Wolves make roadways safer, generating large economic returns to predator conservation.

Recent studies uncover cascading ecological effects resulting from removing and reintroducing predators into a landscape, but little is known about effects on human lives and property. We quantify the effects of restoring wolf populations by evaluating their influence on deer-vehicle collisions (DVCs) in Wisconsin. We show that, for the average county, wolf entry reduced DVCs by 24%, yielding an economic benefit that is 63 times greater than the costs of verified wolf predation on livestock. Most of the reduction is due to a behavioral response of deer to wolves rather than through a deer population decline from wolf predation. This finding supports ecological research emphasizing the role of predators in creating a "landscape of fear." It suggests wolves control economic damages from overabundant deer in ways that human deer hunters cannot.

Cardiovascular and lifestyle risk factors of mild cognitive impairment in UK veterans and non-veterans.

BACKGROUND: The link between poor cardiovascular health (CVH), lifestyle and mild cognitive impairment (MCI) has been well established in the general population. However, there is limited research exploring these associations in ageing UK veterans. AIMS: This study explored the risk of MCI and its association with nine CVH and lifestyle risk factors (including diabetes, heart disease, high cholesterol, high blood pressure, obesity, stroke, physical inactivity, the frequency of alcohol consumption and smoking) in UK veterans and non-veterans. METHODS: This prospective cohort study comprised data from the PROTECT study between 2014 and 2022. Participants comprised of UK military veterans and non-veterans aged ≥50 years at baseline. Veteran status was defined using the Military Service History Questionnaire. CVH and lifestyle risk factors were defined using a combination of self-report measures, medication history or physical measurements. MCI was defined as the presence of subjective and objective cognitive impairment. RESULTS: Based on a sample of 9378 veterans (n = 488) and non-veterans (n = 8890), the findings showed the risk of MCI significantly reduced in veterans with obesity, those who frequently consumed alcohol and were physically inactive compared to non-veterans. The risk of MCI significantly increased in veterans with diabetes (hazards ratio [HR] = 2.22, 95% confidence interval [CI] 1.04-4.75, P ≤ 0.05) or high cholesterol (HR = 3.11, 95% CI 1.64-5.87, P ≤ 0.05) compared to veterans without. CONCLUSIONS: This study identified CVH and lifestyle factors of MCI in UK veterans and non-veterans. Further work is needed to understand these associations and the underpinning mechanisms which could determine intervention strategies to reduce the risk of MCI.

Rumination moderates the longitudinal associations of awareness of age-related change with depressive and anxiety symptoms.

OBJECTIVE: Lower awareness of age-related gains (AARC-gains) and higher awareness of age-related losses (AARC-losses) may be risk factors for depressive and anxiety symptoms. We explored whether: (1) Baseline AARC-gains and AARC-losses predict depressive and anxiety symptoms at one-year follow-up; (2) age and rumination moderate these associations; (3) levels of AARC-gains and AARC-losses differ among individuals with different combinations of current and past depression and/or with different combinations of current and past anxiety. METHODS: In this one-year longitudinal cohort study participants (N = 3386; mean age = 66.0; SD = 6.93) completed measures of AARC-gains, AARC-losses, rumination, depression, anxiety, and lifetime diagnosis of depression and anxiety in 2019 and 2020. Regression models with tests of interaction were used. RESULTS: Higher AARC-losses, but not lower AARC-gains, predicted more depressive and anxiety symptoms. Age did not moderate these associations. Associations of lower AARC-gains and higher AARC-losses with more depressive symptoms and of higher AARC-losses with more anxiety symptoms were stronger in those with higher rumination. Individuals with both current and past depression reported highest AARC-losses and lowest AARC-gains. Those with current, but not past anxiety, reported highest AARC-losses. CONCLUSION: Perceiving many age-related losses may place individuals at risk of depressive and anxiety symptoms, especially those who frequently ruminate.

Heterozygous CAPN3 missense variants causing autosomal-dominant calpainopathy in seven unrelated families.

