Muscle architectural properties indicate a primary role in support for the pelvic limb of three-toed sloths (Bradypus variegatus).

Tree sloths evolved below-branch locomotion making them one of few mammalian taxa beyond primates for which suspension is nearly obligatory. Suspension requires strong limb flexor muscles that provide both propulsion and braking/support, and available locomotor kinetics data indicate that these roles differ between fore- and hindlimb pairs. Muscle structure in the pelvic limb is hypothesized to be a key anatomical correlate of function in braking/support during suspensory walking and propulsion and/or support during vertical climbing. This expectation was tested by quantifying architecture properties in the hindlimb limb musculature of brown-throated three-toed sloths (Bradypus variegatus: N = 7) to distinguish the roles of the flexor/extensor functional muscle groups at each joint. Measurements of muscle moment arm (rm ), mass, belly length, fascicle length, pennation angle, and physiological cross-sectional area (PCSA) were taken from n = 45 muscles. Overall, most muscles studied show properties for contractile excursion and fast joint rotational velocity. However, the flexor musculature is more massive (p = 0.048) and has larger PCSA (p = 0.003) than the extensors, especially at the knee joint and digits where well-developed and strong flexors are capable of applying large joint torque. Moreover, selected hip flexors/extensors and knee flexors have modified long rm that can amplify applied joint torque in muscles with otherwise long, parallel fascicles, and one muscle (m. iliopsoas) was capable of moderately high power in B. variegatus. The architectural properties observed in the hip flexors and extensors match well with roles in suspensory braking and vertical propulsion, respectively, whereas strong knee flexors and digital flexors appear to be the main muscles providing suspensory support in the pelvic limb. With aid in support by the forelimbs and the use of adaptive slow locomotion and slow muscle fiber recruitment patterns, structure-function in the tensile limb systems of sloths appears to collectively represent an additional mechanism for energy conservation.

The denture microbiome in health and disease: an exploration of a unique community.

The United Nations suggests the global population of denture wearers (an artificial device that acts as a replacement for teeth) is likely to rise significantly by the year 2050. Dentures become colonized by microbial biofilms, the composition of which is influenced by complex factors such as patient's age and health, and the nature of the denture material. Since colonization (and subsequent biofilm formation) by some micro-organisms can significantly impact the health of the denture wearer, the study of denture microbiology has long been of interest to researchers. The specific local and systemic health risks of denture plaque are different from those of dental plaque, particularly with respect to the presence of the opportunist pathogen Candida albicans and various other nonoral opportunists. Here, we reflect on advancements in our understanding of the relationship between micro-organisms, dentures, and the host, and highlight how our growing knowledge of the microbiome, biofilms, and novel antimicrobial technologies may better inform diagnosis, treatment, and prevention of denture-associated infections, thereby enhancing the quality and longevity of denture wearers.

Design of a 16-channel fiber-optic coupled radiation detection array for radiation asymmetry studies in a 750-kJ dense plasma focus.

A 16-channel fiber optically coupled radiation detection array has been developed for studies of radiation asymmetries and emission histories from the Verus Research 750-kJ Dense Plasma Focus. Each detector in the array consists of a light-tight housing with a plastic scintillator coupled to a fiber optic that is fed into one channel of a multi-anode photomultiplier tube (PMT). The PMT and associated electronics are located in a remote electrically shielded control room. The detector head is configurable for using a Be-9 foil to take advantage of the 9Be(n,α)6He reaction as a fast neutron activation detector or with a bare scintillator alone to record the radiation emission history. Fiber optically coupling the detector head not only provides electrical isolation in the pulsed power environment but also allows the spatial footprint of the detector array to be reduced with concomitant flexibility in positioning each individual detector head. The array allows for spatially resolved neutron yield and radiation waveform measurements for fast z-pinches. The activation detector heads were calibrated for the total neutron yield against silver and indium activation counters for the total neutron yield. Fiber scintillation was found to contribute to the time-resolved detector head signals and was accounted for.

A Horse of a Different Color?: Tensile Strength and Elasticity of Sloth Flexor Tendons.

