Exploring the support needs of Australian parents of young children with Usher syndrome: a qualitative thematic analysis.

BACKGROUND: Advancements in genetic testing have led to Usher syndrome now being diagnosed at a much earlier age than in the past, enabling the provision of early intervention and support to children and families. Despite these developments, anecdotal reports suggest there are substantial gaps in the services and supports provided to parents of children with Usher syndrome. The current study investigated the support needs of parents of children with Usher syndrome Type 1 when their child was aged 0 to 5 years. METHOD: Purposive sampling was used, and six semi-structured interviews were conducted with Australian parents of children with Usher syndrome, Type 1. Data was analysed using modified reflexive thematic analysis. RESULTS: Four key themes were identified as being central to the support needs of parents of children with Usher syndrome aged 0 to 5 years. (1) Social Needs referred to parents' need for various sources of social support, (2) Informational Needs described the lack of information parents received regarding Usher syndrome from treating professionals, (3) Practical Needs included supports needed to assist parents in managing the day-to-day tasks of caring for a child with a disability, and (4) Emotional Needs represented the emotional support (both formal and informal) that parents needed to be a positive support to their child. CONCLUSIONS: Findings provide rich information for relevant support groups, policy makers, individual healthcare professionals, and professional governing bodies regarding the education of stakeholders and the development and implementation of best-practice treatment guidelines.

Physical limits of flight performance in the heaviest soaring bird.

Flight costs are predicted to vary with environmental conditions, and this should ultimately determine the movement capacity and distributions of large soaring birds. Despite this, little is known about how flight effort varies with environmental parameters. We deployed bio-logging devices on the world's heaviest soaring bird, the Andean condor (Vultur gryphus), to assess the extent to which these birds can operate without resorting to powered flight. Our records of individual wingbeats in >216 h of flight show that condors can sustain soaring across a wide range of wind and thermal conditions, flapping for only 1% of their flight time. This is among the very lowest estimated movement costs in vertebrates. One bird even flew for >5 h without flapping, covering ∼172 km. Overall, > 75% of flapping flight was associated with takeoffs. Movement between weak thermal updrafts at the start of the day also imposed a metabolic cost, with birds flapping toward the end of glides to reach ephemeral thermal updrafts. Nonetheless, the investment required was still remarkably low, and even in winter conditions with weak thermals, condors are only predicted to flap for ∼2 s per kilometer. Therefore, the overall flight effort in the largest soaring birds appears to be constrained by the requirements for takeoff.

Turn costs change the value of animal search paths.

The tortuosity of the track taken by an animal searching for food profoundly affects search efficiency, which should be optimised to maximise net energy gain. Models examining this generally describe movement as a series of straight steps interspaced by turns, and implicitly assume no turn costs. We used both empirical- and modelling-based approaches to show that the energetic costs for turns in both terrestrial and aerial locomotion are substantial, which calls into question the value of conventional movement models such as correlated random walk or Lévy walk for assessing optimum path types. We show how, because straight-line travel is energetically most efficient, search strategies should favour constrained turn angles, with uninformed foragers continuing in straight lines unless the potential benefits of turning offset the cost.

The relationship between oxygen consumption and body acceleration in a range of species.

The ability to measure the energy expenditure of free-ranging animals is of great importance but the techniques available each have their limitations. Recently, as an alternative to more established techniques, an integrated measure of body acceleration termed overall dynamic body acceleration (ODBA) has been used as a calibrated proxy for rate of oxygen consumption (V(O(2))) and hence metabolic rate. The present study tested the potential of this technique, firstly by expanding the range of species for which the V(O(2))-ODBA relationship has been defined and secondly by undertaking a validation exercise to explore the accuracy of predictions made using ODBA. V(O(2))-ODBA relationships during terrestrial locomotion were established for several bipedal and quadrupedal endotherms and compiled with similar relationships previously determined in other species. A model incorporating all of these species showed that ODBA is an excellent predictor of V(O(2)) but there is variation in the V(O(2))-ODBA relationship between species, and further variation within some species. Including measurements such as body mass and structural size in prediction equations might further improve the predictive power of the 'ODBA technique' and eliminate species-specific differences. In the validation exercise, estimate errors were calculated for the species-specific predictive equations. The use of ODBA to estimate V(O(2)) was valid across all species examined and may show a greater potential for estimating energy expenditure for individual animals than other techniques.

