Search

Background: Dorsal root ganglion stimulation (DRGS) is an established method for treating persistent and severe pain conditions. However, performing DRGS has significant challenges. Current DRGS systems are expensive, hindering accessibility for many patients and health care systems. Additionally, placing DRGS devices requires specialized training in epidural techniques and lead anchoring methods. Technical and financial requirements also limit the clinical applicability and availability of DRGS., Objectives: This study evaluated the feasibility of a new method for rapidly delivering near- DRG stimulation in human cadavers. The method involves a fluoroscopy-guided transforaminal approach using a fully implantable, injectable electrode, and its associated delivery system., Study Design: A human cadaver feasibility study., Setting: A cadaver laboratory., Methods: In this study, 3 anesthesiologist pain physicians received training on the injectable electrode device and delivery system using spine phantom models. They then applied the device's associated implantation techniques to 2 adult male cadavers. In the first cadaver, a single injectable electrode was placed near the left L2 lumbar DRG. In the second cadaver, injectable electrodes were placed near the left L1 and L2 DRG levels, and a benchmark DRGS device was installed at the left L1 level using fluoroscopic guidance. A careful anatomical dissection was then performed for each implanted device., Results: The stimulating contacts of the injectable electrodes were accurately positioned within one mm of the DRG at the lumbar L1 and L2 levels in both cadavers. The distances of both the injectable lead and benchmark DRGS device at the L1 level were measured as one mm from the posterior aspect of the DRG., Limitations: The findings of this study are based on anatomical examinations of a limited number of human cadavers and may not fully represent living human anatomy., Conclusions: To our knowledge, this feasibility cadaver study is the first of its kind to examine the accuracy and efficiency of a fluoroscopy-guided transforaminal approach to place injectable electrodes near the DRG. These promising results suggest that this method could be a viable alternative to existing DRGS techniques, warranting further investigation into its clinical potential.

(1) Background: Medical devices, especially neuromodulation devices, are often explanted for a variety of reasons. The removal process imparts significant forces on these devices, which may result in device fracture and tissue trauma. We hypothesized that a device's form factor interfacing with tissue is a major driver of the force required to remove a device, and we isolated helical and linear electrode structures as a means to study atraumatic removal. (2) Methods: Ductile linear and helical microwire structure electrodes were fabricated from either Gold (Au) or Platinum-Iridium (Pt-Ir, 90-10). Removal forces were captured from synthetic gel models and following chronic implantation in rodent and porcine models. Devices were fully implanted in the animal models, requiring a small incision (<10 mm) and removal via tissue forceps. (3) Results: Helical devices were shown to result in significantly lower maximal removal forces in both synthetic gel and rodent studies compared to their linear counterparts. Chronically (1 yr.), the maximal removal force of helical devices remained under 7.30 N, for which the Platinum-Iridium device's tensile failure force was 32.90 ± 2.09 N, resulting in a safety factor of 4.50. (4) Conclusions: An open-core helical structure that can freely elongate was shown to result in reduced removal forces both acutely and chronically.

Objective. Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated Platinum/Iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, it is important to note that the effectiveness of stimulation through TES relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures. Approach. We employed a hybrid computational modeling approach to analyze the impact of Injectrode system design parameters on charge delivery and neural response to stimulation. We constructed multiple finite element method models of DRG stimulation, followed by the implementation of multi-compartment models of DRG neurons. By calculating potential distribution during monopolar stimulation, we simulated neural responses using various parameters based on prior acute experiments. Additionally, we developed a canonical monopolar stimulation and full-scale model of bipolar bilateral L5 DRG stimulation, allowing us to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds. Main results. Our findings were in accordance with acute experimental measurements and indicate that the minimally invasive Injectrode system predominantly engages large-diameter afferents (A β -fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (A δ -fibers) activity. Significance. The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired A β activation from the undesired A δ -fiber activation., (Creative Commons Attribution license.)

