A 5,000-year vegetation and fire history for tierra firme forests in the Medio Putumayo-Algodón watersheds, northeastern Peru.

This paper addresses an important debate in Amazonian studies; namely, the scale, intensity, and nature of human modification of the forests in prehistory. Phytolith and charcoal analysis of terrestrial soils underneath mature tierra firme (nonflooded, nonriverine) forests in the remote Medio Putumayo-Algodón watersheds, northeastern Peru, provide a vegetation and fire history spanning at least the past 5,000 y. A tree inventory carried out in the region enables calibration of ancient phytolith records with standing vegetation and estimates of palm species densities on the landscape through time. Phytolith records show no evidence for forest clearing or agriculture with major annual seed and root crops. Frequencies of important economic palms such as Oenocarpus, Euterpe, Bactris, and Astrocaryum spp., some of which contain hyperdominant species in the modern flora, do not increase through prehistoric time. This indicates pre-Columbian occupations, if documented in the region with future research, did not significantly increase the abundance of those species through management or cultivation. Phytoliths from other arboreal and woody species similarly reflect a stable forest structure and diversity throughout the records. Charcoal 14C dates evidence local forest burning between ca. 2,800 and 1,400 y ago. Our data support previous research indicating that considerable areas of some Amazonian tierra firme forests were not significantly impacted by human activities during the prehistoric era. Rather, it appears that over the last 5,000 y, indigenous populations in this region coexisted with, and helped maintain, large expanses of relatively unmodified forest, as they continue to do today.

Geospatial modeling approach to monument construction using Michigan from A.D. 1000-1600 as a case study.

Building monuments was one way that past societies reconfigured their landscapes in response to shifting social and ecological factors. Understanding the connections between those factors and monument construction is critical, especially when multiple types of monuments were constructed across the same landscape. Geospatial technologies enable past cultural activities and environmental variables to be examined together at large scales. Many geospatial modeling approaches, however, are not designed for presence-only (occurrence) data, which can be limiting given that many archaeological site records are presence only. We use maximum entropy modeling (MaxEnt), which works with presence-only data, to predict the distribution of monuments across large landscapes, and we analyze MaxEnt output to quantify the contributions of spatioenvironmental variables to predicted distributions. We apply our approach to co-occurring Late Precontact (ca. A.D. 1000-1600) monuments in Michigan: (i) mounds and (ii) earthwork enclosures. Many of these features have been destroyed by modern development, and therefore, we conducted archival research to develop our monument occurrence database. We modeled each monument type separately using the same input variables. Analyzing variable contribution to MaxEnt output, we show that mound and enclosure landscape suitability was driven by contrasting variables. Proximity to inland lakes was key to mound placement, and proximity to rivers was key to sacred enclosures. This juxtaposition suggests that mounds met local needs for resource procurement success, whereas enclosures filled broader regional needs for intergroup exchange and shared ritual. Our study shows how MaxEnt can be used to develop sophisticated models of past cultural processes, including monument building, with imperfect, limited, presence-only data.

IruO is a reductase for heme degradation by IsdI and IsdG proteins in Staphylococcus aureus.

Staphylococcus aureus is a common hospital- and community-acquired bacterium that can cause devastating infections and is often multidrug-resistant. Iron acquisition is required by S. aureus during an infection, and iron acquisition pathways are potential targets for therapies. The gene NWMN2274 in S. aureus strain Newman is annotated as an oxidoreductase of the diverse pyridine nucleotide-disulfide oxidoreductase (PNDO) family. We show that NWMN2274 is an electron donor to IsdG and IsdI catalyzing the degradation of heme, and we have renamed this protein IruO. Recombinant IruO is a FAD-containing NADPH-dependent reductase. In the presence of NADPH and IruO, either IsdI or IsdG degraded bound heme 10-fold more rapidly than with the chemical reductant ascorbic acid. Varying IsdI-heme substrate and monitoring loss of the heme Soret band gave a K(m) of 15 ± 4 µM, a k(cat) of 5.2 ± 0.7 min(-1), and a k(cat)/K(m) of 5.8 × 10(3) M(-1) s(-1). From HPLC and electronic spectra, the major heme degradation products are 5-oxo-δ-bilirubin and 15-oxo-ß-bilirubin (staphylobilins), as observed with ascorbic acid. Although heme degradation by IsdI or IsdG can occur in the presence of H2O2, the addition of catalase and superoxide dismutase did not disrupt NADPH/IruO heme degradation reactions. The degree of electron coupling between IruO and IsdI or IsdG remains to be determined. Homologs of IruO were identified by sequence similarity in the genomes of Gram-positive bacteria that possess IsdG-family heme oxygenases. A phylogeny of these homologs identifies a distinct clade of pyridine nucleotide-disulfide oxidoreductases likely involved in iron uptake systems. IruO is the likely in vivo reductant required for heme degradation by S. aureus.