Correlates of early sexual activity among Hispanic children in middle adolescence

OBJECTIVE: We analyzed early sexual activity among Hispanic 14 to 15-year-old adolescents residing in a poor neighborhood in Puerto Rico. METHODS: Information from a sample of 325 adolescents was collected from a randomized sample of community households. Logistic regression analysis was used to identify the variables that help explained adolescents' sexual behavior. RESULTS: Adolescents whose parents reported poor communication and poor parent control were more likely to engage in early sexual activity that those peers that did not report this type of family relationship. Adolescents who reported poor parent bonding and lack of discipline were more likely to engage in early sexual relationships. CONCLUSIONS: Intervention and prevention programs need to be aware and address the role of the Hispanic culture in gender differences in early sexual activity in adolescence. If sexual norms related to gender role are changing in Puerto Rico, is a question that needs to be answered in future research.

Iranian STR variation at the fringes of biogeographical demarcation.

The integrative relationship between population genetics and forensic biology allows for a thorough genetic characterization of extant human populations. This study aimed to genetically characterize 150 unrelated healthy donors from a general population in Iran both forensically and phylogenetically. The allelic frequencies of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were generated. This constitutes the core of polymerase chain reaction (PCR)-based DNA genetic markers in the US Combined DNA Index System (CODIS) plus two additional loci (D2S1338 and D19S433) that together are consistent with several other worldwide database requirements. There were no deviations from Hardy-Weinberg expectations. Based upon the allelic frequencies, several important forensic parameters were calculated including: gene diversity (GD) index, power of discrimination (PD), polymorphic information content (PIC) and power of exclusion (PE). G-tests indicate the allelic frequencies of the Iranians are statistically non-significant compared to two Turkish populations yet, statistically different from the remaining 18 groups obtained from the literature and examined in this study. This suggests that the Iranian dataset may be forensically equivalent to the dataset from the Turkish region of Eastern Anatolia and the general population from Turkey. Phylogenetic analysis of our population with the full set of 15 loci indicate the Iranians occupy an intermediate position relative to the major Caucasian and East Asian clades on a global level. A regional phylogenetic analysis using 13 of the 15 loci indicate the Iranians segregate in a more compact association with groups from southeastern Spain, Arabs from Morocco and Syria, and especially with the general population from Turkey and those from Eastern Anatolia. These groups are flanked by highly differentiated populations from northern India and a Berber group from Tunisia on opposing ends of the regional phylogram. This report also demonstrates the necessity to thoroughly characterize the genetic composition of populations located in geographic intersections in order to choose the appropriate dataset on which to base forensic calculations, not only at an intra-population level, but also at an inter-population level as well.

Autosomal STR variation in five Austronesian populations.

Human population characteristics at the genetic level are integral to both forensic biology and population genetics. This study evaluates biparental microsatellite markers in five Austronesian-speaking groups to characterize their intra- and interpopulation differences. Genetic diversity was analyzed using 15 short tandem repeat (STR) loci from 338 unrelated individuals from 5 Pacific islands populations, including the aboriginal Ami and Atayal groups from Taiwan, Bali and Java in Indonesia, and the Polynesian islands of Samoa. Allele frequencies from the STR profiles were determined and compared to other geographically targeted worldwide populations procured from recent literature. Hierarchical AMOVA analysis revealed a large number of loci that exhibit significant correspondence to linguistic partitioning among groups of populations. A pronounced divide exists between Samoa and the East (Formosa) and Southeast Asian (Bali and Java) islands. This is clearly illustrated in the topology of the neighbor-joining tree. Phylogenetic analyses also indicate clear distinctions between the Ami and Atayal and between Java and Bali, which belie the respective geographic proximities of the populations in each set. This differentiation is supported by the higher interpopulation variance components of the Austronesian populations compared to other Asian non-Austronesian groups. Our phylogenetic data indicate that, despite their linguistic commonalities, these five groups are genetically distinct. This degree of genetic differentiation justifies the creation of population-specific databases for human identification.

Accessing hard-to-reach populations: the illicit drug market as a workplace of the outreach worker in Puerto Rico

This descriptive paper reports findings from a formative research study on the drug market as a workplace of the outreach worker in Puerto Rico, and outlines strategies used by outreach workers to enable them to work effectively in these sites. Data were collected via outreach worker focus groups and participant observations at drug market sites. A social system theoretical model was used for analyzing data on drug market sites, and results are reported in terms of three basic social system components: structure, culture, and process. The authors recommend utilizing outreach workers as part of prevention and treatment teams in organizations providing services to drug users, as well as other hard-to-reach populations such as street sex workers and the homeless.

3-pyrrolines are mechanism-based inactivators of the quinone-dependent amine oxidases but only substrates of the flavin-dependent amine oxidases.

