Landscape biodiversity correlates with respiratory health in Australia.

Megatrends of urbanisation and reducing contact with natural environments may pose a largely unappreciated risk to human health, particularly in children, through declining normal (healthy) immunomodulatory environmental exposures. On the other hand, building knowledge of connections between environments, biodiversity and human health may offer new integrated ways of addressing global challenges of rising population health costs and declining biodiversity. In this study we are motivated to build insight and provide context and priority for emerging research into potential protective (e.g. immunomodulatory) environmental exposures. We use respiratory health as a test case to explore whether some types and qualities of environment may be more beneficial than others, and how such exposures may compare to known respiratory health influences, via a cross-sectional ecological epidemiology study for the continent of Australia. Using Lasso penalized regression (to interpret key predictors from many candidate variables) and 10-fold cross-validation modelling (to indicate reproducibility and uncertainty), within different socio-geographic settings, our results show surrogate measures of landscape biodiversity correlate with respiratory health, and rank amongst known predictors. A range of possible drivers for this relationship are discussed. Perhaps most novel and interesting of these is the possibility of protective immunomodulatory influence from microbial diversity (suggested by the understudied 'biodiversity hypothesis') and other bioactive agents associated with biodiverse environments. If beneficial influences can be demonstrated from biodiverse environments on immunomodulation and human health, there may be potential to design new cost-effective nature-based health intervention programs to reduce the risk of immune-related disease at a population level. Our approach and findings are also likely to have use in the evaluation of environment and health associations elsewhere.

Insight into molecular basis of curing of [PSI+] prion by overexpression of 104-kDa heat shock protein (Hsp104).

Yeast prions are a powerful model for understanding the dynamics of protein aggregation associated with a number of human neurodegenerative disorders. The AAA+ protein disaggregase Hsp104 can sever the amyloid fibrils produced by yeast prions. This action results in the propagation of "seeds" that are transmitted to daughter cells during budding. Overexpression of Hsp104 eliminates the [PSI+] prion but not other prions. Using biochemical methods we identified Hsp104 binding sites in the highly charged middle domain of Sup35, the protein determinant of [PSI+]. Deletion of a short segment of the middle domain (amino acids 129-148) diminishes Hsp104 binding and strongly affects the ability of the middle domain to stimulate the ATPase activity of Hsp104. In yeast, [PSI+] maintained by Sup35 lacking this segment, like other prions, is propagated by Hsp104 but cannot be cured by Hsp104 overexpression. These results provide new insight into the enigmatic specificity of Hsp104-mediated curing of yeast prions and sheds light on the limitations of the ability of Hsp104 to eliminate aggregates produced by other aggregation-prone proteins.

From the city to the bush: increases in patient co-payments for medicines have impacted on medicine use across Australia.

AIM: To determine whether the national declines in prescription medicine use occurring after the 2005 21% increase in co-payments affected all areas of Australia or were specific to remote and disadvantaged areas. METHODS: Observed dispensing of proton pump inhibitors (PPIs) and statins were obtained for 1392 statistical local areas (SLA) of Australia in 2004 and 2006. Expected dispensing was based on national dispensing rates and was age standardised to each SLA. Expected dispensing for 2006 was based on pre-2005 prescription trends. Ratios of observed to expected dispensing (dispensing ratios) for each SLA were calculated. Mean dispensing ratios for each medicine and year were calculated for all remoteness and disadvantage groups. Generalised regression models compared the percentage change in dispensing ratios from 2004 to 2006. RESULTS: Between 2004 and 2006 PPI dispensing fell significantly in major cities (-13.7%, 95% CI=-17.3--9.8), inner regional (-14.0, 95%CI=-19.5--8.2), outer regional (-14.6%, 95%CI=-19.9--9.0) and remote areas (-9.4%, 95%CI=-16.4--1.8). Statin dispensing fell in all groups but the most remote (range 6-7%). When focussing on disadvantage, PPI dispensing fell significantly in all groups (range 12-15%). Statins dispensing did not fall significantly in the most disadvantaged areas (-2.9%, 95%CI=-8.6-3.2) but did in the least (-6.5%, -11.3--1.5) and second-least (-5.8, -10.5--0.9) disadvantaged areas. Dispensing of PPIs and statins in the most remote and disadvantaged areas remained substantially below levels expected for Australia after the 21% co-payments increase. CONCLUSIONS: The findings suggest that the 2005 21% in patient co-payments adversely affected prescription medicine use in all areas of Australia and was not specific to remote or disadvantaged areas. Indeed, dispensing of statins fell significantly in all but the most remote and disadvantaged areas, and the existing gap in dispensing of PPIs and statins was not widened by the co-payments increase. PPIs, which are used at above-prevalence rates in Australia and have cheaper over-the-counter substitutes available, were more sensitive to co-payment increases than were statins.

