Electroporation of tissue and cells: A three-equation model of drug delivery.

The exposure of the cell membrane to electric pulses of sufficient intensity is known to result in an increased permeability due to the formation of microscopic pores. This is electroporation, and it has been implemented to increase the efficacy of targeted drug delivery. In this study we introduce a novel three-equation model of transport that is able to distinguish the drug uptake in reversibly electroporated cells from that in irreversibly electroporated cells. In order to relate the permeability increases and the cell survival to the local electric field, sigmoidal functions are fit to published experimental data. The resealing of reversibly electroporated cells is also considered. A numerical study is presented that considers two different electrode configurations with different initial drug distributions. This model is able to capture the existence of an optimal applied voltage, above which any increases in voltage act to decrease the total drug delivery to the surviving cells, illustrating the competing influences of increased cell permeability and decreased cell survival.

NCRP Program Area Committee 7: Radiation Education, Risk Communication, Outreach, and Policy.

Recognizing the central importance of effective communication, education, and policy across all of the domains of radiation safety and radiation protection, the National Council on Radiation Protection and Measurements (NCRP) established a new committee in 2013. Program Area Committee 7 (PAC 7) was created to develop projects and provide guidance on "Radiation Education, Risk Communication, Outreach, and Policy." After identifying individuals with relevant expertise who were willing to serve, the Committee held its inaugural meeting in 2014. In 2015, the Committee increased its membership and began carrying out an expanded program of activities. One area of activity has involved providing input and feedback on risk communication issues to NCRP and other agencies. Another area of work has involved liaising with other NCRP committees (e.g., Council Committee 1 and PAC 3) to help incorporate psychosocial and risk communication issues into projects. Future efforts of NCRP's newest PAC are expected to include the development of authoritative reports and commentaries dealing with critical issues and challenges in radiation risk communication, education, and policy.

Adaptive smoothing of multi-shell diffusion weighted magnetic resonance data by msPOAS.

We present a novel multi-shell position-orientation adaptive smoothing (msPOAS) method for diffusion weighted magnetic resonance data. Smoothing in voxel and diffusion gradient space is embedded in an iterative adaptive multiscale approach. The adaptive character avoids blurring of the inherent structures and preserves discontinuities. The simultaneous treatment of all q-shells improves the stability compared to single-shell approaches such as the original POAS method. The msPOAS implementation simplifies and speeds up calculations, compared to POAS, facilitating its practical application. Simulations and heuristics support the face validity of the technique and its rigorousness. The characteristics of msPOAS were evaluated on single and multi-shell diffusion data of the human brain. Significant reduction in noise while preserving the fine structure was demonstrated for diffusion weighted images, standard DTI analysis and advanced diffusion models such as NODDI. MsPOAS effectively improves the poor signal-to-noise ratio in highly diffusion weighted multi-shell diffusion data, which is required by recent advanced diffusion micro-structure models. We demonstrate the superiority of the new method compared to other advanced denoising methods.

Identifying environmental health priorities in underserved populations: a study of rural versus urban communities.

OBJECTIVES: Understanding and effectively addressing persistent health disparities in minority communities requires a clear picture of members' concerns and priorities. This study was intended to engage residents in urban and rural communities in order to identify environmental health priorities. Specific emphasis was placed on how the communities: defined the term environment; their perceptions of environmental exposures as affecting their health; specific priorities in their communities; and differences in urban versus rural populations. STUDY DESIGN: A community-engaged approach was used to develop and implement focus groups and compare environmental health priorities in urban versus rural communities. METHODS: A total of eight focus groups were conducted: four in rural and four in urban communities. Topics included: defining the term environment; how the environment may affect health; and environmental priorities within their communities, using both open discussion and a predefined list. Data were analysed both qualitatively and quantitatively to identify patterns and trends. RESULTS: There were important areas of overlap in priorities between urban and rural communities; both emphasized the importance of the social environment and shared a concern over air pollution from industrial sources. In contrast, for urban focus groups, abandoned houses and their social and physical sequelae were a high priority while concerns about adequate sewer and water services and road maintenance were high priorities in rural communities. CONCLUSIONS: This study was able to identify environmental health priorities in urban versus rural minority communities. In contrast to some previous risk perception research, the results of this study suggest prioritization of tangible, known risks in everyday life instead of rare, disaster-related events, even in communities that have recently experienced devastating damage from tornadoes. The findings can help inform future efforts to study, understand and effectively address environmental issues, and are particularly relevant to developing effective community-based strategies in vulnerable populations.