Objective: Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated platinum/iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, effectiveness of stimulation relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures., Approach: We employed a hybrid computational modeling approach to analyze the impact of the Injectrode system design parameters on charge delivery and the neural response to stimulation. We constructed multiple finite element method models of DRG stimulation and multi-compartment models of DRG neurons. We simulated the neural responses using parameters based on prior acute preclinical experiments. Additionally, we developed multiple human-scale computational models of DRG stimulation to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds., Main Results: Our findings were in accordance with acute experimental measurements and indicated that the Injectrode system predominantly engages large-diameter afferents (Aβ-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity., Significance: The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aβ activation from the undesired Aδ-fiber activation.

Exercise is a first-line treatment for type 2 diabetes and preserves β-cell function by hitherto unknown mechanisms. We postulated that proteins from contracting skeletal muscle may act as cellular signals to regulate pancreatic β-cell function. We used electric pulse stimulation (EPS) to induce contraction in C2C12 myotubes and found that treatment of β-cells with EPS-conditioned medium enhanced glucose-stimulated insulin secretion (GSIS). Transcriptomics and subsequent targeted validation revealed growth differentiation factor 15 (GDF15) as a central component of the skeletal muscle secretome. Exposure to recombinant GDF15 enhanced GSIS in cells, islets, and mice. GDF15 enhanced GSIS by upregulating the insulin secretion pathway in β-cells, which was abrogated in the presence of a GDF15 neutralizing antibody. The effect of GDF15 on GSIS was also observed in islets from GFRAL-deficient mice. Circulating GDF15 was incrementally elevated in patients with pre- and type 2 diabetes and positively associated with C-peptide in humans with overweight or obesity. Six weeks of high-intensity exercise training increased circulating GDF15 concentrations, which positively correlated with improvements in β-cell function in patients with type 2 diabetes. Taken together, GDF15 can function as a contraction-induced protein that enhances GSIS through activating the canonical signaling pathway in a GFRAL-independent manner., Article Highlights: Exercise improves glucose-stimulated insulin secretion through direct interorgan communication. Contracting skeletal muscle releases growth differentiation factor 15 (GDF15), which is required to synergistically enhance glucose-stimulated insulin secretion. GDF15 enhances glucose-stimulated insulin secretion by activating the canonical insulin release pathway. Increased levels of circulating GDF15 after exercise training are related to improvements in β-cell function in patients with type 2 diabetes., (© 2023 by the American Diabetes Association.)

