Depletion of four nitrofuran antibiotics and their tissue-bound metabolites in porcine tissues and determination using LC-MS/MS and HPLC-UV

Depletion of the nitrofuran antibiotics furazolidone, furaltadone, nitrofurantoin and nitrofurazone and their tissue-bound metabolites AOZ, AMOZ, AHD and SEM from pig muscle, liver and kidney tissues is described. Groups of pigs were given feed medicated with one of the nitrofuran drugs at a therapeutic concentration (400 mg kg(-1)) for ten days. Animals were slaughtered at intervals and tissue samples collected for analysis for six weeks following withdrawal of medicated feed. These samples were analysed both for parent nitrofurans (using LC-MS/MS and HPLC-UV), and for tissue-bound metabolites (using LC-MS/MS). The parent drugs were detectable only sporadically and only in pigs subjected to no withdrawal period whatsoever. This confirms the instability of the four major nitrofuran antibiotics in edible tissues. In contrast, the metabolites accumulated to high concentrations in tissues (ppm levels) and had depletion half lives of between 5.5 and 15.5 days. The metabolites of all four drugs were still readily detectable in tissues six weeks after cessation of treatment. This emphasizes the benefits of monitoring for the stable metabolites of the nitrofurans.

Through the lens of the hospital magazine - Downshire and Holywell psychiatric hospitals in the 1960s and 1970s

An exploration of the pages of two psychiatric hospital magazines, Speedwell from Holywell Hospital, Antrim, and The Sketch from Downshire Hospital, Downpatrick, reveals the activity filled lives of patients and staff during the 1960s and 1970s. This was a time of great change in mental health care. It was also a time of political turbulence in Northern Ireland. With large in-patient populations, both hospitals had a range of occupational and sporting activities available to patients and staff. The magazines formed part of the effort to promote the ethos of a therapeutic community. While hospital magazines may be viewed as one aspect of an institutional system that allowed people to cut themselves from the wider society, they also provided opportunities for budding writers to express their views on life in a hospital from the service user perspective. As such they offer some valuable insights into the lives of psychiatric patients.

Pneumonia and lower respiratory infections in nursing home residents:Predictors of hospitalization and mortality

OBJECTIVES: To compare predictors of hospitalization and death in nursing home residents with pneumonia and other lower respiratory infections (LRIs). DESIGN: A nested cohort study. SETTING: Nine nursing homes in southern Ontario. PARTICIPANTS: Three hundred fifty-three nursing home residents with LRIs (enrolled in the control arm of a clinical trial). MEASUREMENTS: Comorbidities, vaccination status, age, health-related quality of life, functional status, and vital statistics were evaluated as potential predictors of hospitalization and mortality at 30 days. RESULTS: Moderate to high disease severity score on a practical severity scale was a strong independent predictor of hospitalization (odds ratio (OR)=7.12, P

Diagnostic accuracy and reproducibility of tendency oriented perimetry in glaucoma

PURPOSE. To evaluate the diagnostic capability of tendency oriented perimetry (TOP) in glaucoma. METHODS. A): The diagnostic accuracy of mean defect (MD), square-root of the loss variance (sLV), and number of pathologic points (NPP) was calculated in 295 normal and 414 glaucoma eyes (179 early, 112 moderate, and 123 advanced) examined with TOP. B): Threshold fluctuation (F) and its relationship with the loss variance (LV) was measured in 34 normal and 33 glaucoma eyes (mean MD=3 dB; SD=3.9) for TOP and for full-threshold perimetry (FT). C): Twenty-eight eyes with stable glaucoma (mean MD=9.5 dB; SD=7.2) were examined six times to quantify LV error. D): TOP and FT were tested with the simulation program PeriSim using different behavior models. RESULTS. A): The best diagnostic index in early glaucoma (MD

Allo-limbal transplantation in patients with limbal stem cell deficiency

Aim - To report the outcome of a series of patients with stem cell deficiency who underwent allo-limbal transplantation and to describe a technique for this procedure. Methods - Six consecutive patients underwent allo-limbal stem cell transplantation. The primary diagnosis included alkali burn (n = 2), trachoma (n = 1), chronic rosacea blepharitis and keratoconjunctivitis (n = 1), aniridia (n = 1), and Stevens-Johnson syndrome (n = 1). The limbal rim consisted of peripheral cornea and perilimbal sclera, FK-506 was used postoperatively for immunosuppression. Results - The length of follow up ranged from 3 to 24 months (mean follow up 11.8 (SD 9.3) months). The outcome was considered satisfactory in five of six cases. The corneal surface was completely epithelialised within 2 weeks, and there was a substantial improvement in vision and symptoms. One patient had recurrent epithelial defects related to eyelid abnormalities. No side effects associated with systemic immunosuppression were noted. Conclusion - Allo-limbal transplantation, with systemic immunosuppression with FK-506 is useful in reconstruction of the ocular surface with improvement in vision in patients with severe stem cell deficiency.