Position-orientation adaptive smoothing of diffusion weighted magnetic resonance data (POAS).

We introduce an algorithm for diffusion weighted magnetic resonance imaging data enhancement based on structural adaptive smoothing in both voxel space and diffusion-gradient space. The method, called POAS, does not refer to a specific model for the data, like the diffusion tensor or higher order models. It works by embedding the measurement space into a space with defined metric, in this case the Lie group of three-dimensional Euclidean motion SE(3). Subsequently, pairwise comparisons of the values of the diffusion weighted signal are used for adaptation. POAS preserves the edges of the observed fine and anisotropic structures. It is designed to reduce noise directly in the diffusion weighted images and consequently also to reduce bias and variability of quantities derived from the data for specific models. We evaluate the algorithm on simulated and experimental data and demonstrate that it can be used to reduce the number of applied diffusion gradients and hence acquisition time while achieving a similar quality of data, or to improve the quality of data acquired in a clinically feasible scan time setting.

Neoplasias del intestino delgado / Small intestinal neoplasms

Small intestine tumors are infrequent lesions during the routine clinical practice. They appear sporadically, in association with genetic diseases (e.g familiar adenomatous polyposis or Peutz-Jeghers syndrome), or associated to chronic inflammatory diseases (e.g Crohn’s disease or celiac disease). Benign tumors of small intestine (e.g leiomyomas, lipomas, adenomas, hamartomas or desmoid tumors) are generally asymptomatic, and may show up with intussusception. Primary malignant small intestine tumors (e.g adenocarcinoma, leiomyosarcoma, carcinoid tumor and lymphoma), can appear with intestinal obstruction, jaundice, digestive bleeding or abdominal pain. Small intestine metastatic lesions can appear by nearness, peritoneal metastasis or by hematological way. This last dissemination type is infrequent and more typically of melanoma. Because of its low prevalence, unspecific symptomatology and relative inaccessibility by conventional endoscopy, the diagnostic of small intestine neoplasm is often made several months after the first symptoms. Enteroclysis is a useful imaging technique towards the small intestine neoplasm suspicion. The endoscopic capsule and enteroscopy are actually the best diagnostic and therapeutic methods for this type of neoplasm. The treatment depends in the type of neoplasm, being the tumoral resection the first-line therapy.

Los tumores de intestino delgado son lesiones infrecuentes en la práctica clínica habitual. Aparecen de forma esporádica en asociación con enfermedades genéticas (por ej., poliposis adenomatosa familiar o síndrome de Peutz-Jeghers), o bien asociados a enfermedades inflamatoria crónicas intestinales (por ej., enfermedad de Crohn o enfermedad celíaca). Los tumores benignos de intestino delgado (por ej., leiomiomas, lipomas, adenoma, hamartoma o tumor desmoide) son generalmente asintomáticos, pudiendomanifestarse con intususcepción. Los tumores malignos primarios de intestino delgado (por ej.,adenocarcinoma, leiomiosarcoma, carcinoide y linfoma), pueden presentarse con obstrucción intestinal, ictericia, sangramiento digestivo o dolor abdominal. Las lesiones metastásicas de intestino delgado pueden aparecer por contigüidad, metástasis peritoneal o por vía hematógena. Este último tipo de diseminación es infrecuente y más típico del melanoma. Debido a su baja prevalencia, sintomatología inespecífica y relativa inaccesibilidad por endoscopía convencional, el diagnóstico de las neoplasias de intestino delgado es realizado a menudo varios meses después de iniciado los síntomas. La enteroclisis es una técnica de imagen útil frente a la sospecha de neoplasia de intestino delgado. La cápsula endoscópica y la enteroscopía son los métodos actualmente de mayor rendimiento para el diagnóstico y eventual terapia de este tipo de neoplasias. El tratamiento depende del tipo de neoplasia, siendo la resección tumoral la terapia de primera línea.

Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica.

