Morphometric analysis of the hominin talus: Evolutionary and functional implications.

The adoption of bipedalism is a key benchmark in human evolution that has impacted talar morphology. Here, we investigate talar morphological variability in extinct and extant hominins using a 3D geometric morphometric approach. The evolutionary timing and appearance of modern human-like features and their contributions to bipedal locomotion were evaluated on the talus as a whole, each articular facet separately, and multiple combinations of facets. Distinctive suites of features are consistently present in all fossil hominins, despite the presence of substantial interspecific variation, suggesting a potential connection of these suites to bipedal gait. A modern human-like condition evolved in navicular and lateral malleolar facets early in the hominin lineage compared with other facets, which demonstrate more complex morphological variation within Homininae. Interestingly, navicular facet morphology of Australopithecus afarensis is derived in the direction of Homo, whereas more recent hominin species such as Australopithecus africanus and Australopithecus sediba retain more primitive states in this facet. Combining the navicular facet with the trochlea and the posterior calcaneal facet as a functional suite, however, distinguishes Australopithecus from Homo in that the medial longitudinal arch had not fully developed in the former. Our results suggest that a more everted foot and stiffer medial midtarsal region are adaptations that coincide with the emergence of bipedalism, whereas a high medial longitudinal arch emerges later in time, within Homo. This study provides novel insights into the emergence of talar morphological traits linked to bipedalism and its transition from a facultative to an obligate condition.

Comparative analysis of trabecular bone structure and orientation in South African hominin tali.

Tali of several hominin taxa are preserved in the fossil record and studies of the external morphology of these often show a mosaic of human-like and ape-like features. This has contributed to a growing recognition of variability characterizing locomotor kinematics of Australopithecus. In contrast, locomotor kinematics of another Plio-Pleistocene hominin, Paranthropus, are substantially less well-documented, in part, because of the paucity of postcranial fossils securely attributed to the genus. Since the talus transmits locomotor-based loads through the ankle and its internal structure is hypothesized to reflect accommodation to such loads, it is a cornerstone structure for reconstructing locomotor kinematics. Here we quantify and characterize trabecular bone morphology within tali attributed to Australopithecus africanus (StW 102, StW 363, StW 486) and Paranthropus robustus (TM 1517), making quantitative comparisons to modern humans, extant non-human apes, baboons, and a hominin talus attributed to Paranthropus boisei (KNM-ER 1464). Using high-resolution images of fossil tali (25 µm voxels), nine trabecular bone subregions of interest beneath the articular surface of the talar trochlea were segmented to quantify localized patterns in distribution and primary strut orientation. It was found that trabecular strut orientation and shape, in some cases, can discriminate amongst species characterized by different locomotor foot kinematics. Discriminant function analyses using standard trabecular bone structural properties align TM 1517 with Pan and Gorilla, while other hominin tali structurally most resemble those of baboons. In primary strut orientation, Paranthropus tali (KNM-ER 1464 and TM 1517) resemble the human condition in the anterior-medial subregion, where strut orientation appears positioned to distribute compressive loads medially and distally toward the talar head. In A. africanus tali (particularly StW 486), primary strut orientation in this region resembles that of apes. These results suggest that Paranthropus may have had a human-like medial weight shift during the last half of stance phase but Australopithecus did not.

Physical activity alters limb bone structure but not entheseal morphology.

Studies of ancient human skeletal remains frequently proceed from the assumption that individuals with robust limb bones and/or rugose, hypertrophic entheses can be inferred to have been highly physically active during life. Here, we experimentally test this assumption by measuring the effects of exercise on limb bone structure and entheseal morphology in turkeys. Growing females were either treated with a treadmill-running regimen for 10 weeks or served as controls. After the experiment, femoral cortical and trabecular bone structure were quantified with µCT in the mid-diaphysis and distal epiphysis, respectively, and entheseal morphology was quantified in the lateral epicondyle. The results indicate that elevated levels of physical activity affect limb bone structure but not entheseal morphology. Specifically, animals subjected to exercise displayed enhanced diaphyseal and trabecular bone architecture relative to controls, but no significant difference was detected between experimental groups in entheseal surface topography. These findings suggest that diaphyseal and trabecular structure are more reliable proxies than entheseal morphology for inferring ancient human physical activity levels from skeletal remains.

Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor.

Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.

Trabecular bone anisotropy and orientation in an Early Pleistocene hominin talus from East Turkana, Kenya.

