The Upside to Down Syndrome: An Educational Manual for Parents

Parents of children with Down syndrome want their child to be as successful as other children in areas of development, specifically play. Play is crucial to a child\u27s development as it assists with the progression through childhood developmental stages. This can help lay a foundation for learning daily life skills such as dressing, feeding, and social interaction. For children with Down syndrome, performing daily living tasks may be more difficult as fine and gross motor skills are affected by low-tone, cognition level, and coordination. Providing children with a variety of play activities to build both fine and gross motor skills can help increase independence and support development. Throughout the literature review, it was noted that there is currently an abundance of research regarding typically developing children and the benefits of play. There is a lack in literature focused on children with Down syndrome and how play can support development within this population. A common theme arising in the literature is parental perceptions about the uncertainty involved in raising a child with Down syndrome. Parents felt as if they do not have enough information on what they can do at home to encourage fine and gross motor skill development and have few resources they may utilize. Some parents reported receiving information from their child\u27s occupational therapist, however, parents felt as if more information is necessary (Menear, 2007). The few parental resources currently available contained language that may decrease user-friendliness and negatively impact the use of some resources. Current literature also described parental concerns about keeping their child active in order to maintain health while providing activities that allow their child to be successful. Occupational therapists can help bridge the gap between activity and success by providing parents with education and suggestions as to what activities can help their child build fine and gross motor skills while using playas the basis for activity. The methodology of this scholarly project included a review of literature regarding play and the impact on the development of children with Down syndrome as well as typically developing children. Local bookstores and internet websites were also explored to determine the availability of resources for parents of children with Down syndrome. To address motor goals through play and structured developmental activities, an educational manual was developed for parents of children with Down syndrome and it is designed to be used under the guidance of an occupational therapist. The manual addresses two types of play; active, which involves gross motor activities such as running and jumping and quiet play which encourages fine motor skills through table-top activities such as coloring, drawing, and using hands to manipulate objects. Parents are able to choose activities which are suitable for their child based on the resources available at home and the energy level of the child

Introducing Allergenic Food into Infants\u27 Diets: Systematic Review

Purpose: The purpose of this systematic review was to explore the association between timing of introduction of potentially allergenic foods to infants and development of food allergies. Methods: CINAHL, Medline, PubMed, Science Direct, and Web of Science were searched using the terms solid food, complementary food, or infant feeding combined with allergy or hypersensitivity for articles published in English in 2000 or later. Inclusion criteria were 1) primary research articles with 2) a focus on association between introduction of complementary foods including potentially allergenic foods into diets of infants less than 12 months of age and development of food allergies. Articles were excluded if they were 1) not primary research, 2) about complementary foods only (without specifi city of allergenic foods), or 3) on allergic conditions other than food allergy (such as asthma or eczema). Results: The initial literature search yielded 533 articles; 14 articles met inclusion criteria. Level of evidence of each study was determined with the SORT criteria. Results found that delayed introduction of solid foods in general and allergenic foods in particular was not associated with decreased risk for allergic diseases among high and low-risk infants. Later introduction was associated with increased risk for allergy development. Clinical Implications: For infants at low risk for development of food allergies, providers should advise caregivers to introduce potentially allergenic foods with other solid foods between 4 and 6 months of age when children show an interest in eating solids. Infants at high risk for peanut allergy, should be evaluated by an allergy specialist prior to introduction of peanuts and work with providers to create an individualized plan for introduction of peanuts and other allergenic foods as needed

Integration of Sexuality Content into an Occupational Therapy Curriculum

Sexuality is a broad term that can be used to encompass other terms such as sexual expression and sexual functioning, and can be defined as a holistic concept of the individual that is more than just physical sexual behavior but also relates to thoughts and feelings of everyday life (Couldrick, 1998a). Sexuality and sexual functioning are considered an activity of daily living (ADL) by the Occupational Therapy Practice Framework: Domain and Process (2008); however, it is a topic that is not being routinely addressed with clients by occupational therapists or other healthcare professionals (Hattjar, 2012). Studies show there is a significant lack of information given to clients in regard to sexuality, as well as dissatisfaction with the services that are provided for sexuality. This information implies an increase in knowledge, experience, and comfort levels with sexuality needs to be addressed with occupational therapists and occupational therapy students in order to treat clients in a holistic and client-centered manner. A comprehensive literature review was completed to identify key aspects of sexuality. The literature review revealed a significant lack in student and practitioner confidence and competence in addressing sexuality in a clinical setting. After an extensive search regarding the topic of sexuality within the profession of occupational therapy it was found that much of the limited literature stems from the late 1980’s to early 1990’s, yet the literature from the 2000’s continue to address the same issues. Due to the reported low levels of comfort for occupational therapy students and practitioners regarding sexuality and the role occupational therapists play in addressing the subject with clients, the following product was developed. There was a dearth of the information and no evidenced-based articles were located regarding sexuality or how to teach about the topic. The product created includes lesson plans that address different aspects of physical and/or psychosocial impairments that may impact sexuality. The product lesson plans consist of varying lectures, readings and activities, to be incorporated into several courses throughout the duration of an occupational therapy professional program. The goal of this product is to increase exposure to issues of sexuality and sexual functioning throughout the curricula of a Midwestern professional occupational therapy program in order to create competent and comfortable practitioners within the field