Leptin is an adipocytokine that links nutrition to immunity. Previous observation that a genetic polymorphism in the leptin receptor affected susceptibility to Entamoeba histolytica infection led to the hypothesis that leptin signaling has a protective role during intestinal amebic infection. In this study we show that mice lacking the functional leptin receptor developed devastating mucosal destruction after E. histolytica infection. Bone marrow chimera experiments demonstrated that leptin receptor expressed on hematopoietic cells was not sufficient to confer resistance. Similarly, peripheral knockout of the leptin receptor rendered animals susceptible, indicating that central expression of the leptin receptor was not sufficient to confer protection. The site of leptin action was localized to the gut via an intestinal epithelium-specific deletion of the leptin receptor, which rendered mice susceptible to infection and mucosal destruction by the parasite. Mutation of tyrosine 985 or 1138 in the intracellular domain of the leptin receptor, which mediates signaling through the SH2-containing tyrosine phosphatase/extracellular signal-regulated kinase (SHP2/ERK) and signal transducer and activator of transcription 3 (STAT3) pathways, respectively, demonstrated that both were important for mucosal protection. We conclude that leptin-mediated resistance to amebiasis is via its actions on intestinal epithelium rather than hematopoietic cells or the brain, and requires leptin receptor signaling through both the STAT3 and SHP2/ERK pathways.

Local temperature rises influence in vivo electroporation pore development: a numerical stratum corneum lipid phase transition model.

Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. Electroporation temporarily destabilizes the structure of the outer skin layer, the stratum corneum, by creating microscopic pores through which agents, ordinarily unable to pass into the skin, are able to pass through this outer barrier. Long duration electroporation pulses can cause localized temperature rises, which result in thermotropic phase transitions within the lipid bilayer matrix of the stratum corneum. This paper focuses on electroporation pore development resulting from localized Joule heating. This study presents a theoretical model of electroporation, which incorporates stratum corneum lipid melting with electrical and thermal energy equations. A transient finite volume model is developed representing electroporation of in vivo human skin, in which stratum corneum lipid phase transitions are modeled as a series of melting processes. The results confirm that applied voltage to the skin results in high current densities within the less resistive regions of the stratum corneum. The model captures highly localized Joule heating within the stratum corneum and subsequent temperature rises, which propagate radially outward. Electroporation pore development resulting from the decrease in resistance associated with lipid melting is captured by the lipid phase transition model. As the effective pore radius grows, current density and subsequent Joule heating values decrease.

Numerical assessment of thermal response associated with in vivo skin electroporation: the importance of the composite skin model.

Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. The structure of the transport inhibiting outer layer, the stratum corneum, is temporarily destabilized due to the development of microscopic pores. Consequently agents that are ordinarily unable to pass into the skin are able to pass through this outer barrier. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with Joule heating. This paper shows the importance of using a composite model in calculating the electrical and thermal effects associated with skin electroporation. A three-dimensional transient finite-volume model of in vivo skin electroporation is developed to emphasize the importance of representing the skin's composite layers and to illustrate the underlying relationships between the physical parameters of the composite makeup of the skin and resulting thermal damage potential.

Numerical modeling of in vivo plate electroporation thermal dose assessment.

Electroporation is an approach used to enhance the transport of large molecules to the cell cytosol in which a targeted tissue region is exposed to a series of electric pulses. The cell membrane, which normally acts as a barrier to large molecule transport into the cell interior, is temporarily destabilized due to the development of pores in the cell membrane. Consequently, agents that are ordinarily unable enter the cell are able to pass through the cell membrane. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with joule heating. This paper explores the thermal effects of various geometric, biological, and electroporation pulse parameters including the blood vessel presence and size, plate electrode configuration, and pulse duration and frequency. A three-dimensional transient finite volume model of in vivo parallel plate electroporation of liver tissue is used to develop a better understanding of the underlying relationships between the physical parameters involved with tissue electroporation and resulting thermal damage potential.

Consanguinity and congenital heart disease in Saudi Arabia.

First-cousin marriage may be a significant risk factor for specific types of congenital heart disease in a consanguineous population. Inbreeding studies suggest an autosomal recessive component in the cause of some congenital heart defects. We studied a large sample of patients with structural congenital heart defects (CHD) identified through the Congenital Heart Disease Registry at King Faisal Specialist Hospital in Riyadh, Saudi Arabia. After exclusions of chromosome abnormalities and non-participation, data were collected on 891 consecutive patients who were registered between January and August, 1998. Data on first-cousin consanguinity and type of CHD diagnosis were collected. A z test of proportions was used to determine the association between consanguinity and subtypes of CHD. Data indicate that the proportion of first cousins in the CHD sample is higher than the proportion in the general population, supporting a hypothesis of autosomal recessive gene involvement in congenital heart disease. When subgroups of CHD were analyzed, first-cousin consanguinity was significantly associated with ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defect (AVSD), pulmonary stenosis (PS), and pulmonary atresia (PA). There was no relationship between consanguinity and tetralogy of Fallot (TOF), tricuspid atresia (TA), aortic stenosis (AS), co-arctation of the aorta (CoA), and patent ductus arteriosus (PDA). Thus, in a population with a high degree of inbreeding, consanguinity may exacerbate underlying genetic risk factors, particularly in the offspring of first cousins. There may be a recessive component in the causation of some cardiac defects.