Tendons must be able to withstand the tensile forces generated by muscles to provide support while avoiding failure. The properties of tendons in mammal limbs must therefore be appropriate to accommodate a range of locomotor habits and posture. Tendon collagen composition provides resistance to loading that contributes to tissue strength which could, however, be modified to not exclusively confer large strength and stiffness for elastic energy storage/recovery. For example, sloths are nearly obligate suspenders and cannot run, and due to their combined low metabolic rate, body temperature, and rate of digestion, they have an extreme need to conserve energy. It is possible that sloths have a tendon "suspensory apparatus" functionally analogous to that in upright ungulates, thus allowing for largely passive support of their body weight below-branch, while concurrently minimizing muscle contractile energy expenditure. The digital flexor tendons from the fore- and hindlimbs of two-toed (Choloepus hoffmanni) and three-toed (Bradypus variegatus) sloths were loaded in tension until failure to test this hypothesis. Overall, tensile strength and elastic (Young's) modulus of sloth tendons were low, and these material properties were remarkably similar to those of equine suspensory "ligaments." The results also help explain previous findings in sloths showing relatively low levels of muscle activation in the digital flexors during postural suspension and suspensory walking.

Los tendones deben ser capaces de soportar las fuerzas de tracción generadas por los músculos para proporcionar apoyo evitando el fracaso. Por lo tanto, las propiedades de los tendones en las extremidades de los mamíferos deben ser apropiadas para acomodar una serie de hábitos locomotores y postura. La composición del colágeno de tendón proporciona resistencia a la carga que contribuye a la resistencia del tejido que, sin embargo, podría ser modificada para no conferir exclusivamente gran resistencia y rigidez para el almacenamiento/recuperación de energía elástica. Por ejemplo, los perezosos son tirantes casi obligatorios y no pueden funcionar, y debido a su baja tasa metabólica combinada, temperatura corporal y tasa de digestión, tienen una necesidad extrema de conservar energía. Es posible que los perezosos tengan un tendón «aparato suspensor¼ funcionalmente análogo al de los ungulados verticales, lo que permite un soporte en gran medida pasivo de su peso corporal por debajo de la rama, al tiempo que minimiza el gasto de energía contráctil muscular. Los tendones flexores digitales de las patas delanteras y traseras de los perezosos de dos dedos (Choloepus hoffmanni) y de tres dedos (Bradypus variegatus) fueron cargados en tensión hasta que no se probando esta hipótesis. En general, la resistencia a la tracción y el módulo elástico (de Young) de los tendones perezosos eran bajos, y estas propiedades materiales eran notablemente similares a las de los "ligamentos" suspensivos equinos. Los resultados también ayudan a explicar los hallazgos anteriores en perezosos que muestran niveles relativamente bajos de activación muscular en los flexores digitales durante la suspensión postural y la marcha suspensiva.

Ontogenetic allometry and architectural properties of the paravertebral and hindlimb musculature in Eastern cottontail rabbits (Sylvilagus floridanus): functional implications for developmental changes in locomotor performance.

Due to small body size, an immature musculoskeletal system, and other growth-related limits on performance, juvenile mammals frequently experience a greater risk of predation than their adult counterparts. As a result, behaviorally precocious juveniles are hypothesized to exhibit musculoskeletal advantages that permit them to accelerate rapidly and evade predation. This hypothesis was tested through detailed quantitative evaluation of muscle growth in wild Eastern cottontail rabbits (Sylvilagus floridanus). Cottontail rabbits experience high rates of mortality during the first year of life, suggesting that selection might act to improve performance in growing juveniles. Therefore, it was predicted that muscle properties associated with force and power capacity should be enhanced in juvenile rabbits to facilitate enhanced locomotor performance. We quantified muscle architecture from 24 paravertebral and hindlimb muscles across ontogeny in a sample of n = 29 rabbits and evaluated the body mass scaling of muscle mass (MM), physiological cross-sectional area (PCSA), isometric force (Fmax ), and instantaneous power (Pinst ), along with several dimensionless architectural indices. In contrast to our hypothesis, MM and PCSA for most muscles change with positive allometry during growth by scaling at Mb1.3 and Mb1.1 , respectively, whereas Fmax and Pinst generally scale indistinguishably from isometry, as do the architectural indices tested. However, scaling patterns indicate that the digital flexors and ankle extensors of juvenile S. floridanus have greater capacities for force and power, respectively, than those in adults, suggesting these muscle properties may be a part of several compensatory features that promote enhanced acceleration performance in young rabbits. Overall, our study implies that body size constraints place larger, more mature rabbits at a disadvantage during acceleration, and that adults must develop hypertrophied muscles in order to maintain mechanical similarity in force and power capacities across development. These findings challenge the accepted understanding that juvenile animals are at a performance detriment relative to adults. Instead, for prey-predator interactions necessitating short intervals of high force and power generation relative to body mass, as demonstrated by rapid acceleration of cottontail rabbits fleeing predators, it may be the adults that struggle to keep pace with juveniles.

