pyHeart4Fish: Chamber-specific heart phenotype quantification of zebrafish in high-content screens.

Cardiovascular diseases (CVDs) are the leading cause of death. Of CVDs, congenital heart diseases are the most common congenital defects, with a prevalence of 1 in 100 live births. Despite the widespread knowledge that prenatal and postnatal drug exposure can lead to congenital abnormalities, the developmental toxicity of many FDA-approved drugs is rarely investigated. Therefore, to improve our understanding of drug side effects, we performed a high-content drug screen of 1,280 compounds using zebrafish as a model for cardiovascular analyses. Zebrafish are a well-established model for CVDs and developmental toxicity. However, flexible open-access tools to quantify cardiac phenotypes are lacking. Here, we provide pyHeart4Fish, a novel Python-based, platform-independent tool with a graphical user interface for automated quantification of cardiac chamber-specific parameters, such as heart rate (HR), contractility, arrhythmia score, and conduction score. In our study, about 10.5% of the tested drugs significantly affected HR at a concentration of 20 µM in zebrafish embryos at 2 days post-fertilization. Further, we provide insights into the effects of 13 compounds on the developing embryo, including the teratogenic effects of the steroid pregnenolone. In addition, analysis with pyHeart4Fish revealed multiple contractility defects induced by seven compounds. We also found implications for arrhythmias, such as atrioventricular block caused by chloropyramine HCl, as well as (R)-duloxetine HCl-induced atrial flutter. Taken together, our study presents a novel open-access tool for heart analysis and new data on potentially cardiotoxic compounds.

Factors influencing water intake in dairy cows: a review.

Water is a very critical nutrient in the diet of lactating animals as it performs several functions, viz., transfer of nutrients and excretions of waste products produced during metabolism, digestion, and body temperature regulation of all living organisms. Besides growth, other parameters like milk production, reproduction, adaptive potential, and feed consumption are also influenced by water status in feed and body reserves. Water intake in dairy cows is influenced directly or indirectly by several factors; direct factors include animal-related factors such as breed, body size, physiological stage, age, health, stress, and ecological adaptations and environmental factors, viz., season of the year, environmental temperature, humidity, wind speed, and precipitation. These factors significantly influence the drinking water intake of dairy cows. Nonetheless, different managemental practices such as rearing type, feeding practices, housing, water availability, and its quality can also affect water intake indirectly. However, overall understanding of these factors affecting water intake in dairy cows could help to improve the dairy husbandry practices and subsequently health, production, and welfare of dairy cows.

The behaviour of residual tumour after the intentional incomplete excision of a vestibular schwannoma: is it such a bad thing to leave some behind?

OBJECTIVES: To evaluate the biological behaviour of tumour remnants intentionally left in the surgical bed following the incomplete excision of vestibular schwannomas (VS) and to review the relation between extent of resection and preservation of facial nerve function. METHODS: A retrospective chart review of 450 patients who underwent surgery for resection of VS over 23 years (1992-2014). Of these, 50 (11%) patients had residual tumour intentionally left on/around the facial nerve (near-total or subtotal excision) to preserve facial nerve function intra-operatively. The growth of residual tumour was evaluated using serial magnetic resonance imaging scanning; pre- and postoperative facial nerve function was assessed using the House-Brackmann grading scale. SETTING: Tertiary referral neurotology unit. RESULTS: Of the 42 non-NF2 cases where the tumour was intentionally incompletely excised, 28 (67%) patients underwent subtotal resection (mean follow-up 68.5 ± 39.0 months) and 14 (33%) underwent near-total resection (mean follow-up 72.9 ± 48.3 months). Three patients (all in subtotal resection group) showed regrowth. This was not statistically different from the near-total resection group (χ2 = 0.92, P = 0.31). The mean overall growth for these cases was 0.68 mm ± 0.32 mm/year. 5 (one near total, four subtotal) of the eight NF2 patients (62.5%) were excluded from our analysis. In the non-NF2 group, poor facial nerve outcomes (House-Brackmann scores of III-IV) were seen in 2/14 and V-VI in 3/14 of the near total compared with 7/25 and 4/25 respectively in the subtotal group. CONCLUSIONS: Given that the primary surgery for the VS was only for tumours that were relatively large or grew during conservative treatment, the low rate of tumour remnant growth (7%) is reassuring. It may be appropriate to have a lower threshold for leaving tumour on the facial nerve in non-NF2 patients where complete resection may jeopardise facial nerve function.

