Long-term efficacy and safety of porcine islet macrobeads in nonimmunosuppressed diabetic cynomolgus macaques.

Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue.

Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates.

Background: We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes.

Methods: Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs.

Long-Term Management of Vascular Access Ports in Nonhuman Primates Used in Preclinical Efficacy and Tolerability Studies.

Vascular access ports (VAPs) are an essential tool for long-term vascular access in preclinical studies and disease modeling in non-human primates (NHPs). We retrospectively reviewed central (inferior vena cava, IVC) and portal VAP implantation with the maintenance at our center from 15 January 2010 to 31 January 2018. In total, 209 VAPs were implanted for long-term drug administration and sampling.

Neurodevelopmental disorders in prison inmates: comorbidity and combined associations with psychiatric symptoms and behavioural disturbance.

The identification and management of inmates with neurodevelopmental disorders (ND) has been insufficiently addressed in the literature. We estimated the proportion of cases with Attention deficit/hyperactivity disorder (ADHD), Autism spectrum disorder (ASD) and Intellectual disability (ID) in prison, their comorbidity, and associations with disruptive behaviours and with psychiatric symptoms. Further, we examined the role of coexisting ND on psychiatric symptoms and attitudes toward violence.

Cross-validation of commercial enzyme-linked immunosorbent assay and radioimmunoassay for porcine C-peptide concentration measurements in non-human primate serum.

Background: C-peptide concentration is widely used as a marker of insulin secretion and is especially relevant in evaluating islet graft function following transplantation, because its measurement is not confounded by the presence of exogenous insulin. To address the shortage of human islet donors, the use of porcine islets has been proposed as a possible solution and the stringent pig-to-non-human primate (NHP) model is often the most relevant for pre-clinical evaluation of the potential for diabetes reversal resulting from an islet xenograft. The Millipore radioimmunoassay (RIA) was exclusively used to measure porcine C-peptide (PCP) until 2013 when the assay was discontinued and subsequently a commercially available enzyme-linked immunosorbent assay (ELISA) from Mercodia has been widely adopted.

Transitions and Motivations for Substance Misuse in Prison Inmates With ADHD and Conduct Disorder: Validation of a New Instrument.

Objective: There is a reasonable theoretical base for understanding the possible causes and motivations behind substance misuse and its dependency. There is a need for a reliable and valid measure that delineates the markers of substance use from its initiation and identifies different motivations for drug use transitioning, maintenance, and dependency. We addressed this gap in the United Kingdom by examining and validating the Substance Transitions in Addiction Rating Scale (STARS).

Establishing a Large-Animal Model for In Vivo Reprogramming of Bile Duct Cells into Insulin-Secreting Cells to Treat Diabetes.

Type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. Both of these approaches have severe limitations. Repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures.

Substance and Alcohol Misuse, Drug Pathways, and Offending Behaviors in Association With ADHD in Prison Inmates.

The objective of the study is to quantify the extent of specific polysubstance use, drug transitions to current substances, and describe the association with alcohol use disorders among inmates with ADHD. We also examined health risk behaviors and patterns of offending in relation with ADHD. A total of 387 male British prison inmates were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.

Diagnostic accuracy of a brief screening tool for attention deficit hyperactivity disorder in UK prison inmates.

Background: Attention deficit hyperactivity disorder (ADHD) is overrepresented in prison, making it imperative to identify a screening tool that can be quickly applied to efficiently detect the disorder. We explored the discrimination ability of a widely used ADHD screen, the Barkley Adult ADHD Rating Scale (BAARS-IV), against a clinical diagnostic interview. A brief version of the screen was then developed in order to simplify its use in the prison context, and maximize its diagnostic properties.

Evaluation of commercial ELISA and RIA for measuring porcine C-peptide: implications for research.

Background: Pre-clinical demonstration of porcine islet graft function is necessary to support the clinical transplantation of pig islets. C-peptide concentration is an especially useful marker of insulin secretion, because its measurement is not confounded by the presence of exogenous insulin. To measure porcine C-peptide (PCP), researchers in the field exclusively used the Millipore (previously Linco Research) radioimmunoassay (RIA) until 2011, when Mercodia released an alternative enzyme-linked immunosorbent assay (ELISA).

Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion.

Directed cell migration is critical for numerous physiological processes including development and wound healing. However chemotaxis is also exploited during cancer progression. Recent reports have suggested links between vesicle trafficking pathways and directed cell migration.

Management of adverse side-effects after chemotherapy in macaques as exemplified by streptozotocin: case studies and recommendations.

The chemotherapeutic streptozotocin is used for induction of diabetes in animal models including non-human primates. Being a cytotoxic nitrosourea compound, it can be associated with adverse events (AEs), mainly nausea and emesis, nephrotoxicity, elevated liver transaminase levels, pulmonary oedema and, most prominently, metabolic acidosis: these can be severe in some cases. The incidence and gravity are to some extent related to the characteristics of the individual animal, diagnostic tools, prompt recognition of symptoms and supportive measures.

Successful implementation of cooperative handling eliminates the need for restraint in a complex non-human primate disease model.

Background: Streptozotocin-induced diabetic non-human primates are used to study efficacy and safety of innovative immunosuppression after islet transplantation. We implemented a training program for medical management of a chronic disease state.