A versatile polyacrylamide gel electrophoresis based sulfotransferase assay

<p>Abstract</p> <p>Background</p> <p>Sulfotransferases are a large group of enzymes that regulate the biological activity or availability of a wide spectrum of substrates through sulfation with the sulfur donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS). These enzymes are known to be difficult to assay. A convenient assay is needed in order to better understand these enzymes.</p> <p>Results</p> <p>A universal sulfotransferase assay method based on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is described. This assay has been successfully applied to substrates as small as α-naphthol and as big as proteoglycans. As examples, we present the assays for recombinant human CHST4, TPST1, CHST3 and HS6ST1. In order to assess whether a small molecule can be applicable to this type of assay, a method to estimate the relative mobility of a molecule to PAPS is also presented. The estimated relative mobilities of various sulfated small molecules generated by SULT1A1, SULT1E1, SULT2A1 and CHST4 are in the range of ± 0.2 of the actual relative mobilities.</p> <p>Conclusion</p> <p>The versatility of the current method comes from the ability that SDS-PAGE can separate proteins and small molecules according to different parameters. While mobilities of proteins during SDS-PAGE are inversely related to their sizes, mobilities of small molecules are positively related to their charge/mass ratios. The predicted relative mobility of a product to PAPS is a good indicator of whether a sulfotransferase can be assayed with SDS-PAGE. Because phosphorylation is most similar to sulfation in chemistry, the method is likely to be applicable to kinases as well.</p

Recombinant factor VIIa analog NN1731 (V158D/E296V/M298Q-FVIIa) enhances fibrin formation, structure and stability in lipidated hemophilic plasma

Introduction—The bypassing agent recombinant factor VIIa (rFVIIa) is efficacious in treating bleeding in hemophilia patients with inhibitors. Efforts have focused on the rational engineering of rFVIIa variants with increased hemostatic potential. One rFVIIa analog (V158D/E296V/M298QFVIIa, NN1731) improves thrombin generation and clotting in purified systems, whole blood from hemophilic patients and factor VIII-deficient mice. Methods—We used calibrated automated thrombography and plasma clotting assays to compare effects of bypassing agents (rFVIIa, NN1731) on hemophilic clot formation, structure, and ability to resist fibrinolysis. Results—Both rFVIIa and NN1731 shortened the clotting onset and increased the maximum rate of fibrin formation and fibrin network density in hemophilic plasma clots. In the presence of tissue plasminogen activator, both rFVIIa and NN1731 shortened the time to peak turbidity (TTPeaktPA) and increased the area under the clot formation curve (AUCtPA). Phospholipids increased both rFVIIa and NN1731 activity in a lipid concentration-dependent manner. Estimated geometric mean concentrations of rFVIIa and NN1731 producing similar onset, rate, TTPeaktPA, and AUCtPA as seen with 100% factors VIII and IX were: 24.5, 74.3, 29.7, and 37.1 nM rFVIIa, and 8.6, 31.2, 9.0, and 11.3 nM NN1731, respectively. In each case, the NN1731 concentration was significantly lower than rFVIIa. Conclusions—These findings suggest that like rFVIIa, NN1731 improves the formation, structure, and stability of hemophilic clots. Higher lipid concentrations may facilitate assessment of both rFVIIa and NN1731 activity. NN1731 appears likely to support rapid clot formation in tissues with high endogenous fibrinolytic activity

Global fund financing to the 34 malaria-eliminating countries under the new funding model 2014-2017 : an analysis of national allocations and regional grants

The Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM) has been the largest financial supporter of malaria since 2002. In 2011, the GFATM transitioned to a new funding model (NFM), which prioritizes grants to high burden, lower income countries. This shift raises concerns that some low endemic countries, dependent on GFATM financing to achieve their malaria elimination goals, would receive less funding under the NFM. This study aims to understand the projected increase or decrease in national and regional funding from the GFATM's NFM to the 34 malaria-eliminating countries.; Average annual disbursements under the old funding model were compared to average annual national allocations for all eligible 34 malaria-eliminating countries for the period of 2014-2017. Regional grant funding to countries that are due to receive additional support was then included in the comparison and analysed. Estimated funding ranges for the countries under the NFM were calculated using the proposed national allocation plus the possible adjustments and additional funding. Finally, the minimum and maximum funding estimates were compared to average annual disbursements under the old funding model.; A cumulative 31 % decrease in national financing from the GFATM is expected for the countries included in this analysis. Regional grants augment funding for almost half of the eliminating countries, and increase the cumulative percent change in GTFAM funding to 32 %, though proposed activities may not be funded directly through national malaria programmes. However, if countries receive the maximum possible funding, 46 % of the countries included in this analysis would receive less than they received under the previous funding model.; Many malaria-eliminating countries have projected national declines in funding from the GFATM under the NFM. While regional grants enhance funding for eliminating countries, they may not be able to fill country-level funding gaps for local commodities and implementation. If the GFATM is able to nuance its allocation methodology to mitigate drastic funding declines for malaria investments in low transmission countries, the GFATM can ensure previous investments are not lost. By aligning with WHO's Global Technical Strategy for Malaria and investing in both high- and low-endemic countries, the Global Fund can tip the scale on a global health threat and contribute toward the goal of eventual malaria eradication