How much do we spend on prescription medicines? Out-of-pocket costs for patients in Australia and other OECD countries.

OBJECTIVES: To determine changes in out-of-pocket expenditure on prescription medicines for Australian patients, and how patient expenditure compares with other Organisation for Economic Co-operation and Development (OECD) countries. METHODS: We examined out-of-pocket expenditure on prescription medicines by patients in Australia between 1970 and 2007, and between Australia and 15 other OECD countries (Canada, Czech Republic, Denmark, Finland, France, Germany, Japan, Republic of Korea (South Korea), Luxembourg, Poland, Slovak Republic, Spain, Sweden, Switzerland and the United States) in 2005. FINDINGS: Spending on publicly subsidised medicines by Australian patients increased from $16 per person in 1971 to $62 in 2007. Patient expenditure on all prescription medicines had risen to $134 per person in 2007. Out-of-pocket expenditure for Australian patients ranked 4th of 14 OCED countries with universal pharmaceutical subsidies. Australian patients pay 28% of national pharmaceutical expenditure; more than patients in South Korea (27%), Slovak Republic (26%), Sweden (22%), France, Luxembourg, Japan and Switzerland (17%), Germany (15%), Czech Republic (11%) and Spain (6%), but less than patients in Finland (36%), Denmark (33%) and Poland (34%). CONCLUSIONS: Compared to other OECD countries, Australian out-of-pocket costs are now in the mid to upper range. Further increases have the potential to significantly affect access to care.

Increased patient co-payments and changes in PBS-subsidised prescription medicines dispensed in Western Australia.

OBJECTIVE: To determine whether a 24% increase in patient co-payments in January 2005 and two related co-payment changes for medicines subsidised under the Australian Pharmaceutical Benefits Scheme (PBS) were associated with changes in dispensings in Western Australia (WA). METHOD: We analysed aggregate monthly prescription counts and defined daily dose per 1,000 population per day (DDD/1,000/day) for atypical antipsychotics, combination asthma medicines, HmgCoA reductase inhibitors (statins) and proton-pump inhibitors (PPIs). Trends pre and post the co-payment increase in January 2005 were compared. RESULTS: In three of the four categories examined, prescription counts were significantly lower following the increase in co-payment thresholds. Compared with dispensings prior to the co-payment increase, prescriptions fell by 8% for combination asthma medicines (p<0.001), 9% for PPIs (p<0.001) and 5% for statins (p<0.001). Following the rise in co-payments, DDD/1,000/day decreased for all four categories. Decreases in dispensings to concessional beneficiaries were between 4% and 5% larger than for general beneficiary patients. CONCLUSIONS AND IMPLICATIONS: The reduction in the both prescription counts and DDD/1,000/day observed for combination asthma medicines, PPIs and statins, which all remained above co-payment thresholds, suggests the increase in PBS co-payments has affected utilisation of these subsidised medicines. The results indicate that increases in patient contributions particularly impact on concessional patients' ability to afford prescription medicines.

The geographic distribution of private health insurance in Australia in 2001.