AIMS: Recessive variants in CAPN3 gene are the cause of the commonest form of autosomal recessive limb girdle muscle dystrophy. However, two distinct in-frame deletions in CAPN3 (NM_000070.3:c.643_663del21 and c.598_621del15) and more recently, Gly445Arg and Arg572Pro substitutions have been linked to autosomal dominant (AD) forms of calpainopathy. We report 21 affected individuals from seven unrelated families presenting with an autosomal dominant form of muscular dystrophy associated with five different heterozygous missense variants in CAPN. METHODS: We have used massively parallel gene sequencing (MPS) to determine the genetic basis of a dominant form of limb girdle muscular dystrophy in affected individuals from seven unrelated families. RESULTS: The c.700G> A, [p.(Gly234Arg)], c.1327T> C [p.(Ser443Pro], c.1333G> A [p.(Gly445Arg)], c.1661A> C [p.(Tyr554Ser)] and c.1706T> C [p.(Phe569Ser)] CAPN3 variants were identified. Affected individuals presented in young adulthood with progressive proximal and axial weakness, waddling walking and scapular winging or with isolated hyperCKaemia. Muscle imaging showed fatty replacement of paraspinal muscles, variable degrees of involvement of the gluteal muscles, and the posterior compartment of the thigh and minor changes at the mid-leg level. Muscle biopsies revealed mild myopathic changes. Western blot analysis revealed a clear reduction in calpain 3 in skeletal muscle relative to controls. Protein modelling of these variants on the predicted structure of calpain 3 revealed that all variants are located in proximity to the calmodulin-binding site and are predicted to interfere with proteolytic activation. CONCLUSIONS: We expand the genotypic spectrum of CAPN3-associated muscular dystrophy due to autosomal dominant missense variants.

Contextual influences on Latino men's sexual and substance use behaviors following immigration to the Midwestern United States.

Objectives: Latinos in the United States experience a disproportionate number of HIV and other sexually transmitted infections (STIs) and higher use of alcohol and illegal drugs, which has been attributed to increases in risk behaviors following immigration. Whereas substantial research documents these behavioral changes, little is known about how immigrants increase their risk or why some immigrants increase their risk and other immigrants do not. This study explored how the social and normative context affects sexual and substance use behaviors among Latino immigrant men in a midsized Midwestern city of the United States.Methods: We interviewed 64 Latino immigrant men recruited from community sites in Milwaukee, Wisconsin (mean age = 32.6 years). Participants reported the social and normative contexts preceding and following immigration, including social networks and support, perceptions of the law, and familiar and peer normative influences.Results: Immigrants attributed changes in their sexual and substance use behaviors to their immigration goals, social support, peer and familial normative influences, and restrictions related to their immigrant status. Immigration for economic and personal advancement was generally protective from behaviors that would interfere with those goals as were extended familial networks that could provide support, resources, and normative control. The need to stay under the radar of authorities, the proportion of Latinos in the community, the social and normative changes associated with immigrants' age, and the higher perceptions of risk for HIV in the United States compared with their home countries also influenced immigrants' sexual and substance use behaviors.Conclusions: Changes in risk behavior after immigration to the United States reflect a combination of social and normative factors and personal goals. Interventions and policies aiming to prevent HIV and substance use among Latino immigrants should understand the contextual conditions that decrease or increase their risk behaviors in the United States.

Online assessment of risk factors for dementia and cognitive function in healthy adults.

OBJECTIVE: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. METHOD: Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. RESULTS: Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. CONCLUSION: Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan.

Delayed Carotid Dissection Following Lower Lip Revascularization in the Setting of Hyoid Fracture--A Case Report and Review of the Literature.

Traumatic injuries to the lip are common, but injuries that require revascularization of the lower lip are infrequent and pose a major challenge to the reconstructive surgeon. This report describes the case of a 53-year-old woman who sustained a lower lip avulsion injury, a comminuted mandibular parasymphyseal fracture, and a hyoid bone fracture secondary to a bicycle accident. Trauma workup included computed tomographic angiography of the head and neck, which did not show vascular injury. Despite successful revascularization of the lower lip, on postoperative day 11 the patient developed a large internal carotid artery dissection and middle cerebral artery stroke. This case highlights the importance of careful postoperative monitoring after high-energy facial trauma, particularly in the setting of vascular and bony injuries.

