Military Veterans' End of Life: Supporting Them in Their Last Deployment.

More than 600,000 U.S. Veterans die from illness each year. Clinicians in civilian settings are increasingly providing care to Veterans at end of life. Veteran care should be distinctive and individualized to meet their unique needs. There is limited information to guide civilian clinicians in providing care to Veterans at end of life. This article provides bio-psycho-social information to holistically guide Veteran healthcare and assist them with solace, respect, and serenity at end of life. Various options for end-of-life care are discussed, as well as specific concerns of women, lesbian, gay, bisexual, and transgender Veterans. Some end-of-life entitlements for all Veterans and sometimes their spouses/children are included.

The Risks, Invisibility, and Health Issues Facing Women Veterans Who Are Homeless.

Women veterans may experience a variety of traumatizing events and conditions before, during, and after their military service, such as intimate partner violence, military sexual trauma, moral injury, and posttraumatic stress disorder. These experiences put them at greater risk for significant behavioral and physical health sequelae, which can be associated with difficulty with civilian reintegration and complexities around homelessness. Homeless women military veterans are often uncounted, undergo different environmental situations than their male counterparts, and are vulnerable to sexual violence and unintended pregnancies. Identifying homeless women military veterans is an important first step; otherwise, they remain "invisible." Comprehensive, collaborative, interdisciplinary health care in which trust is established and care is holistic and individualized will produce the most optimal outcomes.

Delivery of mobile dental services to dependent elderly people: results from a pilot study in rural Switzerland.

The objective of this pilot study was to provide data on the oral health status and oral health behaviour of care-dependent elderly people in the canton of Uri. The study aimed at assessing whether age and duration of living in a nursing home is associated with dental attendance, whether there is a relationship between age and the DMF-T index, and how high the risk was for participants to develop oral health problems. The study offered mobile dental services to people residing in nursing homes (NHG) and to community dwellers (CDG). Data was collected on demographics, medical history, presence of pain, ability to eat and oral health behaviour by means of a questionnaire. A clinical examination was performed and data on the oral status was collected. Statistical methods were: median tests, linear regressions and descriptive statistics. Uptake of the programme was low. 56 participants were examined. 47 participants (24 females, 23 males, average age 86.3 ± 7.36 years) resided in nursing home, nine participants (seven females, two males, average age 76 ± 12.8 years) were community dwellers. No significant differences were found between frequency of dental attendance and age (p = 0.35) or duration of stay in a nursing home (p = 0.55). The number of decayed teeth (p=0.005), missing teeth (p=0.01), and the DMF-T index (average in NHG = 26.5, CDG = 20.2, p < 0.001) increased, the number of filled teeth (p=0.02) decreased as age increased. Upon calculation of the 'Teamwerk-index', which takes into account oral health behaviour, dental caries, periodontal status, the majority of participants had a medium risk of developing oral health problems. Our pilot study in rural Switzerland provides first results of the oral health status in dependent elderly people. As people age, oral health deteriorates. More attention should be given in order to achieve better oral hygiene maintenance and more regular dental visits, to ensure a better oral health status in dependent elderly people.

Calcium release-activated calcium (CRAC) channels mediate the ß(2)-adrenergic regulation of Na,K-ATPase.

ß2-Adrenergic agonists have been shown to regulate Na,K-ATPase in the alveolar epithelium by recruiting Na,K-ATPase-containing vesicles to the plasma membrane of alveolar epithelial cells (AEC). Here, we provide evidence that ß2-agonists induce store-operated calcium entry (SOCE) in AECs. This calcium entry is necessary for ß2-agonist-induced recruitment of Na,K-ATPase to the plasma membrane of AECs. Specifically, we show that ß2-agonists induce SOCE via stromal interaction molecule 1 (STIM1)-associated calcium release-activated calcium (CRAC) channels. We also demonstrate that the magnitude of SOCE affects the abundance of Na,K-ATPase at the plasma membrane of AECs.

Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase A-CREB-TORC2 signaling cascade in human pluripotent embryonal NTera2 cells.

The triggering mechanisms underlying reactivation of human cytomegalovirus (HCMV) in latently infected persons are unclear. During latency, HCMV major immediate-early (MIE) gene expression breaks silence to initiate viral reactivation. Using quiescently HCMV-infected human pluripotent embryonal NTera2 cells (NT2) to model HCMV reactivation, we show that vasoactive intestinal peptide (VIP), an immunomodulatory neuropeptide, immediately and dose-dependently (1 to 500 nM) activates HCMV MIE gene expression. This response requires the MIE enhancer cyclic AMP response elements (CRE). VIP quickly elevates CREB Ser133 and ATF-1 Ser63 phosphorylation levels, although the CREB Ser133 phosphorylation level is substantial at baseline. VIP does not change the level of HCMV genomes in nuclei, Oct4 (pluripotent cell marker), or hDaxx (cellular repressor of HCMV gene expression). VIP-activated MIE gene expression is mediated by cellular protein kinase A (PKA), CREB, and TORC2. VIP induces PKA-dependent TORC2 Ser171 dephosphorylation and nuclear entry, which likely enables MIE gene activation, as TORC2 S171A (devoid of Ser171 phosphorylation) exhibits enhanced nuclear entry and desilences the MIE genes in the absence of VIP stimulation. In conclusion, VIP stimulation of the PKA-CREB-TORC2 signaling cascade activates HCMV CRE-dependent MIE gene expression in quiescently infected NT2 cells. We speculate that neurohormonal stimulation via this signaling cascade is a possible means for reversing HCMV silence in vivo.

