Communicative Predictors of a Shared Family Identity: Comparison of Grandchildren’s Perceptions of Family-of-Origin Grandparents and Stepgrandparents

From an intergroup perspective on family relationships, the current study investigates family-of-origin grandparents and stepgrandparents to determine similarities and differences in communication and relational dimensions. Participants (N = 88) completed questionnaires on family-of-origin grandparents and stepgrandparent relationships. From the perspective of young adult grandchildren, the research explores the role of supportive communication, reciprocal self-disclosure, nonaccommodative communication, and parental encouragement in predicting a sense of shared family identity with each grandparent type. Results are discussed in terms of implications for intergroup research, grandparent-grandchild communication, and stepfamily relationships

In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic reticulum (ER) folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S) with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT), V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50–200 mg/kg/d intraperitoneally) had minor effects on increasing GCase activity in brain and liver (1.2-fold). Diltiazem treatment (10 mg/kg/d) had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold) in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses

Fluorescence-Quenched Substrates for Live Cell Imaging of Human Glucocerebrosidase Activity

Deficiency of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) leads to abnormal accumulation of glucosyl ceramide in lysosomes and the development of the lysosomal storage disease known as Gaucher’s disease. More recently, mutations in the&nbsp;GBA1&nbsp;gene that encodes GCase have been uncovered as a major genetic risk factor for Parkinson’s disease (PD). Current therapeutic strategies to increase GCase activity in lysosomes involve enzyme replacement therapy (ERT) and molecular chaperone therapy. One challenge associated with developing and optimizing these therapies is the difficulty in determining levels of GCase activity present within the lysosomes of live cells. Indeed, visualizing the activity of endogenous levels of any glycoside hydrolases, including GCase, has proven problematic within live mammalian cells. Here we describe the successful modular design and synthesis of fluorescence-quenched substrates for GCase. The selection of a suitable fluorophore and quencher pair permits the generation of substrates that allow convenient time-dependent monitoring of endogenous GCase activity within cells as well as localization of activity within lysosomes. These efficiently quenched (∼99.9%) fluorescent substrates also permit assessment of GCase inhibition in live cells by either confocal microscopy or high content imaging. Such substrates should enable improved understanding of GCase in situ as well the optimization of small-molecule chaperones for this enzyme. These findings also suggest routes to generate fluorescence-quenched substrates for other mammalian glycoside hydrolases for use in live cell imaging

Predictors of nurturant parenting in teen mothers living in three generational families

Direct and indirect effects of grandparents on maternal nurturance in teen mothers (TM) living in three-generational families were explored with path analytic techniques in a sample of 107 working-class families. Perceived support from the teen's mother, grandparents' nurturance toward the baby, and the presence of the grandfather as a father figure in the home were hypothesized as increasing TM nurturance. TM nurturance was found to be positively predicted by grandparent nurturance and negatively predicted by TM perceived support from her mother. The strongest predictor of TM nurturance was grandfather nurturance toward the baby.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43953/1/10578_2006_Article_BF02353198.pd

Treatment algorithm for hyaluronic acid-related complication based on a systematic review of case reports, case series, and clinical experience

Study Design: Systematic review of hyaluronic acid (HA)-related complications.Objective: To systematically review all available literature including case reports and case series to identify a pattern forthe management of vascular compromise resulting in facial skin ischemia and ocular manifestations following HA injection.Methods: This review was based on a systematic search of 3 electronic databases PubMed, CINAHL, and Scopus for allavailable literature including case series and case reports from database inception to July 2019. Only a total of 52 casereports/series were eligible for review and included 107 patients.Results: The reviewed literature available was comprised from case reports/series and indicated that management ofboth impending skin necrosis and visual disturbances is variable with no repetitive pattern of action. Yet, successfulmanagement is time dependent as early interventions stopped progression and, in some cases, even reversed adverseeffects.Conclusion: Results found no universal protocol for achieving optimal results for adverse effects and as such, we presenta step-by-step algorithm for the emergency management of complications following HA injection