Bioglass and bioactive glasses and their impact on healthcare

Glass caused a revolution in healthcare when Bioglass was discovered by Larry Hench. It was the first material to bond with bone, rather than be encapsulated by fibrous tissue, launching the field of bioactive ceramics . Bioglass is also biodegradable. Almost 50 years on from its discovery that revolution continues. Bioactive glasses stimulate more bone regeneration than other bioactive ceramics , which is attributed to their dissolution products stimulating cells at the genetic level. This second discovery has changed the way clinicians, scientists and regulatory bodies think about medical devices and the concept of bioactivity. The original 45S5 Bioglass has only re cently found really widespread use in orthop a edics, having regenerated the bones of more than 1.5 million patients. Its full potential is still yet to be fulfilled. Th is article takes the reader from Hench’s Bioglass 45S5 to its clinical uses and products, before giving examples of non - surgical products that now use Bioglass, from consumer products , such as toothpaste, to cosmetics . Other glasses have also found important healthcare applications, such as borate based glasses that heal chronic wounds. The re volution looks set to continue as new healthcare applications are being found for bioactive glasses, contributing to extending the glass age

Courtship Initiation Is Stimulated by Acoustic Signals in Drosophila melanogaster

Finding a mating partner is a critical task for many organisms. It is in the interest of males to employ multiple sensory modalities to search for females. In Drosophila melanogaster, vision is thought to be the most important courtship stimulating cue at long distance, while chemosensory cues are used at relatively short distance. In this report, we show that when visual cues are not available, sounds produced by the female allow the male to detect her presence in a large arena. When the target female was artificially immobilized, the male spent a prolonged time searching before starting courtship. This delay in courtship initiation was completely rescued by playing either white noise or recorded fly movement sounds to the male, indicating that the acoustic and/or seismic stimulus produced by movement stimulates courtship initiation, most likely by increasing the general arousal state of the male. Mutant males expressing tetanus toxin (TNT) under the control of Gr68a-GAL4 had a defect in finding active females and a delay in courtship initiation in a large arena, but not in a small arena. Gr68a-GAL4 was found to be expressed pleiotropically not only in putative gustatory pheromone receptor neurons but also in mechanosensory neurons, suggesting that Gr68a-positive mechanosensory neurons, not gustatory neurons, provide motion detection necessary for courtship initiation. TNT/Gr68a males were capable of discriminating the copulation status and age of target females in courtship conditioning, indicating that female discrimination and formation of olfactory courtship memory are independent of the Gr68a-expressing neurons that subserve gustation and mechanosensation. This study suggests for the first time that mechanical signals generated by a female fly have a prominent effect on males' courtship in the dark and leads the way to studying how multimodal sensory information and arousal are integrated in behavioral decision making

Highly Tissue Specific Expression of Sphinx Supports Its Male Courtship Related Role in Drosophila melanogaster

Sphinx is a lineage-specific non-coding RNA gene involved in regulating courtship behavior in Drosophila melanogaster. The 5′ flanking region of the gene is conserved across Drosophila species, with the proximal 300 bp being conserved out to D. virilis and a further 600 bp region being conserved amongst the melanogaster subgroup (D. melanogaster, D. simulans, D. sechellia, D. yakuba, and D. erecta). Using a green fluorescence protein transformation system, we demonstrated that a 253 bp region of the highly conserved segment was sufficient to drive sphinx expression in male accessory gland. GFP signals were also observed in brain, wing hairs and leg bristles. An additional ∼800 bp upstream region was able to enhance expression specifically in proboscis, suggesting the existence of enhancer elements. Using anti-GFP staining, we identified putative sphinx expression signal in the brain antennal lobe and inner antennocerebral tract, suggesting that sphinx might be involved in olfactory neuron mediated regulation of male courtship behavior. Whole genome expression profiling of the sphinx knockout mutation identified significant up-regulated gene categories related to accessory gland protein function and odor perception, suggesting sphinx might be a negative regulator of its target genes

Turning Males On: Activation of Male Courtship Behavior in Drosophila melanogaster

The innate sexual behaviors of Drosophila melanogaster males are an attractive system for elucidating how complex behavior patterns are generated. The potential for male sexual behavior in D. melanogaster is specified by the fruitless (fru) and doublesex (dsx) sex regulatory genes. We used the temperature-sensitive activator dTRPA1 to probe the roles of fruM- and dsx-expressing neurons in male courtship behaviors. Almost all steps of courtship, from courtship song to ejaculation, can be induced at very high levels through activation of either all fruM or all dsx neurons in solitary males. Detailed characterizations reveal different roles for fruM and dsx in male courtship. Surprisingly, the system for mate discrimination still works well when all dsx neurons are activated, but is impaired when all fruM neurons are activated. Most strikingly, we provide evidence for a fruM-independent courtship pathway that is primarily vision dependent

Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome after renal transplantation in the United States

