Some Methodological Issues in Neuroethics: The Case of Responsibility and Psychopathy.

There are some distinct methodological challenges, and possible pitfalls, for neuroethics when it evaluates neuroscientific results and links them to issues such as moral or legal responsibility. Some problems emerge in determining the requirements for responsibility. We will show how philosophical proposals in this area need to interact with legal doctrine and practice. Problems can occur when inferring normative implications from neuroscientific results. Other problems arise when it is not recognized that data about brain anatomy or physiology are relevant to the ascription of responsibility only when they are significantly correlated with the psychological capacities contemplated by the legal formulations of responsibility. We will demonstrate this by considering two significant cases concerning psychopathy. Some paradigms that aim at measuring higher-order capacities, such as moral understanding, have limited validity. More robust paradigms for the study of learning in restricted controlled conditions, on the other hand, have limited ecological validity across individuals and context to be of any use for the law.

Intestinal nerve cell injury occurs prior to insulin resistance in female mice ingesting a high-fat diet.

Diabetic patients suffer from gastrointestinal disorders associated with dysmotility, enteric neuropathy and dysbiosis of gut microbiota; however, gender differences are not fully known. Previous studies have shown that a high-fat diet (HFD) causes type two diabetes (T2D) in male mice after 4-8 weeks but only does so in female mice after 16 weeks. This study seeks to determine whether sex influences the development of intestinal dysmotility, enteric neuropathy and dysbiosis in mice fed HFD. We fed 8-week-old C57BL6 male and female mice a standard chow diet (SCD) or a 72% kcal HFD for 8 weeks. We analyzed the associations between sex and intestinal dysmotility, neuropathy and dysbiosis using motility assays, immunohistochemistry and next-generation sequencing. HFD ingestion caused obesity, glucose intolerance and insulin resistance in male but not female mice. However, HFD ingestion slowed intestinal propulsive motility in both male and female mice. This was associated with decreased inhibitory neuromuscular transmission, loss of myenteric inhibitory motor neurons and axonal swelling and loss of cytoskeletal filaments. HFD induced dysbiosis and changed the abundance of specific bacteria, especially Allobaculum, Bifidobacterium and Lactobacillus, which correlated with dysmotility and neuropathy. Female mice had higher immunoreactivity and numbers of myenteric inhibitory motor neurons, matching larger amplitudes of inhibitory junction potentials. This study suggests that sex influences the development of HFD-induced metabolic syndrome but dysmotility, neuropathy and dysbiosis occur independent of sex and prior to T2D conditions. Gastrointestinal dysmotility, neuropathy and dysbiosis might play a crucial role in the pathophysiology of T2D in humans irrespective of sex.

An RNAi-Based Control of Fusarium graminearum Infections Through Spraying of Long dsRNAs Involves a Plant Passage and Is Controlled by the Fungal Silencing Machinery.

Meeting the increasing food and energy demands of a growing population will require the development of ground-breaking strategies that promote sustainable plant production. Host-induced gene silencing has shown great potential for controlling pest and diseases in crop plants. However, while delivery of inhibitory noncoding double-stranded (ds)RNA by transgenic expression is a promising concept, it requires the generation of transgenic crop plants which may cause substantial delay for application strategies depending on the transformability and genetic stability of the crop plant species. Using the agronomically important barley-Fusarium graminearum pathosystem, we alternatively demonstrate that a spray application of a long noncoding dsRNA (791 nt CYP3-dsRNA), which targets the three fungal cytochrome P450 lanosterol C-14α-demethylases, required for biosynthesis of fungal ergosterol, inhibits fungal growth in the directly sprayed (local) as well as the non-sprayed (distal) parts of detached leaves. Unexpectedly, efficient spray-induced control of fungal infections in the distal tissue involved passage of CYP3-dsRNA via the plant vascular system and processing into small interfering (si)RNAs by fungal DICER-LIKE 1 (FgDCL-1) after uptake by the pathogen. We discuss important consequences of this new finding on future RNA-based disease control strategies. Given the ease of design, high specificity, and applicability to diverse pathogens, the use of target-specific dsRNA as an anti-fungal agent offers unprecedented potential as a new plant protection strategy.

Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.

The aim of the current study (Clinical trial reg. no. NCT02715193, clinicaltrials.gov) was to study the efficacy and safety of REMD-477, a glucagon receptor antagonist, in type 1 diabetes. This was a randomized controlled trial in which 21 patients with type 1 diabetes were enrolled. Glycaemic control and insulin use were evaluated in outpatient and inpatient settings, before and after a single 70-mg dose of REMD-477 (half-life 7-10 days) or placebo. Inpatient insulin use was 26% (95% CI, 47%, 4%) lower 1 day after dosing with REMD-477 than with placebo (P = .02). Continuous glucose monitoring during post-treatment days 6 to 12 showed that average daily glucose was 27 mg/dL lower (P < .001), percent time-in-target-range (70-180 mg/dL) was ~25% greater (~3.5 h/d) (P = .001), and percent time-in-hyperglycaemic-range (> 180 mg/dL) was ~40% lower (~4 h/d) (P = .001) in the REMD-477 group than in the placebo group, without a difference in percent time-in-hypoglycaemic-range (<70 mg/dL). No serious adverse events were reported. Glucagon receptor antagonism decreases insulin requirements and improves glycaemic control in patients with type 1 diabetes.

Ethics Education in New Zealand Medical Schools.

This article describes the well-developed and long-standing medical ethics teaching programs in both of New Zealand's medical schools at the University of Otago and the University of Auckland. The programs reflect the awareness that has been increasing as to the important role that ethics education plays in contributing to the "professionalism" and "professional development" in medical curricula.

Examining the use of metaphors to understand the experience of community treatment orders for patients and mental health workers.

BACKGROUND: Community Treatment Orders (CTOs) are often complex because of the ethical tensions created by an intervention that aims at promoting the patient's good through an inherently coercive process. There is limited research that examines the complexity of CTOs and how patients on CTOs and workers administering CTOs make sense of their experiences. METHODS: The study involved in-depth interviews with 8 patients on CTOs and 10 community mental health workers in South Australia, to explore how they constructed their experiences of CTOs. Critical discourse analysis (CDA) was used to analyse the data, supported by NVIVO software. RESULTS: Analysis of the interviews revealed that patients and workers experienced the CTO process as multi-dimensional, including some positive as well as more negative constructions. The positive metaphor of CTOs as a safety net is described, followed by a more detailed description of the metaphors of power and control as the dominant themes, with five sub-themes of the CTO as control, wake-up, punishment, surveillance, and tranquiliser. DISCUSSION: Metaphors are a way that mental health patients and mental health workers articulate the nature of CTOs. The language used to construct these metaphors was quite different, with patients overwhelmingly experiencing and perceiving CTOs as coercive (that is, punishing, controlling and scrutinizing), whereas workers tended to perceive them as necessary, beneficial and supportive, despite their coerciveness. CONCLUSIONS: By acknowledging the role of metaphors in these patients' lives, workers could enhance opportunities to engage these patients in more meaningful dialogue about their personal experiences as an alternative to practice predominantly focused on risk. Such a dialogue could enhance workers' reflection on their work and promote recovery-based practice. More understanding of how to promote autonomy, capacity and supported decision-making, and how to address the impacts of coercion within care, is needed.