Among the structural properties of trabecular bone, the degree of anisotropy is most often found to separate taxa with different habitual locomotor modes. This study examined the degree of anisotropy, the elongation, and primary orientation of trabecular bone in the KNM-ER 1464 Early Pleistocene hominin talus as compared with extant hominoid taxa. Modern human tali were found to have a pattern of relatively anisotropic and elongated trabeculae on the lateral aspect, which was not found in Pan, Gorilla, Pongo, or KNM-ER 1464. Trabecular anisotropy in the fossil talus most closely resembled that of the African apes except for a region of high anisotropy in the posteromedial talus. The primary orientation of trabeculae in the anteromedial region of KNM-ER 1464 was strikingly different from that of the great apes and very similar to that of modern humans in being directed parallel to the talar neck. These results suggest that, relative to that of modern humans, the anteromedial region of the KNM-ER 1464 talus may have transmitted body weight to the midfoot in a similar manner while the lateral aspect may have been subjected to more variable loading conditions.

Novel insights into bicuspid aortic valve (BAV) aortopathy: Long non-coding RNAs TUG1 and MIAT are differentially expressed in BAV ascending aortas.

BACKGROUND: Whilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood. METHODS: Utilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ΔΔCT, with fold-change calculated as RQ=2-ΔΔCT. RESULTS: When comparing samples from BAV patients (n=29, males n=25; median age 58 years, Q1-Q3 51-65, maximum aortic dimension 50±5 mm) with healthy controls (n=7; males n=4, P=.12; median age 39 years, Q1-Q3 18-47, P=.001), there were two differentially expressed lncRNA: TUG1 expression was significantly lower in BAV aortic tissue (RQ 0.59, 95% CI 0.50-0.69, P=.02), whilst MIAT expression was significantly higher (RQ 2.87, 95% CI 1.96-4.20, P=.01). Sensitivity analysis including only patients with normal BAV function showed similar trends of differential expression of TUG1 (RQ 0.69, 95% CI 0.50-0.90, P=.29) and MIAT (RQ 2.55, 95% CI 1.21-5.36, P=.29) compared to controls. CONCLUSIONS: LncRNA TUG1 and MIAT are differentially expressed in BAV aortopathy compared to healthy controls, independent of BAV hemodynamics. Aberrant lncRNA expression may be involved in the pathogenesis of BAV aortopathy.

Whole-genome comparative analysis of Malaysian Burkholderia pseudomallei clinical isolates.

Burkholderia pseudomallei, a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of B. pseudomallei infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across B. pseudomallei strains. We previously characterized B. pseudomallei strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical B. pseudomallei isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in B. pseudomallei and Burkholderia mallei, but not Burkholderia thailandensis. Genes encoding known B. pseudomallei virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding B. pseudomallei pathogenicity to guide the design of new therapeutics for treating melioidosis.

Trauma Education and Stigma Reduction in Global Settings: An Evaluation of the Impact of a One-Day Trauma Psychoeducation Workshop with Community Stakeholders in the Caribbean Nation of Saint Lucia.

The independent island nation of Saint Lucia and surrounding Caribbean countries have fairly well-documented high reported rates of trauma, but limited training infrastructure for trauma-related mental health support and treatment services. This study addresses this disparity between high trauma exposure and sparse trauma-related resources by studying how a one-day training workshop impacted self-rated knowledge about trauma and stigma towards trauma survivors. The training was provided by a licensed clinical psychologist in partnership with a local women's rights group. Participants (n = 41) included school counselors, nurses, psychiatric providers, health educators, and advocates on the island. Participants completed pre- and post-workshop measures examining the variables of interest. The one-day workshop provided training on trauma types, post-trauma reactions, options for treatment, and hands-on training for trauma crisis-management and short-term interventions. Following the workshop, participants reported increased knowledge of trauma, more accurate perceptions of its prevalence, better understanding of evidence-based treatments, and lower trauma survivor-related stigma. This is the first trauma-focused workshop tested in St. Lucia, where the need for such training is considerable given few treatment options for trauma survivors in this area. Work is underway to provide more expansive services for trauma across the Caribbean region, given these preliminary promising findings.

Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity.