Glycemic control in a medical intensive care setting: revision of an intensive care unit nurse-driven hyperglycemia protocol.

The purpose of this study was to determine whether the addition of rapid-acting insulin bolus for enteral feed coverage and a reduction in basal insulin improve glycemic control and decrease hypoglycemia in a medical intensive care unit. A quasi-experimental posttest design assessing glucose control postimplementation of a revised nurse-driven ICU hyperglycemia protocol was conducted on a 16-bed medical intensive care unit at a multicenter hospital system. A daily report of all patients on the ICU hyperglycemia protocol was automated for the inpatient diabetes management team, and pertinent data were collected. Univariate statistics were conducted for all variables. The variability in blood glucose based on different clinical variables was compared using t tests. The hypoglycemic rate was only 0.72%, and no glucose value was less than 40 mg/dL. In addition, the mean glucose value throughout the study was 160.9 ± 35.6 mg/dL. Findings from this study will hopefully provide insight on an effective way to control glucose within a medical intensive care unit as well as reduce hypoglycemia rates within this setting.

Mean platelet volume is decreased in HIV-infected women.

OBJECTIVES: HIV infection is associated with higher than expected cardiovascular event rates and lowered platelet counts. These conditions are associated with an elevation of mean platelet volume (MPV). The present study compared MPV in HIV-infected and uninfected women and identified factors influencing MPV values in HIV-infected women. METHODS: A total of 234 HIV-infected and 134 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had MPV values obtained. HIV-infected women were older, were more likely to have diabetes and had higher triglyceride levels than HIV-uninfected women. RESULTS: The mean platelet count was lower in HIV-infected vs. uninfected women [249 cells/µL (95% confidence interval (CI) 238, 259 cells/µL) vs. 276 cells/µL (95% CI 265, 287 cells/µL), respectively; P < 0.01]. Adjusted mean MPV values were lower in the HIV-infected than in the uninfected group [8.66 fL (95% CI 8.52, 8.79 fL) vs. 9.05 fL (95% CI 8.87, 9.24 fL), respectively]. In multiple regression analysis, after adjusting for other covariates, MPV was positively associated with platelet count, and negatively with HIV infection (model R² = 0.20; P < 0.01). In multiple regression analysis confined to HIV-infected women, a lower MPV was independently associated with a history of AIDS-defining illness (R² = 0.28; P = 0.03), but not with nadir CD4 count or highly active antiretroviral therapy (HAART) use. CONCLUSIONS: HIV-infected women had lower MPV values than uninfected women, suggesting impaired production rather than increased destruction. Higher than expected cardiovascular event rates cannot be attributed to greater platelet reactivity as measured by MPV.

High interferon-stimulated gene ISG-15 expression affects HCV treatment outcome in patients co-infected with HIV and HCV.

Increased baseline expression and lack of induction of interferon-stimulated genes (ISG) are strong negative predictors of therapeutic response to PegIFN/RBV in patients co-infected with HIV and hepatitis C virus (HCV). This study specifically addressed whether ISG-15 expression influences therapeutic responses in 20 HIV/HCV genotype-1 subjects undergoing HCV treatment. Non-responders had significantly higher baseline expression and selective induction of ISG-15 after IFN-α treatment relative to participants with sustained virological response. High baseline levels of ISG-15 were also associated with less induction of ISG with treatment. These results support a role for ISG-15 as a prognostic indicator and resistance factor to IFN-α.