Aims: Cardiomyopathy is a diabetic comorbidity with few molecular targets. To address this, we evaluated transfer RNA (tRNA) modifications in the diabetic heart because tRNA modifications have been implicated in diabetic etiologies., Main Methods: tRNA was isolated from aorta, apex, and atrial tissue of healthy and diabetic murine hearts and related hyperglycemic cell models. tRNA modifications and canonical ribonucleosides were quantified by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using stable isotope dilution. Correlations between ribonucleosides and diabetic comorbidity pathology were assessed using statistical analyses., Key Findings: Total tRNA ribonucleoside levels were analyzed from cell types and healthy and diabetic murine heart tissue. Each heart structure had characteristic ribonucleoside profiles and quantities. Several ribonucleosides were observed as significantly different in hyperglycemic cells and diabetic tissues. In hyperglycemic models, ribonucleosides N 4 -acetylcytidine (ac 4 C), 5-methoxycarbonylmethyl-2-thiouridine (mcm 5 s 2 U), 5-methylcytidine (m 5 C), and N 1 -methylguanosine (m 1 G) were anomalous. Specific tRNA modifications known to be on murine tRNA Ini(CAU) were higher in diabetic heart tissue which suggests that tRNA modifications could be regulating translation in diabetes., Significance: We identified tRNA ribonucleosides and tRNA species associated with hyperglycemia and diabetic etiology., Competing Interests: Declaration of competing interest At the time of submission, the authors have no competing interests (financial, professional or personal) that are relevant to the submitted work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective . The goal of this work was to compare afferent fiber recruitment by dorsal root ganglion (DRG) stimulation using an injectable polymer electrode (Injectrode ® ) and a more traditional cylindrical metal electrode. Approach . We exposed the L6 and L7 DRG in four cats via a partial laminectomy or burr hole. We stimulated the DRG using an Injectrode or a stainless steel (SS) electrode using biphasic pulses at three different pulse widths (80, 150, 300 μ s) and pulse amplitudes spanning the range used for clinical DRG stimulation. We recorded antidromic evoked compound action potentials (ECAPs) in the sciatic, tibial, and common peroneal nerves using nerve cuffs. We calculated the conduction velocity of the ECAPs and determined the charge-thresholds and recruitment rates for ECAPs from A α , A β , and A δ fibers. We also performed electrochemical impedance spectroscopy measurements for both electrode types. Main results . The ECAP thresholds for the Injectrode did not differ from the SS electrode across all primary afferents (A α , A β , A δ ) and pulse widths; charge-thresholds increased with wider pulse widths. Thresholds for generating ECAPs from A β fibers were 100.0 ± 32.3 nC using the SS electrode, and 90.9 ± 42.9 nC using the Injectrode. The ECAP thresholds from the Injectrode were consistent over several hours of stimulation. The rate of recruitment was similar between the Injectrodes and SS electrode and decreased with wider pulse widths. Significance . The Injectrode can effectively excite primary afferents when used for DRG stimulation within the range of parameters used for clinical DRG stimulation. The Injectrode can be implanted through minimally invasive techniques while achieving similar neural activation to conventional electrodes, making it an excellent candidate for future DRG stimulation and neuroprosthetic applications., (Creative Commons Attribution license.)

Chronic pain affects millions of people in the United States and pharmacological treatments have been ineffective. Dorsal root ganglion (DRG) stimulation is a neuromodulation method that delivers electrical stimulation to the DRG to relieve pain. DRG electrodes are rigid and cylindrical. The implantation of DRG electrodes requires a technically-challenging surgery that involves steering electrodes laterally towards the DRG. The Injectrode is an injectable conductive polymer that cures in place and is capable of delivering electrical current to stimulate neural tissue. We used the Injectrode to stimulate the L6 and L7 DRG in cats, measuring neural responses evoked in the sciatic, tibial, and common peroneal nerves to measure the thresholds for activating fibers. A cylindrical stainless-steel electrode was used for comparison. Thresholds were 38% higher with the Injectrode versus stainless-steel, likely owing to its larger contact surface area with the DRG. Both Aα and Aβ sensory fibers were activated using DRG stimulation. The Injectrode has the potential to offer a new and simple method for DRG stimulation that can potentially offer more complete coverage of the DRG., Competing Interests: Conflicts of Interest K.L. and A.S. are consultants to and co-founders of Neuronoff, Inc. M.F. is a co-founder and employee of Neuronoff, Inc. S.N is an employee of Neuronoff, Inc.

Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long-term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet-induced obesity. Exposure to BAM15 in vitro enhanced mitochondrial respiratory kinetics, improved insulin action, and stimulated nutrient uptake by sustained activation of AMPK. C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15-treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid-rich tissues. We provide the first phenotypic characterization and demonstration of pre-clinical efficacy for BAM15 as a pharmacological approach for the treatment of obesity and related diseases., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

