Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.

BackgroundReported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response.Hypothesis/objectivesTo determine if the progression-free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin.AnimalsFifty dogs with TCC without azotemia.MethodsProspective open-label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6-week intervals. Twenty-four dogs received carboplatin and 26 received mitoxantrone.ResultsResponse was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47-1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005).Conclusions and clinical importanceThis study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

Bacterial urinary tract infections associated with transitional cell carcinoma in dogs.

BackgroundUrinary tract infections (UTI) are believed to be common in dogs with transitional cell carcinoma (TCC), but incidence and contributing factors have not been reported.ObjectivesTo determine the frequency and bacterial agents associated with UTI in dogs with TCC and define contributing factors.AnimalsEighty-five dogs with a history of urogenital TCC undergoing treatment with chemotherapy that had at least 1 urine culture performed.MethodsMedical records and culture results were retrospectively reviewed and ultrasound images were reviewed when available. Clinical factors were evaluated statistically for association with positive culture.ResultsFifty-five percent (47/85) of dogs had at least 1 positive culture during the course of treatment. Female dogs (80%, 40/50) were more likely than male dogs (29%, 10/35) to have at least 1 positive culture. Ultrasound examination determined that female dogs were more likely to have urethral (74%, 31/42) or trigonal tumor involvement (71%, 30/42) compared to male dogs (32%, 9/28 and 43%, 12/28, respectively). The most commonly isolated organisms were Staphylococcus spp. (23.9%, 29/121) and Escherichia coli (19.8%, 24/121). Dogs with urethral involvement of TCC were significantly more likely to have at least 1 positive culture than dogs without urethral involvement (75%, 30/40 versus 30%, 9/30).ConclusionsUrinary tract infection is common in dogs with TCC highlighting the importance of regular monitoring for bacterial cystitis in dogs with TCC. In addition, clinical factors such as tumor location and sex may be predictive of positive culture and can help clinicians assess the risk of UTI

Cyfluthrin-induced hepatotoxicity in rats

The hepatotoxic effect of continous administration of cyfluthrin was investigated in rats. Rats (Rattus norvegicus) were grouped into A (0 ppm) control, B (100 ppm) and C (200 ppm) with the indicatedamount of cyfluthrin administered orally for 15 weeks.The hepatotoxicity level was assessed by monitoring the changes in the organ to body; weight ratio, micronutrient level (iron, zinc, copper andselenium), the nutritional status (total carbohydrate, total glucose, total protein, total amino acids, total lipid and total cholesterol), the lipid peroxidation level (reduced glutathione and thiobarbiturate) and theantioxidant enzyme activities (glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase). A dose-dependent decrease in the organ-to-body ratio was observed. Themicronutrient level in the test groups increase significantly. The total carbohydrate, total glucose, total amino acids and total protein show a significant decrease in the test groups. There is no significantdifference observed in the tissue cholesterol at both dosages under investigation. Lipid peroxidation was increased in the test groups as indicated by a significant increase in the thiobarbiturate level and asignificant decrease in the reduced glutathione level. All the antioxidant enzymes studied increased significantly. Cyfluthrin is potentially hepatotoxic under continuous administration in rats

Chlamydia trachomatis IgG antibodies seroprevalence among students in two tertiary institutions in Anambra state, Nigeria: a comparative study

Chlamydia infection is a common sexually transmitted infection (STI) in humans caused by the bacterium Chlamydia trachomatis. This study assessed the seroprevalence of Chlamydia trachomatis antibodies among students in two tertiary institutions in Anambra State, Nigeria. It was a comparative cross-sectional survey using enzyme immunoassay kits for the determination of IgG class antibodies, while the multistage sampling technique was used in the selection of participants for the study. The overall prevalence of Chlamydia trachomatis antibodies observed in this survey was 14.3%, which was higher among students from the University (21.6%) than their counterparts from the College of Education (7.4%) (χ2=5.89, df=1p<0.015). Factors found to have significant effect on the seroprevalence of Chlamydia trachomatis in both institutions were: prior sexual exposure (p<0.05); unprotected sexual intercourse in the last one year (p<0.05); multiple sexual partners in the last one year (p<0.05); and presence of symptoms suggestive of STI (p<0.05). Among students in the College of Education, the place of residence significantly affected Chlamydia trachomatis seroprevalence with a preponderance towards students living off-campus (χ2=4.00, df-1, p<0.05). Hence, there is need to institute appropriate prevention and control measures against the transmission of the disease especially among those at risk of contracting the disease.Keywords: Chlamydia trachomatis, seroprevalence, sexual behaviour, students, tertiary institutions

