Autophagy and phagocytosis converge for better vision

The retinal pigment epithelium (RPE) is a single layer of nonregenerating cells essential to homeostasis in the retina and the preservation of vision. While the RPE perform a number of important functions, 2 essential processes are phagocytosis, which removes the most distal tips of the photoreceptors to support disk renewal, and the visual cycle, which maintains the supply of chromophore for regeneration of photo-bleached visual pigments. We recently reported that these processes are linked by a noncanonical form of autophagy termed LC3-associated phagocytosis (LAP) in which components of the autophagy pathway are co-opted by phagocytosis to recover vitamin A in support of optimal vision. Here we summarize these findings

A Study of Juvenile Waiver

In a footnote to its recent decision, In re Dennis M, the California Supreme Court recommended, that juvenile officers and police be prepared to give their compulsory Miranda warning in terms that reflect the language and experience of today’s juveniles. This language stimulated our attempt to draft and test the efficacy of a simplified Miranda warning, potentially more understandable to juveniles, and consistent with juvenile law requirements. The purpose of this article is to relate the findings of an empirical study which sought to answer two questions: 1) should the Miranda warning be revised for the juvenile offender; and 2) does a minor have the capacity knowingly and intelligently to waive his Miranda rights

Correlation Between Caregiver Reports of Physical Function and Performance-based Measures in a Cohort of Older Adults With Alzheimer Disease

The objectives of this report are to determine the association between performance-based measures of physical function with caregiver reports of physical function in older adults with Alzheimer disease (AD) and to examine whether those associations vary by the level of patients' cognitive functioning. Subjects included 180 patient-caregiver dyads who are enrolled in a clinical trial testing the impact of an occupational therapy intervention plus guideline-level care to delay functional decline among older adults with AD. The primary caregiver-reported measure is the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory (ADCS-ADL). Performance-based measures include the Short Physical Performance Battery and the Short Portable Sarcopenia Measure. Analysis of covariance (ANCOVA) models were used to determine the associations of each physical performance measure with ADCS-ADL, adjusting for cognition function and other covariates. We found significant correlations between caregiver reports and observed performance-based measures across all levels of cognitive function, with patients in the lowest cognitive group showing the highest correlation. These findings support the use of proxy reports to assess physical function among older adults with AD

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle

AbstractPKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD

Fostering Equity and Diversity in the Nova Scotia Legal Profession

The Province of Nova Scotia has, for many years, attempted, through a variety of means, to address issues of diversity and affirmative action. However, despite the lessons of history there are still those who question the need for programs and policies that promote, encourage and enforce equality. Even though significant advances have been made on many fronts Nova Scotia continues to struggle with issues of inequality. As with many problems faced by society acknowledging the existence of the problem is the first step towards developing solutions

Targeting Functional Decline: Results from the Alzheimer’s Disease Multiple Intervention Trial

Background Alzheimer’s disease (AD) results in progressive functional decline leading to loss of independence Objective To determine whether collaborative care plus two years of home-based occupational therapy delays functional decline Design Randomized controlled clinical trial Setting Urban public health system Patients 180 community-dwelling subjects who were diagnosed with AD and their informal caregivers Interventions All subjects received collaborative care for dementia. Intervention patients also received in-home occupational therapy delivered in 24 sessions over 2 years. Measurements The primary outcome measures was the Alzheimer’s Disease Cooperative Studies Group Activities of Daily Living Scale (ADCS ADL); performance based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM) Results At baseline, there were no significant between group differences in clinical characteristics; the mean MMSE for both groups was 19 (SD=7). The intervention group received a median of 18 home visits from the study occupational therapists. Both groups declined in ADCS ADL scores over 24 months. At the primary endpoint of 24 months, there were no between group differences in ADCS ADL scores (mean difference 2.34, 95% CI −5.27, 9.96). We were also unable to definitively demonstrate between-group differences in the mean SPPB or SPSM. Limitations The results of this trial are indeterminate and do not rule out potentially clinically important effects of the intervention. Conclusions We were unable to definitively demonstrate whether the addition of two years of in-home occupational therapy to a collaborative care management model slows the rate of functional decline among persons with AD. This trial underscores the burden undertaken by family caregivers as they provide care for persons with AD and the difficulty in slowing functional decline

Decomposition of the tensor product of two Hilbert modules

Given a pair of positive real numbers $\alpha, \beta$ and a sesqui-analytic function $K$ on a bounded domain $\Omega \subset \mathbb C^m$, in this paper, we investigate the properties of the sesqui-analytic function $\mathbb K^{(\alpha, \beta)}:= K^{\alpha+\beta}\big(\partial_i\bar{\partial}_j\log K\big )_{i,j=1}^ m,$ taking values in $m\times m$ matrices. One of the key findings is that $\mathbb K^{(\alpha, \beta)}$ is non-negative definite whenever $K^\alpha$ and $K^\beta$ are non-negative definite. In this case, a realization of the Hilbert module determined by the kernel $\mathbb K^{(\alpha,\beta)}$ is obtained. Let $\mathcal M_i$, $i=1,2,$ be two Hilbert modules over the polynomial ring $\mathbb C[z_1, \ldots, z_m]$. Then $\mathbb C[z_1, \ldots, z_{2m}]$ acts naturally on the tensor product $\mathcal M_1\otimes \mathcal M_2$. The restriction of this action to the polynomial ring $\mathbb C[z_1, \ldots, z_m]$ obtained using the restriction map $p \mapsto p_{|\Delta}$ leads to a natural decomposition of the tensor product $\mathcal M_1\otimes \mathcal M_2$, which is investigated. Two of the initial pieces in this decomposition are identified