Context and group dynamics in a CBPR-developed HIV prevention intervention.

This paper will explore in detail the effects of context and group dynamics on the development of a multi-level community-based HIV prevention intervention for crack cocaine users in the San Salvador Metropolitan Area, El Salvador. Community partners included residents from marginal communities, service providers from the historic center of San Salvador and research staff from a non-profit organization. The community contexts from which partners came varied considerably and affected structural group dynamics, i.e. who was identified as community partners, their research and organizational capacity, and their ability to represent their communities, with participants from marginal communities most likely to hold community leadership positions and be residents, and those from the center of San Salvador most likely to work in religious organizations dedicated to HIV prevention or feeding indigent drug users. These differences also affected the intervention priorities of different partners. The context of communities changed over time, particularly levels of violence, and affected group dynamics and the intervention developed. Finally, strategies were needed to elicit input from stakeholders under-represented in the community advisory board, in particular active crack users, in order to check the feasibility of the proposed intervention and revise it as necessary. Because El Salvador is a very different context than that in which most CBPR studies have been conducted, our results reveal important contextual factors and their effects on partnerships not often considered in the literature.

Associations between risk of mortality and atypical antipsychotic use in vascular dementia: a clinical cohort study.

OBJECTIVES: People with vascular dementia (VaD) are frequently prescribed atypical antipsychotics to treat behavioural and psychological symptoms, but there is an alarming lack of evidence regarding their safety or efficacy in VaD. This study sought to identify the mortality risk associated with the most commonly prescribed atypical antipsychotics in people with VaD compared with people not exposed to these drugs. METHODS: A clinical cohort study of 1531 people with VaD performed using anonymised versions of full electronic health records from the Clinical Record Interactive Search application at the South London and Maudsley NHS Foundation Trust. Patients were identified from 2007 to 2010, of whom 337 were exposed to quetiapine, risperidone or olanzapine. The main outcome measure was mortality. RESULTS: Patients exposed to atypical antipsychotics were not at increased risk of mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI): 0.87-1.26]. Exposure to risperidone did not result in an increased risk of mortality (HR = 0.85; 95% CI: 0.59-1.24), and patients exposed to quetiapine had a non-significant numerical increase in mortality risk (HR = 1.14; 95% CI: 0.93-1.39; p-value = 0.20) compared with untreated patients. Too few patients were exposed to olanzapine alone to provide reliable results. CONCLUSIONS: The absence of a significant increase in mortality risk associated with atypical antipsychotics in people with VaD indicates that a clinical trial of antipsychotics focussing on the treatment of aggression and agitation in this patient group will be justified and feasible following further consideration of possible confounders, which will be critical to determine the role of antipsychotics in treatment of VaD.

Pharmacokinetics of two common antiretroviral regimens in older HIV-infected patients: a pilot study.

OBJECTIVES: The pharmacokinetics (PK) of antiretrovirals (ARVs) in older HIV-infected patients are poorly described. Here, the steady-state PK of two common ARV regimens [tenofovir (TFV)/emtricitabine (FTC)/efavirenz (EFV) and TFV/FTC/atazanavir (ATV)/ritonavir (RTV)] in older nonfrail HIV-infected patients are presented. METHODS: HIV-infected subjects ≥ 55 years old not demonstrating the frailty phenotype were enrolled in an unblinded, intensive-sampling PK study. Blood plasma (for TFV, FTC, EFV, ATV and RTV concentrations) and peripheral blood mononuclear cells [PBMCs; for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations] were collected at 11 time-points over a 24-hour dosing interval. Drug concentrations were analysed using validated liquid chromatography-ultraviolet detection (LC-UV) or liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Noncompartmental pharmacokinetic analysis was used to estimate PK parameters [area under the concentration-time curve over 24 h (AUC0-24h ) and maximal concentration (Cmax )]. These parameters were compared with historical values from the general HIV-infected population. RESULTS: Six subjects on each regimen completed the study. Compared with the general population, these elderly subjects had 8-13% decreased TFV AUC0-24h and Cmax , and 19-78% increased FTC and RTV AUC0-24h and Cmax . Decreased ATV AUC0-24h (12%) and increased Cmax (9%) were noted, while EFV exposure was unchanged (5%) with a 16% decrease in Cmax . Intracellular nucleoside/tide metabolite concentrations and AUC are also reported for these subjects. CONCLUSIONS: This study demonstrates that the PK of these ARVs are altered by 5-78% in an older HIV-infected population. Implications of PK differences for clinical outcomes, particularly with the active nucleoside metabolites, remain to be explored. This study forms the basis for further study of ARV PK, efficacy, and toxicity in older HIV-infected patients.