Bone strain magnitude is correlated with bone strain rate in tetrapods: implications for models of mechanotransduction.

Hypotheses suggest that structural integrity of vertebrate bones is maintained by controlling bone strain magnitude via adaptive modelling in response to mechanical stimuli. Increased tissue-level strain magnitude and rate have both been identified as potent stimuli leading to increased bone formation. Mechanotransduction models hypothesize that osteocytes sense bone deformation by detecting fluid flow-induced drag in the bone's lacunar-canalicular porosity. This model suggests that the osteocyte's intracellular response depends on fluid-flow rate, a product of bone strain rate and gradient, but does not provide a mechanism for detection of strain magnitude. Such a mechanism is necessary for bone modelling to adapt to loads, because strain magnitude is an important determinant of skeletal fracture. Using strain gauge data from the limb bones of amphibians, reptiles, birds and mammals, we identified strong correlations between strain rate and magnitude across clades employing diverse locomotor styles and degrees of rhythmicity. The breadth of our sample suggests that this pattern is likely to be a common feature of tetrapod bone loading. Moreover, finding that bone strain magnitude is encoded in strain rate at the tissue level is consistent with the hypothesis that it might be encoded in fluid-flow rate at the cellular level, facilitating bone adaptation via mechanotransduction.

How is delayed ejaculation defined and treated in North America?

Delayed ejaculation (DE) is an uncommon disorder that is difficult to treat because it is poorly understood. The aim was to evaluate the current opinion and clinical management of DE by practitioners in sexual medicine. Members of the Sexual Medicine Society of North America (SMSNA) were invited by email to participate in a web-based survey. The questionnaire consisted of eight questions pertaining to DE. Questions addressed patient volume, qualification of patient bother, ranking of etiologies, perceived success, treatments used, quantification of symptom resolution, and broad characterization of practitioner type. A total of 94 respondents completed the survey with 73% of those being urologists. Fifty-nine percent of the respondents saw ≤ 2 patients a month with DE and 89% of practitioners felt that DE was moderately or severely bothersome to the patients. Etiology was felt to be from medications and psychological factors primarily. Despite treatment modality, 'seldom' success was obtained for 49% of the time and 'never' for 11%. Carbergoline was the most common selected medication for DE. Academic and private urologists reported 'never' or 'seldom' success with sexual counseling compared to other practitioners, respectively (p = 0.008 and p = 0.001). Respondents who saw ≤ 2 patients per month often reported normalization of hypogonadism 'never' or 'seldom' corrected DE (p = 0.047). Delayed ejaculation is still a poorly understood disorder with inconsistent practice patterns seen among members of the SMSNA. A better understanding of this vexing disorder is needed with efforts placed on research and practitioner education.

Identification of the midline by obese and non-obese women during late pregnancy.

During central neuraxial blockade, identifying the midline in parturients can be difficult, particularly if they are obese. We assessed the ability of women in late pregnancy, both obese and non-obese, to identify the midline of their own back by pointing and by pinprick discrimination with reference to the true midline identified by ultrasound. Thirteen out of 25 (52%) obese women were accurate to within 5 mm in identifying the midline of their back by pointing with their fingertip, compared with 21/25 (84%) non-obese women (p = 0.03). The median (IQR [range]) fingertip-midline distance was greater in obese women (5 (5-10 [0-10]) mm compared with non-obese women (2 (0-5 [0-12]) mm; p = 0.007). Identification of the midline using pinprick was poorer by obese women (median (IQR [range]) 33 (25-45 [3-85]) mm) than by non-obese women (18 (13-25 [8-40]) mm; p < 0.0001). However, women in both groups were correct > 99% of the time in identifying that a stimulus was either to the left or to the right side.

