Understanding the Antecedents to Recruiting Foster Care and Adoptive Parents: A Comparison of White and African-American Families

In response to the “chronic shortage” of caregiving families, social marketing campaigns recruiting parents for foster care and special needs adoption are becoming increasingly important for child welfare agencies. This study attempts to fill the void in the understanding of the antecedents that impact the decision to enroll in programs designed to help children in need. The findings from a large-scale study show that knowledge of the process and select motives positively impact involvement likelihood. In contrast, psychological barriers, concern about the enrolment process, negative perceptions of children in need, and fear are detriments to consideration likelihood. African-American families were found to be more receptive and had fewer psychological concerns surrounding the decision process.     

Of men and mice: Human X-linked retinoschisis and fidelity in mouse modeling

X-linked Retinoschisis (XLRS) is an early-onset transretinal dystrophy, often with a prominent macular component, that affects males and generally spares heterozygous females because of X-linked recessive inheritance. It results from loss-of-function RS1 gene mutations on the X-chromosome. XLRS causes bilateral reduced acuities from young age, and on clinical exam and by ocular coherence tomography (OCT) the neurosensory retina shows foveo-macular cystic schisis cavities in the outer plexiform (OPL) and inner nuclear layers (INL). XLRS manifests between infancy and school-age with variable phenotypic presentation and without reliable genotype-phenotype correlations. INL disorganization disrupts synaptic signal transmission from photoreceptors to ON-bipolar cells, and this reduces the electroretinogram (ERG) bipolar b-wave disproportionately to photoreceptor a-wave changes. RS1 gene expression is localized mainly to photoreceptors and INL bipolar neurons, and RS1 protein is thought to play a critical cell adhesion role during normal retinal development and later for maintenance of retinal structure. Several independent XLRS mouse models with mutant RS1 were created that recapitulate features of human XLRS disease, with OPL-INL schisis cavities, early onset and variable phenotype across mutant models, and reduced ERG b-wave to a-wave amplitude ratio. The faithful phenotype of the XLRS mouse has assisted in delineating the disease pathophysiology. Delivery to XLRS mouse retina of an AAV8-RS1 construct under control of the RS1 promoter restores the retinal structure and synaptic function (with increase of b-wave amplitude). It also ameliorates the schisis-induced inflammatory microglia phenotype toward a state of immune quiescence. The results imply that XLRS gene therapy could yield therapeutic benefit to preserve morphological and functional retina particularly when intervention is conducted at earlier ages before retinal degeneration becomes irreversible. A phase I/IIa single-center, open-label, three-dose-escalation clinical trial reported a suitable safety and tolerability profile of intravitreally administered AAV8-RS1 gene replacement therapy for XLRS participants. Dose-related ocular inflammation occurred after dosing, but this resolved with topical and oral corticosteroids. Systemic antibodies against AAV8 increased in dose-dependent fashion, but no antibodies were observed against the RS1 protein. Retinal cavities closed transiently in one participant. Technological innovations in methods of gene delivery and strategies to further reduce immune responses are expected to enhance the therapeutic efficacy of the vector and ultimate success of a gene therapy approach.     

Efecto de los segmentos anulares intracorneales en la topografía corneal posterior en ojos con queratocono

PurposeTo analyze the changes in the anterior and posterior corneal surfaces measured with a Scheimpflug imaging device in keratoconus patients implanted with intracorneal ring segments and to correlate those changes with the visual outcomes.MethodsThis prospective interventional case series study included 92 eyes of 60 patients with keratoconus who underwent Kerarings (Mediphacos, Belo Horizonte, Brazil) intracorneal ring segments implantation. Keratometric (K) readings, corneal asphericity (Q value) and elevations of both anterior and posterior corneal surfaces were evaluated using a Scheimpflug imaging device preoperatively and at one, 3, 6 and 12 months after surgery.ResultsThe mean best corrected visual acuity (BCVA) improved from 0.61 to 0.19 logMAR at 12 months after surgery. Both anterior and posterior corneal surfaces showed significant flattening with statistically significant reduction of the mean anterior K reading by 3.39 D and the mean posterior K reading by 0.39 D (P < .001) at 12 months. Statistically significant change of the anterior Q to a less negative value (from ?1.05 to ?0.36) was observed (P < .001) with no significant change of the posterior Q value. Improvement of the anterior Q was significantly correlated to better postoperative BCVA (P = .03). Better postoperative BCVA significantly correlated to better preoperative BCVA, flatter preoperative anterior and posterior K, less prolate anterior Q value and lower anterior elevations.ConclusionsImplanted with intracorneal ring segments implantation has a significant flattening effect on both anterior and posterior corneal surfaces. Improvement of corneal asphericity is correlated to better visual outcome. Certain preoperative parameters were predictive factors of the postoperative visual improvement.     

Heavy–light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation

The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development of such pathologies and, in particular, production of autoantibodies of different specificities. The combination of deep-sequencing technology with functional studies of antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features in the repertoires of autoreactive B cells. Here, we have analyzed cross-combinations of the variable regions of human immunoglobulins against the myelin basic protein (MBP) previously selected from a multiple sclerosis (MS)-related scFv phage-display library. On the other hand, we have performed deep sequencing of the sublibraries of scFvs against MBP, Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1), and myelin oligodendrocyte glycoprotein (MOG). Bioinformatics analysis of sequencing data and surface plasmon resonance (SPR) studies have shown that it is the variable fragments of antibody heavy chains that mainly determine both the affinity of antibodies to the parent autoantigen and their cross-reactivity. It is suggested that LMP1-cross-reactive anti-myelin autoantibodies contain heavy chains encoded by certain germline gene segments, which may be a hallmark of the EBV-specific B cell subpopulation involved in MS triggering.     

