Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

Common data elements for clinical research in Friedreich's ataxia

To reduce study start‐up time, increase data sharing, and assist investigators conducting clinical studies, the National Institute of Neurological Disorders and Stroke embarked on an initiative to create common data elements for neuroscience clinical research. The Common Data Element Team developed general common data elements, which are commonly collected in clinical studies regardless of therapeutic area, such as demographics. In the present project, we applied such approaches to data collection in Friedreich's ataxia (FRDA), a neurological disorder that involves multiple organ systems. To develop FRDA common data elements, FRDA experts formed a working group and subgroups to define elements in the following: ataxia and performance measures; biomarkers; cardiac and other clinical outcomes; and demographics, laboratory tests, and medical history. The basic development process included identification of international experts in FRDA clinical research, meeting by teleconference to develop a draft of standardized common data elements recommendations, vetting of recommendations across the subgroups, and dissemination of recommendations to the research community for public comment. The full recommendations were published online in September 2011 at http://www.commondataelements.ninds.nih.gov/FA.aspx . The subgroups′ recommendations are classified as core, supplemental, or exploratory. Template case report forms were created for many of the core tests. The present set of data elements should ideally lead to decreased initiation time for clinical research studies and greater ability to compare and analyze data across studies. Their incorporation into new, ongoing studies will be assessed in an ongoing fashion to define their utility in FRDA. © 2012 Movement Disorder Society     

The reliability of lymphoma diagnosis in small tissue samples is heavily influenced by lymphoma subtype

A specific pathologic diagnosis is important in malignant lymphoma because the diverse disease subtypes require tailored approaches to clinical management. Reliance on small samples obtained with cutting needles has been advocated as a less invasive alternative to using larger, excised samples. Although published studies have demonstrated the safety and apparent sufficiency of this approach in informing clinical care, none have systematically determined the accuracy of pathologic lymphoma subtyping based on very small samples. We used a tissue microarray representing 67 cases of malignant lymphoma and 17 samples of nonneoplastic lymphoid tissue to model lymphoma diagnosis in small samples. Overall, 73.8% of the cases were diagnosed with a level of confidence deemed sufficient for directing clinical management; 85.9% of these diagnoses were accurate. Small cell lymphomas with highly distinctive immunophenotypes, including small lymphocytic, mantle cell, and T-lymphoblastic lymphoma, were recognized most consistently and accurately in the small samples. In contrast, follicular lymphoma and marginal zone lymphoma were especially difficult. Our results indicate that the reliability of lymphoma diagnoses based on small samples is heavily influenced by lymphoma subtype.     

Competencies and skills for remote and rural maternity care: a review of the literature

AIM: This paper reports a review of the literature on skills, competencies and continuing professional development necessary for sustainable remote and rural maternity care. BACKGROUND: There is a general sense that maternity care providers in rural areas need specific skills and competencies. However, how these differ from generic skills and competencies is often unclear. METHODS: Approaches used to access the research studies included a comprehensive search in relevant electronic databases using relevant keywords (e.g. 'remote', 'midwifery', 'obstetrics', 'nurse-midwives', education', 'hospitals', 'skills', 'competencies', etc.). Experts were approached for (un-)published literature, and books and journals known to the authors were also used. Key journals were hand searched and references were followed up. The original search was conducted in 2004 and updated in 2006. FINDINGS: Little published literature exists on professional education, training or continuous professional development in maternity care in remote and rural settings. Although we found a large literature on competency, little was specific to competencies for rural practice or for maternity care. 'Hands-on' skills courses such as Advanced Life Support in Obstetrics and the Neonatal Resuscitation Programme increase confidence in practice, but no published evidence of effectiveness of such courses exists. CONCLUSION: Educators need to be aware of the barriers facing rural practitioners, and there is potential for increasing distant learning facilitated by videoconferencing or Internet access. They should also consider other assessment methods than portfolios. More research is needed on the levels of skills and competencies required for maternity care professionals practising in remote and rural areas.     

In utero repair of myelomeningocele with autologous amniotic membrane in the fetal lamb model

Background

Despite advances in prenatal repair, myelomeningocele (MMC) still produces devastating neurologic deficits. The amniotic membranes (AM) are a biologically active tissue that has been used anecdotally for human fetal MMC repair. This study evaluated the use of autologous AM compared to skin closure in an established fetal MMC model.

Methods

Seven fetal lambs underwent surgical creation of MMC at gestational age of 75 days followed by in utero repair at gestational age of 100 days. Lambs were repaired with an autologous AM patch followed by skin closure (n = 4) or skin closure alone (n = 3). Gross necropsy and histopathology of the spinal cords were performed at term to assess neuronal preservation at the lesion.

Results

An increase in preserved motor neurons and a larger area of spinal cord tissue were seen in AM-repaired lambs, as was decreased wound healing of the overlying skin. Loss of nearly all spinal cord tissue with limited motor neuron preservation was seen in skin only-repaired lambs.

Conclusions

AM-repaired lambs showed increased protection of spinal cord tissue compared to skin only-repaired lambs, but the overlying skin failed to close in AM-repaired lambs. These results suggest a potential role for AM in fetal MMC repair that warrants further study.     

