Setting Our Sights on Infectious Diseases.

In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learnings.

Using ILD or ITD Cues for Sound Source Localization and Speech Understanding in a Complex Listening Environment by Listeners With Bilateral and With Hearing-Preservation Cochlear Implants.

PURPOSE: To assess the role of interaural time differences and interaural level differences in (a) sound-source localization, and (b) speech understanding in a cocktail party listening environment for listeners with bilateral cochlear implants (CIs) and for listeners with hearing-preservation CIs. METHODS: Eleven bilateral listeners with MED-EL (Durham, NC) CIs and 8 listeners with hearing-preservation CIs with symmetrical low frequency, acoustic hearing using the MED-EL or Cochlear device were evaluated using 2 tests designed to task binaural hearing, localization, and a simulated cocktail party. Access to interaural cues for localization was constrained by the use of low-pass, high-pass, and wideband noise stimuli. RESULTS: Sound-source localization accuracy for listeners with bilateral CIs in response to the high-pass noise stimulus and sound-source localization accuracy for the listeners with hearing-preservation CIs in response to the low-pass noise stimulus did not differ significantly. Speech understanding in a cocktail party listening environment improved for all listeners when interaural cues, either interaural time difference or interaural level difference, were available. CONCLUSIONS: The findings of the current study indicate that similar degrees of benefit to sound-source localization and speech understanding in complex listening environments are possible with 2 very different rehabilitation strategies: the provision of bilateral CIs and the preservation of hearing.

The self-management of longer-term depression: learning from the patient, a qualitative study.

BACKGROUND: Depression is a common mental health condition now viewed as chronic or long-term. More than 50 % of people will have at least one further episode of depression after their first, and therefore it requires long-term management. However, little is known about the effectiveness of self-management in depression, in particular from the patients' perspective. This study aimed to understand how people with longer-term depression manage the condition, how services can best support self-management and whether the principles and concepts of the recovery approach would be advantageous. METHODS: Semi-structured in depth interviews were carried out with 21 participants, recruited from a range of sources using maximum variation sampling. Interpretative Phenomenological Analysis was used by a diverse team comprised of service users, practitioners and academics. RESULTS: Four super-ordinate themes were found: experience of depression, the self, the wider environment, self-management strategies. Within these, several prominent sub-themes emerged of importance to the participants. These included how aspects of themselves such as hope, confidence and motivation could be powerful agents; and how engaging in a wide range of chosen activities could contribute to their emotional, mental, physical, social, spiritual and creative wellbeing. CONCLUSIONS: Services in general were not perceived to be useful in specifically facilitating self-management. Increased choice and control were needed and a greater emphasis on an individualised holistic model. Improved information was needed about how to develop strategies and locate resources, especially during the first episode of depression. These concepts echoed those of the recovery approach, which could therefore be seen as valuable in aiding the self-management of depression.

Factors constraining the benefit to speech understanding of combining information from low-frequency hearing and a cochlear implant.

Many studies have documented the benefits to speech understanding when cochlear implant (CI) patients can access low-frequency acoustic information from the ear opposite the implant. In this study we assessed the role of three factors in determining the magnitude of bimodal benefit - (i) the level of CI-only performance, (ii) the magnitude of the hearing loss in the ear with low-frequency acoustic hearing and (iii) the type of test material. The patients had low-frequency PTAs (average of 125, 250 and 500 Hz) varying over a large range (<30 dB HL to >70 dB HL) in the ear contralateral to the implant. The patients were tested with (i) CNC words presented in quiet (n = 105) (ii) AzBio sentences presented in quiet (n = 102), (iii) AzBio sentences in noise at +10 dB signal-to-noise ratio (SNR) (n = 69), and (iv) AzBio sentences at +5 dB SNR (n = 64). We find maximum bimodal benefit when (i) CI scores are less than 60 percent correct, (ii) hearing loss is less than 60 dB HL in low-frequencies and (iii) the test material is sentences presented against a noise background. When these criteria are met, some bimodal patients can gain 40-60 percentage points in performance relative to performance with a CI. This article is part of a Special Issue entitled .

Bimodal cochlear implants: the role of acoustic signal level in determining speech perception benefit.

The aim of this project was to determine for bimodal cochlear implant (CI) patients, i.e. patients with low-frequency hearing in the ear contralateral to the implant, how speech understanding varies as a function of the difference in level between the CI signal and the acoustic signal. The data suggest that (1) acoustic signals perceived as significantly softer than a CI signal can contribute to speech understanding in the bimodal condition, (2) acoustic signals that are slightly softer than, or balanced with, a CI signal provide the largest benefit to speech understanding, and (3) acoustic signals presented at maximum comfortable loudness levels provide nearly as much benefit as signals that have been balanced with a CI signal.

