Search

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17–26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26–36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development. Keywords: Weaning, Infant, Phenylketonuria, Phenylalanine, Phe-free infant formula

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and

In addition to its role in the endogenous synthesis of cysteine, cystathionine gamma-lyase (CGL) is a major physiological source of the vasorelaxant hydrogen sulfide. Cgl null mice are potentially useful for studying the influence of this compound upon vascular tone and endothelial function. Here, we confirm a previous report that female Cgl null mice exhibit an approximate 45-fold increase in plasma total homocysteine compared to wild type controls. This level of homocysteine is approximately 3.5-fold higher than that observed in male Cgl null mice and is essentially equivalent to that observed in mouse models of cystathionine beta synthase deficient homocystinuria. Cgl null mice of both sexes exhibited decreased expression of methylenetetrahydrofolate reductase and cysteinesulfinate decarboxylase compared to WT controls. Female Cgl null mice exhibited a sex-specific induction of betaine homocysteine S-methyltransferase and methionine adenosyltransferase 1, alpha and a 70% decrease in methionine synthase expression accompanied by significantly decreased plasma methionine. Decreased plasma cysteine levels in female Cgl null mice were associated with sex-specific dysregulation of cysteine dioxygenase expression. Comparative histological assessment between cystathionine beta-synthase and Cgl null mice indicated that the therapeutic potential of cystathionine against liver injury merits possible further investigation. Collectively, our data demonstrates the importance of considering sex when investigating mouse models of inborn errors of metabolism and indicate that while female Cgl null mice are of questionable utility for studying the physiological role of hydrogen sulfide, they could serve as a useful model for studying the consequences of methionine synthase deficiency and the methylfolate trap.

Background. Preserving connectivity, or the ability of a landscape to support species movement, is among the most commonly recommended strategies to reduce the negative effects of climate change and human land use development on species. Connectivity analyses have traditionally used a corridor-based approach and rely heavily on least cost path modeling and circuit theory to delineate corridors. Individual-based models are gaining popularity as a potentially more ecologically realistic method of estimating landscape connectivity. However, this remains a relatively unexplored approach. We sought to explore the utility of a simple, individual-based model as a land-use management support tool in identifying and implementing landscape connectivity. Methods. We created an individual-based model of bighorn sheep (Ovis canadensis) that simulates a bighorn sheep traversing a landscape by following simple movement rules. The model was calibrated for bighorn sheep in the Okanagan Valley, British Columbia, Canada, a region containing isolated herds that are vital to conservation of the species in its northern range. Simulations were run to determine baseline connectivity between subpopulations in the study area. We then applied the model to explore two land management scenarios on simulated connectivity: restoring natural fire regimes and identifying appropriate sites for interventions that would increase road permeability for bighorn sheep. Results. This model suggests there are no continuous areas of good habitat between current subpopulations of sheep in the study area; however, a series of stepping-stones or circuitous routes could facilitate movement between subpopulations and into currently unoccupied, yet suitable, bighorn habitat. Restoring natural fire regimes or mimicking fire with prescribed burns and tree removal could considerably increase bighorn connectivity in this area. Moreover, several key road crossing sites that could benefit from wildlife overpasses were identified. Discussion. By linking individual-scale movement rules to landscape-scale outcomes, our individual-based model of bighorn sheep allows for the exploration of how on-the-ground management or conservation scenarios may increase functional connectivity for the species in the study area. More generally, this study highlights the usefulness of individual-based models to identify how a species makes broad use of a landscape for movement. Application of this approach can provide effective quantitative support for decision makers seeking to incorporate wildlife conservation and connectivity into land use planning.

Energy gain constrains resource use, social organization, and landscape organization in human and other living systems. Changes in energy gain have common characteristics across living systems. We describe these commonalities in selected case studies involving imperial taxation, fungus-farming ants, and North American beaver, and propose a suite of hypotheses for the organization of systems that subsist on different levels of energy gain. Organizational constraints arising from energy gain predict changes to settlement and organization in postcarbon societies.