New insight into the evolution of the vertebrate respiratory system and the discovery of unidirectional airflow in iguana lungs

The generally accepted framework for the evolution of a key feature of the avian respiratory system, unidirectional airflow, is that it is an adaptation for efficiency of gas exchange and expanded aerobic capacities, and therefore it has historically been viewed as important to the ability of birds to fly and to maintain an endothermic metabolism. This pattern of flow has been presumed to arise from specific features of the respiratory system, such as an enclosed intrapulmonary bronchus and parabronchi. Here we show unidirectional airflow in the green iguana, a lizard with a strikingly different natural history from that of birds and lacking these anatomical features. This discovery indicates a paradigm shift is needed. The selective drivers of the trait, its date of origin, and the fundamental aerodynamic mechanisms by which unidirectional flow arises must be reassessed to be congruent with the natural history of this lineage. Unidirectional flow may serve functions other than expanded aerobic capacity; it may have been present in the ancestral diapsid; and it can occur in structurally simple lungs.Energetically demanding forms of locomotion, such as powered flight, require a great capacity for gas exchange and selection for aerobic stamina may underlie many unique features of the avian respiratory system (1, 2). The avian respiratory system consists of highly vascularized lungs and avascular air sacs, which are membranous structures that effect ventilation and, in some species, extend between the muscles and even enter the bones (3). The topography of the conducting airways is complex; they form a circular system of tubes, analogous to the loop formed by the blood circulatory system in which arteries connect to veins through numerous small diameter vessels, the capillaries. Likewise, the avian conducting airways connect to each other through numerous tubules, the parabronchi, to form a circular path for respiratory gases (3). Gases flow through most of the parabronchi in the same direction during both inhalation and exhalation (unidirectional flow). This is due to the presence of aerodynamic valves (4–10). In contrast, the mammalian conducting airways arborize with the branch tips ending in blind sacs, there are no valves, and gases travel in the opposite direction along the conducting airways during expiration from the direction followed during inspiration (tidal flow). The presence of aerodynamic valves and unidirectional flow has generally been thought to be a highly derived feature found, among extant animals, only in birds and having evolved either in the crown group with flight or somewhere along the saurischian lineage leading to birds (11), perhaps as a mechanism to meet the high energetic demands of endothermy.The discovery of unidirectional flow in the lungs of alligators (12, 13) and the savannah monitor lizard (14) indicates that we do not understand the distribution of this phenomenon among different lineages of vertebrates and raises questions about its underlying value. It is possible that unidirectional flow evolved convergently in crocodilians and monitor lizards and serves to expand aerobic capacity. Although monitor lizards are ectotherms, their lifestyles are largely convergent with small predatory mammals (15) and they have high aerobic capacities compared with other lizards (16). In contrast, extant alligators have limited aerobic stamina (17) but their common ancestor with birds may have had a great aerobic capacity (18) or may have been endothermic (19, 20). Crocodilians and monitor lizards also share a suite of features of their pulmonary and cardiac anatomy that have been purported to give rise to, or coevolve with, birdlike patterns of flow. These features are: (i) a bronchus that has grown deep into the lung as a mesobronchium, (ii) partitioning of the respiratory system into a mechanical part that functions in ventilation and a gas-exchanging region, (iii) intercameral perforations, and (iv) separation of the heart into right and left sides (1, 21). Crocodilians and monitors are also derived in having evolved mechanisms to supplement costal ventilation while exercising (18, 22, 23). Thus, unidirectional flow in these lineages may be one of many derived traits underpinning exceptionally high rates of oxygen consumption during activity.It is also possible, however, that this pattern of flow evolved before the split of Diapsida into the Lepidosauromorpha (tuatara, lizards, snakes) and Archosauromorpha (crocodilians and birds) in an ectothermic ancestor lacking expanded aerobic capacities and living as long ago as the Permian Period. Unidirectional flow has been purported to serve ectotherms by harnessing the heart as a pump for air during periods of breath-holding (apnea) (12). Light can be shed on this pattern of evolution with observations of more squamates (snakes, lizards), which are the most diverse and largest (∼9,000 species) group of living reptiles (24).To test the hypothesis that unidirectional flow is present in squamates other than varanid lizards; to better understand anatomical features that give rise to these patterns of flow; and to gain insight into the underlying value of this pattern of flow, green iguanas (Iguana iguana) were studied. Green iguanas differ from monitors because they are herbivores and because they have structurally simple lungs that lack an enclosed intrapulmonary bronchus. Iguanas lack septation of the cardiac ventricle and have poor locomotor stamina. The poor stamina is due in part from an impairment during running in their blood and air circulatory systems (19, 25, 26).     

Sexual Healing: Daily Diary Investigation of the Benefits of Intimate and Pleasurable Sexual Activity in Socially Anxious Adults

A growing literature attests to deficits in social and romantic life quality in people with elevated social anxiety, but no research to date has explored how intense intimate encounters influence social anxiety symptoms. This study investigated whether the presence and quality of sexual activity on a given day predicted less social anxiety and negative cognitions on a subsequent day. We also explored whether the benefits of sexual activity would be stronger for more socially anxious individuals. Over 21 days, 172 undergraduate students described the presence and quality of sexual activity, social anxiety symptoms, and use of social comparisons on the day in question. Time-lagged analyses determined that being sexually active on one day was related to less social anxiety symptoms and the generation of fewer negative social comparisons the next day. Furthermore, more intense experiences of pleasure and connectedness during sex predicted greater reductions in social anxiety the next day for people high in trait social anxiety, compared to those low in trait social anxiety. These results were similar regardless of whether sex occurred in the context of romantic relationships or on weekdays versus weekends. The results suggest that sexual activity, particularly when pleasurable and intimate, may mitigate some of the social anxiety and negative comparisons frequently experienced by people with high trait social anxiety.