Meeting the threat of weapons of mass destruction terrorism: toward a broader conception of consequence management.

As the importance of psychosocial issues in domestic preparedness has come to be better understood, it has become evident that there are significant conceptual limitations in existing approaches to weapons of mass destruction consequence management. This article identifies six problems: (1) most understandings of consequence management focus on short-term issues with longer-term recovery issues receiving far less attention; (2) while psychological issues are beginning to be introduced, social issues are generally not addressed; (3) although more attention is being paid to mental health issues, scenarios that are predominantly psychosocial in their effects are not generally considered; (4) social and behavioral science insights are not adequately incorporated; (5) despite the further inclusion of psychological issues, the overall approach is not sufficiently integrated or interdisciplinary; and (6) although psychological issues are receiving more attention, fundamental macro-level issues such as the re-establishment of trust after a weapons of mass destruction terrorist incident rarely receive significant attention. These limitations could seriously weaken efforts to address the consequences of a chemical, biological, radiological, or nuclear terrorist attack. There is an urgent need, therefore, to re-think current approaches and to develop a broader conception of consequence management.

Are the psychosocial aspects of weapons of mass destruction incidents addressed in the Federal Response Plan: summary of an expert panel.

Within the domestic preparedness community, there is a growing recognition of the importance of psychosocial issues in weapons of mass destruction (WMD) incidents. Whereas social and behavioral issues were only infrequently considered just a few years ago, they are now coming to be seen as central to consequence management efforts. As a result, discussions in the domestic preparedness community are beginning to consider the extent to which psychosocial effects are addressed in the Federal Response Plan and the degree to which additional preparedness and response steps may be needed. To grapple with this crucial issue, an expert panel was brought together at the International Conference on the Operational Impact of Psychological Casualties from Weapons of Mass Destruction. The panel brought together a wide range of specialists from federal agencies, the armed services, and the academic community. This article summarizes the views and assessments of the panelists as well as their policy recommendations for enhancing preparedness.

Psychosocial assistance after environmental accidents: a policy perspective.

There is a substantial body of literature on psychosocial impacts of chemical and nuclear accidents. Less attention, however, has been focused on the program and policy issues that are connected with efforts to provide psychosocial assistance to the victims of such accidents. Because psychosocial assistance efforts are certain to be an essential part of the response to future environmental emergencies, it is vital that relevant program and policy issues by more fully considered. This article discusses the highly complex nature of contamination situations and highlights some of the key policy issues that are associated with the provision of psychosocial services after environmental accidents. One issue concerns the potential for assistance efforts to become objects of conflict. In the context of the intense controversy typically associated with chemical or nuclear accidents, and with debates over the causation of illness usually at the center of environmental accidents, psychosocial assistance services may themselves become contested terrain. Other significant program and policy issues include determining how to interface with citizen self-help and other voluntary groups, addressing the problem of stigma, and deciding how to facilitate stakeholder participation in the shaping of service provision. This article offers a series of policy proposals that may help smooth the way for psychosocial assistance programs in future environmental emergencies.

Sudden asphyxial death due to an esophageal leiomyoma.

An exceedingly rare case of an esophageal leiomyoma causing sudden death by asphyxiation due to tracheal compression is presented. A brief discussion of esophageal leiomyomata is included.

Soft tissue metastasis of a chemodectoma: a case report and review of the literature.

A case of a single soft tissue metastases (abdominal wall) occurring 15 years after removal of chemodectoma of the right carotid bifurcation is described. The tumor had apparently been completely removed with excision of portions of the common, external and internal carotid arteries up to the base of the skull. Seven years later osteolytic and osteoblastic lesions were noted in the cervical and thoracic vertebrae which were radiated with 3500 rad. The 19 previously reported cases of chemodectomas with distant metastases are reviewed.