Histone H3 E50K mutation confers oncogenic activity and supports an EMT phenotype.

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype in human cells. Expression of H3E50K is sufficient to transform human cells as evidenced by a dramatic increase in cell migration and invasion, and a statistically significant increase in proliferation and clonogenicity. H3E50K also increases the invasive phenotype in the context of co-occurring BRAF mutations, which are present in patient tumors characterized by H3E50K. H3E50 lies on the globular domain surface in a region that contacts H4 within the nucleosome. We find that H3E50K perturbs proximal H3 post-translational modifications globally and dysregulates gene expression, activating the epithelial to mesenchymal transition. Functional studies using S. cerevisiae reveal that, while yeast cells that express H3E50K as the sole copy of histone H3 show sensitivity to cellular stressors, including caffeine, H3E50K cells display some genetic interactions that are distinct from the characterized H3K36M oncohistone yeast model. Taken together, these data suggest that additional histone H3 mutations have the potential to be oncogenic drivers and function through distinct mechanisms that dysregulate gene expression.

With God's help i can do it: crack users? Formal and informal recovery experiences in El Salvador.

Crack use has increased dramatically in El Salvador in the last few decades. As with other developing countries with sudden onsets of drug problems, El Salvador has few medical staff trained in addictions treatment. Little research has examined drug users? attempts to reduce or abstain from drug use in countries where government-regulated formal medical treatment for drug addiction is scarce. This paper uses qualitative and quantitative data gathered from active crack users to explore their formal and informal strategies to reduce or abstain from drugs, and compares these with components of informal and formal treatment in developed countries.

Design Considerations for Mobile Health Applications Targeting Older Adults.

Mobile technologies are becoming ubiquitous in the world, changing the way we communicate and provide patient care and services. Some of the most compelling benefits of mobile technologies are in the areas of disease prevention, health management, and care delivery. For all the advances that are occurring in mobile health, its full potential for older adults is only starting to emerge. Yet, existing mobile health applications have design flaws that may limit usability by older adults. The aim of this paper is to review barriers and identify knowledge gaps where more research is needed to improve the accessibility of mobile health use in aging populations. The same observations might apply to those who are not elderly, including individuals suffering from severe mental or medical illnesses.

Dynamic localization of the nuclear import receptor and its interactions with transport factors.

Characterization of the interactions between soluble factors required for nuclear transport is key to understanding the process of nuclear trafficking. Using a synthetic lethal screen with the rna1-1 strain, we have identified a genetic interaction between Rna1p, a GTPase activating protein required for nuclear transport, and yeast importin-beta, a component of the nuclear localization signal receptor. By the use of fusion proteins, we demonstrate that Rna1p physically interacts with importin-beta. Mutants in importin-beta exhibit in vivo nuclear protein import defects, and importin-beta localizes to the nuclear envelope along with other proteins associated with the nuclear pore complex. In addition, we present evidence that importin-alpha, but not importin-beta, mislocalizes to the nucleus in cells where the GTPase Ran is likely to be in the GDP-bound state. We suggest a model of nuclear transport in which Ran-mediated hydrolysis of GTP is necessary for the import of importin-alpha and the nuclear localization signal-bearing substrate into the nucleus, while exchange of GDP for GTP on Ran is required for the export of both mRNA and importin-alpha from the nucleus.

Rna1p, a Ran/TC4 GTPase activating protein, is required for nuclear import.