We previously reported that 3-pyrroline and 3-phenyl-3-pyrroline effect a time-dependent inactivation of the copper-containing quinone-dependent amine oxidase from bovine plasma (BPAO) (Lee et al. J. Am. Chem. Soc. 1996, 118, 7241-7242). Quinone cofactor model studies suggested a mechanism involving stoichiometric turnover to a stable pyrrolylated cofactor. Full details of the model studies are now reported along with data on the inhibition of BPAO by a family of 3-aryl-3-pyrrolines (aryl = substituted phenyl, 1-naphthyl, 2-naphthyl), with the 4-methoxy-3-nitrophenyl analogue being the most potent. At the same time, the parent 3-phenyl analogue is a pure substrate for the flavin-dependent mitochondrial monoamine oxidase B from bovine liver. Spectroscopic studies (including resonance Raman) on BPAO inactivated by the 4-methoxy-3-nitrophenyl analogue are consistent with covalent derivatization of the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor. The distinction of a class of compounds acting as an inactivator of one amine oxidase family and a pure substrate of another amine oxidase family represents a unique lead to the development of selective inhibitors of the mammalian copper-containing amine oxidases.

Catalytic turnover of substrate benzylamines by the quinone-dependent plasma amine oxidase leads to H2O2-dependent inactivation: evidence for generation of a cofactor-derived benzoxazole.

Incubation of bovine plasma amine oxidase (BPAO) with benzylamine and various p-substituted analogues results in a time-dependent inactivation that is attributable to buildup of the H(2)O(2)-turnover product on the basis of protection afforded by coincubation with catalase. The mechanism of inactivation is distinct from that effected by H(2)O(2) itself, which requires higher concentrations. Solution studies using models for the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor reveal a loss of catalytic activity arising from oxidation of the dihydrobenzoxazole tautomer of the product Schiff base, that competes with hydrolytic release of benzaldehyde product. The resulting stable benzoxazole exhibits a characteristic absorption depending on the nature of the benzylamine p-substituent. For benzylamine itself, the model benzoxazole absorbs at 313 nm, in an area of strong absorption by the enzyme, whereas for 4-nitrobenzylamine, the absorption of the model benzoxazole is sufficiently red-shifted (at 365 nm) to be discerned above the background enzyme absorption. Inactivation of BPAO by 4-nitrobenzylamine is accompanied by loss of the resting TPQ anion absorption at 480 nm concomitant with generation of a new absorption near 360 nm. Resonance Raman spectra of the inactivated enzyme show a close correspondence with those for the model 4-nitrobenzylamine-derived benzoxazole. Substrate-dependent inactivation is also observed for the other two mammalian enzymes examined, equine plasma amine oxidase and human kidney amine oxidase. Catalase provides complete protection in these instances as well. Benzoxazole formation may constitute a common mechanism of inactivation of quinone-dependent amine oxidases by normal substrates in vitro if the product H(2)O(2) is permitted to accumulate. More importantly, the results suggest that the benzoxazole inactivation pathway may be important physiologically and may have influenced the distribution of amine oxidases and catalase in cells.

Understanding and exploiting nature's chemical arsenal: the past, present and future of calicheamicin research.

The enediyne antitumor antibiotics are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mode of action and many have spawned considerable interest as anticancer agents in the pharmaceutical industry. Of equal importance to these astonishing properties, the enediynes also offer a distinct opportunity to study the unparalleled biosyntheses of their unique molecular scaffolds and what promises to be unprecedented modes of self-resistance to highly reactive natural products. Elucidation of these aspects should unveil novel mechanistic enzymology, and may provide access to the rational biosynthetic modification of enediyne structure for new drug leads, the construction of enediyne overproducing strains and eventually lead to an enediyne combinatorial biosynthesis program. This article strives to compile and present the critical research discoveries relevant to the clinically most promising enediyne, calicheamicin, from a historical perspective. Recent progress, particularly in the areas of biosynthesis, self-resistance, bio-engineering analogs and clinical studies are also highlighted.

The mechanism of delayed selfing in Collinsia verna (Scrophulariaceae).

