Wnt Pathway in Pancreatic Development and Pathophysiology.

The pancreas is an abdominal gland that serves 2 vital purposes: assist food processing by secreting digestive enzymes and regulate blood glucose levels by releasing endocrine hormones. During embryonic development, this gland originates from epithelial buds located on opposite sites of the foregut endoderm. Pancreatic cell specification and maturation are coordinated by a complex interplay of extrinsic and intrinsic signaling events. In the recent years, the canonical Wnt/ß-catenin pathway has emerged as an important player of pancreas organogenesis, regulating pancreatic epithelium specification, compartmentalization and expansion. Importantly, it has been suggested to regulate proliferation, survival and function of adult pancreatic cells, including insulin-secreting ß-cells. This review summarizes recent work on the role of Wnt/ß-catenin signaling in pancreas biology from early development to adulthood, emphasizing on its relevance for the development of new therapies for pancreatic diseases.

Eating behaviors in children with Down syndrome: Results of a home-use test.

Children with Down syndrome (DS) display a disproportionate number of health challenges, including feeding and swallowing difficulties and food texture sensitivities. To start addressing food texture challenges early in life, the aim of this research was to understand mealtime behaviors and identify preferred food textures of children with DS. Children (aged 11 to 58 months) with DS (n = 111) and without (typically developing, TD; n = 107) participated in a home use test evaluating snack products of varying textures. Parents recorded their children's reactions to each food product; a panel of trained coders coded videos for mealtime behaviors. Children were also identified as food texture sensitive (TS) or non-texture sensitive (NTS). Results showed that age, TS, the presence of a DS diagnosis and the TS*DS interaction influenced the child's behaviors to the food products. Children with DS were more likely to increase distance from the food, mouth/suck on the food, and less likely to chew/much on the food compared to children TD. Children with DS also ate significantly less than typically developing children. Similar mealtime behaviors were observed between the children with TD/<30 months of age and children with DS regardless of age (p < .05). While children with DS/TS had a higher disposition for the dissolvable texture, along with products that were salty and cheesy, children with DS/NTS had a greater tolerance for more textures in general, including crunchy and grainy. Overall, this research identified mealtime behaviors in children with DS, determined overall disposition of children with DS to foods of differences sensory properties, and demonstrated the influence of TS on a child's disposition to a food. This research will be extended to develop acceptable and innovative food products for children with DS/TS.

Percutaneous drainage for non-operative management of emphysematous pyelonephritis: Clinical characteristics and predictors of success.

Emphysematous pyelonephritis (EPN) is a necrotizing renal infection that can rapidly progress without urgent intervention. The purpose of this study was to evaluate the safety and efficacy of percutaneous nephrostomy (PN) in the management of EPN, as well as the relationship of outcomes with initial classification by the Huang-Tseng classification system and other prognostic factors such as thrombocytopenia. A retrospective review of medical records revealed seven patients with EPN treated with PN. Thirty-day survival rate was 86%, with the only mortality due to an arrhythmia secondary to underlying cardiomyopathy rather than a complication from EPN or PN. A single nephrostomy procedure served as definitive treatment in 3 patients (43%). Reintervention due to recurrence of EPN symptoms was required in 4 patients (57%), all of which initially presented with Class 3 disease or higher. Two of these four patients required nephrectomy, while the other two were successfully managed with a second drainage procedure without further recurrence of symptoms. PN appears to be a safe and generally effective management option for EPN, especially in patients who are considered poor surgical candidates. PN may serve as definitive treatment in hemodynamically stable patients with lower class of disease. In patients with higher class of disease, PN may be definitive treatment in patients who lack additional risk factors such as thrombocytopenia or serve as an effective bridge to nephrectomy.

Animal models of gene-alcohol interactions.

Most birth defects arise from complex interactions between multiple genetic and environmental factors. However, our current understanding of how these interactions and their contributions affect birth defects remains incomplete. Human studies are limited in their ability to identify the fundamental causes of birth defects due to ethical and practical limitations. Animal models provide a great number of resources not available to human studies and they have been critical in advancing our understanding of birth defects and the complex interactions that underlie them. In this review, we discuss the use of animal models in the context of gene-environment interactions that underlie birth defects. We focus on alcohol which is the most common environmental factor associated with birth defects. Prenatal alcohol exposure leads to a wide range of cognitive impairments and structural deficits broadly termed fetal alcohol spectrum disorders (FASD). We discuss the broad impact of prenatal alcohol exposure on the developing embryo and elaborate on the current state of gene-alcohol interactions. Additionally, we discuss how animal models have informed our understanding of the genetics of FASD. Ultimately, these topics will provide insight into the use of animal models in understanding gene-environment interactions and their subsequent impact on birth defects.

A Case Study of an Effective and Sustainable Antiretroviral Therapy Program in Rural South Africa.