The Saccharomyces cerevisiae gene, RNA1, encodes a protein with extensive homology to the mammalian Ran/TC4 GTPase activating protein. Using indirect immunofluorescence microscopy, we have demonstrated that rna1-1 mutant cells are defective in nuclear import of several proteins. The same result is obtained when nuclear import is examined in living cells using a nuclear protein fused to the naturally green fluorescent protein. These findings suggest a role for the Rna1p in trafficking of proteins across the nuclear membrane. To investigate this role more directly, an in vitro import assay that monitors the import of a fluorescently labeled substrate into the nuclei of semi-intact yeast cells was used. Import to the nucleus requires the addition of exogenous cytosol. Results indicate that, in contrast to wild-type cytosols, extracts made from rna1-1 mutant cells are unable to support import of the fluorescently labeled substrate into competent nuclei. Immunoblotting demonstrates that these mutant-derived extracts are depleted of Rna1p. However, when purified Rna1p is added back to these extracts the import activity is restored in a dose-dependent manner. These results demonstrate that Rna1p plays a direct role in the import of proteins into the nucleus.

The relationship between housing status and HIV risk among active drug users: a qualitative analysis.

This paper examines the relationship between housing status and HIV risk using longitudinal, qualitative data collected in 2004-2005, from a purposeful sample of 65 active drug users in a variety of housed and homeless situations in Hartford, Connecticut. These data were supplemented with observations and in-depth interviews regarding drug use behavior collected in 2001-2005 to evaluate a peer-led HIV prevention intervention. Data reveal differences in social context within and among different housing statuses that affect HIV risk or protective behaviors including the ability to carry drug paraphernalia and HIV prevention materials, the amount of drugs in the immediate environment, access to subsidized and supportive housing, and relationships with those with whom drug users live. Policy implications of the findings, limitations to the data, and future research are discussed.

Nucleocytoplasmic transport of macromolecules.

Nucleocytoplasmic transport is a complex process that consists of the movement of numerous macromolecules back and forth across the nuclear envelope. All macromolecules that move in and out of the nucleus do so via nuclear pore complexes that form large proteinaceous channels in the nuclear envelope. In addition to nuclear pores, nuclear transport of macromolecules requires a number of soluble factors that are found both in the cytoplasm and in the nucleus. A combination of biochemical, genetic, and cell biological approaches have been used to identify and characterize the various components of the nuclear transport machinery. Recent studies have shown that both import to and export from the nucleus are mediated by signals found within the transport substrates. Several studies have demonstrated that these signals are recognized by soluble factors that target these substrates to the nuclear pore. Once substrates have been directed to the pore, most transport events depend on a cycle of GTP hydrolysis mediated by the small Ras-like GTPase, Ran, as well as other proteins that regulate the guanine nucleotide-bound state of Ran. Many of the essential factors have been identified, and the challenge that remains is to determine the exact mechanism by which transport occurs. This review attempts to present an integrated view of our current understanding of nuclear transport while highlighting the contributions that have been made through studies with genetic organisms such as the budding yeast, Saccharomyces cerevisiae.

Sporadic inclusion body myositis: phenotypic variability and influence of HLA-DR3 in a cohort of 57 Australian cases.

BACKGROUND AND AIMS: There have been few studies of the variability in the clinical phenotype in sporadic inclusion body myositis (sIBM) and it is not known whether the human leucocyte antigen (HLA) haplotype influences the phenotype and course of the disease. We studied a large cohort of patients with sIBM in order to determine the degree of phenotypic variability and different modes of presentation, as well as the influence of HLA haplotypes. METHOD: A cross-sectional study of 57 biopsy-proven sIBM cases from three Australian centres was performed. Patients were interviewed and examined by a single investigator, and had HLA typing and autoantibody studies. RESULTS: Although the initial symptoms in the majority of cases were attributable to quadriceps weakness (79%), a proportion of patients presented due to finger weakness (12%), foot drop (7%) or dysphagia (1.8%). Although the majority had the classic combination of quadriceps and forearm muscle involvement, some patients had predominantly forearm weakness with sparing of the quadriceps, or severe involvement of the anterior tibial muscles. Asymmetrical involvement was common (82%), particularly of the forearm muscles, with the non-dominant side being more severely affected in most cases. Carriage of the HLA-DRB1*0301 (DR3) allele was associated with lower quadriceps muscle strength and a more rapid decline in strength. CONCLUSIONS: The findings emphasise the variability in the mode of presentation, patterns of muscle involvement and clinical course of sIBM in this population, and indicate that the HLA-DRB1*0301 (DR3) allele may influence the rate of progression as well as susceptibility to the disease.

