The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI. METHODS: With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions. DISCUSSION: The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Durable and scalable icephobic surfaces: similarities and distinctions from superhydrophobic surfaces.

Formation, adhesion, and accumulation of ice, snow, frost, glaze, rime, or their mixtures can cause severe problems for solar panels, wind turbines, aircrafts, heat pumps, power lines, telecommunication equipment, and submarines. These problems can decrease efficiency in power generation, increase energy consumption, result in mechanical and/or electrical failure, and generate safety hazards. To address these issues, the fundamentals of interfaces between liquids and surfaces at low temperatures have been extensively studied. This has lead to development of so called "icephobic" surfaces, which possess a number of overlapping, yet distinctive, characteristics from superhydrophobic surfaces. Less attention has been given to distinguishing differences between formation and adhesion of ice, snow, glaze, rime, and frost or to developing a clear definition for icephobic, or more correctly pagophobic, surfaces. In this review, we strive to clarify these differences and distinctions, while providing a comprehensive definition of icephobicity. We classify different canonical families of icephobic (pagophobic) surfaces providing a review of those with potential for scalable and robust development.

Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia.

Clinical studies report associations between cannabis use during adolescence and later onset of schizophrenia. We examined the causal relationship between developmental cannabinoid administration and long-term behavioral and molecular alterations in mice. Mice were administered either WIN 55,212-2 (WIN), a cannabinoid receptor 1 (CB1) agonist or vehicle (Veh) during adolescence (postnatal day 30-35) or early adulthood (postnatal day 63-70). Behavioral testing was conducted after postnatal day 120 followed by biochemical assays. Adolescent cannabinoid treatment (ACU) leads to deficits in prepulse inhibition and fear conditioning in adulthood. Metabotropic glutamate receptors type 5 (mGluR5), a receptor critically involved in fear conditioning and endocannabinoid (eCB) signaling, is significantly reduced in the ACU mouse hippocampus. Next, we examined expression profiles of genes involved in eCB synthesis (diacylglycerol lipase (DGL)) and uptake (monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH)) in the experimental mice. We find evidence of increased MGL and FAAH in ACU mice, reflecting increases in eCB uptake and degradation. These data suggest that administration of cannabinoids during adolescence leads to a behavioral phenotype associated with a rodent model of schizophrenia, as indexed by alterations in sensorimotor gating and hippocampal-dependent learning and memory deficits. Further, these deficits are associated with a reduction in hippocampal mGluR5 and a sustained change in eCB turnover, suggesting reduced eCB signaling in the ACU hippocampus. These data suggest that significant cannabis use during adolescence may be a contributory causal factor in the development of certain features of schizophrenia and may offer mGluR5 as a potential therapeutic target.

Perspectives on communication in labor and delivery: a focus group analysis.

OBJECTIVE: The objective of this study was to elicit and explore perceptions of barriers to optimal communication among clinicians on a labor and delivery unit, and to use this information to select and design approaches to improve communication. STUDY DESIGN: A qualitative research design using a focus group format was utilized. Attending and resident obstetricians and anesthesiologists, as well as staff nurses, pharmacists and unit secretaries participated in the focus groups, which were recorded and transcribed. Data were analyzed using a framework analysis approach. RESULT: In total, 18 focus groups with a total of 92 participants were conducted. Eight key themes emerged regarding specific barriers to effective communication among clinicians in the labor and delivery setting. The most prominent of these themes included issues with inter-departmental coordination, clinical accessibility (the ability to reach other clinicians), lack of a consistent approach for clinical documentation, and the involvement of multiple care providers. On the basis of these themes, multiple interventions were designed to enhance communication. CONCLUSION: Focus group methodology can be used to elicit a detailed description of communication practices of clinicians on a labor and delivery unit, permitting an exploration of specific barriers to communication and the identification of potential solutions to those barriers.

Stable biopassive insulation synthesized by initiated chemical vapor deposition of poly(1,3,5-trivinyltrimethylcyclotrisiloxane).