New Findings: What is the central question of this study? Does short-duration, high-intensity exercise training that combines functional aerobic and resistance exercises into training sessions lasting 8-20 min benefit individuals with type 2 diabetes? What is the main finding and its importance? Functional high-intensity training improves insulin sensitivity and reduces cardiometabolic risk in individuals with type 2 diabetes. This type of exercise training may be an effective exercise mode for managing type 2 diabetes. The increase in insulin sensitivity addresses a key defect in type 2 diabetes., Abstract: Functional high-intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high-intensity in workouts that range from ∼8 to 20 min per session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34.5 ± 3.6 kg m -2 , means ± SD) with T2D to participate in a 6-week (3 days week -1 ) supervised F-HIT programme. An oral glucose tolerance test was used to derive measures of insulin sensitivity. F-HIT significantly reduced fat mass (43.8 ± 83.8 vs. 41.6 ± 7.9 kg; P < 0.01), diastolic blood pressure (80.2 ± 7.1 vs. 74.5 ± 5.8; P < 0.01), blood lipids (triglyceride and VLDL, both P < 0.05) and metabolic syndrome z-score (6.4 ± 4.5 vs. -0.2 ± 5.2 AU; P < 0.001), and increased basal fat oxidation (0.08 ± 0.03 vs. 0.10 ± 0.04 g min -1 ; P = 0.05), and high molecular mass adiponectin (214.4 ± 88.9 vs. 288.8 ± 127.4 ng mL -1 ; P < 0.01). Importantly, F-HIT also increased insulin sensitivity (0.037 ± 0.010 vs. 0.042 ± 0.010 AU; P < 0.05). Increases in high molecular mass adiponectin and basal fat oxidation correlated with the change in insulin sensitivity (ρ, 0.75, P < 0.05 and ρ, 0.81, P < 0.01, respectively). Compliance with the training programme was >95% and no injuries or adverse events were reported. These data suggest that F-HIT may be an effective exercise mode for managing T2D. The increase in insulin sensitivity addresses a key defect in T2D and is consistent with improvements observed after more traditional aerobic exercise programmes in overweight/obese adults with T2D., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

Background: Mothers rely heavily on health worker advice to make infant feeding decisions. Confusing or misleading advice can lead to suboptimal feeding practices. From 2001, HIV positive mothers in South Africa were counseled to choose either exclusive breastfeeding or exclusive formula feeding to minimize vertical HIV transmission. On the basis of revised World Health Organization guidelines, the government amended this policy in 2011, by promoting exclusive breastfeeding and discontinuing the provision of free formula. We explored how health workers experienced this new policy in an HIV endemic community in 2015-16, with attention to their knowledge of the policy, counselling practices, and observations of any changes., Methods: We interviewed eleven health workers, from four community health clinics, who had counseled mothers before and after the policy change. The transcribed interviews were analyzed thematically, using a hybrid coding approach., Results: The scientific rationale of the policy was not explained to most health workers, who mostly thought that the discontinuation of the formula program was cost-related. The content of their counseling reflected knowledge about promoting breastfeeding for all women, and accordingly they mentioned the nutritional and developmental benefits of breastfeeding. The importance of exclusive breastfeeding for all infants was not emphasized, instead counseling focused on HIV prevention, even for uninfected mothers. The health workers noted an increased incidence of breastfeeding, but some worried that to avoid HIV disclosure, HIV positive mothers were mixed feeding rather than exclusively breastfeeding., Conclusions: Causal links between the policy, counseling content and feeding practices were unclear. Some participants believed that breastfeeding practices were driven by finance or family pressures rather than the health information they provided. Health workers generally lacked training on the policy's evidence base, particularly the health benefits of exclusive breastfeeding for non-exposed infants. They wanted clarity on their counseling role, based on individual risk or to promote exclusive breastfeeding as a single option. If the latter, they needed training on how to assist mothers with community-based barriers. Infant feeding messages from health workers are likely to remain confusing until their uncertainties are addressed. Their insights should inform future guideline development as key actors., Competing Interests: Ethics approval for this study was obtained from the Human Research Ethics Committee of the University of the Witwatersrand (M140803), the City of Johannesburg Research Committee and each facility. To address potential cultural and language sensitivities, the PI always offered participants the option of having a RA who spoke multiple local languages to support the interviews. Only the PI and RAs were involved in direct recruitment to avoid coercion from managers. Participation was voluntary. All participants provided prior written consent for the study and audio recordings. To preserve anonymity, codes were assigned to each participant based on the number of the visit. All recordings and transcripts are stored in password-protected files. Signed consent forms are stored in a locked cupboard at the University of the Witwatersrand.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

