Advances in Trace Element Supplementation for Parenteral Nutrition

Parenteral nutrition (PN) provides support for patients lacking sufficient intestinal absorption of nutrients. Historically, the need for trace element (TE) supplementation was poorly appreciated, and multi-TE products were not initially subjected to rigorous oversight by the United States Food and Drug Administration (FDA). Subsequently, the American Society for Parenteral and Enteral Nutrition (ASPEN) issued dosage recommendations for PN, which are updated periodically. The FDA has implemented review and approval processes to ensure access to safer and more effective TE products. The development of a multi-TE product meeting ASPEN recommendations and FDA requirements is the result of a partnership between the FDA, industry, and clinicians with expertise in PN. This article examines the rationale for the development of TRALEMENT^® (Trace Elements Injection 4*) and the FDA’s rigorous requirements leading to its review and approval. This combination product contains copper, manganese, selenium, and zinc and is indicated for use in adults and pediatric patients weighing ≥10 kg. Comprehensive management of PN therapy requires consideration of many factors when prescribing, reviewing, preparing, and administering PN, as well as monitoring the nutritional status of patients receiving PN. Understanding patients’ TE requirements and incorporating them into PN is an important part of contemporary PN therapy.     

Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson''s correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.     

Clinical correlation and molecular evaluation confirm that the MLH1 p.Arg182Gly (c.544A>G) mutation is pathogenic and causes Lynch syndrome

Approximately 25 % of mismatch repair (MMR) variants are exonic nucleotide substitutions. Some result in the substitution of one amino acid for another in the protein sequence, so-called missense variants, while others are silent. The interpretation of the effect of missense and silent variants as deleterious or neutral is challenging. Pre-symptomatic testing for clinical use is not recommended for relatives of individuals with variants classified as ‘of uncertain significance’. These relatives, including non-carriers, are considered at high-risk as long as the contribution of the variant to disease causation cannot be determined. This results in continuing anxiety, and the application of potentially unnecessary screening and prophylactic interventions. We encountered a large Irish Lynch syndrome kindred that carries the c.544A>G (p.Arg182Gly) alteration in the MLH1 gene and we undertook to study the variant. The clinical significance of the variant remains unresolved in the literature. Data are presented on cancer incidence within five kindreds with the same germline missense variant in the MLH1 MMR gene. Extensive testing of relevant family members in one kindred, a review of the literature, review of online MMR mutation databases and use of in silico phenotype prediction tools were undertaken to study the significance of this variant. Clinical, histological, immunohistochemical and molecular evidence from these families and other independent clinical and scientific evidence indicates that the MLH1 p.Arg182Gly (c.544A>G) change causes Lynch syndrome and supports reclassification of the variant as pathogenic.     

HPV and HPV Vaccines: The Knowledge Levels, Opinions, and Behavior of Parents

To measure parent knowledge levels and opinions related to the human papillomavirus (HPV) and the two vaccines used to prevent it. To measure parent behavior in terms of whether or not to have their children vaccinated. Between June 19, 2012, and August 24, 2012, questionnaires were distributed to parents while waiting for their child to see their pediatrician at a local group practice. The survey was reviewed for face validity by College of Pharmacy social science and clinical faculty members, and an earlier version of it had been used successfully in a published study of biomedical students’ knowledge of and attitudes toward the HPV vaccine. 129 usable surveys were obtained. 48.1 % of subjects said they learned about the HPV vaccines from the media, while 47.3 % identified health care practitioner(s) as a source of knowledge. The mean score on a 20-item knowledge test regarding the infection and vaccines was 36 % (range 0–80 %). Opinions on the subject varied widely. For example, 22.4 % of subjects agreed that schools should require that students be vaccinated before enrolling, while 3.2 % agreed that vaccination causes patients to become sexually active. Subjects reported vaccination status for 253 children (mean age 13) as follows: 33 % vaccinated; 28 % not vaccinated but will be; 11 % will never be vaccinated; and 28 % not decided. These results are somewhat encouraging, because many parents are hearing about the vaccines from their providers. Although not an equally valid source, the media are also raising awareness. Based on the knowledge and opinion results of this study, there is a need for pharmacists and other providers to educate their patients about the vaccines and the virus and to converse with them regarding the moral and psychological implications of vaccination. Still, it is encouraging that these subjects had or plan to have over half (61 %) of their children vaccinated.     

Religious Faith and Transformational Processes in Marriage

Leading scholars of marital processes strongly recommend supplementing the current focus on marital conflict to include research on transformative processes. This qualitative study examines the connection between religion and the transformative processes of commitment and coping in marriage. The sample for this study includes 184 married couples (N = 368 individuals), making it far larger than most in‐depth, qualitative interview‐based studies. Participants included Christians, Jews, and Muslims with an over sampling of minorities and immigrant families living in all eight regions of the United States. For several decades studies have shown a largely positive correlation between (a) religiosity and marital commitment and (b) religiosity and (generally) positive coping, but with little explanation regarding how and why. Findings of this study indicate that there are specific religious beliefs and practices related to how these couples approach their marriages—including several that relate to the two transformative processes of commitment and coping.