The permanent implantation of electronic probes capable of recording neural activity patterns requires long-term electrical insulation of these devices by biopassive coatings. In this work, the material properties and neural cell compatibility of a novel polymeric material, poly(trivinyltrimethylcyclotrisiloxane) (poly(V3D3)), are demonstrated to be suitable for application as permanently bioimplanted electrically insulating films. The poly(V3D3) polymeric films are synthesized by initiated chemical vapor deposition (iCVD), allowing for conformal and flexible encapsulation of fine wires. The poly(V3D3) also exhibits high adhesive strength to silicon substrates, a common material of manufacture for neural probes. The poly(V3D3) films were found to be insoluble in both polar and nonpolar solvents, consistent with their highly cross-linked structure. The films are pinhole-free and extremely smooth, having a root-mean-square (rms) roughness of 0.4 nm. The material possesses a bulk resistivity of 4 x 1015 Ohm-cm exceeding that of Parylene-C, the material currently used to insulate neurally implanted devices. The iCVD poly(V3D3) films are hydrolytically stable and are demonstrated to maintain their electrical properties under physiological soak conditions, and constant electrical bias, for more than 2 years. In addition, biocompatibility studies with PC12 neurons demonstrate that this material is noncytotoxic and does not influence cell proliferation.

Initiated chemical vapor deposition of antimicrobial polymer coatings.

The vapor phase deposition of polymeric antimicrobial coatings is reported. Initiated chemical vapor deposition (iCVD), a solventless low-temperature process, is used to form thin films of polymers on fragile substrates. For this work, finished nylon fabric is coated by iCVD with no affect on the color or feel of the fabric. Infrared characterization confirms the polymer structure. Coatings of poly(dimethylaminomethyl styrene) of up to 540 microg/cm2 were deposited on the fabric. The antimicrobial properties were tested using standard method ASTM E2149-01. A coating of 40 microg/cm2 of fabric was found to be very effective against gram-negative Escherichia coli, with over a 99.99%, or 4 log, kill in just 2 min continuing to over a 99.9999%, or 6 log, reduction in viable bacteria in 60 min. A coating of 120 microg/cm2 was most effective against the gram-positive Bacillus subtilis. Further tests confirmed that the iCVD polymer did not leach off the fabric.

Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P.

OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.

A provisional database for the silicon content of foods in the United Kingdom.

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma-optical emission spectrometry following microwave-assisted digestion with nitric acid and H(2)O(2). The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.

Sequential magnetic resonance monitoring of pulmonary flow with endovascular stents placed across the pulmonary valve in growing Swine.

BACKGROUND: Patients with endovascular stent implantation for the treatment of right ventricular outflow tract obstruction are often left with incomplete relief of the obstruction and significant pulmonary regurgitation. A noninvasive and reproducible method for monitoring such patients is desirable. MRI in the presence of a stent, however, has to overcome the problem of potential metallic artifacts. METHODS AND RESULTS: Under x-ray fluoroscopic guidance, endovascular nitinol stents were placed across the pulmonary valve in 6 young pigs to induce pulmonary regurgitation. Five additional pigs served as controls. Initial MRI was performed after 2 days (13.5+/-1.8 kg) and follow-up after 3 months (32+/-2.9 kg). Pulmonary flow volumes and regurgitant fraction were quantified by velocity-encoded cine (VEC) MRI through (VEC-TS) and distal to (VEC-DS) the stent. VEC-TS was compared with VEC-DS and volumetric measurements of left and right ventricular stroke volumes provided by cine MRI ("gold standard"). Antegrade and retrograde pulmonary flow volumes by VEC-TS were slightly but significantly less than those with VEC-DS and cine MRI. Excellent correlations (r>0.97) for phasic pulmonary flow volumes as measured by VEC-TS and VEC-DS were shown. Pulmonary regurgitant fraction increased from 32.8+/-15% to 49.6+/-17% (P<0.05) over the course of 3 months with VEC-TS. CONCLUSIONS: MRI demonstrates the progression of pulmonary regurgitation in growing swine. VEC MRI has the ability to quantify pulmonary blood flow inside the lumen of nitinol stents. MRI appears to be ideally suited for monitoring patients with endovascular nitinol stents in the pulmonary artery or pulmonary valve position.

Maternal attachment representations, maternal sensitivity, and the infant-mother attachment relationship.

The role of maternal sensitivity as a mediator accounting for the robust association between maternal attachment representations and the quality of the infant-mother attachment relationship was examined. Sixty mother-infant dyads were observed at home and in the Strange Situation at 13 months, and mothers participated in the Adult Attachment Interview (AAI) within the next 6 months. A strong association was found between AAI and Strange Situation classifications, and autonomous mothers were more sensitive at home than were nonautonomous mothers. Mothers in secure relationships were more sensitive at home than mothers in nonsecure relationships. Likewise, infants in secure relationships were more secure as assessed by the Waters' Attachment Q sort than infants in nonsecure relationships. A test of the mediational model revealed that maternal sensitivity accounted for 17% of the relation between AAI and Strange Situation classifications.

