A Note From the Field In Search of Roland Wayne, Jr. (Not His Real Name): Comment on Social Connectivity.

This brief report article is a retrospective, descriptive, first-person account of following-up on a difficult-to-find client of an HIV/AIDS community-based pre-post intervention and disease prevention Research and Demonstration project in Houston, TX. Through the story about the personal journey of searching for the client, the author experiences an epiphany, especially in light of current events. Specifically, as opposed to social distancing and disconnection, public health disease prevention probably would be better served through leveraging the powerful and positive natural human features of social connectivity and closeness.

A research study review of effectiveness of treatments for psychiatric conditions common to end-stage cancer patients: needs assessment for future research and an impassioned plea.

BACKGROUND: Rates of psychiatric conditions common to end-stage cancer patients (delirium, depression, anxiety disorders) remain unchanged. However, patient numbers have increased as the population has aged; indeed, cancer is a chief cause of mortality and morbidity in older populations. Effectiveness of psychiatric interventions and research to evaluate, inform, and improve interventions is critical to these patients' care. This article's intent is to report results from a recent review study on the effectiveness of interventions for psychiatric conditions common to end-stage cancer patients; the review study assessed the state of research regarding treatment effectiveness. Unlike previous review studies, this one included non-traditional/alternative therapies and spirituality interventions that have undergone scientific inquiry. METHODS: A five-phase systematic strategy and a theoretic grounded iterative methodology were used to identify studies for inclusion and to craft an integrated, synthesized, comprehensive, and reasonably current end-product. RESULTS: Psychiatric medication therapies undoubtedly are the most powerful treatments. Among them, the most effective (i.e., "best practices benchmarks") are: (1) for delirium, typical antipsychotics-though there is no difference between typical vs. atypical and other antipsychotics, except for different side-effect profiles, (2) for depression, if patient life expectancy is ≥4-6 weeks, then a selective serotonin reuptake inhibitor (SSRI), and if < 3 weeks, then psychostimulants or ketamine, and these generally are useful anytime in the cancer disease course, and (3) for anxiety disorders, bio-diazepams (BDZs) are most used and most effective. A universal consensus suggests that psychosocial (i.e., talk) therapy and spirituality interventions fortify the therapeutic alliance and psychiatric medication protocols. However, trial studies have had mixed results regarding effectiveness in reducing psychiatric symptoms, even for touted psychotherapies. CONCLUSIONS: This study's findings prompted a testable linear conceptual model of co-factors and their importance for providing effective psychiatric care for end-stage cancer patients. The complicated and tricky part is negotiating patients' diagnoses while articulating internal intricacies within and between each of the model's co-factors. There is a relative absence of scientifically derived information and need for more large-scale, diverse scientific inquiry. Thus, this article is an impassioned plea for accelerated study and better care for end-stage cancer patients' psychiatric conditions.

Toward a US Army Pacific (USARPAC) rapid deployment medical component in support of Human Assistance/Disaster Relief (HA/DR) operations: challenges with "Going in Light".

BACKGROUND: This article reports the exploratory development and study efforts regarding the viability of a novel "going-in light" or "Going Light" medical component in support of US Army Pacific (USARPAC) Humanitarian Assistance/Disaster Relief (HA/DR) missions, namely, a BLU-MED® incremental modular equipment package along with a Rapid Deployment Medical Team (RDMT). The study was conducted to uncover a way for the U.S. Army to: (1) better medically support the greater U.S. military Pacific Command, (2) prepare the Army for Pacific HA/DR contingencies, and (3) imprint a swift presence and positive contribution to Pacific HA/DR operations. METHODS: The findings were derived from an intensive quasi-Military Decision Making Planning (MDMP) process, specifically, the Oracle Delphi. This process was used to: (1) review a needs assessment on the profile of disasters in general and the Pacific in particular and (2) critically examine the viability and issues surrounding a Pacific HA/DR medical response of going in light and incrementally. RESULTS: The Pacific area of operations contains 9 of 15 countries most at risk for disasters in the most disaster-prone region of the world. So, it is not a matter of whether a major, potentially large-scale lethal disaster will occur but rather when. Solid empirical research has shown that by every outcome measured Joint Forces (Army, Navy, Air Force, and Marines) medical HA/DR operations have been inordinately successful and cost-effective when they employed U.S. Army medical assets inland near disasters' kinetic impact and combined sister services' logistical support and expertise. In this regard, USARPAC has the potential to go in light and successfully fill a vital HA/DR medical response gap with the RDMT and a BLU-MED®. However, initially going in fast and light and expanding and contracting as the situation dictates comes with subsequent challenges as briefly described herein that must be addressed. CONCLUSIONS: The challenges to going in light are not insurmountable "show stoppers." They can be identified and addressed through planning and preparation. Hopefully, the acquisition rapid response light components will equip commanders with more effective options with which to conduct Pacific HA/DR operations and be a focal point for effective joint operations.

