Reaching Out, Helping Hands Helping Minds: A Hawai'ian Model for Aiding Friends Coping With Dementia.

Reaching a certain age places one in a particular landscape in which dementia may be part of the scenery. This costly public health problem is personally devastating not only for dementia sufferers but for their surrounding interpersonal circle, which is not limited to immediate family. Indeed, friends often become the family you choose; their issues become, at some level, shared issues.

Mountains, Melting Pot, and Microcosm: Health Care Delay and Dengue/Zika Interplay on Hawaii Island.

Human history in the Hawaiian Islands offers a sobering study in the population dynamics of infectious disease. The indigenous population numbering an estimated half million people prior to Western contact in 1778 was reduced to less than 24,000 by 1920. Much of the decline occurred in the earliest decades after contact with Western diseases including measles, chicken pox, polio, tuberculosis, and venereal disease.

Keeping Abreast of Developments in the Cancer Wars: A View From the Front.

Cancer somehow lends itself to military analogies, perhaps because of its status as a threat to life itself. We've declared war on cancer over several decades, viewing cancer as a cell going rogue, dividing uncontrollably, and ultimately breaking through local boundaries to spread. Less well known, but critically relevant to the health care impact of questioning authority, is the war within the breast cancer management community, among those studying molecular and cellular targets in breast cancer biology and those managing the human targets that represent cancer's toll.

The glycan-specific sulfotransferase (R77W)GalNAc-4-ST1 putatively responsible for peeling skin syndrome has normal properties consistent with a simple sequence polymorphisim.

Expanded access to DNA sequencing now fosters ready detection of site-specific human genome alterations whose actual significance requires in-depth functional study to rule in or out disease-causing mutations. This is a particular concern for genomic sequence differences in glycosyltransferases, whose implications are often difficult to assess. A recent whole-exome sequencing study identifies (c.

Painful Reality: Inappropriate Provider Management of Pain as a Determinant of Health Care Avoidance.

Although pain is often characterized as a subjective, highly individualized phenomenon, in fact, numerous elements which are simply biological in nature underlie interpersonal differences in pain experience that influence the effectiveness of provider pain management. Elements acting at the level of tissues and cells include signal-transmitting molecules in pain pathways; elements acting at the level of the whole person comprise entire brain networks and anatomic elements fostering pain vulnerability. However, knowledge of these elements and translation of such knowledge into practical means for relieving patient pain is dismayingly sparse across the total spectrum of health care professionals.

Molecular profiling reveals diversity of stress signal transduction cascades in highly penetrant Alzheimer's disease human skin fibroblasts.

The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD) as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R) inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD.

Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation.

Increased Ser phosphorylation of tau microtubule-associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B2 receptor activation leads to selective Ser phosphorylation of tau in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in tau Ser phosphorylation reflects modification of the G protein-coupled BK B2 receptors themselves.