Pregnant women's views on informed consent for research in labour.

BACKGROUND: Studies of the optimal treatment of accidental dural puncture occurring during epidural insertion in labour are difficult for practical reasons and because of the ethical issues around seeking consent. In a recent study of accidental dural puncture, participants were assigned to one of two treatment groups and only informed about the study and consent sought, after treatment. We sought the views of parturients on the timing of consent for such a study. METHODS: After ethical approval and written consent, 100 nulliparous women in the third trimester of pregnancy completed a structured, facilitated questionnaire, rating the acceptability of the consent process occurring: (i) in antenatal clinic; (ii) after the epidural was requested in labour; (iii) after the accidental dural puncture had occurred but before treatment; (iv) after the allocated treatment; or (v) without consent (waived consent). Results were analysed with the Friedman and Wilcoxon signed-rank tests. RESULTS: Antenatal consent was considered the most acceptable option, whilst consent on request for epidural analgesia and after accidental dural puncture were least acceptable. Consent after treatment and waived consent were rated in-between these extremes. There was a statistically significant difference between these three groups (P<0.0001). There was a wide range of opinions on each option presented. CONCLUSIONS: Antenatal consent was the preferred option but if this is not possible and the need for the research is strong, consent for the use of women's data after intervention, or waived consent, is acceptable to many women. It is important to seek the views of the participants themselves before planning research with difficult ethical aspects.

Efficacy of cardiopulmonary resuscitation in the supine position with manual displacement of the uterus vs lateral tilt using a firm wedge: a manikin study.

Prevention of aortocaval compression is essential for effective cardiopulmonary resuscitation in late pregnancy. This can be achieved by either lateral maternal tilt or lateral uterine displacement. Results from a previous manikin study show that a firm foam-rubber wedge allowed successful chest compressions whilst providing stable and reliable lateral tilt. However, it did not investigate resuscitation in the supine position with manual uterine displacement. The aim of this study was to compare the effectiveness of chest compressions in a manikin in the supine position vs lateral tilt using a foam-rubber wedge, both on the floor and on a typical patient bed. Overall, we found that compressions were easier to perform in the supine position (p = 0.007 (bed) and 0.048 (floor)), and with greater stability in the supine position on the floor (p = 0.011). The effectiveness of chest compressions was similar in both the supine/uterine displacement and the lateral tilt positions, suggesting that either method may be suitable for CPR.

Myosin isoform expression in the prehensile tails of didelphid marsupials: functional differences between arboreal and terrestrial opossums.

Prehensile tails are defined as having the ability to grasp objects and are commonly used as a fifth appendage during arboreal locomotion. Despite the independent evolution of tail prehensility in numerous mammalian genera, data relating muscle structure, physiology, and function of prehensile tails are largely incomplete. Didelphid marsupials make an excellent model to relate myosin heavy chain (MHC) isoform fiber type with structure/function of caudal muscles, as all opossums have a prehensile tail and tail use varies between arboreal and terrestrial forms. Expanding on our previous work in the Virginia opossum, this study tests the hypothesis that arboreal and terrestrial opossums differentially express faster versus slower MHC isoforms, respectively. MHC isoform expression and percent fiber type distribution were determined in the flexor caudae longus (FCL) muscle of Caluromys derbianus (arboreal) and Monodelphis domestica (terrestrial), using a combination of gel electrophoresis and immunohistochemistry analyses. C. derbianus expresses three MHC isoforms (1, 2A, 2X) that are distributed (mean percentage) as 8.2% MHC-1, 2.6% 1/2A, and 89.2% 2A/X hybrid fibers. M. domestica also expresses MHC-1, 2A, and 2X, in addition to the 2B isoform, distributed as 17.0% MHC-1, 1.3% 1/2A, 9.0% 2A, 75.2% 2A/X, and 0.3% 2X/B hybrid fibers. The distribution of similar isoform fiber types differed significantly between species (P < 0.001). Although not statistically significant, C. derbianus was observed to have larger cross-sectional area (CSA) for each corresponding fiber type along with a greater amount of extra-cellular matrix. An overall faster fiber type composition (and larger fibers) in the tail of an arboreal specialist supports our hypothesis, and correlates with higher muscle force required for tail hanging and arboreal maneuvering on terminal substrates. Conversely, a broader distribution of highly oxidative fibers in the caudal musculature is well suited for tail nest building/remodeling behaviors of terrestrial opossums.