A non-randomized comparison of mindfulness-based stress reduction and healing arts programs for facilitating post-traumatic growth and spirituality in cancer outpatients.

GOALS OF WORK: The aim of this study was to compare a mindfulness-based stress reduction (MBSR) program and a healing through the creative arts (HA) program on measures of post-traumatic growth (PTGI-R), spirituality (FACIT-Sp), stress (SOSI), and mood disturbance (POMS) in cancer patients. MATERIALS AND METHODS: A sample of cancer outpatients (MBSR, n = 60; HA, n = 44) with a variety of diagnoses chose to attend either an 8-week MBSR program or a 6-week HA program and were assessed pre- and post-intervention. The majority of participants were female, married, and had breast cancer. MAIN RESULTS: Repeated measures analysis of variance indicated that participants in both groups improved significantly over time on overall post-traumatic growth (p = 0.015). Participants in the MBSR group improved on measures of spirituality more than those in the HA group (p = 0.029). Participants in the MBSR group also showed more improvement than those in HA on measures of anxiety (POMS, p = 0.038), anger (POMS, p = 0.004), overall stress symptoms (SOSI, p = 0.041), and mood disturbance (POMS, p = 0.023). Several main effects of time were also observed in both groups. These results were found despite attrition in both groups. CONCLUSIONS: Both programs may improve facilitation of positive growth after traumatic life experiences for those who choose to participate. MBSR may be more helpful than HA in enhancing spirituality and reducing stress, depression, and anger.

Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat.

The use of soy-based products in the diet of infants has raised concerns regarding the reproductive toxicity of genistein and daidzein, the predominant isoflavones in soybeans with estrogenic activity. Time-bred Long-Evans dams were fed diets containing 0, 5, 50, 500, or 1000 ppm of soy isoflavones from gestational d 12 until weaning at d 21 postpartum. Male rats in all groups were fed soy-free diets from postnatal d 21 until 90 d of age. The mean +/- SD concentration of unconjugated (i.e. biologically active) genistein and daidzein in serum from the group of dams maintained on the diet containing the highest amount of isoflavones (1000 ppm) were 17 +/- 27 and 56 +/- 30 nM, respectively, at d 21 postpartum. The concentrations were considerably greater in male offspring (genistein: 73 +/- 46 nM; daidzein: 106 +/- 53 nM). Although steroidogenesis was decreased in individual Leydig cells, male rats from the highest exposure group (1000 ppm diet) exhibited elevated serum levels of the sex steroid hormones androsterone at 21 d (control: 15 +/- 1.5 vs.28 +/- 3.5 ng/ml; P < 0.05) and testosterone at 90 d of age (control: 7.5 +/- 1 vs.17 +/- 2 ng/ml; P < 0.05). Testosterone secretion by immature Leydig cells, isolated from 35-d-old male rats, decreased on exposure to 0.1 nm genistein in vitro (control: 175 +/- 5 vs. 117 +/- 3 ng/10(6) cells per 24 h; P < 0.05), indicative of direct phytoestrogen action. Thus, phytoestrogens have the ability to regulate Leydig cells, and additional studies to assess potential adverse effects of dietary soy-based products on reproductive tract development in neonates are warranted.

Use of traditional Mi'kmaq medicine among patients at a First Nations community health centre.

INTRODUCTION: The provision of complete, effective, and culturally sensitive health care to First Nations communities requires a familiarity with and respect for patients' healing beliefs and practices. PURPOSE: This study addresses one aspect of cross-cultural care by attempting to understand the use of Mi'kmaq medicine among patients at a community health centre and their attitudes toward both Mi'kmaq and Western medicine. METHODS: A questionnaire was completed by 100 patients (14 men, 86 women) at the clinic. The majority (66%) of respondents had used Mi'kmaq medicine, and 92.4% of these respondents had not discussed this with their physician. Of those who had used Mi'kmaq medicine, 24.3% use it as first-line treatment when they are ill, and 31.8% believe that Mi'kmaq medicine is better overall than Western. Even among patients who have not used Mi'kmaq medicine, 5.9% believe that it is more effective than Western medicine in treating illness. CONCLUSION: These results have implications for the delivery of health care to First Nations patients, especially in terms of understanding patients' health care values and in meeting the need to provide effective cross-cultural care.