Health-related quality of life in children with craniofacial anomalies

The purpose of this study was to examine parents' perceptions of the health and health-related quality of life in a series of children and adolescents with cleft and other craniofacial anomalies. The subjects for this prospective study were a consecutive series of 54 children and adolescents presenting to an outpatient craniofacial anomalies surgery clinic, ages 5 to 18 years (mean, 8.9 +/- 4.2 years), 50 percent with cleft lip and/or palate, 9 percent synostotic (two coronal, two bicoronal, and one sagittal), 17 percent syndromic (two Apert, one Crouzon, one Noonan, two Goldenhar, two Smith-Lemli-Opitz, and one brachio-oto-renal), and 24 percent with other diagnoses. Subjects were divided into two groups, those with primary cleft lip and/or palate and those with other craniofacial anomalies. Health and health-related quality of life were assessed with the Child Health Questionnaire version PF28, a reliable and valid 28-Likert-item questionnaire completed by parents and yielding physical and psychosocial status scale scores. Physical and psychosocial scale scores largely fell within normal limits for the subset of children with cleft lip and/or palate. There were significant group differences in parents' ratings of global health status, with greater health concerns noted in the non-cleft lip and/or palate group. There were no significant associations between either age or sex and physical or psychosocial health. Physical health, behavior, and psychological status were highly correlated. Using a health status and quality-of-life assessment instrument, findings indicate perceived health differences between groups with and without primary cleft lip and/or palate. In contrast to normative data with the Child Health Questionnaire, findings suggest that there is a significant association between perceived physical health and psychosocial adjustment in the population of children with craniofacial anomalies. The significant perceived health needs of the non-cleft lip and/or palate group and the association between physical health and psychological adjustment highlight the importance of the interdisciplinary nature of craniofacial teams.     

Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy

Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.     

HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions

Mammalian Alix is a multifunctional adaptor protein involved in cell death, receptor endocytosis, endosomal protein sorting and cell adhesion by associating with various proteins such as ALG-2, CIN85/Rukl/SETA, endophilins, CHMP4s and TSG101. HD-PTP is a paralog of Alix and a putative protein tyrosine phosphatase (PTP) that contains a Bro1 domain, coiled-coils, a proline-rich region (PRR) in addition to a PTP domain. We investigated interactions between HD-PTP and Alix-binding proteins. In the yeast two-hybrid assay, HD-PTP showed positive interactions with CHMP4b/Shax1, TSG101, endophilin A1 and ALG-2 but not with either RabGAPLP or CIN85. We confirmed the interactions in a mammalian system by Strep-pulldown assays in which pulldown products from the lysates of HEK293T cells expressing either Strep-tagged HD-PTP alone or co-expressing with epitope-tagged proteins were analyzed by Western blotting using specific antibodies. While Alix associated with both ALG-2 and TSG101 in a Ca2+-dependent manner, HD-PTP interacted with ALG-2 Ca2+-dependently but with TSG101 Ca2+-independently.     

Spindle regulation in neural precursors of flies and mammals

The mitotic spindle is the cellular scaffold that facilitates proper segregation of genetic material during cell division. Far from being static, the spindle is a dynamically regulated tool that can alter its size, shape and position during mitosis. Work in both insect and vertebrate systems has shown that regulation of this structure involves an array of highly conserved proteins. Moreover, it is now clear that tight regulation of the spindle during the process of neurogenesis is paramount to proper cell division and generation of the nervous system as a whole.     

Parasitic nematode fatty acid- and retinol-binding proteins compromise host immunity by interfering with host lipid signaling pathways

Parasitic nematodes cause significant morbidity and mortality globally. Excretory/secretory products (ESPs) such as fatty acid- and retinol- binding proteins (FARs) are hypothesized to suppress host immunity during nematode infection, yet little is known about their interactions with host tissues. Leveraging the insect parasitic nematode, Steinernema carpocapsae, we describe here the first in vivo study demonstrating that FARs modulate animal immunity, causing an increase in susceptibility to bacterial co-infection. Moreover, we show that FARs dampen key components of the fly immune response including the phenoloxidase cascade and antimicrobial peptide (AMP) production. Our data also reveal that FARs deplete lipid signaling precursors in vivo as well as bind to these fatty acids in vitro, suggesting that FARs elicit their immunomodulatory effects by altering the availability of lipid signaling molecules necessary for an efficient immune response. Collectively, these data support a complex role for FARs in immunosuppression in animals and provide detailed mechanistic insight into parasitism in phylum Nematoda.     

Modification of membrane sulfhydryl groups in bacteriostatic action of nitrite

The mechanism by which nitrite inhibits outgrowing spores of Bacillus cereus T was examined by using techniques developed earlier for nitrite analogs. The morphological stage of inhibition, cooperativity effects, effect of pH on inhibition, kinetics of protection against iodoacetate incorporation into membrane sulfhydryl groups, and protection against the bacteriocidal effect of carboxymethylation by iodoacetate indicate that nitrite acts as a membrane-directed sulfhydryl agent. The mechanism by which nitrite modifies the chemical reactivity of the sulfhydryl group could be either direct covalent modification or inactivation through communication with another modified membrane component. Profiles of pH effects suggest that the active agent is the protonated form of nitrite. The nitrite concentrations which modify membrane sulfhydryl activity coincide with those which have a bacteriostatic effect. These results are consistent with membrane sulfhydryl modification as a component of the mechanism of nitrite-induced bacteriostasis in this aerobic sporeformer.