A Review of Supplementary Medical Aspects of Post-Cold War UN Peacekeeping Operations: Trends, Lessons Learned, Courses of Action, and Recommendations.

Post-Cold War United Nations Peace Keeping Operations (UN PKOs) have been increasingly involved in dangerous areas with ill-defined boundaries, harsh and remote geographies, simmering internecine armed conflict, and disregard on the part of some local parties for peacekeepers' security and role. In the interest of force protection and optimizing operations, a key component of UN PKOs is healthcare and medical treatment. The expectation is that UN PKO medical support will adjust to the general intent and structure of UN PKOs. To do so requires effective policies and planning informed by a review of all medical aspects of UN PKO operations, including those considered supplementary, that is, less crucial but contributing nonetheless. Medical aspects considered paramount and key to UN PKOs have received relatively thorough treatment elsewhere. The intent of this article is to report on ancillary and supplemental medical aspects practical to post-Cold War UN PKO operations assembled through an iterative inquiry of open-source articles. Recommendations are made about possible courses of action in terms of addressing trends found in such medical aspects of PKOs and relevance of US/NATO/European Union models and research.

MAT2A mutations predispose individuals to thoracic aortic aneurysms.

Up to 20% of individuals who have thoracic aortic aneurysms or acute aortic dissections but who do not have syndromic features have a family history of thoracic aortic disease. Significant genetic heterogeneity is established for this familial condition. Whole-genome linkage analysis and exome sequencing of distant relatives from a large family with autosomal-dominant inheritance of thoracic aortic aneurysms variably associated with the bicuspid aortic valve was used for identification of additional genes predisposing individuals to this condition. A rare variant, c.1031A>C (p.Glu344Ala), was identified in MAT2A, which encodes methionine adenosyltransferase II alpha (MAT IIα). This variant segregated with disease in the family, and Sanger sequencing of DNA from affected probands from unrelated families with thoracic aortic disease identified another MAT2A rare variant, c.1067G>A (p.Arg356His). Evidence that these variants predispose individuals to thoracic aortic aneurysms and dissections includes the following: there is a paucity of rare variants in MAT2A in the population; amino acids Glu344 and Arg356 are conserved from humans to zebrafish; and substitutions of these amino acids in MAT Iα are found in individuals with hypermethioninemia. Structural analysis suggested that p.Glu344Ala and p.Arg356His disrupt MAT IIα enzyme function. Knockdown of mat2aa in zebrafish via morpholino oligomers disrupted cardiovascular development. Co-transfected wild-type human MAT2A mRNA rescued defects of zebrafish cardiovascular development at significantly higher levels than mRNA edited to express either the Glu344 or Arg356 mutants, providing further evidence that the p.Glu344Ala and p.Arg356His substitutions impair MAT IIα function. The data presented here support the conclusion that rare genetic variants in MAT2A predispose individuals to thoracic aortic disease.

Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1.

Although thoracic aortic aneurysms and dissections (TAAD) can be inherited as a single-gene disorder, the genetic predisposition in the majority of affected people is poorly understood. In a multistage genome-wide association study (GWAS), we compared 765 individuals who had sporadic TAAD (STAAD) with 874 controls and identified common SNPs at a 15q21.1 locus that were associated with STAAD, with odds ratios of 1.6-1.8 that achieved genome-wide significance. We followed up 107 SNPs associated with STAAD with P < 1 × 10(-5) in the region, in two separate STAAD cohorts. The associated SNPs fall into a large region of linkage disequilibrium encompassing FBN1, which encodes fibrillin-1. FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD. This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD.

Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections.

Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0 × 10⁻5, OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes.

Rare copy number variants disrupt genes regulating vascular smooth muscle cell adhesion and contractility in sporadic thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysms and dissections (TAAD) cause significant morbidity and mortality, but the genetic origins of TAAD remain largely unknown. In a genome-wide analysis of 418 sporadic TAAD cases, we identified 47 copy number variant (CNV) regions that were enriched in or unique to TAAD patients compared to population controls. Gene ontology, expression profiling, and network analysis showed that genes within TAAD CNVs regulate smooth muscle cell adhesion or contractility and interact with the smooth muscle-specific isoforms of α-actin and ß-myosin, which are known to cause familial TAAD when altered. Enrichment of these gene functions in rare CNVs was replicated in independent cohorts with sporadic TAAD (STAAD, n = 387) and inherited TAAD (FTAAD, n = 88). The overall prevalence of rare CNVs (23%) was significantly increased in FTAAD compared with STAAD patients (Fisher's exact test, p = 0.03). Our findings suggest that rare CNVs disrupting smooth muscle adhesion or contraction contribute to both sporadic and familial disease.