Interaction between cytokines and inflammatory cells in islet dysfunction, insulin resistance and vascular disease.

Inflammation is an established pathogenic player in insulin resistance, islet demise and atherosclerosis. The complex interactions between cytokines, immune cells and affected tissues result in sustained inflammation in diabetes and atherosclerosis. 12- and 15-lipoxygenase (LO), such as 12/15-LO, produces a variety of metabolites through peroxidation of fatty acids and potentially contributes to the complex molecular crosstalk at the site of inflammation. 12- and 15-LO pathways are frequently activated in tissues affected by diabetes and atherosclerosis including adipose tissue (AT), islets and the vasculature. Moreover, mice with whole body and tissue-specific knockout of 12/15-LO are protected against insulin resistance, hyperglycaemia and atherosclerosis supporting functional contribution of 12- and 15-LO pathways in diabetes and atherosclerosis. Recently, it has emerged that there is a temporal regulation of the particular isoforms of 12- and 15-LO in human AT and islets during the development of type 1 and type 2 diabetes and obesity. Analyses of tissues affected by diabetes and atherosclerosis also implied the roles of interleukin (IL)-12 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX-1) in islets and IL-17A in atherosclerosis. Future studies should aim to test the efficacy of inhibitions of these mediators for treatment of diabetes and atherosclerosis.

Handling the sequelae of breast cancer treatment: use of NPWT to enhance patient independence.

A cancer diagnosis can be an overwhelming experience and has devastating implications for an individual, their family and friends. Radical treatment, although often essential, can have its own health consequences. This case study describes the management of a 38-year-old woman with a portable, non-electrical negative pressure wound therapy device, suggesting benefits in terms of healing, patient independence and improved quality of life. The case study also highlights the importance of effective communication, patient involvement and empowerment in clinical decision-making, showing that an effective client-clinician relationship can help overcome the physical and emotional sequelae of this diagnosis.

Myosin isoform fiber type and fiber size in the tail of the Virginia opossum (Didelphis virginiana).

Muscle fiber type is a well studied property in limb muscles, however, much less is understood about myosin heavy chain (MHC) isoform expression in caudal muscles of mammalian tails. Didelphid marsupials are an interesting lineage in this context as all species have prehensile tails, but show a range of tail-function depending on either their arboreal or terrestrial locomotor habits. Differences in prehensility suggest that MHC isoform fiber types may also be different, in that terrestrial opossums may have a large distribution of oxidative fibers for object carrying tasks instead of faster, glycolytic fiber types expected in mammals with long tails. To test this hypothesis, MHC isoform fiber type and their regional distribution (proximal/transitional/distal) were determined in the tail of the Virginia opossum (Didelphis virginiana). Fiber types were determined by a combination of myosin-ATPase histochemistry, immunohistochemistry, and SDS-PAGE. Results indicate a predominance of the fast MHC-2A and -2X isoforms in each region of the tail. The presence of two fast isoforms, in addition to the slow MHC-1 isoform, was confirmed by SDS-PAGE analysis. The overall MHC isoform fiber type distribution for the tail was: 25% MHC-1, 71% MHC-2A/X hybrid, and 4% MHC-1/2A hybrid. Oxidative MHC-2A/X isoform fibers were found to be relatively large in cross-section compared to slow, oxidative MHC-1 and MHC-1/2A hybrid fibers. A large percentage of fast MHC-2A/X hybrids fibers may be suggestive of an evolutionary transition in MHC isoform distribution (fast-to-slow fiber type) in the tail musculature of an opossum with primarily a terrestrial locomotor habit and adaptive tail-function.

An evaluation of the skin stripping of wound dressing adhesives.