We are interested in understanding mechanisms that govern the protective role of exercise against lipid-induced insulin resistance, a key driver of type 2 diabetes. In this context, cell culture models provide a level of abstraction that aid in our understanding of cellular physiology. Here we describe the development of an in vitro myotube contraction system that provides this protective effect, and which we have harnessed to investigate lipid-induced insulin resistance. C2C12 myocytes were differentiated into contractile myotubes. A custom manufactured platinum electrode system and pulse stimulator, with polarity switching, provided an electrical pulse stimulus (EPS) (1 Hz, 6-ms pulse width, 1.5 V/mm, 16 h). Contractility was assessed by optical flow flied spot noise mapping and inhibited by application of ammonium acetate. Following EPS, myotubes were challenged with 0.5 mM palmitate for 4 h. Cells were then treated with or without insulin for glucose uptake (30 min), secondary insulin signaling activation (10 min), and phosphoinositide 3-kinase-α (PI3Kα) activity (5 min). Prolonged EPS increased non-insulin-stimulated glucose uptake (83%, P = 0.002), Akt (Thr308) phosphorylation ( P = 0.005), and insulin receptor substrate-1 (IRS-1)-associated PI3Kα activity ( P = 0.048). Palmitate reduced insulin-specific action on glucose uptake (-49%, P < 0.001) and inhibited insulin-stimulated Akt phosphorylation ( P = 0.049) and whole cell PI3Kα activity ( P = 0.009). The inhibitory effects of palmitate were completely absent with EPS pretreatment at the levels of glucose uptake, insulin responsiveness, Akt phosphorylation, and whole cell PI3Kα activity. This model suggests that muscle contraction alone is a sufficient stimulus to protect against lipid-induced insulin resistance as evidenced by changes in the proximal canonical insulin-signaling pathway., (Copyright © 2017 the American Physiological Society.)

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D., (Copyright © 2017 the American Physiological Society.)

Exercise is typically one of the first management strategies advised for patients newly diagnosed with type 2 diabetes. Together with diet and behavior modification, exercise is an essential component of all diabetes and obesity prevention and lifestyle intervention programs. Exercise training, whether aerobic or resistance training or a combination, facilitates improved glucose regulation. High-intensity interval training is also effective and has the added benefit of being very time-efficient. While the efficacy, scalability, and affordability of exercise for the prevention and management of type 2 diabetes are well established, sustainability of exercise recommendations for patients remains elusive., (Copyright © 2017 Cleveland Clinic.)

Globally, communication plays an integral role in public health strategies, from infectious diseases to diseases related to lifestyles. The evolution of the field of social and behaviour change communication (SBCC), combined with the need for evidence based practice and multi-level interventions to promote health, and human resource gaps in sub-Saharan Africa have led to the imperative to standardise and formalise the field. Moreover, current practitioners come from different disciplinary backgrounds underlining the need to define common core skills and competencies. This paper describes the partnership between the Wits School of Public Health and the Soul City Institute for Health and Development Communication and how the partners responded to this need. It highlights the factors influencing sustainable institutional capacity to provide quality assured, accredited training. We describe an unexpected positive response from a number of practitioner organisations that have chosen to send multiple staff members for training, specifically to build a critical mass within their organisations. Finally, we note the interest from (mostly) southern-based academic institutions in setting up similar programmes and postulate that south-south collaborations can contribute to building sustainable context specific and evidence-informed SBCC programmes in the global south.