The delivery of high-quality HIV care in rural settings is a global challenge. Despite the successful expansion of antiretroviral therapy (ART) in Africa, viral load (VL) monitoring and ART adherence are poor, especially in rural communities. This article describes a case study of an ART program in the deeply rural Eastern Cape of South Africa. The Zithulele ART Program initiated five innovations over time: (1) establishing district hospital as the logistical hub for all ART care in a rural district, (2) primary care clinic delivery of prepackaged ART and chronic medications for people living with HIV (PLH), (3) establishing central record keeping, (4) incentivizing VL monitoring, and (5) providing hospital-based outpatient care for complex cases. Using a pharmacy database, on-time VL monitoring and viral suppression were evaluated for 882 PLH initiating ART in the Zithulele catchment area in 2013. Among PLH initiating ART, 12.5% (n = 110) were lost to follow-up, 7.7% (n = 68) transferred out of the region, 10.2% (n = 90) left the program and came back at a later date, and 4.0% (n = 35) died. Of the on-treatment population, 82.9% (n = 480/579) had VL testing within 7 months and 92.6% (n = 536/579) by 1 year. Viral suppression was achieved in 85.2% of those tested (n = 457/536), or 78.9% (n = 457/579) overall. The program's VL testing and suppression rates appear about twice as high as national data and data from other rural centers in South Africa, despite fewer resources than other programs. Simple system innovations can ensure high rates of VL testing and suppression, even in rural health facilities.

Validity of the South African Triage Scale in a rural district hospital.

INTRODUCTION: The implementation of a triage system is a vital step in improving the functioning and patient flow of the emergency centre in a rural district hospital. The South African Triage Scale (SATS) is a well validated and reliable tool used widely in South Africa and other low- and middle-income countries. This study aims to assess the validity of the SATS in a rural district hospital context. METHODS: This is a cross-sectional study. All patients presenting to the Zithulele Hospital emergency centre from 1 October 2015 to 31 December 2015 were triaged using the SATS system, routinely collected data was used to determine the correlation between assigned acuity and outcome to determine rates of under- and over-triage. Patient demographics were collected and waiting times were compared to existing standards of the SATS tool. RESULTS: Of the 4002 patients presenting to the emergency centre during the study period, 2% were triaged as emergency patients, 15% as very urgent, 38% as urgent and 45% as routine. The assigned acuities correlate well with outcome (f = 0.37; p < 0.0001) and an acceptable rate of over-triage (49%) and under-triage (9%) was found. Waiting time targets were poorly achieved with only 49% of emergency, 23% very urgent, 46% urgent and 69% routine patients seen within ideal target times. DISCUSSION: The SATS is a valid tool to implement in a rural district emergency centre. Strict waiting time goals may not be achievable in this setting without structural and resource allocation changes to allow for improvements in the surge capacity of staff to manage urgent and emergency patients.

STUDIES OF MOLECULAR CHANGES IN INTERVERTEBRAL DISC DEGENERATION IN ANIMAL MODEL.

OBJECTIVE: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. METHODS: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15(th) and 28(th) days after degenerative induction. RESULTS: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. CONCLUSION: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study.

STUDIES OF MOLECULAR CHANGES IN INTERVERTEBRAL DISC DEGENERATION IN ANIMAL MODEL

ABSTRACT Objective: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. Methods: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15th and 28th days after degenerative induction. Results: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. Conclusion: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study.

Pancreatic islet allograft in spleen with immunosuppression with cyclosporine. Experimental model in dogs.

PURPOSE: To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. METHODS: Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. RESULTS: The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. CONCLUSIONS: In the animals with immunosuppression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

Comparison of uniatrial and biatrial radiofrequency ablation procedures in atrial fibrillation: initial results.

BACKGROUND: Atrial fibrillation (AF) is the most commonly sustained cardiac rhythm disturbance. Surgical ablation techniques were developed involving the left atrium only and modifications of the maze procedure in ablating both atria. OBJECTIVE: The aim of this study was to compare, in patients with permanent AF, the efficacy of uniatrial versus biatrial radiofrequency ablation procedure in the treatment of chronic atrial fibrillation in patients with associated cardiac disease. METHOD: Between September 2003 and May 2009, 30 patients were submitted to the radiofrequency ablation procedure for AF associated with concomitant cardiac surgery; 15 patients underwent a uniatrial procedure, and 15 patients underwent biatrial ablation. The mean age was 47.73 ± 9.85 years, and 53.4% were men. The average followup time was 12.16 ± 10.89 months for the uniatrial group and 7.0 ± 4.0 months for the biatrial group. RESULTS: Neither hospital mortality nor complications related to radiofrequency ablation were was registered. At the time of hospital discharge, 9 patients (60%) were in a state of sinus rhythm in both groups. However, patients undergoing biatrial ablation (range 73.3% versus 46.7%) demonstrated complete freedom from atrial fibrillation at all times. CONCLUSION: Biatrial ablation surgical procedures were more effective in controlling atrial fibrillation than procedures limited to the left atrium.