A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity. Black sea cucumber (Holothuria atra) is a tropical sea cucumber species traditionally consumed as a remedy for many ailments. There is a paucity of knowledge on the anti-infective capacity of H. atra and the underlying mechanisms involved. The objective of this study is to utilize the Caenorhabditis elegans-P. aeruginosa infection model to elucidate the anti-infective properties of H. atra. A bioactive H. atra extract and subsequently its fraction were shown to have the capability of promoting the survival of C. elegans during a customarily lethal P. aeruginosa infection. The same entities also attenuate the production of elastase, protease, pyocyanin and biofilm in P. aeruginosa. The treatment of infected transgenic lys-7::GFP worms with this H. atra fraction restores the repressed expression of the defense enzyme lys-7, indicating an improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid, and inosine in this fraction. Collectively, our findings show that H. atra possesses anti-infective properties against P. aeruginosa infection, by inhibiting pathogen virulence and, eventually, reinstating host lys-7 expression.

The bipedalism of the Dmanisi hominins: pigeon-toed early Homo?

In the recent description of the hominin postcranial material from Dmanisi, Georgia, Lordkipanidze and colleagues (Lordkipanidze et al. [2007] Nature 449: 305-310) claim that the Dmanisi hominins walked with more medially oriented feet than do modern humans. They draw this functional inference from two postcranial features: a wide talar neck angle and a slight medial torsion of the tibia. However, we believe that the data provided by the authors fail to support their conclusions. Talar neck angle and tibial torsion values from the Dmanisi specimens fall comfortably within the range of modern human variation. We further submit that foot orientation cannot be reliably deduced from the tibia and talus alone.

Attitudes and beliefs towards complementary and alternative medicine (CAM): a cross-cultural approach comparing Singapore and the United Kingdom.

This study examined Eastern (Singapore) and Western (United Kingdom) attitudes and beliefs towards complementary and alternative medicine (CAM), and towards orthodox medicine (OM). In all 60 individuals from Singapore and 50 from the United Kingdom (total n = 110) filled in an 8-page questionnaire. UK participants were more willing to use various forms of CAM, and had a generally more optimistic view of the usefulness and efficacy of CAM. Singaporeans were more in favour of OM, prescription drugs, and general practitioners (GPs). Explanations for this observation include the differences in availability and accessibility of CAM in each country, as well as the medical models that are valued and supported in each culture.

A weighted least squares method for inverse dynamic analysis.

Internal forces in the human body can be estimated from measured movements and external forces using inverse dynamic analysis. Here we present a general method of analysis which makes optimal use of all available data, and allows the use of inverse dynamic analysis in cases where external force data is incomplete. The method was evaluated for the analysis of running on a partially instrumented treadmill. It was found that results correlate well with those of a conventional analysis where all external forces are known.

Beyond Traditional Antimicrobials: A Caenorhabditis elegans Model for Discovery of Novel Anti-infectives.

The spread of antibiotic resistance amongst bacterial pathogens has led to an urgent need for new antimicrobial compounds with novel modes of action that minimize the potential for drug resistance. To date, the development of new antimicrobial drugs is still lagging far behind the rising demand, partly owing to the absence of an effective screening platform. Over the last decade, the nematode Caenorhabditis elegans has been incorporated as a whole animal screening platform for antimicrobials. This development is taking advantage of the vast knowledge on worm physiology and how it interacts with bacterial and fungal pathogens. In addition to allowing for in vivo selection of compounds with promising anti-microbial properties, the whole animal C. elegans screening system has also permitted the discovery of novel compounds targeting infection processes that only manifest during the course of pathogen infection of the host. Another advantage of using C. elegans in the search for new antimicrobials is that the worm itself is a source of potential antimicrobial effectors which constitute part of its immune defense response to thwart infections. This has led to the evaluation of effector molecules, particularly antimicrobial proteins and peptides (APPs), as candidates for further development as therapeutic agents. In this review, we provide an overview on use of the C. elegans model for identification of novel anti-infectives. We highlight some highly potential lead compounds obtained from C. elegans-based screens, particularly those that target bacterial virulence or host defense to eradicate infections, a mechanism distinct from the action of conventional antibiotics. We also review the prospect of using C. elegans APPs as an antimicrobial strategy to treat infections.

Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection.