Novel Mouse Model for Analysis of Macrophage Function in Neuroblastoma

Background: Neuroblastoma is the third most common childhood cancer and accounts for 12% of cancer-associated deaths in children under the age of 15. Patients with high risk neuroblastoma have a poor 5-year survival rate of less than 50%. Neuroblastoma tumors treated with the histone deacetylase inhibitor (HDACi) vorinostat have increased infiltration of macrophages with upregulated immune cell-surface receptors. Neuroblastoma cells release VEGF and M-CSF, which may alter intratumoral macrophage populations. VEGF has also been implicated in alteration of amyloid precursor protein family processing. Our lab demonstrated that amyloid precursor protein 2 (APLP2), a member of the amyloid precursor protein family, plays an important role in the migration of tumor cells. APLP2 is known to be expressed by macrophages, but no studies have previously examined macrophage functions that are impacted by APLP2 in the context of neuroblastoma disease and its treatment by HDACi drugs. Significance of Problem: Because of the high morbidity and mortality associated with neuroblastoma, studies such as this one that are designed to comprehend the interaction of immunity and treatment in neuroblastoma are clinically significant. The results from this study are also expected to expand our comprehension of macrophage function and regulation, and thus will be of broad value in the immunology and oncology fields. Experimental Design and Results: We have treated neuroblastoma tumor cells in vitro with M344, an HDACi with structural similarity to vorinostat, and showed that M344 decreases neuroblastoma cell growth. In addition, we have generated mice that lack APLP2 expression in cells expressing the Csf-1 receptor (a protein characteristically expressed by macrophages and dendritic cells). We discovered that following polarization, macrophages collected from the bone marrow of these mice have an altered distribution of M1 and M2 sub-populations, which are macrophage sub-populations known to differ in their migratory capabilities. Furthermore, we have shown that M1 and M2 subpopulations of bone marrow-derived macrophages from normal mice differ in their expression of APLP2. Thus, APLP2 is influential in macrophage biology, and we have created a novel mouse model for defining its specific contributions in mice treated with HDACi that influence macrophage biology. Conclusions: Based on the data that we have acquired, we are well positioned to fully explore both the impact of HDACi drugs on macrophage/dendritic cell populations in a syngeneic neuroblastoma mouse model, and to define the role of APLP2 in the function of these cell populations in the context of neuroblastoma.https://digitalcommons.unmc.edu/chri_forum/1000/thumbnail.jp

Design, assessment, and in vivo evaluation of a computational model illustrating the role of CAV1 in CD4+ T-lymphocytes

Caveolin-1 (CAV1) is a vital scaffold protein heterogeneously expressed in both healthy and malignant tissue. We focus on the role of CAV1 when overexpressed in T-cell leukemia. Previously, we have shown that CAV1 is involved in cell-to-cell communication, cellular proliferation, and immune synapse formation; however, the molecular mechanisms have not been elucidated. We hypothesize that the role of CAV1 in immune synapse formation contributes to immune regulation during leukemic progression, thereby warranting studies of the role of CAV1 in CD4+ T-cells in relation to antigen-presenting cells. To address this need, we developed a computational model of a CD4+ immune effector T-cell to mimic cellular dynamics and molecular signaling under healthy and immunocompromised conditions (i.e., leukemic conditions). Using the Cell Collective computational modeling software, the CD4+ T-cell model was constructed and simulated under CAV1+/+, CAV1+/−, and CAV1−/− conditions to produce a hypothetical immune response. This model allowed us to predict and examine the heterogeneous effects and mechanisms of CAV1 in silico. Experimental results indicate a signature of molecules involved in cellular proliferation, cell survival, and cytoskeletal rearrangement that were highly affected by CAV1 knock out. With this comprehensive model of a CD4+ T-cell, we then validated in vivo protein expression levels. Based on this study, we modeled a CD4+ T-cell, manipulated gene expression in immunocompromised versus competent settings, validated these manipulations in an in vivo murine model, and corroborated acute T-cell leukemia gene expression profiles in human beings. Moreover, we can model an immunocompetent versus an immunocompromised microenvironment to better understand how signaling is regulated in patients with leukemia