BACKGROUND: Private health insurance has been a major focus of Commonwealth Government health policy for the last decade. Over this period, the Howard government introduced a number of policy changes which impacted on the take up of private health insurance. The most expensive of these was the introduction of the private health insurance rebate in 1997, which had an estimated cost of $3 billion per annum. METHODS: This article uses information on the geographic distribution of the population with private health insurance cover to identify associations between rates of private health insurance cover and socioeconomic status. The geographic analysis is repeated with survey data on expenditure on private health insurance, to provide an estimate of the rebate flowing to different socioeconomic groups. RESULTS: The analysis highlights the strong association between high rates of private health insurance cover and high socioeconomic status and shows the substantial transfer of funds, under the private health insurance rebate, to those living in areas of highest socioeconomic status, compared with those in areas of lower socioeconomic status, and in particular those in the most disadvantaged areas. The article also provides estimates of private health insurance cover by federal electorate, emphasising the substantial gaps in cover between Liberal Party and Australian Labor Party seats. CONCLUSION: The article concludes by discussing implications of the uneven distribution of private health insurance cover across Australia for policy formation. In particular, the study shows that the prevalence of private health insurance is unevenly distributed across Australia, with marked differences in prevalence in rural and urban areas, and substantial differences by socioeconomic status. Policy formation needs to take this into account. Evaluating the potential impact of changes in private health insurance requires more nuanced consideration than has been implied in the rhetoric about private health insurance over the last decade.

Prevalence of childhood lead poisoning and respiratory disease associated with lead smelter emissions.

BACKGROUND: The city of Port Pirie in South Australia has been a world leading centre for lead and zinc smelting and processing since 1889 that continues to cause contamination of its environment and resident population. This study quantifies the effect of lead and SO2 emissions from Nyrstar Port Pirie Pty Ltd's smelter on blood lead and respiratory health outcomes, respectively, and establishes what air quality values are required to better protect human health. METHOD: Blood lead and emergency department presentation data collected by South Australia Health (SA Health) and lead in air and SO2 data collected by the South Australian Environment Protection Authority (SAEPA) were obtained and analysed to quantify health outcomes due to smelter emissions in Port Pirie. Regression analysis was used to assess the relationship between the concentration of lead in air and children's blood lead levels between the years of available data: 2003 to 2017. Ambient SO2 concentrations (SAEPA) measured continuously between 2008 and 2018 were 24-hour averaged and compared to daily local emergency department respiratory presentation rates (available from July 2012 to October 2018). Rates of emergency department respiratory presentations at Port Pirie and regional comparators were calculated as age-standardised rates. RESULTS: The data show that increases in ambient SO2 concentrations are associated with increased rates of emergency department respiratory presentations of Port Pirie residents, in which children are over-represented. The 30-day rolling average of respiratory presentations was significantly associated (p < 0.05) with incremental increases in SO2. Analysis of the relationship between lead in air and blood lead shows that annual geometric mean air lead concentrations need to be <0.11 µg/m3 to ensure the geometric mean blood lead of Port Pirie children under 5 years is ≤5 µg/dL. For children aged 24 months, lead in air needs to be no greater than 0.082 µg/m3 (annual geometric mean) to ensure geometric mean blood lead does not exceed 5 µg/dL. CONCLUSION: Current smelting emissions continue to pose a clear risk of harm to Port Pirie children. Allowable emissions must be lowered significantly to limit adverse childhood health outcomes including respiratory illness and IQ, academic achievement and socio-behavioural problems that are associated with lead exposure at levels experienced by Port Pirie children. Current SO2 levels are likely to be responsible for increased rates of emergency department respiratory presentations in Port Pirie compared with other South Australian locations. As a minimum, Australian SO2 air quality standards need to be enforced in Port Pirie to better protect human health. Lead in air needs to be approximately 80% lower than the current national standard (0.5 µg/m3) to ensure that the geometric blood lead of children under 5 years is less than or equal to 5 µg/dL.

BAG5 inhibits parkin and enhances dopaminergic neuron degeneration.