The tropical pathogen Burkholderia pseudomallei requires long-term parenteral antimicrobial treatment to eradicate the pathogen from an infected patient. However, the development of antibiotic resistance is emerging as a threat to this form of treatment. To meet the need for alternative therapeutics, we proposed a screen of natural products for compounds that do not kill the pathogen, but in turn, abrogate bacterial virulence. We suggest that the use of molecules or compounds that are non-bactericidal (bacteriostatic) will reduce or abolish the development of resistance by the pathogen. In this study, we adopted the established Caenorhabditis elegans-B. pseudomallei infection model to screen a collection of natural products for any that are able to extend the survival of B. pseudomallei infected worms. Of the 42 natural products screened, only curcumin significantly improved worm survival following infection whilst not affecting bacterial growth. This suggested that curcumin promoted B. pseudomallei-infected worm survival independent of pathogen killing. To validate that the protective effect of curcumin was directed toward the pathogen, bacteria were treated with curcumin prior to infection. Worms fed with curcumin-treated bacteria survived with a significantly extended mean-time-to-death (p < 0.0001) compared to the untreated control. In in vitro assays, curcumin reduced the activity of known virulence factors (lipase and protease) and biofilm formation. To determine if other bacterial genes were also regulated in the presence of curcumin, a genome-wide transcriptome analysis was performed on curcumin-treated pathogen. A number of genes involved in iron acquisition and transport as well as genes encoding hypothetical proteins were induced in the presence of curcumin. Thus, we propose that curcumin may attenuate B. pseudomallei by modulating the expression of a number of bacterial proteins including lipase and protease as well as biofilm formation whilst concomitantly regulating iron transport and other proteins of unknown function.

Sagittal plane biomechanics cannot injure the ACL during sidestep cutting.

BACKGROUND: Knee joint sagittal plane forces are a proposed mechanism of anterior cruciate ligament injury during sport movements such as sidestep cutting. Ligament force magnitudes for these movements however, remain unknown. The need to examine injury-causing events suggests elucidation via model-based investigations is possible. Using this approach, the current study determined whether sagittal plane knee loading during sidestep cutting could in isolation injure the anterior cruciate ligament. METHODS: Experiments were performed on subject-specific forward dynamic musculoskeletal models, generated from data obtained from 10 male and 10 female athletes. Models were optimized to simulate subject-specific cutting movements. Random perturbations (n=5000) were applied to initial contact conditions and quadriceps/hamstrings activation levels to simulate their effect on peak 3D knee loads. Injury via the sagittal plane mechanism was based on the criterion of an anterior drawer force greater than 2000 N. FINDINGS: Realistic neuromuscular perturbations produced significant increases in external knee anterior force and valgus and internal rotation moments. Peak anterior drawer force never exceeded 2000 N in any model, and thus failed to cause anterior cruciate ligament injuries. Valgus loads reached values that were high enough to rupture the ligament, occurring more frequently in females than in males. INTERPRETATION: Sagittal plane knee joint forces cannot rupture the anterior cruciate ligament during sidestep cutting. The interaction between muscle and joint mechanics and external ground reaction forces in this plane, places a ceiling on ligament loads. Valgus loading is a more likely injury mechanism, especially in females. Modifying sagittal plane biomechanics will thus unlikely contribute to the prevention of anterior cruciate ligament injuries.

Research conducted on Caribbean women's perceived human immunodeficiency virus risks: A narrative review and methodological critique.

Background: Caribbean women have the highest human immunodeficiency virus (HIV) infection rates among women in the Americas; however, their self-assessment of HIV risk is alarmingly low. This reflects a low perceived risk for HIV. English-speaking Caribbean countries are typically understudied in this area. It is important for health researchers and practitioners to understand the underlying perceptions of women who are now driving this epidemic. This review discusses and critiques the published literature that examines Caribbean women's perceived HIV risks. Methods: Medline, PsycINFO, Global Health, Women's Studies International, and Academic Search Complete databases were searched using various combinations of the following keywords: Caribbean, women, HIV, STD, AIDS, risk, perceived risk, risk perception, and sex. Searches were restricted to English. A total of 69 peer-reviewed studies were obtained from the initial 239 records. The reviewer screened the peer-reviewed articles and excluded 50 studies that did not directly assess perceived HIV risks in Caribbean women. An additional 12 studies were excluded based on the following exclusion criteria: an undetermined proportion or more than 50% of the sample consisted of pregnant women, sex workers, drug users, Latinas, and/or people living with HIV/AIDS. Results: Seven studies on perceived HIV risk in Caribbean women were reviewed. Jamaican women were the most represented ethnic demographic (43%). All studies assessed perceived risk as a subset of HIV psychosocial factors, sexual-risk behaviors, HIV knowledge, attitudes, and beliefs. Four studies used cross-sectional research design and two studies used qualitative methodology. Only one study described items used to measure perceived risk. General findings indicate overall perceptions of invulnerability among Caribbean women, despite high sexual-risk behaviors. Conclusions: Published studies that specifically assess Caribbean women's HIV risk perceptions are currently lacking. Qualitative research is needed to further evaluate and explore perceived risks. This will better inform practical strategies that can enable women to discern between their perceived and actual risks, and invariably reduce sexual risk-taking behaviors.