Association of the rs3743205 variant of DYX1C1 with dyslexia in Chinese children.

BACKGROUND: Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. METHOD AND RESULTS: Eight single nucleotide polymorphisms (SNPs) were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (p(corrected) = 0.0072). This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis. CONCLUSION: Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.

The Implementation of a Stress Management Program for Health Care Workers Through a Rural Occupational Health Clinic.

BACKGROUND: Stress affects U.S. healthcare workers (HCWs) and costs US$191 billion annually. About 30% to 50% of healthcare providers report burnout. Based on an assessment of a U.S. rural hospital system, 94% of workers experienced negative health consequences. We conducted a quality improvement (QI) project for the purpose of implementing a stress management program for HCWs in a hospital system. METHODS: A total of 500 HCWs were informed of the program through hospital communication channels. Using the Plan-Do-Study-Act (PDSA) process, we screened workers presenting to the occupational health clinic for care. Project team members recruited other workers for stress screening throughout the organization. Interventions included contacting workers with elevated scores on the Perceived Stress Survey (PSS; N = 213). The nurse practitioner scheduled them for a shared-decision-making (SDM) appointment (N = 33) where workers were informed of and encouraged to participate in stress reduction activities. Surveys were used to assess effectiveness of SDM appointments and the stress reduction activities. After each 2-week PDSA cycle, interventions were adjusted. FINDINGS: Of the 42% (N = 213) of workers who were screened for stress, 24% (n = 52) had elevated scores. Fifty percent (n = 26) completed an SDM appointment. Participants reported an 86% assurance level that they would use personalized stress management plans. Participants utilizing the interventions (n = 271) reported 25% to 72% reduced stress levels. CONCLUSIONS/APPLICATION TO PRACTICE: This successful project, in a rural setting, included workers across job classifications. Team engagement, PSS screening, SDM opportunities, and stress management activities were project strengths. This low-cost project can be replicated.

A Comparison of Ketamine or Etomidate Combined with Xylazine for Intraperitoneal Anesthesia in Four Mouse Strains.

Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has been used in both human and veterinary medicine yet has not been widely studied in mice. The purpose of this study was to evaluate etomidate-xylazine (EX) anesthesia as an alternative to KX. We hypothesized that EX would be as safe and effective as KX, with both sex- and strain-dependent differences. Male and female Crl:CD1(ICR), C57BL/6NCrl, BALB/cJ and NU/J mice were given a single IP dose of ketamine 100 mg/kg and xylazine 10 mg/kg or etomidate 20 mg/kg and xylazine 10 mg/kg. Sedation times were similar between KX and EX, with CD1 mice exhibiting shorter sedation times. Surgical anesthesia was achieved in 44% of EX mice, compared with 4% of KX mice. C57BL/6NCrl mice were significantly more likely to achieve surgical anesthesia when given EX (94%) or KX (18%) than were other strains. In all strains except C57BL/6NCrl mice, females were more likely to reach surgical anesthesia than males. Several mice experienced an adverse hyperexcitement response during induction, with BALB/cJ (79%) and NU/J (87%) mice given EX significantly more likely than other strains to experience hyperexcitement. EX and KX protocols had no overall differences in lowest respiration rate, lowest systolic blood pressure, lowest rectal temperature, or levels of acidosis, although the lowest heart rates were significantly higher with EX, indicating that EX and KX have similar safety profiles. Thus, EX and KX administration were associated with several significant physiologic differences when comparing sexes or individual strains. Our results indicate that EX is an equally effective sedative and a more effective surgical anesthetic than KX; however, EX is only recommended for invasive procedures in C57BL/6 mice due to the high rate of hyper-excitement and inconsistent surgical depth seen in other strains. Further study is needed to optimize EX for use in multiple mouse strains.

Human Infant Pants for Postoperative Protection during Social Housing of New Zealand White Rabbits (Oryctolagus cuniculus).

