low in both adults and children and below that of countries with quantity-specific guidance. We also found a reduction in C-reactive protein concentrations and leucocyte counts with increased WG intake, although no association with other markers of cardio-metabolic health. The recent recommendations by the UK Scientific Advisory Committee on Nutrition to increase dietary fibre intake will require a greater emphasis on consuming more WG. Specific recommendations on WG intake in the UK are warranted as is the development of public health policy to promote consumption of these important foods.
Increased whole grain intake has been shown to reduce the risk of many non-communicable diseases. Countries including the USA, Canada, Denmark and Australia have specific dietary guidelines on whole grain intake but others, including the UK, do not. Data from 1986/87 and 2000/01 have shown that whole grain intake is low and declining in British adults. The aim of the present study was to describe whole grain intakes in the most current dietary assessment of UK households using data from the National Diet and Nutrition Survey rolling programme 2008–11. In the present study, 4 d diet diaries were completed by 3073 individuals between 2008 and 2011, along with details of socio-economic status (SES). The median daily whole grain intake, calculated for each individual on a dry weight basis, was 20 g/d for adults and 13 g/d for children/teenagers. The corresponding energy-adjusted whole grain intake was 27 g/10 MJ per d for adults and 20 g/10 MJ per d for children/teenagers. Whole grain intake (absolute and energy-adjusted) increased with age, but was lowest in teenagers (13–17 years) and younger adults up to the age of 34 years. Of the total study population, 18 % of adults and 15 % of children/teenagers did not consume any whole-grain foods. Individuals from lower SES groups had a significantly lower whole grain intake than those from more advantaged classifications. The whole grain intake in the UK, although higher than in 2000/01, remains low and below that in the US and Danish recommendations in all age classes. Favourable pricing with increased availability of whole-grain foods and education may help to increase whole grain intake in countries without whole-grain recommendations. Teenagers and younger adults may need targeting to help increase whole grain consumption.
Epidemiological evidence suggests an inverse association between whole grain consumption and the risk of non-communicable diseases, such as CVD, type 2 diabetes, obesity and some cancers. A recent analysis of the National Diet and Nutrition Survey rolling programme (NDNS-RP) has shown lower intake of whole grain in the UK. It is important to understand whether the health benefits associated with whole grain intake are present at low levels of consumption. The present study aimed to investigate the association of whole grain intake with intakes of other foods, nutrients and markers of health (anthropometric and blood measures) in the NDNS-RP 2008–11, a representative dietary survey of UK households. A 4-d diet diary was completed by 3073 individuals. Anthropometric measures, blood pressure levels, and blood and urine samples were collected after diary completion. Individual whole grain intake was calculated with consumers categorised into tertiles of intake. Higher intake of whole grain was associated with significantly decreased leucocyte counts. Significantly higher concentrations of C-reactive protein were seen in adults in the lowest tertile of whole grain intake. No associations with the remaining health markers were seen, after adjustments for sex and age. Over 70 % of this population did not consume the minimum recommend intake associated with disease risk reduction, which may explain small variation across health markers. Nutrient intakes in consumers compared with non-consumers were closer to dietary reference values, such as higher intakes of fibre, Mg and Fe, and lower intakes of Na, suggesting that higher intake of whole grain is associated with improved diet quality.