The benefit of silicone stents in primary endonasal dacryocystorhinostomy: a systematic review and meta-analysis.

OBJECTIVE: To critically evaluate the evidence comparing success rates of endonasal dacryocystorhinostomy (EN-DCR) with and without silicone tubing and to thus determine whether silicone intubation is beneficial in primary EN-DCR. DESIGN: Systematic review and meta-analysis. SEARCH STRATEGY: A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders groups trials register using a combination of various MeSH. The date of last search was January 2016. This review was limited to randomised controlled trials (RCTs) in English language. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool. Chi-square and I2 statistics were calculated to determine the presence and extent of statistical heterogeneity. EVALUATION METHOD: Study selection, data extraction and risk of bias scoring were performed independently by two authors in concordance with the PRISMA statement. RESULTS: Five RCTs (447 primary EN-DCR procedures in 426 patients) were included for analysis. Moderate interstudy statistical heterogeneity was demonstrated (Chi2 = 6.18; d.f. = 4; I2 = 35%). Bicanalicular silicone stents were used in 229 and not used in 218 procedures. The overall success rate of EN-DCR was 92.8% (415/447). The success rate of EN-DCR was 93.4% (214/229) with silicone tubing and 92.2% (201/218) without silicone tubing. Meta-analysis using a random-effects model showed no statistically significant difference in outcomes between the two groups (P = 0.63; RR = 0.79; 95% CI = 0.3-2.06). CONCLUSIONS: Our review and meta-analysis did not demonstrate an additional advantage of silicone stenting. A high-quality well-powered prospective multicentre RCT is needed to further clarify on the benefit of silicone stents.

Olfactory and cochleovestibular dysfunction after head injury in the workplace: an updated series.

OBJECTIVES: The objective of this study was to determine the incidence of olfactory dysfunction in workers following head injury in the work place, to define its relationship to the site, severity of injury and direction of force. The demographics of head injured workers were also assessed to determine whether those with olfactory loss were more likely to have sustained a cochleovestibular injury. DESIGN: Retrospective case analysis. SETTING: Tertiary referral university hospital in Toronto, Ontario. PARTICIPANTS: A total of 3438 consecutive patients referred from the Workplace Safety and Insurance Board (WSIB) in the province of Ontario who sustained a work-related head injury were assessed between 1987 and 2014. MAIN OUTCOME MEASURES: Olfactory and cochleovestibular dysfunction assessed by history, clinical examination and subjective and objective tests. RESULTS: Olfactory dysfunction (OD) was identified in 413 of 3438 patients (12.0%) of which 321 were diagnosed with anosmia and 92 with hyposmia. In our series, injuries from a fall were the commonest cause for OD and a frontal or mid-face impact was more likely to result in OD than other regions (P = 0.0002). A loss of consciousness (LOC) of any duration correlated with OD. In those with olfactory dysfunction, an associated skull fracture occurred in 37.1% of patients and a CSF leak in 4.1%, which was significantly higher compared with those without OD(<0.0001). Patients with OD had a higher incidence of cochlear and vestibular loss (19.9% and 20.6%, respectively) compared with those without OD (14.3% and 17.1%, respectively). CONCLUSIONS: Post-traumatic olfactory dysfunction is more likely to occur in patients who experienced a moderate to severe head injury, LOC and more likely to result from a frontal or mid-face blow to the skull. Cochleovestibular dysfunction is likely to occur concurrently with olfactory dysfunction.

A new analgesia regimen after (adeno) tonsillectomy in children: a pilot study.

OBJECTIVE: The objective was to ascertain the efficacy of a new analgesic regimen introduced in children undergoing (adeno)tonsillectomy in view of the ban on codeine use in children <12 years by the European Medicines Agency (EMA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA). DESIGN: Prospective pilot study at a paediatric tertiary referral centre. MATERIALS AND METHODS: A total of 176 children undergoing (adeno) tonsillectomy over a 5-month period (Sept 2013-Jan 2014) were included in the study. Data were prospectively collected on analgesia used peri-operatively and patients were discharged on regular paracetamol and ibuprofen for 7 days and three doses of oral morphine sulphate solution to be used on days 3, 4 and 5. Pain scores were recorded on days 1-10 post-operatively using the Wong Baker Faces Pain Rating scale. RESULTS: The pain scores were significantly better (P-value < 0.0001) in children who were compliant with morphine (n = 93) than those who were not (n = 32). We also found that children who were compliant with morphine were less likely to seek help out of hours (P-value < 0.001). CONCLUSIONS: Oral morphine sulphate solution provides a reasonable alternative to codeine, albeit one should bear in mind that parental concerns and adverse effects of the drug were seen in a minority of patients (n = 11) and anaesthetists were reluctant to prescribe the drug in cases of severe OSA or associated central apnoeas (n = 7).