Collinsia verna, blue-eyed Mary, has floral attributes of an outcrossing species, yet most flowers readily self-pollinate under greenhouse conditions. Here we describe the mechanism of self-pollination in C. verna via changes in relative positions of the stigma and anthers and late timing of receptivity, resulting in delayed selfing. Each flower contains four anthers that dehisce sequentially over ∼1 wk. Pollen that is not collected by pollinators accumulates in the keel petal and retains high viability (>80% pollen germination) up to the time of corolla abscission. The stigmatic surface does not become receptive until after the third anther dehisces. This overlap in the sexual phases is concurrent with a change in herkogamy during floral development. In most flowers (70%), the stigma has moved to the front of the keel and is positioned near the anthers when the third anther dehisces. Under field conditions, fruiting success of plants within pollinator exclosures was ∼75% of the fruiting success in open-pollinated plants (33% fruiting success via autogamy vs. 44% fruiting success, respectively). Collinsia verna plants in pollinator exclosures exhibit variation in autogamy rates within natural populations (range 0-80%). In addition, only half of naturally pollinated, receptive flowers examined had pollen tubes growing in their styles. In contrast, shortly after corolla abscission, nearly all flowers examined (96%) had pollen tubes in their styles. Thus we find that in C. verna, autogamy occurs late in floral development, which has the potential to provide substantial reproductive assurance, and that individuals vary in their ability to set fruit through this mechanism. We suggest that delayed selfing mechanisms may be overlooked in other species and that variable pollinator availability may play a significant role in the maintenance of mixed mating in species with delayed selfing, such as C. verna.

Isolation from human fetal liver of cells co-expressing CD34 haematopoietic stem cell and CAM 5.2 pancytokeratin markers.

BACKGROUND/AIMS: Ductal plate and bile duct cells in developing human liver express haematopoietic stem cell markers, such as c-kit and CD34, in association with cytokeratin markers CAM 5.2 and CK 18. The identification of such ductal plate cells as likely progenitors for both bile duct epithelial cells and hepatocytes and their possible reappearance as oval cells in the regenerating liver have generated much interest in their pluripotential capacities. This study aimed to isolate cells from human fetal liver that co-express haematopoietic stem cell and epithelial cell markers. METHODS: Human fetal liver was harvested following legal termination of pregnancy at week 14-22. CD34+ mononuclear cells were isolated from liver cell suspensions with immunomagnetic beads. Immunofluorescent staining, using anticytokeratin CAM 5.2 against CK 8 and 18, was performed on permeabilised CD34+ cells for flow cytometry and fluorescent microscopy. CD34+ cells were also stained for other stem cell markers (HLA-DR, c-kit) and committed haematopoietic cell markers (CD33, CD38). RESULTS: Approximately 0.9% (range 0.07-4.0%) of the mononuclear cells isolated were CD34+ cells. The number of mononuclear cells isolated correlated with fetal liver weight (r=0.508). About 3-8% of these CD34+ cells stained positively for CAM 5.2. In addition, CD34+ cells were positive for HLA-DR, but only a small percentage was positive for c-kit. Staining for the committed haematological markers, CD33 and CD38, was consistently negative. CONCLUSIONS: This study describes an immunoaffinity method for the enrichment from human fetal liver of cells that co-express haematopoietic stem cell and epithelial cell markers. Such cellular subsets may correspond to pluripotential ductal plate and bile duct cells.

Targeted reduction of oxytocin expression provides insights into its physiological roles.

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 hours without milk in their stomachs. OT injection into the dams or rescue with the rat OT gene restores the milk ejection in response to suckling. OT is also needed for post-partum alveolar proliferation. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice. Furthermore, homozygous mutant mice show reduced aggression in some tests.

Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition.

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk injection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk injection, but not for mating, parturition and milk production, in mice.

Ventilation-perfusion abnormalities in the preterm infant with hyaline membrane disease: a two-compartment model of the neonatal lung.

Arterial-alveolar differences for oxygen, carbon dioxide, and nitrogen were measured in 7 non-distressed preterm infants and 21 ventilator-dependent preterm infants with hyaline membrane disease. The preterm infants with hyaline membrane disease had a significantly lower average arterial pH (7.34 vs. 7.44; P less than 0.001), and significantly higher arterial-alveolar differences for oxygen (286 mm Hg vs. 34 mm Hg; P less than 0.005) and nitrogen (118 mm Hg vs. 7 mm Hg; P less than 0.005). Both groups had elevated arterial-alveolar differences for PCO2 (9 mm Hg in infants with hyaline membrane disease, 5 mm Hg in nondistressed infants; P less than 0.2). When acute changes in mean airway pressure were produced in 14 distressed infants, arterial-alveolar CO2 and N2 differences moved in opposite directions in 11 infants. This observation suggests that changes in mean airway pressure do not acutely recruit atelectatic alveoli, but cause redistribution of ventilation within alveoli already ventilated.