Fluvial morphology as a driver of lead and zinc geochemical dispersion at a catchment scale

This is the final version. Available on open access from MDPI via the DOI in this record. Data Availability Statement: The data are available upon request. Please contact the corresponding author.Metal-mining exploitation has caused ecosystem degradation worldwide. Legacy wastes are often concentrated around former mines where monitoring and research works are mostly focused. Geochemical and physical weathering can affect metal-enriched sediment locations and their capacity to release metals at a catchment scale. This study investigated how fluvial geomorphology and soil geochemistry drive zinc and lead dispersion along the Nant Cwmnewyddion (Wales, UK). Sediments from different locations were sampled for geochemical and mineralogical investigations (portable X-ray fluorescence, scanning electron microscope, X-ray diffraction, and electron microprobe analysis). The suspended sediment fluxes in the streamwater were estimated at different streamflows to quantify the metal dispersion. Topographical and slope analysis allowed us to link sediment erosion with the exposure of primary sulphide minerals in the headwater. Zinc and lead entered the streamwater as aqueous phases or as suspended sediments. Secondary sources were localised in depositional stream areas due to topographical obstruction and a decrease in stream gradient. Sediment zinc and lead concentrations were lower in depositional areas and associated with Fe-oxide or phyllosilicates. Streamwater zinc and lead fluxes highlighted their mobility under high-flow conditions. This multi-disciplinary approach stressed the impact of the headwater mining work on the downstream catchment and provided a low-cost strategy to target sediment sampling via geomorphological observations.John Moores Universit

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

Fluvial morphology as a driver of lead and zinc geochemical dispersion at a catchment scale

Metal-mining exploitation has caused ecosystem degradation worldwide. Legacy wastes are often concentrated around former mines where monitoring and research works are mostly focused. Geochemical and physical weathering can affect metal-enriched sediment locations and their capacity to release metals at a catchment scale. This study investigated how fluvial geomorphology and soil geochemistry drive zinc and lead dispersion along the Nant Cwmnewyddion (Wales, UK). Sediments from different locations were sampled for geochemical and mineralogical investigations (portable X-ray fluorescence, scanning electron microscope, X-ray diffraction, and electron microprobe analysis). The suspended sediment fluxes in the streamwater were estimated at different streamflows to quantify the metal dispersion. Topographical and slope analysis allowed us to link sediment erosion with the exposure of primary sulphide minerals in the headwater. Zinc and lead entered the streamwater as aqueous phases or as suspended sediments. Secondary sources were localised in depositional stream areas due to topographical obstruction and a decrease in stream gradient. Sediment zinc and lead concentrations were lower in depositional areas and associated with Fe-oxide or phyllosilicates. Streamwater zinc and lead fluxes highlighted their mobility under high-flow conditions. This multi-disciplinary approach stressed the impact of the headwater mining work on the downstream catchment and provided a low-cost strategy to target sediment sampling via geomorphological observations

The diet-body offset in human nitrogen isotopic values: a controlled dietary study

The ‘trophic level enrichment’ between diet and body results in an overall increase in nitrogen isotopic values as the food chain is ascended. Quantifying the diet–body Δ15N spacing has proved difficult, particularly for humans. The value is usually assumed to be +3-5‰ in the archaeological literature. We report here the first (to our knowledge) data from humans on isotopically known diets, comparing dietary intake and a body tissue sample, that of red blood cells. Samples were taken from 11 subjects on controlled diets for a 30-d period, where the controlled diets were designed to match each individual’s habitual diet, thus reducing problems with short-term changes in diet causing isotopic changes in the body pool. The Δ15Ndiet-RBC was measured as +3.5‰. Using measured offsets from other studies, we estimate the human Δ15Ndiet-keratin as +5.0-5.3‰, which is in good agreement with values derived from the two other studies using individual diet records. We also estimate a value for Δ15Ndiet-collagen of ≈6‰, again in combination with measured offsets from other studies. This value is larger than usually assumed in palaeodietary studies, which suggests that the proportion of animal protein in prehistoric human diet may have often been overestimated in isotopic studies of palaeodiet

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations