Functional Outcomes After Hip Fracture in Independent Community-Dwelling Patients.

OBJECTIVES: To determine predictors of new activities of daily living (ADLs) disability and worsened mobility disability and secondarily increased daily care hours received, in previously independent hip fracture patients. DESIGN: Retrospective cohort study. SETTING: Academic hospital with ambulatory follow-up. PARTICIPANTS: Community-dwelling adults 65 years or older independent in ADLs undergoing hip fracture surgery in 2015 (n = 184). MEASUREMENTS: Baseline, 3- and 6-month ADLs, mobility, and daily care hours received were ascertained by telephone survey and chart review. Comorbidities, medications, and characteristics of hospitalization were extracted from patient charts. Models for each outcome used logistic regression with a backward elimination strategy, adjusting a priori for age, sex, and race. RESULTS: Predictors of new ADL disability at 3 months were dementia (odds ratio [OR] = 11.81; P = .001) and in-hospital delirium (OR = 4.20; P = .002), and at 6 months were age (OR = 1.04; P = .014), dementia (OR = 9.91; P = .001), in-hospital delirium (OR = 3.00; P = .031) and preadmission opiates (OR = 7.72; P = .003). Predictors of worsened mobility at 3 months were in-hospital delirium (OR = 4.48; P = .001) and number of medications (OR = 1.13; P = .003), and at 6 months were age (OR = 1.06; P = .001), preadmission opiates (OR = 7.23; P = .005), in-hospital delirium (OR = 3.10; P = .019), and number of medications (OR = 1.13; P = .013). Predictors of increased daily care hours received at 3 and 6 months were age (3 months: OR = 1.07; P = .014; 6 months: OR = 1.06; P = .017) and number of medications (3 months: OR = 1.13; P = .004; 6 months: OR = 1.22; P = .013). The proportion of patients with ADL disability and care hours received did not change from 3 to 6 months, yet there were significant improvements in mobility. CONCLUSION: Age, dementia, in-hospital delirium, number of medications, and preadmission opiate use were predictors of poor outcomes in independent older adults following hip fracture. Further investigation is needed to identify factors associated with improved mobility measures from 3 to 6 months to ultimately optimize recovery.

Select 3',5'-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain.

3',5'-cyclic nucleotide phosphodiesterases (PDEs) are the only known enzymes to compartmentalize cAMP and cGMP, yet little is known about how PDEs are dynamically regulated across the lifespan. We mapped mRNA expression of all 21 PDE isoforms in the adult rat and mouse central nervous system (CNS) using quantitative polymerase chain reaction (qPCR) and in situ hybridization to assess conservation across species. We also compared PDE mRNA and protein in the brains of old (26 months) versus young (5 months) Sprague-Dawley rats, with select experiments replicated in old (9 months) versus young (2 months) BALB/cJ mice. We show that each PDE isoform exhibits a unique expression pattern across the brain that is highly conserved between rats, mice, and humans. PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A showed an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). In contrast, mRNA expression of PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A did not change with age. Age-related increases in PDE11A4, PDE8A3, PDE8A4/5, and PDE1C1 protein expression were confirmed in hippocampus of old versus young rodents, as were age-related increases in PDE8A3 protein expression in the striatum. Age-related changes in PDE expression appear to have functional consequences as, relative to young rats, the hippocampi of old rats demonstrated strikingly decreased phosphorylation of GluR1, CaMKIIα, and CaMKIIß, decreased expression of the transmembrane AMPA regulatory proteins γ2 (a.k.a. stargazin) and γ8, and increased trimethylation of H3K27. Interestingly, expression of PDE11A4, PDE8A4/5, PDE8A3, and PDE1C1 correlate with these functional endpoints in young but not old rats, suggesting that aging is not only associated with a change in PDE expression but also a change in PDE compartmentalization.

What's new in prognostication of melanoma in the dermatopathology laboratory?

With the advent of genetic and epigenetic research, molecular techniques could someday be used to discriminate nevus from melanoma so that ambiguous melanocytic lesions could be more accurately classified or that prognostication could be improved in melanoma patients. That promised day might be closer than realized. The last 20 years of research in cytogenetic and genetic alterations in melanoma have culminated in defined chromosomal lesions discriminating benign from malignant melanocytic tumors. Exploiting these differences, fluorescence in situ hybridization (FISH) can reproducibly discriminate unequivocal melanomas from melanocytic nevi with high sensitivity and specificity. The discriminating power of FISH in melanocytic tumors with ambiguous histopathology is questionable, however, because there is no standard definition of "malignancy." Additional FISH studies on ambiguous cases are needed through international collaborations where large collections of such cases are shared and the "proof of malignancy" is established by adequate clinical follow-up. This contribution reviews the diagnostic utility of DNA-based FISH technology as it compares the diagnostic accuracy in melanocytic tumors with unambiguous vs ambiguous histopathology. The melanoma epigenome is further characterized through research into various activities of small interfering RNAs, such as microRNAs, providing the pathway for the application of microRNA-based strategies that could be the basis for future diagnostic biomarkers and molecular therapies in melanoma.

Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's disease.

Inhibition of phosphodiesterase 10A (PDE10A) promotes cyclic nucleotide signaling, increases striatal activation, and decreases behavioral activity. Enhanced cyclic nucleotide signaling is a well established route to producing changes in gene expression. We hypothesized that chronic suppression of PDE10A activity would have significant effects on gene expression in the striatum. A comparison of the expression profile of PDE10A knockout (KO) mice and wild-type mice after chronic PDE10A inhibition revealed altered expression of 19 overlapping genes with few significant changes outside the striatum or after administration of a PDE10A inhibitor to KO animals. Chronic inhibition of PDE10A produced up-regulation of mRNAs encoding genes that included prodynorphin, synaptotagmin10, phosphodiesterase 1C, glutamate decarboxylase 1, and diacylglycerol O-acyltransferase and a down-regulation of mRNAs encoding choline acetyltransferase and Kv1.6, suggesting long-term suppression of the PDE10A enzyme is consistent with altered striatal excitability and potential utility as a antipsychotic therapy. In addition, up-regulation of mRNAs encoding histone 3 (H3) and down-regulation of histone deacetylase 4, follistatin, and claspin mRNAs suggests activation of molecular cascades capable of neuroprotection. We used lentiviral delivery of cAMP response element (CRE)-luciferase reporter constructs into the striatum and live animal imaging of 2-{4-[-pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid (TP-10)-induced luciferase activity to further demonstrate PDE10 inhibition results in CRE-mediated transcription. Consistent with potential neuroprotective cascades, we also demonstrate phosphorylation of mitogen- and stress-activated kinase 1 and H3 in vivo after TP-10 treatment. The observed changes in signaling and gene expression are predicted to provide neuroprotective effects in models of Huntington's disease.

The North American Menopause Society: from abstract to publication.

OBJECTIVE: The North American Menopause Society (NAMS) provides a forum through which researchers can present scientific abstracts. After presenting an abstract, the goal is to publish the research as a full-length article. The objective for this study was to determine the publication rate of abstracts presented at NAMS meetings. DESIGN: The PubMed database was searched for full-length, peer-reviewed publications, corresponding to the abstracts presented at the 1999 to 2003 NAMS meetings. When a full-length article was found, the title, authors, date of publication, and the journal were collected. RESULTS: Of the 661 abstracts presented at the five consecutive annual meetings, 253 (38.3%) have been published in peer-reviewed journals. The average time to publication was 2.0 +/- 1.5 years. The average time to publication for oral presentations was 1.7 +/- 1.3 years, and that for poster presentations was 2.0 +/- 1.5 years (P = 0.241). The publication rate of oral presentations was significantly greater than that of poster presentations (57.7% vs 36.5%; P < 0.003). Manuscripts were published in a total of 97 journals, with four (Menopause, Journal of Clinical Endocrinology and Metabolism, Climacteric, and Maturitas) accounting for 38.3% of the publications. CONCLUSIONS: The percentage of abstracts published by NAMS is within the range and within a similar time frame compared with other scientific meetings. Oral presentations are more likely to be rapidly published and may therefore be of higher interest and clinical relevance along with sound methodology and results. Menopause contained the most manuscripts, demonstrating a possible preference of submission to the Society's journal.