Integrated semi-continuous manufacturing of lentiviral vectors

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Distinct Molecular Effects of Angiotensin II and Angiotensin III in Rat Astrocytes

It is postulated that central effects of angiotensin (Ang) II may be indirect due to rapid conversion to Ang III by aminopeptidase A (APA). Previously, we showed that Ang II and Ang III induced mitogen-activated protein (MAP) kinases ERK1/2 and stress-activated protein kinase/Jun-terminal kinases (SAPK/JNK) phosphorylation in cultured rat astrocytes. Most importantly, both peptides were equipotent in causing phosphorylation of these MAP kinases. In these studies, we used brainstem and cerebellum astrocytes to determine whether Ang II’s phosphorylation of these MAP kinases is due to the conversion of the peptide to Ang III. We pretreated astrocytes with 10 μM amastatin A or 100 μM glutamate phosphonate, selective APA inhibitors, prior to stimulating with either Ang II or Ang III. Both peptides were equipotent in stimulating ERK1/2 and SAPK/JNK phosphorylation. The APA inhibitors failed to prevent Ang II- and Ang III-mediated phosphorylation of the MAP kinases. Further, pretreatment of astrocytes with the APA inhibitors did not affect Ang II- or Ang III-induced astrocyte growth. These findings suggest that both peptides directly induce phosphorylation of these MAP kinases as well as induce astrocyte growth. These studies establish both peptides as biologically active with similar intracellular and physiological effects

Food Insecurity in Kalamazoo

Introduction: Food insecurity is both an inconvenience and problem. As of 2013, over 16 million children in the USA were food insecure. The consequences of food insecurity include health issues from nutritional deficits, developmental difficulties, and behavioral problems that manifest in educational, personal and professional challenges. Overall, food insecurity and its impact on individuals and families is under-recognized. Additionally, the extent to which physicians play a role in helping patients secure access to food assistance programs remains unclear. Objective: The objective of this study was to assess the efficacy and methodologies of current healthcare practices based in Kalamazoo County, MI, in identifying pediatric patients who are food insecure. Results will help local assistance resources, such as Kalamazoo Loaves and Fishes, improve outreach efforts and re-focus their programs. Furthermore, results could impact physician practices regarding identifying those who are food insecure. Methods: The American Academy of Pediatrics (AAP) developed a 2-question survey with 97% sensitivity for identifying food insecurity. The questions are: Within the past 12 months, we worried whether our food would run out before we got money to buy more and Within the past 12 months, the food we bought just didn\u27t last and we didn\u27t have money to buy more. Using these questions as a foundation, we developed an electronically distributed 20-question survey that assessed awareness of food insecurity among Kalamazoo pediatric and family medicine physicians. Survey questions covered years of practice, usage of the AAP questions, level of formal training on food insecurity, mid-level and support staff, and resources recommended to patients. Results and Discussion: The 25 responses were analyzed for differences between groups. Although no significant relationships were found, 76% of respondents believed food insecurity directly related to their patient\u27s illness, though only 52% ask direct questions about food insecurity. Women, Infants and Children (WIC) program referrals were common and almost all respondents were willing to include the two AAP-validated food insecurity screening questions in their practice. A consensus emerged that a list of local resources would be helpful in addressing food insecurity. Conclusion: Kalamazoo pediatricians and family medicine physicians believe food insecurity directly relates to the problems affecting their patients. However, only half of physicians ask patients about food insecurity. Future work should focus on expanding physician-patient conversations about food insecurity, addition of validated food insecurity questions to patient questionnaires, and compiling a list of local resources for distribution to local providers

Amigas Latinas Motivando el ALMA (ALMA): Development and Pilot Implementation of a Stress Reduction Promotora Intervention

Use of mental health care services for psychological distress is limited among Latino immigrants. In geographic areas where migration has been rapid, mental health systems possess limited capacity to provide bilingual and bicultural assistance. The development of a bilingual and bicultural workforce is a necessary yet long-term solution. More immediate strategies, however, are needed to meet the needs of immigrant Latinos. This paper describes the development of a stress-reduction focused, lay health advisor training that targets individual behavior change among Latina immigrants. The theoretical foundation, curriculum components, and pilot implementation of the training are discussed. As natural leaders, Latina promotoras disseminated learned strategies and resources within their communities. The lay health advisor model is a salient method for disseminating information regarding mental health and stress reduction among Latinas

Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy Related?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163471/1/hep31144.pd