Innervation and receptor profiles of the human apocrine (epitrichial) sweat gland: routes for intervention in bromhidrosis.

BACKGROUND: Human apocrine (epitrichial) sweat glands secrete in response to local or systemic administration of catecholamines and cholinergic agonists. As the process of secretion in human apocrine glands is not fully understood and no literature detailing the expression of adrenergic, cholinergic and purinergic receptors is available, there is a need to know the receptor types. Such data could provide new approaches for the treatment of axillary bromhidrosis. OBJECTIVES: To investigate the localization of nerve fibres, adrenergic, cholinergic and purinergic receptors in human axillary apocrine sweat glands by immunohistochemistry. METHODS: Human axillary apocrine sweat glands were investigated by serial sectioning of paraffin wax-embedded skin samples from volunteers. Sections were examined by light microscopy and immunohistochemistry, using antibodies against neurofilament, alpha- and beta-adrenoceptors, P2Y(1), P2Y(2) and P2Y(4) purinoceptors, and M(3) cholinoceptors. RESULTS: Neurofilaments were found near the eccrine but not the apocrine gland. Apocrine glands demonstrated the presence of beta-2 and beta-3 adrenoceptors in the secretory coil of the gland, but not alpha-1, beta-1 or M(3) receptors. Glandular purinergic staining (P2Y(1), P2Y(2) and P2Y(4)) was found in what looked like myoepithelial cells, while P2Y(1) and P2Y(2) staining was found on apical membranes and diffusely throughout secretory cells. Eccrine gland staining acted as internal positive controls. CONCLUSIONS: No nerve fibres were found near the apocrine gland, suggesting that any catecholamine influence is through humoral effects and that glands could be influenced by beta-adrenoceptor subtypes and purinoceptors. Blockage of both these types of receptors offers a route to controlling apocrine secretion from axillary glands and reducing the opportunity for the development of bromhidrosis.

Oral administration of Ginkgo biloba extract, EGb-761 inhibits thermal hyperalgesia in rodent models of inflammatory and post-surgical pain.

BACKGROUND AND PURPOSE: Studies in vitro suggest that the standardised extract of Ginkgo biloba, EGb-761 has anti-inflammatory properties and modulatory effects on key pain-related molecules. This study investigated the analgesic and anti-inflammatory effects of EGb-761 on carrageenan-induced inflammatory and hindpaw incisional pain. EXPERIMENTAL APPROACH: Adult male Wistar rats (n=6-10/group; 250-420 g) were injected intradermally with carrageenan into the left hindpaw or anaesthetised with isoflurane (2%) and a longitudinal 1 cm incision was made through the skin, fascia and plantaris muscle of the hindpaw. EGb-761 (3, 10, 30, 100 or 300 mg kg(-1)), diclofenac (5 mg kg(-1)) or drug-vehicle was administered 3 h post-carrageenan/post-surgery. Hindpaw withdrawal latency (in seconds) to thermal stimulation, response threshold (in grams) to mechanical stimulation and paw volume were measured. KEY RESULTS: Carrageenan induced significant mechanical allodynia, thermal hyperalgesia and paw oedema at 6 h post-carrageenan, while paw incision surgery induced significant mechanical allodynia and thermal hyperalgesia at 6 and 24 h post-surgery. Administration of EGb-761 dose-dependently inhibited thermal hyperalgesia and was equally effective as diclofenac (5 mg kg(-1)) in both the carrageenan and hindpaw incision model. EGb-761 had no effect on carrageenan- or incision-induced mechanical allodynia or paw oedema. Diclofenac significantly reduced mechanical allodynia in both models and carrageenan-induced paw oedema. CONCLUSIONS AND IMPLICATIONS: EGb-761 dose-dependently alleviates acute inflammatory and surgically induced thermal hyperalgesia and is comparable to diclofenac, a commonly prescribed non-steroidal anti-inflammatory drug. This indicates that EGb-761 has analgesic potential in acute inflammatory pain.