Exploring “Home” at an Assisted Living Facility: Looking through Residents’ Lenses with Photovoice

An increasing number of older adults are moving into assisted living facilities when living independently becomes difficult. These facilities afford older adults a home-like environment with opportunities for social activity and a minimal level of professional care, although relocation can negatively impact well-being. Because it is important to study home environments of aging adults, 10 residents of an assisted living facility were engaged in Photovoice to explore perceptions of the facility as home. Through photographic expression, residents identified environment enhancements for home at an assisted living facility. Findings of this study have implications for program planning at long-term care facilities

Generation and characterisation of gallium titanate surfaces through hydrothermal ion-exchange processes

Infection negation and biofilm prevention are necessary developments needed for implant materials. Furthermore, an increase in publications regarding gallium (Ga) as an antimicrobial ion has resulted in bacterial-inhibitory surfaces incorporating gallium as opposed to silver (Ag). The authors present the production of novel gallium titanate surfaces through hydrothermal ion-exchange reactions. Commercially-pure Ti (S0: Cp-Ti) was initially suspended in NaOH solutions to obtain sodium titanate (S1: Na2TiO3) layers ca. 0.5–1 μm in depth (2.4 at.% Na). Subsequent suspension in Ga(NO3)3 (S2: Ga2(TiO3)3), and post-heat-treatment at 700 °C (S3: Ga2(TiO3)3-HT), generated gallium titanate layers (9.4 and 4.1 at.% Ga, respectively). For the first time, RHEED analysis of gallium titanate layers was conducted and demonstrated titanate formation. Degradation studies in DMEM showed S2: Ga2(TiO3)3 released more Ga compared to S3: Ga2(TiO3)3-HT (2.76 vs. 0.68 ppm) over 168 h. Furthermore, deposition of Ca/P in a Ca:P ratio of 1.71 and 1.34, on S2: Ga2(TiO3)3 and S3: Ga2(TiO3)3-HT, respectively, over 168 h was seen. However, the study failed to replicate the antimicrobial effect presented by Yamaguchi who utilised A. baumannii, compared to S. aureus used presently. The authors feel a full antimicrobial study is required to assess gallium titanate as a candidate antimicrobial surface

Cortical and subcortical alterations associated with precision visuomotor behavior in individuals with autism spectrum disorder

In addition to core deficits in social-communication abilities and repetitive behaviors and interests, many 2 patients with autism spectrum disorder (ASD) experience developmental comorbidities, including 3 sensorimotor issues. Sensorimotor issues are common in ASD and associated with more severe clinical 4 symptoms. Importantly, sensorimotor behaviors are precisely quantifiable and highly translational, 5 offering promising targets for neurophysiological studies of ASD. We used functional MRI to identify 6 brain regions associated with sensorimotor behavior using a visually-guided precision gripping task in 7 individuals with ASD (N=20) and age-, IQ-, and handedness-matched controls (N=18). During 8 visuomotor behavior, individuals with ASD showed greater force variability than controls. BOLD signal 9 for multiple cortical and subcortical regions was associated with force variability, including motor and 10 premotor cortex, posterior parietal cortex, extrastriate cortex, putamen, and cerebellum. Activation in 11 right premotor cortex scaled with sensorimotor variability in controls, but not in ASD. Individuals with 12 ASD showed greater activation than controls in left putamen and left cerebellar lobule VIIb and activation 13 in these regions was associated with more severe clinically-rated symptoms of ASD. Together, these 14 results suggest that greater sensorimotor variability in ASD is associated with altered cortical-striatal 15 processes supporting action selection and cortical-cerebellar circuits involved in feedback-guided reactive 16 adjustments of motor output. Our findings also indicate that atypical organization of visuomotor cortical 17 circuits may result in heightened reliance on subcortical circuits typically dedicated to motor skill 18 acquisition. Overall, these results provide new evidence that sensorimotor alterations in ASD involve 19 aberrant cortical and subcortical organization that may contribute to key clinical issues in patients. 20 21 New and noteworthy: This is the first known study to examine functional brain activation during 22 precision visuomotor behavior in autism spectrum disorder (ASD). We replicate previous findings of 23 elevated force variability in ASD and find these deficits are associated with atypical function of ventral 24 premotor cortex, putamen, and posterolateral cerebellum, indicating cortical-striatal processes supporting 25 action selection and cortical-cerebellar circuits involved in feedback-guided reactive adjustments of motor 26 output may be key targets for understanding the neurobiology of ASD.NICHD 055751NIMH R01 12743-01NCATS TL1 TR002368,Kansas Center for Autism Research and Training (K-CART) Research Investment Council Strategic Initiative Gran

Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers

PURPOSE: Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. EXPERIMENTAL DESIGN: Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). RESULTS: Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. CONCLUSIONS: The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual

Developing alkaline titanate surfaces for medical applications

Improving the surface of medical implants by plasma spraying of a hydroxyapatite coating can be of critical importance to their longevity and the patient’s convalescence. However, residual stresses, cracking, undesired crystallisation and delamination of the coating compromise the implants lifetime. A promising alternative surface application is an alkali-chemical treatment to generate bioactive surfaces, such as sodium and calcium titanate and their derivatives. Such surfaces obviate the need for high temperatures and resulting micro-crack formation and potentially improve the bioactive and bone integration properties through their nanoporous structures. Also, metallic ions such as silver, gallium and copper can be substituted into the titanate structure with the potential to reduce or eliminate the infections. This review examines the formation and mechanisms of bioactive/antibacterial alkaline titanate surfaces, their successes and limitations, and explores the future development of implant interfaces via multifunctional titanate surfaces on Ti-based alloys and on alternative substrate materials

TGC repeat expansion in the TCF4 gene increases the risk of Fuchs' endothelial corneal dystrophy in Australian cases

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Fuchs’ endothelial corneal dystrophy (FECD) is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs) and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC), in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR) assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats) in TCF4 and advanced FECD (P = 2.58 × 10−22; OR = 15.66 (95% CI: 7.79–31.49)). Genotypic analysis showed that 51% of cases (97) compared to 5% of controls (9) were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population

The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence

MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in EμMyc mice occur in almost all cases of Burkitt lymphoma as well as in other B-cell lymphoproliferative disorders. Deregulated expression of MYC results in increased mTOR complex 1 (mTORC1) signaling. As tumors with mTORC1 activation are sensitive to mTORC1 inhibition, we used everolimus, a potent and specific mTORC1 inhibitor, to test the requirement for mTORC1 in the initiation and maintenance of EμMyc lymphoma. Everolimus selectively cleared premalignant B cells from the bone marrow and spleen, restored a normal pattern of B-cell differentiation, and strongly protected against lymphoma development. Established EμMyc lymphoma also regressed after everolimus therapy. Therapeutic response correlated with a cellular senescence phenotype and induction of p53 activity. Therefore, mTORC1-dependent evasion of senescence is critical for cellular transformation and tumor maintenance by MYC in B lymphocytes

Optical and microstructural characterization of Er3+^{3+} doped epitaxial cerium oxide on silicon

Rare-earth ion dopants in solid-state hosts are ideal candidates for quantum communication technologies such as quantum memory, due to the intrinsic spin-photon interface of the rare-earth ion combined with the integration methods available in the solid-state. Erbium-doped cerium oxide (Er:CeO$_2$) is a particularly promising platform for such a quantum memory, as it combines the telecom-wavelength (~1.5 $\mu$m) 4f-4f transition of erbium, a predicted long electron spin coherence time supported by CeO$_2$, and is also near lattice-matched to silicon for heteroepitaxial growth. In this work, we report on the epitaxial growth of Er:CeO$_2$ thin films on silicon using molecular beam epitaxy (MBE), with controlled erbium concentration down to 2 parts per million (ppm). We carry out a detailed microstructural study to verify the CeO$_2$ host structure, and characterize the spin and optical properties of the embedded Er$^{3+}$ ions. In the 2-3 ppm Er regime, we identify EPR linewidths of 245(1) MHz, optical inhomogeneous linewidths of 9.5(2) GHz, optical excited state lifetimes of 3.5(1) ms, and spectral diffusion-limited homogenoeus linewidths as narrow as 4.8(3) MHz in the as-grown material. We test annealing of the Er:CeO$_2$ films up to 900 deg C, which yields modest narrowing of the inhomogeneous linewidth by 20% and extension of the excited state lifetime by 40%. We have also studied the variation of the optical properties as a function of Er doping and find that the results are consistent with the trends expected from inter-dopant charge interactions.Comment: 15 pages, 6 figures (including supplemental information

Progress Toward a Human CD4/CCR5 Transgenic Rat Model for De Novo Infection by Human Immunodeficiency Virus Type 1

The development of a permissive small animal model for the study of human immunodeficiency virus type (HIV)-1 pathogenesis and the testing of antiviral strategies has been hampered by the inability of HIV-1 to infect primary rodent cells productively. In this study, we explored transgenic rats expressing the HIV-1 receptor complex as a susceptible host. Rats transgenic for human CD4 (hCD4) and the human chemokine receptor CCR5 (hCCR5) were generated that express the transgenes in CD4+ T lymphocytes, macrophages, and microglia. In ex vivo cultures, CD4+ T lymphocytes, macrophages, and microglia from hCD4/hCCR5 transgenic rats were highly susceptible to infection by HIV-1 R5 viruses leading to expression of abundant levels of early HIV-1 gene products comparable to those found in human reference cultures. Primary rat macrophages and microglia, but not lymphocytes, from double-transgenic rats could be productively infected by various recombinant and primary R5 strains of HIV-1. Moreover, after systemic challenge with HIV-1, lymphatic organs from hCD4/hCCR5 transgenic rats contained episomal 2–long terminal repeat (LTR) circles, integrated provirus, and early viral gene products, demonstrating susceptibility to HIV-1 in vivo. Transgenic rats also displayed a low-level plasma viremia early in infection. Thus, transgenic rats expressing the appropriate human receptor complex are promising candidates for a small animal model of HIV-1 infection