An analysis of the masking of speech by competing speech using self-report data (L)

Many of the items in the “Speech, Spatial, and Qualities of Hearing” scale questionnaire [S. Gatehouse and W. Noble, Int. J. Audiol.43, 85–99 (2004)] are concerned with speech understanding in a variety of backgrounds, both speech and nonspeech. To study if this self-report data reflected informational masking, previously collected data on 414 people were analyzed. The lowest scores (greatest difficulties) were found for the two items in which there were two speech targets, with successively higher scores for competing speech (six items), energetic masking (one item), and no masking (three items). The results suggest significant masking by competing speech in everyday listening situations.

Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia

Chromosome 5q22-33 is a region where studies have repeatedly found evidence for linkage to schizophrenia. In this report, we took a stepwise approach to systematically map this region in the Irish Study of High Density Schizophrenia Families (ISHDSF, 267 families, 1337 subjects) sample. We typed 289 SNPs in the critical interval of 8 million basepairs and found a 758 kb interval coding for the SPEC2/PDZ-GEF2/ACSL6 genes to be associated with the disease. Using sex and genotype-conditioned transmission disequilibrium test analyses, we found that 19 of the 24 typed markers were associated with the disease and the associations were sex-specific. We replicated these findings with an Irish case-control sample (657 cases and 414 controls), an Irish parent-proband trio sample (187 families, 564 subjects), a German nuclear family sample (211 families, 751 subjects) and a Pittsburgh nuclear family sample (247 families, 729 subjects). In all four samples, we replicated the sex-specific associations at the levels of both individual markers and haplotypes using sex- and genotype-conditioned analyses. Three risk haplotypes were identified in the five samples, and each haplotype was found in at least two samples. Consistent with the discovery of multiple estrogen-response elements in this region, our data showed that the impact of these haplotypes on risk for schizophrenia differed in males and females. From these data, we concluded that haplotypes underlying the SPEC2/PDZ-GEF2/ACSL6 region are associated with schizophrenia. However, due to the extended high LD in this region, we were unable to distinguish whether the association signals came from one or more of these genes.

Worked to Death? A census-based longitudinal study of the relationship between the numbers of hours spent working and mortality risk

Background There has been an increasing interest in the health effects of long
working hours, but little empirical evidence to substantiate early
10 case series suggesting an increased mortality risk. The aim of the
current study is to quantify the mortality risk associated with long
working hours and to see if this varies by employment relations and
conditions of occupation.
Methods A census-based longitudinal study of 414 949 people aged 20-59/64
15 years, working at least 35 h/week, subdivided into four occupational
classes (managerial/professional, intermediate, own account workers,
workers in routine occupations) with linkage to deaths records
over the following 8.7 years. Cox proportional hazards models were
used to examine all-cause and cause-specific mortality risk.
20 Results Overall 9.4% of the cohort worked 55 or more h/week, but this
proportion was greater in the senior management and professional
occupations and in those who were self-employed. Analysis of 4447
male and 1143 female deaths showed that hours worked were
associated with an increased risk of all-cause mortality only for
25 men working for more than 55 or more h/week in routine/semiroutine
occupations [adjusted hazard ratios (adjHR) 1.31: 95%
confidence intervals (CIs) 1.11, 1.55)] compared with their peers
working 35–40 h/week. Their equivalent risk of death from cardiovascular
disease was (adjHR 1.49: 95% CIs 1.10, 2.00).
30 Conclusions These findings substantiate and add to the earlier studies indicating
the deleterious impact of long working hours but also suggest that
the effects are moderated by employment relations or conditions of
occupation. The policy implications of these findings are discussed.

A sparse representation based fast detection method for surface defect detection of bottle caps

A practical machine-vision-based system is developed for fast detection of defects occurring on the surface of bottle caps. This system can be used to extract the circular region as the region of interests (ROI) from the surface of a bottle cap, and then use the circular region projection histogram (CRPH) as the matching features. We establish two dictionaries for the template and possible defect, respectively. Due to the requirements of high-speed production as well as detecting quality, a fast algorithm based on a sparse representation is proposed to speed up the searching. In the sparse representation, non-zero elements in the sparse factors indicate the defect's size and position. Experimental results in industrial trials show that the proposed method outperforms the orientation code method (OCM) and is able to produce promising results for detecting defects on the surface of bottle caps.