Loss-of-function mutations in the parkin gene, which encodes an E3 ubiquitin ligase, are the major cause of early-onset Parkinson's disease (PD). Decreases in parkin activity may also contribute to neurodegeneration in sporadic forms of PD. Here, we show that bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacts with parkin and the chaperone Hsp70. Within this complex, BAG5 inhibits both parkin E3 ubiquitin ligase activity and Hsp70-mediated refolding of misfolded proteins. BAG5 enhances parkin sequestration within protein aggregates and mitigates parkin-dependent preservation of proteasome function. Finally, BAG5 enhances dopamine neuron death in an in vivo model of PD, whereas a mutant that inhibits BAG5 activity attenuates dopaminergic neurodegeneration. This contrasts with the antideath functions ascribed to BAG family members and suggests a potential role for BAG5 in promoting neurodegeneration in sporadic PD through its functional interactions with parkin and Hsp70.

The impact of co-payment increases on dispensings of government-subsidised medicines in Australia.

PURPOSE: Patient co-payments for medicines subsidised under the Australian Pharmaceutical Benefits Scheme (PBS) increased by 24% in January 2005. We investigated whether this increase and two related co-payment changes were associated with changes in dispensings of selected subsidised medicines in Australia. METHOD: We analysed national aggregate monthly prescription dispensings for 17 medicine categories, selected to represent a range of treatments (e.g. for diabetes, cardiovascular diseases, gout). Trends in medication dispensings from January 2000 to December 2004 were compared with those from January 2005 to September 2007 using segmented regression analysis. RESULTS: Following the January 2005 increase in PBS co-payments, significant decrease in dispensing volumes were observed in 12 of the 17 medicine categories (range: 3.2-10.9%), namely anti-epileptics, anti-Parkinson's treatments, combination asthma medicines, eye-drops, glaucoma treatments, HmgCoA reductase inhibitors, insulin, muscle relaxants, non-aspirin antiplatelets, osteoporosis treatments, proton-pump inhibitors (PPIs) and thyroxine. The largest decrease was observed for medicines used in treating asymptomatic conditions or those with over-the-counter (OTC) substitutes. Decrease in dispensings to social security beneficiaries was consistently greater than for general beneficiaries following the co-payment changes (range: 1.8-9.4% greater, p = 0.028). CONCLUSIONS: The study findings suggest that recent increase in Australian PBS co-payments have had a significant effect on dispensings of prescription medicines. The results suggest large increase in co-payments impact on patients' ability to afford essential medicines. Of major concern is that, despite special subsidies for social security beneficiaries in the Australian system, the recent co-payment increase has particularly impacted on utilisation for this group.

Ambient soil cation exchange capacity inversely associates with infectious and parasitic disease risk in regional Australia.

Human contact with soil may be important for building and maintaining normal healthy immune defence mechanisms, however this idea remains untested at the population-level. In this continent-wide, cross-sectional study we examine the possible public health benefit of ambient exposures to soil of high cation exchange capacity (CEC), a surrogate for potential immunomodulatory soil microbial diversity. We compare distributions of normalized mean 2011/12-2012/13 age-standardized public hospital admission rates (cumulative incidence) for infectious and parasitic diseases across regional Australia (representing an average of 29,516 patients/year in 228 local government areas), within tertiles of socioeconomic status and soil exposure. To test the significance of soil CEC, we use probabilistic individual-level environmental exposure data (with or without soil), and group-level variables, in robust non-parametric multilevel modelling to predict disease rates in unseen groups. Our results show that in socioeconomically-deprived areas with high CEC soils, rates of infectious and parasitic disease are significantly lower than areas with low CEC soils. Also, health inequality (relative risk) due to socioeconomic status is significantly lower in areas with high CEC soils compared to low CEC soils (Δ relative risk = 0.47; 95% CI: 0.13, 0.82). Including soil exposure when modelling rates of infectious and parasitic disease significantly improves prediction performance, explaining an additional 7.5% (Δ r2 = 0.075; 95% CI: 0.05, 0.10) of variation in disease risk, in local government areas that were not used for model building. Our findings suggest that exposure to high CEC soils (typically high soil biodiversity) associates with reduced risk of infectious and parasitic diseases, particularly in lower socioeconomic areas.

Detection of pseudosinusoidal epileptic seizure segments in the neonatal EEG by cascading a rule-based algorithm with a neural network.

