Molecularly engineered electroplex emission for an efficient near-infrared light-emitting electrochemical cell (NIR-LEC)

Electroplex emission is rarely seen in ruthenium polypyridyl complexes, and there have been no reports from light-emitting electrochemical cells (LECs) to date. Here, for the first time, near-infrared (NIR) emission via the electroplex mechanism in a LEC based on a new blend of ruthenium polypyridyl complexes is described. The key factor in the design of the new complexes is the 0.4 V decrease in the oxidation half-potential of Ru(ii)/Ru(iii) in [Ru(DPCO)(bpy)₂]ClO₄ (DPCO = diphenylcarbazone, bpy = 2,2 bipyridine), which is about one-third of the value for benchmark [Ru(bpy)₃](ClO₄)₂, as well as the long lifetime of excited states of 350–450 ns. The LEC based on the new blend with a narrow band gap (≈1.0 eV) of a Ru(DPCO) complex and Ru(bpy)₃²⁺ can produce an electroluminescence spectrum centred at about 700 nm, which extends to the NIR region with a high external quantum efficiency (EQE) of 0.93% at a very low turn-on voltage of 2.6 V. In particular, the very simple LEC structure was constructed from indium tin oxide (anode)/Ru(DPCO):Ru(bpy)₃²⁺/Ga:In (cathode), avoiding any polymer or transporting materials, as well as replacing Al or Au by a molten alloy cathode. This system has promising applications in the production of LECs via microcontact or inkjet printing.

Electroplex emission is rarely seen in ruthenium polypyridyl complexes, and there have been no reports from light-emitting electrochemical cells (LECs) to date. Here, near-infrared (NIR) emission via the electroplex mechanism in a LEC was reported.     

Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions

Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient.     

Chronic high-inspired CO2 decreases excitability of mouse hippocampal neurons

To examine the effect of chronically elevated CO(2) on excitability and function of neurons, we exposed mice to 8 and 12% CO(2) for 4 wk (starting at 2 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Chronic CO(2)-treated neurons (CC) had a similar input resistance (R(m)) and resting membrane potential (V(m)) as control (CON). Although treatment with 8% CO(2) did not change the rheobase (64 +/- 11 pA, n = 9 vs. 47 +/- 12 pA, n = 8 for CC 8% vs. CON; means +/- SE), 12% CO(2) treatment increased it significantly (73 +/- 8 pA, n = 9, P = 0.05). Furthermore, the 12% CO(2) but not the 8% CO(2) treatment decreased the Na(+) channel current density (244 +/- 36 pA/pF, n = 17, vs. 436 +/- 56 pA/pF, n = 18, for CC vs. CON, P = 0.005). Recovery from inactivation was also lowered by 12% but not 8% CO(2). Other gating properties of Na(+) current, such as voltage-conductance curve, steady-state inactivation, and time constant for deactivation, were not modified by either treatment. Western blot analysis showed that the expression of Na(+) channel types I-III was not changed by 8% CO(2) treatment, but their expression was significantly decreased by 20-30% (P = 0.03) by the 12% treatment. We conclude from these data and others that neuronal excitability and Na(+) channel expression depend on the duration and level of CO(2) exposure and maturational changes occur in early life regarding neuronal responsiveness to CO(2).     

Tau Phosphorylation is Impacted by Rare <Emphasis Type="Italic">AKAP9</Emphasis> Mutations Associated with Alzheimer Disease in African Americans

We studied the effect of two rare mutations (rs144662445 and rs149979685) in the A-kinase anchoring protein 9 (AKAP9) gene, previously associated with Alzheimer disease (AD) in African Americans (AA), on post-translational modifications of AD-related pathogenic molecules, amyloid precursor protein (APP) and microtubule-associated protein Tau using lymphoblastoid cell lines (LCLs) from 11 AA subjects with at least one AKAP9 mutation and 17 AA subjects lacking these mutations. LCLs were transduced by viral vectors expressing causative AD mutations in APP or human full-length wild type Tau. Cell lysates were analyzed for total APP, Aβ₄₀, and total and T181 phospho-Tau (pTau). AKAP9 mutations had no effect on Aβ₄₀/APP, but significantly increased pTau/Tau ratio in LCLs treated with phosphodiesterase-4 inhibitor rolipram, which activates protein kinase A. Proteomic analysis of Tau interactome revealed enrichment of RNA binding proteins and decrease of proteasomal molecules in rolipram-treated cells with AKAP9 mutations. This study shows the impact of rare functional AKAP9 mutations on Tau, a central mechanism of AD pathogenesis, in LCLs derived from AD and control subjects.     

Determinants and Outcomes of Hospice Utilization Among Patients with Advance-Staged Hepatocellular Carcinoma in a Veteran Affairs Population

Background

Hospice provides integrative palliative care for advance-staged hepatocellular carcinoma (HCC) patients, but hospice utilization in HCC patients in the USA is not clearly understood.

Aims

We examined hospice use and subsequent clinical course in advance-staged HCC patients.

Methods

We conducted a retrospective study on a national, Veterans Affairs cohort with stage C or D HCC. We evaluated demographics, clinical factors, treatment, and clinical course in relation to hospice use.

Results

We identified 814 patients with advanced HCC, of whom 597 (73.3%) used hospice. Oncologist management consistently predicted hospice use, irrespective of HCC treatment [no treatment: OR 2.25 (1.18–4.3), treatment: OR 1.80 (1.10–2.95)]. Among patients who received HCC treatment, hospice users were less likely to have insurance beyond VA benefits (47.2 vs. 60.0%, p = 0.01). Among patients without HCC treatment, hospice users were older (62.2 [17.2] vs. 60.2 [14.0] years, p = 0.05), white (62.1 vs. 52.9%, p = 0.01), resided in the Southern USA (39.5 vs. 31.8%, p = 0.05), and had a performance score ≥ 3 (41.9 vs. 31.8%, p = 0.01). The median time from hospice entry to death or end of study was 1.05 [2.96] months for stage C and 0.53 [1.18] months for stage D patients.

Conclusions

26.7% advance-staged HCC patients never entered hospice, representing potential missed opportunities for improving end-of-life care. Age, race, location, performance, insurance, and managing specialty can predict hospice use. Differences in managing specialty and short-term hospice use suggest that interventions to optimize early palliative care are necessary.