Molecular Cloning of a Novel Tryptophyllin Peptide from the Skin of the Orange-Legged Monkey Frog, Phyllomedusa hypochondrialis

Tryptophyllins are a group of small (4–14 amino acids), heterogenous peptides, mostly from the skins of hylid frogs from the genera, Phyllomedusa and Litoria. To date, more than forty TPHs have been discovered in species from these two genera. Here, we describe the identification of a novel tryptophyllin type 3 peptide, PhT-3, from the extracts of skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis, and molecular cloning of its precursor-encoding cDNA from a cDNA library constructed from the same skin sample. Full primary structural characterization was achieved using a combination of direct Edman degradation, mass spectrometry and deduction from cloned skin-derived cDNA. The open-reading frame of the precursor cDNA was found to consist of 63 amino acid residues. The mature peptide arising from this precursor contains a post-translationally modified N-terminal pyroglutamate (pGlu) residue, formed from acid-mediated cyclization of an N-terminal Gln (Q) residue, and with the structure: pGlu-Asp-Lys-Pro-Phe-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met. Pharmacological assessment of a synthetic replicate of this peptide on phenylephrine preconstricted rat tail artery segments, revealed a reduction in relaxation induced by bradykinin. PhT-3 was also found to mediate antiproliferative effects on human prostate cancer cell lines.

Chronic cough as a neuropathic disorder

Chronic cough is a common symptom that can be a daunting challenge for clinicians since treatment of the underlying cause does not always provide adequate relief, an obvious cause can remain elusive, and current antitussives have fairly poor efficacy and undesirable side-effects. Patients with chronic cough typically describe a range of sensory symptoms suggestive of upper-airway and laryngeal neural dysfunction. Additionally, patients often report cough triggered by low-level physical and chemical stimuli, which is suggestive of cough-reflex hyperresponsiveness. Pathophysiological mechanisms underlying peripheral and central augmentation of the afferent cough pathways have been identified, and compelling evidence exists for a neuropathy of vagal sensory nerves after upper-respiratory viral infections or exposure to allergic and non-allergic irritants. In this Personal View, we argue that chronic cough is a neuropathic disorder that arises from neural damage caused by a range of inflammatory, infective, and allergic factors. In support of this idea, we discuss evidence of successful treatment of chronic cough with agents used for treatment of neuropathic pain, such as gabapentin and amitriptyline. Regarding cough as a neuropathic disorder could lead to new, more effective antitussives.

Medication use review in Qatar: Are community pharmacists prepared for the extended professional role?

Background
The incidence of chronic illnesses is increasing globally. Non-adherence to medications and other medication-related problems are common among patients receiving long-term medications. Medication use review (MUR) is a service provision with an accredited pharmacist undertaking structured, adherence-centered reviews with patients receiving multiple medications. MUR services are not yet available in community pharmacies in Qatar.

Objective
The current study aims to evaluate community pharmacists' knowledge, attitudes, and perception towards establishing MUR as an extended role in patient care.

Setting
Private community pharmacies in Qatar including chains and independent pharmacies.

Methodology
A cross-sectional survey using a self-administered questionnaire was conducted among licensed community pharmacists from December 2012 to January 2013. Data analysis was conducted using descriptive and inferential statistics.

Main outcome measures
Knowledge, attitudes, and practices related to MUR concept and services.

Results A total of 123 participants responded to the survey (response rate 56 %). The mean total knowledge score was 71.4 ± 14.7 %. An overwhelming proportion of the participants (97 %) were able to identify the scope of MUR in relation to chronic illnesses and at enhancing the quality of pharmaceutical care. Furthermore, 80 % of the respondents were able to identify patients of priority for inclusion in an MUR program. However, only 43 % of the participants knew that acute medical conditions were not the principal focus of an MUR service, while at least 97 % acknowledged that the provision of MUR services is a great opportunity for an extended role of community pharmacists and that MUR makes excellent use of the pharmacist's professional skills in the community. The participants generally reported concerns about time, dedicated consultation area, and support staff as significant barriers towards MUR implementation.

Conclusion
This study suggests that community pharmacists in Qatar had sufficient knowledge about the concept of MUR and its scope, but there were still important deficiencies that warrant further education. The findings have important implications on policy and practice pertaining to the implementation of MUR as an extended role of pharmacists and as part of Qatar's National Health Strategy to move primary health care forward.