BACKGROUND: The incidence and risk factors for diabetic ketoacidosis (diabetic ketoacidosis) and hyperglycemic hyperosmolar syndrome (hyperglycemic hyperosmolar syndrome, previously called non-ketotic hyperosmolar coma) have not been reported in a national population of renal transplant (renal transplantation) recipients. METHODS: We performed a historical cohort study of 39,628 renal transplantation recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998, followed until 31 Dec 1999. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (ICD-9 code 250.1x) and hyperglycemic hyperosmolar syndrome (code 250.2x). Cox Regression analysis was used to calculate adjusted hazard ratios for time to hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. RESULTS: The incidence of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were 33.2/1000 person years (PY) and 2.7/1000 PY respectively for recipients with a prior diagnosis of diabetes mellitus (DM), and 2.0/1000 PY and 1.1/1000 PY in patients without DM. In Cox Regression analysis, African Americans (AHR, 2.71, 95 %CI, 1.96–3.75), females, recipients of cadaver kidneys, patients age 33–44 (vs. >55), more recent year of transplant, and patients with maintenance TAC (tacrolimus, vs. cyclosporine) had significantly higher risk of diabetic ketoacidosis. However, the rate of diabetic ketoacidosis decreased more over time in TAC users than overall. Risk factors for hyperglycemic hyperosmolar syndrome were similar except for the significance of positive recipient hepatitis C serology and non-significance of female gender. Both diabetic ketoacidosis (AHR, 2.44, 95% CI, 2.10–2.85, p < 0.0001) and hyperglycemic hyperosmolar syndrome (AHR 1.87, 95% CI, 1.22–2.88, p = 0.004) were independently associated with increased mortality. CONCLUSIONS: We conclude that diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were associated with increased risk of mortality and were not uncommon after renal transplantation. High-risk groups were identified

Sensory Integration Regulating Male Courtship Behavior in Drosophila

The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i) between initiation and maintenance of courtship, (ii) between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii) between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior

Mating alters gene expression patterns in Drosophila melanogaster male heads

<p>Abstract</p> <p>Background</p> <p>Behavior is a complex process resulting from the integration of genetic and environmental information. <it>Drosophila melanogaster </it>rely on multiple sensory modalities for reproductive success, and mating causes physiological changes in both sexes that affect reproductive output or behavior. Some of these effects are likely mediated by changes in gene expression. Courtship and mating alter female transcript profiles, but it is not known how mating affects male gene expression.</p> <p>Results</p> <p>We used <it>Drosophila </it>genome arrays to identify changes in gene expression profiles that occur in mated male heads. Forty-seven genes differed between mated and control heads 2 hrs post mating. Many mating-responsive genes are highly expressed in non-neural head tissues, including an adipose tissue called the fat body. One fat body-enriched gene, <it>female-specific independent of transformer </it>(<it>fit</it>), is a downstream target of the somatic sex-determination hierarchy, a genetic pathway that regulates <it>Drosophila</it> reproductive behaviors as well as expression of some fat-expressed genes; three other mating-responsive loci are also downstream components of this pathway. Another mating-responsive gene expressed in fat, <it>Juvenile hormone esterase </it>(<it>Jhe</it>), is necessary for robust male courtship behavior and mating success.</p> <p>Conclusions</p> <p>Our study demonstrates that mating causes changes in male head gene expression profiles and supports an increasing body of work implicating adipose signaling in behavior modulation. Since several mating-induced genes are sex-determination hierarchy target genes, additional mating-responsive loci may be downstream components of this pathway as well.</p

The contribution of female community health volunteers (FCHVs) to maternity care in Nepal: a qualitative study.

BACKGROUND: In resource-poor settings, the provision of basic maternity care within health centres is often a challenge. Despite the difficulties, Nepal reduced its maternal mortality ratio by 80% from 850 to an estimated 170 per 100,000 live births between 1991 and 2011 to achieve Millennium Development Goal Five. One group that has been credited for this is community health workers, known as Female Community Health Volunteers (FCHVs), who form an integral part of the government healthcare system. This qualitative study explores the role of FCHVs in maternal healthcare provision in two regions: the Hill and Terai. METHODS: Between May 2014 and September 2014, 20 FCHVs, 11 health workers and 26 service users were purposefully selected and interviewed using semi-structured topic guides. In addition, four focus group discussions were held with 19 FCHVs. Data were analysed using thematic analysis. RESULTS: All study participants acknowledged the contribution of FCHVs in maternity care. All FCHVs reported that they shared key health messages through regularly held mothers' group meetings and referred women for health checks. The main difference between the two study regions was the support available to FCHVs from the local health centres. With regular training and access to medical supplies, FCHVs in the hill villages reported activities such as assisting with childbirth, distributing medicines and administering pregnancy tests. They also reported use of innovative approaches to educate mothers. Such activities were not reported in Terai. In both regions, a lack of monetary incentives was reported as a major challenge for already overburdened volunteers followed by a lack of education for FCHVs. CONCLUSIONS: Our findings suggest that the role of FCHVs varies according to the context in which they work. FCHVs, supported by government health centres with emphasis on the use of local approaches, have the potential to deliver basic maternity care and promote health-seeking behaviour so that serious delays in receiving healthcare can be minimised. However, FCHVs need to be reimbursed and provided with educational training to ensure that they can work effectively. The study underlines the relevance of community health workers in resource-poor settings

Inositol 1,4,5- Trisphosphate Receptor Function in Drosophila Insulin Producing Cells

The Inositol 1,4,5- trisphosphate receptor (InsP3R) is an intracellular ligand gated channel that releases calcium from intracellular stores in response to extracellular signals. To identify and understand physiological processes and behavior that depends on the InsP3 signaling pathway at a systemic level, we are studying Drosophila mutants for the InsP3R (itpr) gene. Here, we show that growth defects precede larval lethality and both are a consequence of the inability to feed normally. Moreover, restoring InsP3R function in insulin producing cells (IPCs) in the larval brain rescues the feeding deficit, growth and lethality in the itpr mutants to a significant extent. We have previously demonstrated a critical requirement for InsP3R activity in neuronal cells, specifically in aminergic interneurons, for larval viability. Processes from the IPCs and aminergic domain are closely apposed in the third instar larval brain with no visible cellular overlap. Ubiquitous depletion of itpr by dsRNA results in feeding deficits leading to larval lethality similar to the itpr mutant phenotype. However, when itpr is depleted specifically in IPCs or aminergic neurons, the larvae are viable. These data support a model where InsP3R activity in non-overlapping neuronal domains independently rescues larval itpr phenotypes by non-cell autonomous mechanisms