Determination of the location of the mental foramen: a critical review.

INTRODUCTION: The mental foramen (MF) is an important landmark to consider during surgical endodontic procedures. The purpose of this review article was to discuss the variety of techniques that have been developed to determine the location of the MF, to make recommendations for the current best technique available, and to discuss upcoming technologies. METHODS: Articles that have addressed the location of the MF were evaluated for information pertinent to include in this review. RESULTS: Different technologies have been used to help operators determine the clinical location of the MF. Most of the techniques have shortcomings such as magnification, radiation, and cost. Cone-beam computed tomographic imaging is the best current available imaging technology to determine the accurate location of the MF, but it has shortcomings such as radiation, cost, and not being real time, which means the data must be interpreted at a later time than when the information was computed. CONCLUSIONS: In the future, magnetic resonance imaging and ultrasound technologies seem to provide promising noninvasive imaging techniques.

Systematic literature review of Internet interventions across health behaviors.

Purpose: This review examines Internet interventions aiming to change health behaviors in the general population. Methods: Internet health interventions in the USA published between January 2005 and December 2013 were identified through Medline and CINAHL. Keywords used were (Internet or e-health or social media or web) paired with (intervention or program*). A total of 38 articles met all criteria and were reviewed. Results: Studies were analyzed by targeted health behavior interventions: tobacco (5), alcohol (4), weight loss (7), physical activity (PA) (7), nutrition (2), PA and nutrition combined (5), HIV or sexual health (4), and chronic diseases (4). Interventions ranged from one session to 24  weeks (average 6-12 weeks). Common strategies used, including web-based information, tailored feedback, weekly e-mails, goal setting, and self-assessment. Social cognitive theory and the transtheoretical models were the most commonly used frameworks. Recruitment strategies were typically media based varied by settings and populations. Except for the tobacco interventions, the majority studies yielded significant outcomes. Conclusion: This review provides updates and synthesized knowledge on the design and consistent effectiveness of Internet interventions across health behaviors. Results have implications for public health and healthcare professionals, as they play a key role in developing and delivering health promotion interventions as well as in assisting the communities and clients serviced obtaining evidence-based health information.

Postcranial pneumaticity and bone structure in two clades of neognath birds.

Most living birds exhibit some degree of postcranial skeletal pneumaticity, aeration of the postcranial skeleton by pulmonary air sacs and/or directly from the lungs. The extent of pneumaticity varies greatly, ranging from taxa that are completely apneumatic to those with air filling most of the postcranial skeleton. This study examined the influence of skeletal pneumatization on bone structural parameters in a sample of two size- and foraging-style diverse (e.g., subsurface diving vs. soaring specialists) clades of neognath birds (charadriiforms and pelecaniforms). Cortical bone thickness and trabecular bone volume fraction were assessed in one cervical and one thoracic vertebra in each of three pelecaniform and four charadriiform species. Results for pelecaniforms indicate that specialized subsurface dive foragers (e.g., the apneumatic anhinga) have thicker cortical bone and a higher trabecular bone volume fraction than their non-diving clademates. Conversely, the large-bodied, extremely pneumatic brown pelican (Pelecanus occidentalis) exhibits thinner cortical bone and a lower trabecular bone volume fraction. Such patterns in bone structural parameters are here interpreted to pertain to decreased buoyancy in birds specialized in subsurface dive foraging and decreased skeletal density (at the whole bone level) in birds of larger body size. The potential to differentially pneumatize the postcranial skeleton and alter bone structure may have played a role in relaxing constraints on body size evolution and/or habitat exploitation during the course of avian evolution. Notably, similar patterns were not observed within the equally diverse charadriiforms, suggesting that the relationship between pneumaticity and bone structure is variable among different clades of neognath birds.