Intratympanic therapy in Meniere's syndrome or disease: up to date evidence for clinical practice.

BACKGROUND: Meniere's syndrome or disease (MS/D) is typically characterised by episodic vertigo, aural fullness, tinnitus and fluctuating hearing loss. There are multiple options available for treatment with variation in consensus on the best intervention. OBJECTIVE: To evaluate the evidence on the efficacy of intratympanic therapies [steroids, gentamicin, antivirals and other therapies] on the frequency and severity of vertigo and other symptoms of MS/D. SEARCH STRATEGY: A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders group trials register using various MeSH. The search was restricted to English and human subjects, and the last date of search was December 2014. SELECTION CRITERIA: Randomised controlled trials of intratympanic therapies [steroids, gentamicin antivirals and latanoprost] versus a placebo or another treatment. RESULTS: We analysed 8 RCT's comparing intratympanic steroids, gentamicin, ganciclovir (antiviral) and latanoprost versus another form of intratympanic treatment or placebo. CONCLUSIONS: On the basis of 6 RCT's (n = 242), there is evidence to support the effectiveness of intratympanic steroids and gentamicin to control symptoms of vertigo in MS/D albeit with a risk of hearing loss with gentamicin. However, there was no consensus found on doses or treatment protocols. There was no evidence to support the use of other forms of intratympanic therapy (antivirals and latanoprost) in MS/D.

Positive pressure therapy for Meniere's syndrome/disease with a Meniett device: a systematic review of randomised controlled trials.

BACKGROUND: Incidence rates of Meniere's syndrome/disease vary considerably from 157 per 100 000 in the United Kingdom to 15 per 100 000 in the United States. A wide range of treatments are used for the treatment of the condition with no consensus on the most effective intervention. OBJECTIVES: To assess the effectiveness of the Meniett device in reducing the frequency and severity of vertigo in Meniere's syndrome/disease. SEARCH METHODS: The Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific abstracts; ICTRP and additional sources for published and unpublished trials were searched. The date of the last search was 13th May 2014. SELECTION CRITERIA: Four randomised controlled trials (RCTs) were identified that compared the efficacy of the Meniett device versus a placebo device in patients with Meniere's 'disease' as defined by the AAOO criterion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and risk of bias and extracted data. The outcome data were dichotomous for all the included trials. MAIN RESULTS: The four RCTs compared 123 patients with the Meniett device against 114 patients with the placebo device from four RCT's over a follow-up period of 2 weeks to 4 months. There was a significant overall 61% reduction in the frequency of vertigo in both groups (mean no vertigo days per month of 8-3). However, this reduction was not significantly different between the two groups in any study or on meta-analysis [mean difference in vertigo-free days between Meniett and placebo device of 0.77 days over a 1-month period (95% CI - 0.82, 1.83) P = 0.45]. There were also no substantive data to support a greater reduction in the severity of the vertigo or any other outcome with the Meniett device compared with the placebo device. AUTHORS CONCLUSIONS: No evidence was found to justify the use of the Meniett device in Meniere's syndrome/disease.

Progressive, reversible sensorineural hearing loss caused by azathioprine.

OBJECTIVE: This paper describes the first reported case of progressive sensorineural hearing loss caused by azathioprine, which was reversed on stoppage of the drug. CASE REPORT: A female patient with previously normal hearing presented with progressive sensorineural hearing loss after being started on azathioprine. Otological and neurological examination findings were unremarkable. After stopping the drug, the patient reported an improvement in hearing, which was confirmed on pure tone audiometry. CONCLUSION: This previously unreported side effect of azathioprine is highlighted in order to increase clinical awareness. Early recognition of this adverse effect is important to minimise the possibility of permanent sensorineural hearing loss.