Clinical comparison of St. Jude and porcine mitral valve prostheses.

One hundred and six consecutive patients who had mitral valve replacement with either a St. Jude or porcine heterograft prosthesis were prospectively studied. The 2 groups are similar with respect to 67 clinical and operative factors and allow comparison of valve performance as an independent variable. Total follow-up is 3,312 patient-months (mean 36 months, range 2-57 months, 94% complete). There are no statistical differences in symptomatic improvement or mortality by life table analysis. Valve-related complications expressed as percent per patient-year are: reoperation: 1.8 St. Jude and 3.8 porcine; endocarditis: 1.2 and 1.9; regurgitant murmur: 2.3 and 1.9; hemolysis: 1.8 and 0.0; late thromboembolism: 1.8 and 1.0; hemorrhage: 2.9 and 2.9; and valve failure: 0.0 and 1.0. There were no significant differences found. Actuarial survival at 3 years was 78% in St. Jude and 81% in porcine patients. Forty-six percent of patients with St. Jude valves and 55% of patients with porcine valves were alive and free of all complications at latest follow-up. The clinical performance of St. Jude and porcine mitral valves are similar over this period of intermediate follow-up.

Geometrical aspects of sorted patterned ground in recurrently frozen soil.

A model for sorted patterned ground shows that some types arise from density-driven Rayleigh free convection that occurs during thawing of water-saturated recurrently frozen soils. The regularly spaced convection cells result in an uneven melting of the underlying ice front. Frost action causes stones to be upthrusted and to form in a pattern on the ground surface that mirrors the corrugation in the underlying ice front. The implications of the water circulation direction in the cells on the sorting process are considered.

Organization of rabbit immunoglobulin genes. I. Structure and multiplicity of germ-line VH genes.

Two rabbit germ-line VH gene segments have been isolated from a recombinant phage DNA library. Nucleotide sequence analysis indicates that both of the genes share structural and regulatory features common to mouse and human VH genes, although one appears to be a pseudogene. Comparison of the protein sequences encoded by these genes to the protein sequences of rabbit immunoglobulin V regions indicates that both genes encode VH a-negative-like molecules. Quantitative genomic blot analysis with a VH probe capable of recognizing most, if not all, germ-line VH genes indicates that there are approximately 100 VH genes in the haploid genome of rabbits. The average spacing between the germ-line VH genes was determined to be approximately 6 kb. The molecular basis for the allelic inheritance of rabbit VH allotypes is discussed in view of the structural organization of germ-line VH genes.

Familial IgA nephropathy. Evidence of an inherited mechanism of disease.

The evaluation of familial glomerulonephritis in patients with IgA nephropathy who were from central and eastern Kentucky resulted in the discovery of potentially related pedigrees containing 14 patients. An additional 17 members of the pedigrees had clinical glomerulonephritis, and 6 had "chronic nephritis" noted on their death certificates. Six patients with IgA nephropathy had a common ancestor. In addition, both parents of six patients with the disease came from families with other cases of IgA nephropathy. No single HLA haplotype or antigen was found in all the patients with IgA nephropathy. Our data on these pedigrees strongly support an inherited mechanism in the pathogenesis of IgA nephropathy in some patients.

Differences in T15 expression of primary and secondary anti-PC responses with T cells from T15+ and T15- donors.

The expression of T15 idiotype dominance with T cells from T15- mice was investigated. It was found that T15 dominance in the T-dependent response to phosphorylcholine (PC) could be generated by unprimed BALB/c B cells with T cells from T15+ and xid T15- mice. T15 dominance was also expressed when T15 neonatally suppressed BALB/c were used as T cell donors. With PC-primed B cells, however, T15 dominance was not established until 3 wk after adoptive co-transfer with T helper cells from xid NBF1 mice. To further study the different efficiencies of T cells for T15 dominance, limiting dilution analysis was performed. The data demonstrate that T15-specific T cell populations in BALB/c mice and NBF1 male mice differ in their precursor frequencies. In BALB/c mice, a frequent set of T15/M167-recognizing T helper cells is present; a corresponding frequent set of cells is absent in NBF1 males. This difference is likely to be one of the reasons why dominance is not immediately established after transfer of T cells from xid mice.