The cystic fibrosis V232D mutation inhibits CFTR maturation by disrupting a hydrophobic pocket rather than formation of aberrant interhelical hydrogen bonds

Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis. Repair of CFTR mutants requires an understanding of the mechanisms of misfolding caused by processing mutations. Previous studies on helix-loop-helix fragments of the V232D processing mutation suggested that its mechanism was to lock transmembrane (TM) segments 3 and 4 together by a non-native hydrogen bond (Asp232(TM4)/Gln207(TM3)). Here, we performed mutational analysis to test for Asp232/Gln207 interactions in full-length CFTR. The rationale was that a V232N mutation should mimic V232D and a V232D/Q207A mutant should mature if the processing defect was caused by hydrogen bonds. We report that only Val232 mutations to charged amino acids severely blocked CFTR maturation. The V232N mutation did not mimic V232D as V232N showed 40% maturation compared to 2% for V232D. Mutation of Val232 to large nonpolar residues (Leu, Phe) had little effect. The Q207L mutation did not rescue V232D because Q207L showed about 50% maturation in the presence of corrector VX-809 while V232D/Q207A could no longer be rescued. These results suggest that V232D inhibits maturation by disrupting a hydrophobic pocket between TM segments rather than forming a non-native hydrogen bond. Disulfide cross-linking analysis of cysteines W356C(TM6) and W1145C(TM12) suggest that the V232D mutation inhibits maturation by trapping CFTR as a partially folded intermediate. Since correctors can efficiently rescue V232D CFTR, the results suggest that hydrophilic processing mutations facing a hydrophobic pocket are good candidates for rescue with pharmacological chaperones.     

Clinical effectiveness of intrastromal corneal ring segments among keratoconus patients

AIM: To evaluate the clinical effectiveness of intrastromal corneal ring segments (ICRS) among the patients suffering from keratoconus. METHODS: A retrospective and non-comparative interventional design had been utilized on the basis of postoperative follow-up among 56 keratoconus patients. Visual acuity was significantly assessed during complete ophthalmic examination of the patients. The femtosecond laser had been used to create the corneal tunnels in 15 eyes; whereas, the corneal tunnels were created in 72 eyes mechanically. RESULTS: The ranges and standard deviations had been used to obtain results. It had been revealed through ophthalmic assessment that the mean preoperative uncorrected visual acuity observed was 1.38±0.37 logarithm of Minimal Angle of Resolution. Moreover, a significant improvement was observed postoperatively in visual acuity by 0.58±0.32 during the 4th month. The improvement was also witnessed in the 16th month by 0.48±0.30. CONCLUSION: The implantation of ICRS is an efficient and effective surgical intervention for the treatment of keratoconus. Thus, identified intervention seems to be associated with appropriate visual outcomes and safety after the development of femtosecond as well as mechanical tunnels.     

Preparation and properties of biomedical segmented polyurethanes based on poly(ether ester) and uniform-size diurethane diisocyanates

This study describes the preparation and properties of a novel aliphatic cost-effective segmented polyurethanes (SPUs) based on poly(ether ester) (poly-(ε-caprolactone-co-l-lactide)-poly(ethylene glycol)-poly-(ε-caprolactone-co-l-lactide), PECLA) and uniform-size diurethane diisocyanates (HDI-BDO-HDI). PECLA was synthesized via bulk ring-opening polymerization with poly(ethylene glycol) (PEG) as an initiator and ε-caprolactone, l-lactide as monomers. By chain extension of PECLA diol with HDI-BDO-HDI, three SPUs with different hydrophilic segments content and hard segments content were obtained. The chemical structures of the chain extender, PECLA and SPUs were confirmed by ¹H NMR, ¹³C NMR, FT-IR, HR-TOF-MS and GPC. The influences of PEG content and uniform-size hard segments on in vitro degradability and mechanical properties of SPU films were researched. Similar thermostability observed in TGA curves of SPU films indicated that the hard segments and PEG content had little influence on the thermostability. The formation of microsphase-separated morphologies, which were demonstrated by the results of DSC and XRD, and physical-linking (H-bonds) network structures led to better mechanical properties of SPU films (ultimate stress: 23.1–17.9 MPa; elongation at break: 840–1130%). The results of water absorption and water contact angle showed that the bulk and surface hydrophilicity were closely related with the hydrophilic PEG content in SPU backbone. And the water absorption being less than 10 wt% indicated that the SPU films had low swelling property. In vitro hydrolytic degradation studies showed that the time of the SPU films becoming fragments was 34–19 days and the degradation rate increased with the increasing content of hydrophilic segments in SPUs, indicating that the degradation rate of SPU films could be controlled by adjusting PEG content. Cytotoxicity test of film extracts were conducted using L929 cells, and the relative growth rate exceeded 90% after incubation for 24, 48 and 72 h, showing excellent cytocompatibility. The acceptable mechanical properties, controllable biodegradability and excellent cytocompatibility of the polyurethanes can make them good candidates for further biomedical applications.