Insights into the evolutionary history of the vertebrate zic3 locus from a teleost-specific zic6 gene in the zebrafish, Danio rerio.

The Zic gene family of zinc-finger transcription factors includes five orthologues, zic1-5, that are common to the Euteleostian vertebrates (fish, frogs, birds, and mammals). The Zic genes have been implicated as regulators of a number of critical developmental processes, including neurulation, neuronal differentiation, neural crest specification, the establishment of left-right asymmetry, and regulation of cell proliferation. The different Zic genes encode proteins that are expressed in broadly overlapping spatial domains, have conserved DNA-binding domains that recognize a common motif, are capable of physical interactions, and can co-regulate one another's transcription. Thus, the transcriptional regulation of individual proteins and their effects on downstream targets must be assessed within the context of co-expression with other family members. We describe a novel gene, zic6, that is specific to the teleost fishes and lacks the lateral and rostral expression domains typical of the other Zic family members. We present evidence that zic6 is an ancestral locus arising by chromosomal duplication early in the Euteleostomi that was subsequently lost in the terrestrial vertebrates.

Reversal of human cytomegalovirus major immediate-early enhancer/promoter silencing in quiescently infected cells via the cyclic AMP signaling pathway.

The human cytomegalovirus (HCMV) major immediate-early (MIE) enhancer contains five functional cyclic AMP (cAMP) response elements (CRE). Because the CRE in their native context do not contribute appreciably to MIE enhancer/promoter activity in lytically infected human fibroblasts and NTera2 (NT2)-derived neurons, we postulated that they might have a role in MIE enhancer/promoter reactivation in quiescently infected cells. Here, we show that stimulation of the cAMP signaling pathway by treatment with forskolin (FSK), an adenylyl cyclase activator, greatly alleviates MIE enhancer/promoter silencing in quiescently infected NT2 neuronal precursors. The effect is immediate, independent of de novo protein synthesis, associated with the phosphorylation of ATF-1 serine 63 and CREB serine 133, dependent on protein kinase A (PKA) and the enhancer's CRE, and linked to viral-lytic-cycle advancement. Coupling of FSK treatment with the inhibition of either histone deacetylases or protein synthesis synergistically activates MIE gene expression in a manner suggesting that MIE enhancer/promoter silencing is optimally relieved by an interplay of multiple regulatory mechanisms. In contrast, MIE enhancer/promoter silence is not overcome by stimulation of the gamma interferon (IFN-gamma) signaling pathway, despite the enhancer having two IFN-gamma-activated-site-like elements. We conclude that stimulation of the cAMP/PKA signaling pathway drives CRE-dependent MIE enhancer/promoter activation in quiescently infected cells, thus exposing a potential mode of regulation in HCMV reactivation.

Requirement of multiple cis-acting elements in the human cytomegalovirus major immediate-early distal enhancer for viral gene expression and replication.

We have shown previously that the human cytomegalovirus (HCMV) major immediate-early (MIE) distal enhancer is needed for MIE promoter-dependent transcription and viral replication at low multiplicities of infection (MOI). To understand how this region works, we constructed and analyzed a series of HCMVs with various distal enhancer mutations. We show that the distal enhancer is composed of at least two parts that function independently to coordinately activate MIE promoter-dependent transcription and viral replication. One such part is contained in a 47-bp segment that has consensus binding sites for CREB/ATF, SP1, and YY1. At low MOI, these working parts likely function in cis to directly activate MIE gene expression, thus allowing viral replication to ensue. Three findings support the view that these working parts are likely cis-acting elements. (i) Deletion of either part of a bisegmented distal enhancer only slightly alters MIE gene transcription and viral replication. (ii) Reversing the distal enhancer's orientation largely preserves MIE gene transcription and viral replication. (iii) Placement of stop codons at -300 or -345 in all reading frames does not impair MIE gene transcription and viral replication. Lastly, we show that these working parts are dispensable at high MOI, partly because of compensatory stimulation of MIE promoter activity and viral replication that is induced by a virion-associated component(s) present at a high viral particle/cell ratio. We conclude that the distal enhancer is a complex multicomponent cis-acting region that is required to augment both MIE promoter-dependent transcription and HCMV replication.