Elizabethan collars (E-collars) are commonly used in various species to safeguard healing wounds. However, E-collars inadvertently restrict the expression of normal species-typical behaviors, including coprophagy, self-grooming, and social housing. To maintain social housing in accordance with recommendations in the 8th edition of the Guide for the Care and Use of Laboratory Animals, we implemented the use of human infant pants instead of E-collars for postsurgical protection. We retrospectively reviewed the medical records of 154 intact male New Zealand white rabbits (age, 2 to 3 mo) regarding the use of E-collars (group 1; n = 72) compared with human infant pants (group 2; n = 82) for postoperative protection after 308 femoral angioplasty procedures. Maintenance of social pairs throughout the postoperative phase, replacement rate of infant pants, and self-mutilation rates were measured. Our findings indicate that using infant pants for postoperative protection was most successful in maintaining social housing, offers a more cost-effective option to E-collars, and does not increase the rate of self-mutilation in intact male New Zealand white rabbits.

SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet.

Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury.

Secreted-protein response to sigmaU activity in Streptomyces coelicolor.

The filamentous bacterium Streptomyces coelicolor forms an aerial mycelium as a prerequisite to sporulation, which occurs in the aerial hyphae. Uncontrolled activity of the extracytoplasmic function sigma factor sigmaU blocks the process of aerial mycelium formation in this organism. Using a green fluorescent protein transcriptional reporter, we have demonstrated that sigU transcription is autoregulated. We have defined a sigmaU-dependent promoter sequence and used this to identify 22 likely sigmaU regulon members in the S. coelicolor genome. Since many of these genes encode probable secreted proteins, we characterized the extracellular proteome of a mutant with high sigmaU activity caused by disruption of rsuA, the presumed cognate anti-sigma factor of sigmaU. This mutant secreted a much greater quantity and diversity of proteins than the wild-type strain. Peptide mass fingerprinting was used to identify 79 proteins from the rsuA mutant culture supernatant. The most abundant species, SCO2217, SCO0930, and SCO2207, corresponded to secreted proteins or lipoproteins of unknown functions whose genes are in the proposed sigmaU regulon. Several unique proteases were also detected in the extracellular proteome of the mutant, and the levels of the protease inhibitor SCO0762 were much reduced compared to those of the wild type. Consequently, extracellular protease activity was elevated about fourfold in the rsuA mutant. The functions of the proteins secreted as a result of sigmaU activity may be important for combating cell envelope stress and modulating morphological differentiation in S. coelicolor.

Attitudes of oncology nurses concerning pharmacogenomics.

The field of oncology has been permeated with the use of pharmacogenomics. There have been a few studies on oncology nurses' attitudes surrounding this topic. A study conducted in 2015 revealed six themes: consistency, effectiveness, cost, disparity, genetic counseling needs and need for further education. Further information obtained while conducting a pilot study for continuing education related to pharmacogenomics have revealed novel perspectives surrounding pharmacogenomics among oncology nurses. The previous six themes were substantiated. Additionally, four new themes were identified: change in scope of practice, standardized communication, access to up-to-date information and advocacy. Further validation of the prior six themes and the addition of the new themes reveal the continual impact of pharmacogenomics on nursing practice. The main theme that resounding among the majority of the nurses was the need for further education. This validates the development of educational programs that focus on pharmacogenomics within oncology.

Pharmacogenomics: Principles and Relevance to Oncology Nursing
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BACKGROUND: Pharmacogenomics is the fastest growing field in precision medicine. Based on current use, oncology encompasses the largest share of the precision medicine market, necessitating that oncology nurses understand the principles of pharmacogenomics and how it affects clinical practice.
. OBJECTIVES: This article will define precision medicine and pharmacogenomics and will provide examples of pharmacogenomic tests, including those associated with tumor markers, and nursing implications.
. METHODS: Educational and clinical resources are supplied for oncology nurses to expand their pharmacogenomics expertise.
. FINDINGS: The knowledge surrounding precision medicine and pharmacogenomics will position oncology nurses to engage in current research, improve practice, and educate patients. As the focus of health care remains on reducing costs and improving morbidity and mortality, the reduction in adverse drug reactions will continue to be highlighted. Tailoring medications based on individual responses will not only help improve patient outcomes but also potentially affect the cost of health care as these genetic tests become a standard of care.