Methods: Cooperation with hand feeding and drinking, shifting, and limb presentation were trained utilizing predominately positive but also negative reinforcement in 52 animals compared with 28 macaques subjected to conventional physical and/or chemical restraint.

Bioleaching in brackish waters--effect of chloride ions on the acidophile population and proteomes of model species.

High concentrations of chloride ions inhibit the growth of acidophilic microorganisms used in biomining, a problem particularly relevant to Western Australian and Chilean biomining operations. Despite this, little is known about the mechanisms acidophiles adopt in order to tolerate high chloride ion concentrations. This study aimed to investigate the impact of increasing concentrations of chloride ions on the population dynamics of a mixed culture during pyrite bioleaching and apply proteomics to elucidate how two species from this mixed culture alter their proteomes under chloride stress.

Refining the high-dose streptozotocin-induced diabetic non-human primate model: an evaluation of risk factors and outcomes.

In preparation for islet transplantation, diabetes was induced using streptozotocin (STZ) in non-human primates ranging from juveniles to adults with diverse body types: we studied the process with respect to the diabetic state and emergence of adverse events (AEs) and their severity, and identified risk factors for clinical and laboratory AEs. Pharmaceutical-grade STZ was given based on body surface area (BSA) (1050-1250 mg/m(2), equivalent to 80-108 mg/kg) or on body weight (BW) (100 mg/kg) to 54 cynomolgus and 24 rhesus macaques. AEs were related to risk factors, i.

Long-term hepatic vascular access in the nonhuman primate for recurrent portal vein infusion.

Islet cell transplantation in nonhuman primates is generally performed in the liver, by infusion of the transplant into the portal vein. We introduced a vascular access port with the catheter tip located in the splenic vein to avoid multiple major survival surgeries. This procedure was conducted in 16 cynomolgus and 9 rhesus macaques.

Refinement of vascular access port placement in nonhuman primates: complication rates and outcomes.

Chronic vascular access is often needed in experimental animal studies, and vascular access ports (VAP) have been proposed as an alternative to conventional venipuncture. We previously reported on VAP implantation by using femoral venous cutdown (FVC) and tunneling. In an attempt to decrease the moderate complications associated with the FVC method, we developed the single-incision, peripheral-insertion (SIPI) method.

A novel alternative placement site and technique for totally implantable vascular access ports in non-human primates.

Background: Two novel approaches to implanting a central venous catheter port in non-human primates (NHPs) using peripheral insertion are presented and compared.

Methods: Sixty vascular access port (VAP) implants were attempted in 52 NHPs by saphenous vein puncture (n = 20) or saphenous vein cutdown (n = 40).

Results: Fifty eight procedures were successful.

Late presentation of opsoclonus-myoclonus-ataxia syndrome in a child with stage 4S neuroblastoma.

Opsoclonus-myoclonus-ataxia syndrome (OMA) in children is most commonly associated with occult neuroblastoma (NB). Although children with OMA and NB have decreased mortality, they suffer from increased neurologic morbidity. The pathogenesis of OMA in NB is not well understood, but current research and treatments support an immune-mediated process.

Behavioral and emotional adjustment of teenagers in mainstream school who were born before 29 weeks' gestation.

Objectives: To investigate behavioral and emotional problems and positive adjustment of 15-to 16-year-olds who were born at extremely low gestational age (ELGA), from the perspective of parents, teachers, and teenagers.

Methods: Prospective follow-up was conducted of birth cohorts, with classroom control subjects. All infants who were born before 29 weeks in 1983-1984 (mean gestational age: 27 weeks) to mothers who resided in 3 regions of the United Kingdom were studied.

Diversity and specificity of Rhizobium leguminosarum biovar viciae on wild and cultivated legumes.

The symbiotic partnerships between legumes and their root-nodule bacteria (rhizobia) vary widely in their degree of specificity, but the underlying reasons are not understood. To assess the potential for host-range evolution, we have investigated microheterogeneity among the shared symbionts of a group of related legume species. Host specificity and genetic diversity were characterized for a soil population of Rhizobium leguminosarum biovar viciae (Rlv) sampled using six wild Vicia and Lathyrus species and the crop plants pea (Pisum sativum) and broad bean (Vicia faba).

Health and school performance of teenagers born before 29 weeks gestation.

Objective: To ascertain the health and school performance of teenagers born before 29 weeks gestation (extremely low gestational age (ELGA)) and to compare those in mainstream school with classroom controls.

Methods: Three geographically defined cohorts of babies born in 1983 and 1984 were traced at the age of 15-16 years. Their health, abilities, and educational performance were ascertained using postal questionnaires to the teenagers themselves, their parents, their general practitioners, and the teachers of those in mainstream school.

Direct amplification of nodD from community DNA reveals the genetic diversity of Rhizobium leguminosarum in soil.

Sequences of nodD, a gene found only in rhizobia, were amplified from total community DNA isolated from a pasture soil. The polymerase chain reaction (PCR) primers used, Y5 and Y6, match nodD from Rhizobium leguminosarum biovar trifolii, R. leguminosarum biovar viciae and Sinorhizobium meliloti.