This paper presents an approach to detect epileptic seizure segments in the neonatal electroencephalogram (EEG) by characterizing the spectral features of the EEG waveform using a rule-based algorithm cascaded with a neural network. A rule-based algorithm screens out short segments of pseudosinusoidal EEG patterns as epileptic based on features in the power spectrum. The output of the rule-based algorithm is used to train and compare the performance of conventional feedforward neural networks and quantum neural networks. The results indicate that the trained neural networks, cascaded with the rule-based algorithm, improved the performance of the rule-based algorithm acting by itself. The evaluation of the proposed cascaded scheme for the detection of pseudosinusoidal seizure segments reveals its potential as a building block of the automated seizure detection system under development.

Effects of age and ACL reconstruction on quadriceps gamma loop function.

BACKGROUND AND PURPOSE: Both aging and anterior cruciate ligament (ACL) reconstruction are associated with strength deficits, which can in turn influence performance of activities of daily living. Thus it is informative to understand mechanisms underlying strength deficits. Age-related declines in strength follow reductions in muscle fiber numbers and size, whereas strength deficits following ACL reconstruction may be caused by the loss of intraligamentous mechanoreceptors. A common link between these conditions is the gamma spindle system, or the gamma loop. Appropriately applied vibration can affect the gamma loop by causing disruption of afferent feedback to a muscle and result in decreased force capabilities. We investigated the effect of age and ACL reconstruction on gamma loop function. METHODS: Maximal isometric strength (MVC) and electromyography (EMG) of the quadriceps were quantified before and after vibration stimulation of the infrapatellar tendon of 3 groups: young healthy (n=4; mean age=23.8 yrs), young ACL reconstructed (n=7; mean age=22.4 yrs), and older healthy (n=4; mean age=66.1 yrs) individuals. RESULTS: The quadriceps MVC, vastus lateralis EMG, vastus medialis EMG, and rectus femoris EMG declined significantly in the young healthy group following vibration stimulation to the infrapatellar tendon, which indicated an intact gamma loop. There were no changes in these variables for the old healthy and ACL reconstructed groups. CONCLUSION: Gamma loop function was impaired in both the older and ACL reconstructed groups possibly due to either decreased muscle spindle sensitivity or the loss of mechanoreceptors.

Giant excised patch recordings of recombinant ion channel currents expressed in mammalian cells.

The giant excised patch variant of patch clamp recording combines microsecond time resolution of macroscopic currents with rapid exchange of the experimental solutions at the intracellular membrane surface. This technique has been applied to a limited number of cell types, including Xenopus oocytes, muscle cells, and photoreceptors. We have applied this technique to recording recombinant ion channel currents expressed in membrane patches excised from HEK293 cell lines. Giant inside-out patch recordings of Na(+) channels and SK(Ca) type calcium-activated potassium channels show high temporal resolution and excellent signal to noise characteristics. This technique will facilitate the study of recombinant ion channels expressed in mammalian cells.

Unpacking analyses relying on area-based data: are the assumptions supportable?

BACKGROUND: In the absence in the major Australian administrative health record collections of a direct measure of the socioeconomic status of the individual about whom the event is recorded, analysis of the association between the health status, use of health services and socioeconomic status of the population relies an area-based measure of socioeconomic status.This paper explores the reliability of the area of address (at the levels typically available in administrative data collections) as a proxy measure for socioeconomic disadvantage. The Western Australian Data Linkage System was used to show the extent to which hospital inpatient separation rates for residents of Perth vary by socioeconomic status of area of residence, when calculated at various levels of aggregation of area, from smallest (Census Collection District) to largest (postcode areas and Statistical Local Areas). Results are also provided of the reliability, over time, of the address as a measure of socioeconomic status. RESULTS: There is a strong association between the socioeconomic status of the usual address of hospital inpatients at the smallest level in Perth, and weaker associations when the data are aggregated to larger areas. The analysis also shows that a higher proportion of people from the most disadvantaged areas are admitted to hospital than from the most well-off areas (13% more), and that these areas have more separations overall (47% more), as a result of larger numbers of multiple admissions.Of people admitted to hospital more than once in a five year period, four out of five had not moved address by the time of their second episode. Of those who moved, the most movement was within, or between, areas of similar socioeconomic status, with people from the most well off areas being the least likely to have moved. CONCLUSION: Postcode level and SLA level data provide a reliable, although understated, indication of socioeconomic disadvantage of area. The majority of Perth residents admitted to hospital in Western Australia had the same address when admitted again within five years. Of those who moved address, the majority had moved within, or between, areas of similar socioeconomic status.Access to data about individuals from the Western Australian Data Linkage System shows that more people from disadvantaged areas are admitted to a hospital, and that they have more episodes of hospitalisation. Were data to be available across Australia on a similar basis, it would be possible to undertake research of greater policy-relevance than is currently possible with the existing separations-based national database.