Convergence Insufficiency Identifies Athletes at Risk of Prolonged Recovery From Sport-Related Concussion.

BACKGROUND: Sensitive and specific screening methods are needed to identify athletes at risk of prolonged recovery after sport-related concussion (SRC). Convergence insufficiency (CI) is a common finding in concussed athletes. PURPOSE: To assess the relationship between CI and recovery after SRC at the initial office visit. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: In this retrospective cohort study, 270 athletes (147 male, 123 female), mean ± SD age 14.7 ± 2.0 years (range, 10-21 years), with the diagnosis of SRC who presented for initial office visit between January 2014 and January 2016 were evaluated for near point of convergence (NPC). The athletes were categorized into 2 groups: normal near point of convergence (NPC ≤6 cm), and convergence insufficiency (NPC >6 cm). These athletes were then followed to determine recovery time. RESULTS: Athletes presented for initial office visit at a mean of 5.2 ± 4.2 days (range, 1-21 days) after SRC. Half of the athletes had CI after SRC (50.4%; n = 136). Athletes with CI (NPC 12.3 ± 4.7 cm) took significantly longer to recover after SRC, requiring 51.6 ± 53.9 days, compared with athletes with normal NPC (4.1 ± 1.3 cm), who required 19.2 ± 14.7 days ( P < .001). After controlling for potential confounding variables, CI significantly increased the odds of prolonged recovery (≥28 days from injury) by 12.3-fold ( P < .001; 95% confidence interval, 6.6-23.0). CI screening correctly classified 75.2% of our sample with 84.2% sensitivity and 70.0% specificity. The positive predictive value for CI and prolonged recovery was 62.5%, and the negative predictive value was 88.1%. CONCLUSION: CI at the initial office visit identified athletes at increased risk of prolonged recovery after SCR. Clinicians should consider measuring NPC in concussed athletes as a quick and inexpensive prognostic screening method.

Comment on "Persistent effects of pre-Columbian plant domestication on Amazonian forest composition".

Levis et al (Research Articles, 3 March 2017, p. 925) concluded that pre-Columbian tree domestication has shaped present-day Amazonian forest composition. The study, however, downplays five centuries of human influence following European arrival to the Americas. We show that the effects of post-Columbian activities in Amazonia are likely to have played a larger role than pre-Columbian ones in shaping the observed floristic patterns.

Juxtaarticular Myxoma in a Pigtail Macaque (Macaca nemestrina).

A 10-y-old pigtail macaque presented with a subcutaneous, soft-tissue mass overlying the right stifle joint. Here we describe the clinical case and histopathologic and immunohistochemical analysis of this lesion. This case represents the first published report of juxtaarticular myxoma in a pigtail macaque.

Gene-nutrient interaction markedly influences yeast chronological lifespan.