Hop Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in Ttc26

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process. Here, we have analyzed hop mice, which walk with a characteristic hopping gait using their hindlimbs in synchrony. Fictive locomotion experiments suggest that a local defect in the ventral spinal cord contributes to the aberrant locomotor phenotype. Hop mutant spinal cords had severe morphologic defects, including the absence of the ventral midline and a poorly defined border between white and gray matter. The hop mice represent the first model where, exclusively found in the lumbar domain, the left and right components of the central pattern generators (CPGs) are fused with a synchronous hindlimb gait as a functional consequence. These defects were associated with abnormal developmental processes, including a misplaced notochord and reduced induction of ventral progenitor domains. Whereas the underlying mutation in hop mice has been suggested to lie within the Ttc26 gene, other genes in close vicinity have been associated with gait defects. Mouse embryos carrying a CRISPR replicated point mutation within Ttc26 displayed an identical morphologic phenotype. Thus, our data suggest that the assembly of the lumbar CPG network is dependent on fully functional TTC26 protein

Assessment of iron oxide nanoparticle ecotoxicity on regeneration and homeostasis in the replacement model system Schmidtea mediterranea

Iron oxide nanoparticles (IONs) are used in a number of applications, from food to cosmetics, from medical applications to magnetic storage. In spite of the 550 tons produced each year in Europe alone, no effective dose limit recommendations are established and the overall risks connected to IONs are still debated. The incorporation of IONs in daily life raises a concern about their effects on the environment, on living organisms, and on human health. In this study, we used freshwater planarians to assess the nanoecotoxicity of IONs. Planarians are free-living invertebrates known for their astonishing regenerative ability. Because of their sensitivity to toxicants, they are often used to determine the effects of toxic, genotoxic and carcinogenic environmental compounds with an approach in line with the 3Rs (Reduce, Refine, Replace) principle. Planarians were exposed to IONs at concentrations up to 1 mg/mL and their effects were evaluated at the behavioral, morphofunctional and molecular levels, with a special emphasis on the regeneration process. Our results indicate that IONs did not affect the stem cell population dynamics, nor did they induce substantial changes in either homeostatic or regenerating planarians. As positive controls, gold nanoparticles coated with the pro-apoptotic anti-cancer drug hexadecylmethylammonium bromide, silver nanoparticles and highly concentrated polystyrene nanoparticles were used. These all elicited toxic effects. Therefore, we conclude that IONs at environmental concentrations are safe for planarians, and that the planarian is a powerful model system that can replace vertebrate animal models in nanoecotoxicology research and for nanoecotoxicology studies

Treatment Burden and Chronic Illness: Who is at Most Risk?

Background: There is a need to ascertain the type and level of treatment burden experienced by people with co-morbidities. This is important to identify the characteristics of participants who are at most risk of treatment burden.  Objective: The aim of this study is to identify the characteristics of participants who are at most risk of treatment burden.  Methods: This cross-sectional study was part of a larger project and recruitment was conducted across four Australian regions: rural, semi-rural and metropolitan. Participants were asked about their treatment burden using an adapted version of a measure, which included the following five dimensions: medication, time and administrative, lifestyle change, social life and financial burden.  Results: In total, 581 participants with various chronic health conditions reported a mean global treatment burden of 56.5 out of 150 (standard deviation = 34.5). Number of chronic conditions (β = .34, p < 0.01), age, (β = −.27, p < 0.01), the presence of an unpaid carer (β = .22, p < 0.001) and the presence of diabetes mellitus and other endocrine conditions (β = .13, p < 0.01) were significant predictors of overall treatment burden. For the five dimensions of treatment burden, social, medicine and administrative burden were predicted by the same cluster of variables: number of conditions, age, presence of an unpaid carer and diabetes. However, in addition to these variables, financial dimensions were also predicted by education level, ethnicity and health insurance. Educational level also influenced lifestyle burden.  Conclusion: A substantial proportion of community-dwelling adults with chronic conditions have considerable levels of treatment burden. Specifically, health professionals should provide greater focus on managing overall treatment burden for persons who are of young age, have an endocrine condition or an unpaid carer, or a combination of these factors

The Use of Tissue Engineering to Fabricate Perfusable 3D Brain Microvessels

Tissue engineering of the blood-brain barrier (BBB) in vitro has been rapidly expanding to address the challenges of mimicking the native structure and function of the BBB. Most of these models utilize 2D conventional microfluidic techniques. However, 3D microvascular models offer the potential to more closely recapitulate the cytoarchitecture and multicellular arrangement of in vivo microvasculature, and also can recreate branching and network topologies of the vascular bed. In this perspective, we discuss current 3D brain microvessel modeling techniques including templating, printing, and self-assembling capillary networks. Furthermore, we address the use of biological matrices and fluid dynamics. Finally, key challenges are identified along with future directions that will improve development of next generation of brain microvasculature models