The socioeconomic gradient and chronic illness and associated risk factors in Australia.

OBJECTIVE: To examine the prevalence of major chronic diseases and their risk factors in different socioeconomic groups in the Australian population, in order to highlight the need for public policy initiatives to reduce socioeconomic inequalities in health. METHODS: Data were provided by the Australian Bureau of Statistics (ABS) from the 2001 National Health Survey (NHS) for selected chronic diseases and associated risk factors. Conditions selected were those, which form the National Health Priority Area (NHPA) conditions (other than injury, which has not been included in this paper, with its focus on chronic disease); plus other 'serious' chronic conditions, in line with the classification developed by Mathers; and for which sufficient cases were available for analysis by socioeconomic status. Indirectly age-standardised prevalence rates were calculated by broad age group for Australia and for five groups of socioeconomic status; rate ratios were calculated to show variations in prevalence between these groups. RESULTS: Significant socioeconomic inequalities were evident for many of the major chronic diseases; the largest was for diabetes mellitus (at ages 25 to 64 years); and for many diseases, there was also a strong, continuous socioeconomic gradient in the rates.Circulatory system diseases (in particular, hypertensive disease) and digestive system diseases also exhibited a strong differential in the 25 to 64 year age group.In the 65 years and over age group, the strongest inequalities were evident for mental and behavioural problems, diabetes (with a continuous socioeconomic gradient in rates) and respiratory system diseases.A number of risk factors for chronic diseases, namely self-reported smoking, alcohol misuse, physical inactivity and excess weight showed a striking association with socioeconomic status, in particular for people who were smokers and those who did not exercise. CONCLUSION: This analysis shows that the prevalence of chronic disease varies across the socioeconomic gradient for a number of specific diseases, as well as for important disease risk factors. Therefore, any policy interventions to address the impact of chronic disease, at a population level, need to take into account these socioeconomic inequalities.

Impact of cost of medicines for chronic conditions on low income households in Australia.

OBJECTIVES: To determine the cost of medicines for selected chronic illnesses and the proportion of discretionary income this would potentially displace for households with different pharmaceutical subsidy entitlements and incomes. METHODS: We analysed household income and expenditure data for 9,774 households participating in two Australian surveys in 2009-10. The amount of 'discretionary' income available to households after basic living and health care expenditure was modelled for households with high pharmaceutical subsidies: pensioner and non-pensioner concessional (social security entitlements); and households with general pharmaceutical subsidies and low, middle or high incomes. We calculated the proportion of discretionary income that would be needed for medicines if one household member had diabetes or acute coronary syndrome, or if one member also had two co-existing illnesses (gastro-oesophageal reflux disease and depression, or asthma and osteoarthritis). RESULTS: Pensioner and low income households had little discretionary income after basic living and health care expenditure (AUD$92 and $164/week, respectively). Medicines for the specified illnesses ranged from $11-$42/month for high subsidy households and $34-$186/month for low subsidy households. Costs reduced substantially once patients reached the annual pharmaceutical cap (safety net), prior to which medicine costs would displace the equivalent of 1%-10% of discretionary income for most household types. However, low income households would have to forego the equivalent of between 5%-26% of their discretionary income for between 7 and 9 months of the year before receiving additional subsidies. CONCLUSIONS: Prescription medicines for chronic conditions pose a substantial financial burden to many households, particularly those with low incomes and general pharmaceutical subsidies. Policies are needed to minimize the cost burden of prescription medicines, particularly for low-income working households.