OBJECTIVE: This study looks at six different modern wound dressings to investigate how likely they are to cause skin stripping and impairment of the skin's barrier function. METHOD: Healthy volunteers had each dressing applied, removed and reapplied to the skin on their back over the study period of 15 days. Skin barrier function was investigated using the amount of transepidermal water loss (TEWL) and then related to the amount of skin stripping, investigated by measuring stained skin removal, the thickness of the stratum corneum after treatment, and the amount of skin attached to the removed dressings. General signs of trauma, such as skin dryness and erythema, were investigated by subjective and objective parameters. RESULTS: TEWL values measured on the untreated test area, as well as after application of Urgotul Trio, remained relatively unchanged and Mepilex Border decreased slightly (?1g/m2/h), while all other dressings displayed an increased in TEWL: Allevyn Adhesive (5g/m2/h), Versiva XC (14g/m2/h), Comfeel Plus (22g/m2/h) and Biatain (28g/m2/h). By the end of the study, only the untreated area (mean 43% dye remaining), Mepilex Border (76%) and Urgotul Trio (34%) areas had visible dye remaining. It is interesting to note that the untreated site had a colour change, suggesting loss of stratum corneum, due to the shedding of skin cells from the surface. The increase in total skin colour for Comfeel Plus and Biatain after day 8 might be assigned to an increased redness due to erythema. All the dressings showed evidence of stratum corneum attached to the adhesive, except Mepilex Border, which appeared to be free of any attached stratum corneum. CONCLUSION: Overall the best performance in terms of skin protection and failure to cause skin trauma was found to be for Mepilex Border. CONFLICT OF INTEREST: This project was funded by a grant from Mölnlycke Healthcare Ltd.

Current views on the functions of interleukin-17A-producing cells in atherosclerosis.

Multiple components of the immune response are involved in the initiation, progression and persistence of atherosclerosis. Interleukin (IL)-17A is produced by a broad variety of leukocytes and plays an important role in host defense. IL-17A is also involved in the pathology of several autoimmune diseases mainly via the regulation of chemokine expression and leukocyte migration to the site of inflammation. There is an increasing body of evidence indicating an association between elevated levels of IL-17A and cardiovascular diseases. Interestingly, this IL-17A-dependent response occurs in parallel with the Th1-dominant immune response during atherogenesis. To date, the precise role of IL-17A+ cells in atherosclerosis is controversial. Several studies have suggested a pro-atherogenic role of IL-17A via the regulation of aortic macrophage numbers, Th1-related cytokines and aortic chemokine expression. However, two studies recently described anti-inflammatory effects of IL-17A on mouse plaque burden via possible regulation of aortic VCAM-1 expression and T cell content. Furthermore, an initial study using IL-17A-deficient mice demonstrated that IL-17A affects the immune composition and inflammatory phenotype of the aortic wall; however, no effects were observed on atherosclerosis. Further studies are necessary to fully address the role of IL-17A and other IL-17 family members in atherosclerosis.

Contractile properties of muscle fibers from the deep and superficial digital flexors of horses.

Equine digital flexor muscles have independent tendons but a nearly identical mechanical relationship to the main joint they act upon. Yet these muscles have remarkable diversity in architecture, ranging from long, unipennate fibers ("short" compartment of DDF) to very short, multipennate fibers (SDF). To investigate the functional relevance of the form of the digital flexor muscles, fiber contractile properties were analyzed in the context of architecture differences and in vivo function during locomotion. Myosin heavy chain (MHC) isoform fiber type was studied, and in vitro motility assays were used to measure actin filament sliding velocity (V(f)). Skinned fiber contractile properties [isometric tension (P(0)/CSA), velocity of unloaded shortening (V(US)), and force-Ca(2+) relationships] at both 10 and 30°C were characterized. Contractile properties were correlated with MHC isoform and their respective V(f). The DDF contained a higher percentage of MHC-2A fibers with myosin (heavy meromyosin) and V(f) that was twofold faster than SDF. At 30°C, P(0)/CSA was higher for DDF (103.5 ± 8.75 mN/mm(2)) than SDF fibers (81.8 ± 7.71 mN/mm(2)). Similarly, V(US) (pCa 5, 30°C) was faster for DDF (2.43 ± 0.53 FL/s) than SDF fibers (1.20 ± 0.22 FL/s). Active isometric tension increased with increasing Ca(2+) concentration, with maximal Ca(2+) activation at pCa 5 at each temperature in fibers from each muscle. In general, the collective properties of DDF and SDF were consistent with fiber MHC isoform composition, muscle architecture, and the respective functional roles of the two muscles in locomotion.