Pancreatic islet allograft in spleen with immunossuppression with cyclosporine. Experimental model in dogs / Alotransplante de ilhotas pancreáticas no baço com imunossupressão com ciclosporina. Modelo experimental em cães

PURPOSE: To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. METHODS: Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. RESULTS: The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. CONCLUSIONS: In the animals with immunosupression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

OBJETIVO: Avaliar o comportamento funcional do alotransplante com imunossupressão de ilhotas pancreáticas no baço. MÉTODOS: Foram utilizados cinco grupos de 10 cães mestiços: grupo A (controle) submetido aos exames bioquímicos; grupo B, submetido à pancreatectomia total; grupo C (autotransplante) submetido à pancreatectomia total e autotransplantação de ilhotas pancreáticas no baço; grupo D, submetido à alotransplantação de ilhotas pancreáticas no baço sem terapia imunossupressiva; grupo E, submetido à alotransplantação de ilhotas no baço e imunossupressão com ciclosporina. Todos os animais transplantados receberam ilhotas pancreáticas isoladas pelo método mecânico-enzimático, digestão estacionária com colagenase e purificação com gradiente de densidade descontínua de dextran e foram implantadas no baço. RESULTADOS: Animais autotransplantados e alotransplantados com imunossupressão que se tornaram normoglicêmicos apresentaram testes de tolerância à glicose intravenosa alterados (p<0,001) e o nível de insulina plasmática periférica e na veia esplênica foram significantemente menores (p<0,001) nos animais alotransplantados com imunossupressão em relação aos autotransplantados. CONCLUSÃO: Nos animais submetidos ao alotransplante de ilhotas pancreáticas com imunossupressão com ciclosporina e preparadas pelo método mecânico-enzimático, digestão estacionária com colagenase e purificação com gradiente de densidade descontínua de dextran, a produção de insulina está diminuída e a resposta à sobrecarga de glicose intravenosa alterada.

Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients.

OBJECTIVE: The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator. MATERIALS AND METHODS: Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1-18 months, with a median follow-up of 6 months. RESULTS: Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3-18 months) with no in-field failures and were able to obtain encouraging toxicity profiles. CONCLUSION: Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity.

The relevance of wing geometry in entomological surveillance of Triatominae, vectors of Chagas disease.

An important epidemiological challenge in controlling the Triatominae (Hemiptera: Reduviidae), vectors of Chagas disease, is identifying the origin of insects re-infesting treated areas, especially when reinfestation occurs during the first 1 or 2 years following insecticide application and in the absence of insecticide resistance. When using strict insect characteristics, the standard approach is to compare reinfesting specimens with those collected prior to treatment. Because of the long generation time of Triatominae, the experimental intent is to reject the hypothesis of a previous population, the one prior to insecticide application, to be the parental population of the reinfesting population. Biometric techniques are based on the hypothesis of more similarity between offspring and parents, and have been tested in the field. Reinfesting specimens are very few when discovered, which might cause sampling problems. The present study used museum material to test the performance of modern morphometrics to assess the origin of a single individual. A configuration of 13 landmarks was used to assign a single wing to its known parental line or relatives. For the 313 wings tested, correct attribution to the parental line was four times higher than expected at random. Moreover, most of the apparently wrong assignments were not random, but driven by lower levels of kinship. These results suggest that the geometry of the wing contains helpful information to identify the possible source of reinfesting specimens.

Crossing experiments detect genetic incompatibility among populations of Triatoma brasiliensis Neiva, 1911 (Heteroptera, Reduviidae, Triatominae).

Triatoma brasiliensis is composed of at least four geographic populations (brasiliensis, melanica, macromelasoma, and juazeiro) that have distinct chromatic, morphologic, biologic and ecologic patterns, and genetic composition. Reciprocal crosses between all pairwise combinations were carried out in order to evaluate the genetic and reproductive compatibility of these four populations. The F1 individuals developed normally and the resulting adults were crossed again to test the F2 and F3 viability. Genetic incompatibility was found between melanica and brasiliensis populations.

Crossing experiments detect genetic incompatibility among populations of Triatoma brasiliensis Neiva, 1911 (Heteroptera, Reduviidae, Triatominae)

Triatoma brasiliensis is composed of at least four geographic populations (brasiliensis, melanica, macromelasoma, and juazeiro) that have distinct chromatic, morphologic, biologic and ecologic patterns, and genetic composition. Reciprocal crosses between all pairwise combinations were carried out in order to evaluate the genetic and reproductive compatibility of these four populations. The F1 individuals developed normally and the resulting adults were crossed again to test the F2 and F3 viability. Genetic incompatibility was found between melanica and brasiliensis populations