Early pancreatic morphogenesis is characterized by the transformation of an uncommitted pool of pancreatic progenitor cells into a branched pancreatic epithelium that consists of 'tip' and 'trunk' domains. These domains have distinct molecular signatures and differentiate into distinct pancreatic cell lineages. Cells at the branched tips of the epithelium develop into acinar cells, whereas cells in the trunk subcompartment differentiate into endocrine and duct cells. Recent genetic analyses have highlighted the role of key transcriptional regulators in the specification of these subcompartments. Here, we analyzed in mice the role of Notch signaling in the patterning of multipotent pancreatic progenitor cells through mosaic overexpression of a Notch signaling antagonist, dominant-negative mastermind-like 1, resulting in a mixture of wild-type and Notch-suppressed pancreatic progenitor cells. We find that attenuation of Notch signaling has pronounced patterning effects on multipotent pancreatic progenitor cells prior to terminal differentiation. Relative to the wild-type cells, the Notch-suppressed cells lose trunk marker genes and gain expression of tip marker genes. The Notch-suppressed cells subsequently differentiate into acinar cells, whereas duct and endocrine populations are formed predominantly from the wild-type cells. Mechanistically, these observations could be explained by a requirement of Notch for the expression of the trunk determination gene Nkx6.1. This was supported by the finding of direct binding of RBP-jκ to the Nkx6.1 proximal promoter.

Resistance to natural infections of Haemonchus contortus (wireworm) was studied in Merino sheep. From February 1995 to July 1996 data were collected from the OTK Merino Stud on the farm Wildebeesfontein near Hendrina in Mpumalanga province. From March 1998 to January 2000 another Merino flock at Irene in Gauteng province was included in the study. In both cases, 50 randomly-chosen animals from each group of lambs weaned were sampled weekly for faecal egg count (FEC) until a mean of 2500 eggs per gram faeces (epg) was reached. At this stage, all lambs in the group were sampled for FEC, packed cell volume (PCV) and live mass in the case of the Wildebeesfontein flock. Animals were monitored from weaning to about 1 year of age. Data from 5 different groups of lambs (583 animals and 1722 records in total) with genetic links were accumulated and analysed. Variance components and resulting heritabilities for logFEC and PCV were estimated using a bivariate animal model with repeated records. The estimated heritabilities were 0.24 +/- 0.02 for logFEC and 0.14 +/- 0.02 for PCV. A strong negative correlation (-0.84 +/- 0.06) existed between the 2 traits. The genetic correlation between PCV and live mass for the Wildebeesfontein flock was low (0.28 +/- 0.09), while that between logFEC and live mass was negative, although not significantly different from zero (-0.13 +/- 0.09). These results suggest that FEC can be used as a selection criterion for resistance to H. contortus infections in Merino sheep.

Stress is caused by the demands of everyday life and is an integral part of our lives. The manner in which stress is coped with, remains the responsibility of the individual herself. To be in the nursing profession today, is highly demanding. The psychiatric nurse experiences more stressors, because she is involved in a specialised area, where she uses herself as a therapeutic instrument on a scientific basis. The psychiatric nursing student finds herself in a situation where she is confronted by stressors from her personal and professional environment, as well as stressors caused by her present training in psychiatric nursing. To ensure quality nursing and job satisfaction by the psychiatric nursing students, it is important that their stressors must be identified and that they must learn in good time ways how to effectively cope with it. The psychiatric nursing student must learn ways to cope with her own stressors and consequently she will be in a position to be of assistance to her patients. Coping with stress unsuccessfully and not identifying a high stress load, can have disastrous consequences for both the psychiatric nursing student as well as for the specific organisation in which she is involved. The purpose of this research is to identify the precise stressors which influence the psychiatric nursing student during her training, as well as to establish guidelines to direct the psychiatric nursing student where coping with stress is concerned. A descriptive contextual field study was executed by identifying the stressors of a psychiatric nursing student in the area that she was involved in during her training.(ABSTRACT TRUNCATED AT 250 WORDS)