PURPOSE: Research into the genetic mechanisms of aging has expanded rapidly over the past two decades. This has in part been the result of the use of model organisms (particularly yeast, worms and flies) and high-throughput technologies, combined with a growing interest in aging research. Despite this progress, widespread consensus regarding the pathways that are fundamental to the modulation of cellular aging and lifespan for all organisms has been limited due to discrepancies between different studies. We have compared results from published genome-wide, chronological lifespan (CLS) screens of individual gene deletion strains in Saccharomyces cerevisiae in order to identify gene deletion strains with consistent influences on longevity as possible indicators of fundamental aging processes from this single-celled, eukaryotic model organism. METHODS: Three previous reports have described genetic modifiers of chronological aging in the budding yeast (S. cerevisiae) using the yeast gene deletion strain collection. We performed a comparison among the data sets using correlation and decile distribution analysis to describe concordance between screens and identify strains that consistently increased or decreased CLS. We used gene enrichment analysis in an effort to understand the biology underlying genes identified in multiple studies. We attempted to replicate the different experimental conditions employed by the screens to identify potential sources of variability in CLS worth further investigating. RESULTS: Among 3209 strains present in all three screens, nine deletions strains were in common in the longest-lived decile (2.80%) and thirteen were in common in the shortest-lived decile (4.05%) of all three screens. Similarly, pairwise overlap between screens was low. When the same comparison was extended to three deciles to include more mutants studied in common between the three screens, enrichment of cellular processes based on gene ontology analysis in the long-lived strains remained very limited. To test the hypothesis that different parental strain auxotrophic requirements or media formulations employed by the respective genome-wide screens might contribute to the lack of concordance, different CLS assay conditions were assessed in combination with strains having different ploidy and auxotrophic requirements (all relevant to differences in the way the three genome-wide CLS screens were performed). This limited but systematic analysis of CLS with respect to auxotrophy, ploidy, and media revealed several instances of gene-nutrient interaction. CONCLUSIONS: There is surprisingly little overlap between the results of three independently performed genome-wide screens of CLS in S. cerevisiae. However, differences in strain genetic background (ploidy and specific auxotrophic requirements) were present, as well as different media and experimental conditions (e.g., aeration and pooled vs. individual culturing), which, along with stochastic effects such as genetic drift or selection of secondary mutations that suppress the loss of function from gene deletion, could in theory account for some of the lack of consensus between results. Considering the lack of overlap in CLS phenotypes among the set of genes reported by all three screens, and the results of a CLS experiment that systematically tested (incorporating extensive controls) for interactions between variables existing between the screens, we propose that discrepancies can be reconciled through deeper understanding of the influence of cell intrinsic factors such as auxotrophic requirements ploidy status, extrinsic factors such as media composition and aeration, as well as interactions that may occur between them, for example as a result of different pooling vs. individually aging cultures. Such factors may have a more significant impact on CLS outcomes than previously realized. Future studies that systematically account for these contextual factors, and can thus clarify the interactions between genetic and nutrient factors that alter CLS phenotypes, should aid more complete understanding of the underlying biology so that genetic principles of CLS in yeast can be extrapolated to differential cellular aging observed in animal models.

Choline chloride fails to improve cognition of Alzheimer's disease.

Seven mildly to moderately demented patients with Alzheimer's disease were treated with either placebo or choline chloride (50, 100 and 200 mg/kg/24 hrs) in a double blind, crossover study. Detailed psychometric analysis was carried out at the end of each two-week period of drug or placebo administration. No subjects showed significant overall improvement at any dose level despite more than a doubling of the baseline plasma choline level.

Correlations of synaptic and pathological markers with cognition of the elderly.

It has been suggested that the physical basis for dementia is structural or functional loss of synapses. To confirm this finding, we performed an enzyme-linked immunoassay (ELISA) with a monoclonal antibody (EP10) to a synaptophysin-like protein in brain samples from 45 prospectively studied elderly subjects with an average age of 83.3 +/- 10.1 years. We compared the synaptic marker to immunoreactivity with a newly developed PHF antibody (TG3). The cases were selected on the basis of availability of frozen tissue, and included subjects ranging from clinically normal to end-stage dementia. As an initial assessment, we determined Pearson product moment correlations for two clinical measures--the Blessed test of information, concentration, and memory (BICM) and the Fuld object Memory Evaluation (FOME)--with ELISA data and with traditional pathologic markers. We found strong correlations (p < 0.01-0.001) for BICM with brain weight, neuronal loss in the basal nucleus of Meynert (nbM), counts of senile plaques (SP) in the neocortex and hippocampus, and neurofibrillary tangles (NFT) in all areas except the parahippocampal cortex. Except in the occipital lobe, where paired helical filament changes are relatively uncommon, TG3-immunoreactivity also correlated strongly with BICM. Weak correlations (p < 0.05) were found for BICM with EP10-immunoreactivity in only the temporal and parietal lobes. Only the pathologic variables showed any significant correlations with FOME. Because inclusion of normal subjects with few or no pathologic lesions could have been driving the strong correlations with pathologic markers, we limited the analysis to those subjects with dementia (BICM; 8). After making this correction, EP10-immunoreactivity in all cortical areas and the hippocampus correlated better (p < 0.05-0.01) with BICM but not FOME. The present univariate analysis suggests that synaptic markers may not be the best structural correlate of dementia and that markers indicative of cytoskeletal changes, e.g., SP, NFT and PHF protein accumulation, may be better correlates of dementia in the elderly.