Unraveling the mechanism of protein disaggregation through a ClpB-DnaK interaction.

HSP-100 protein machines, such as ClpB, play an essential role in reactivating protein aggregates that can otherwise be lethal to cells. Although the players involved are known, including the DnaK/DnaJ/GrpE chaperone system in bacteria, details of the molecular interactions are not well understood. Using methyl-transverse relaxation-optimized nuclear magnetic resonance spectroscopy, we present an atomic-resolution model for the ClpB-DnaK complex, which we verified by mutagenesis and functional assays. ClpB and GrpE compete for binding to the DnaK nucleotide binding domain, with GrpE binding inhibiting disaggregation. DnaK, in turn, plays a dual role in both disaggregation and subsequent refolding of polypeptide chains as they emerge from the aggregate. On the basis of a combined structural-biochemical analysis, we propose a model for the mechanism of protein aggregate reactivation by ClpB.

Frequency of counterstrain tender points in osteopathic medical students.

CONTEXT: Counterstrain is 1 osteopathic manipulative treatment technique taught to osteopathic medical students, but teaching all 300 counterstrain tender points is not feasible at most colleges of osteopathic medicine (COMs) because of time limitations. OBJECTIVE: To identify high-yield tender points in osteopathic medical students for teaching and to assess for correlations between tender points and demographic information, weight, and history of pain or trauma. METHODS: First- and second-year osteopathic medical students at 5 COMs were surveyed regarding the presence and absence of tender points found on themselves by fellow students. Demographic information, weight, and history of pain and trauma data were collected. The McNemar test was used to compare the frequency of positive tender points between the right and left sides. Multiple logistic regression models were fit to the data to determine if participant characteristics were related to having 1 or more positive tender points in a tender point group. Wilcoxon signed rank tests were used to compare the percentage of positive anterior vs posterior tender points. Multiple logistic regression models were used to test for differences between COMs after accounting for differences in participant characteristics. RESULTS: Frequency of 78 tender point groups was obtained. Forty tender point groups (51%) were positive for the presence of 1 or more tender points by 50% or more of the participants. Positive tender points were more common on the right side for 23 groups (all P<.001). Female participants were more likely to have tender points for 22 groups (all P<.001). The 20- to 25-year-olds had more tender points for 6 groups (all P≤.03). Tender points were more common in participants with a history of pain for 29 groups (all P<.001) and with a history of trauma for 4 groups (all P≤.05). Anterior tender points were more common for cervical, thoracic, rib, and lumbar body regions (P<.001). Differences were found between COMs for all tender point groups (P≤.02). CONCLUSION: Nearly half of the tender point groups surveyed were reported positive by 50% or more of participants, and high-yield tender points were found in each body region. Ultimately, these results may guide counterstrain curricula for COMs.

A new perspective on Hsp104-mediated propagation and curing of the yeast prion [PSI (+) ].

Most prions in yeast form amyloid fibrils that must be severed by the protein disaggregase Hsp104 to be propagated and transmitted efficiently to newly formed buds. Only one yeast prion, [PSI (+) ], is cured by Hsp104 overexpression. We investigated the interaction between Hsp104 and Sup35, the priongenic protein in yeast that forms the [PSI (+) ] prion.1 We found that a 20-amino acid segment within the highly-charged, unstructured middle domain of Sup35 contributes to the physical interaction between the middle domain and Hsp104. When this segment was deleted from Sup35, the efficiency of [PSI (+) ] severing was substantially reduced, resulting in larger Sup35 particles and weakening of the [PSI (+) ] phenotype. Furthermore, [PSI (+) ] in these cells was completely resistant to Hsp104 curing. The affinity of Hsp104 was considerably weaker than that of model Hsp104-binding proteins and peptides, implying that Sup35 prions are not ideal substrates for Hsp104-mediated remodeling. In light of this finding, we present a modified model of Hsp104-mediated [PSI (+) ] propagation and curing that requires only partial remodeling of Sup35 assembled into amyloid fibrils.