Sperm Limitation Produces Male Biased Offspring Sex Ratios in the Wasp, Nasonia vitripennis (Hymenoptera: Pteromalidae).

Haplo-diploid sex determination in the parasitoid wasp, Nasonia vitripennis (Walker), allows females to adjust their brood sex ratios. Females influence whether ova are fertilized, producing diploid females, or remain unfertilized, producing haploid males. Females appear to adjust their brood sex ratios to minimize 'local mate competition,' i.e., competition among sons for mates. Because mating occurs between siblings, females may optimize mating opportunities for their offspring by producing only enough sons to inseminate daughters when ovipositing alone, and producing more sons when superparasitism is likely. Although widely accepted, this hypothesis makes no assumptions about gamete limitation in either sex. Because sperm are used to produce daughters, repeated oviposition could reduce sperm supplies, causing females to produce more sons. In contrast, if egg-limited females produce smaller broods, they might use fewer sperm, making sperm limitation less likely. To investigate whether repeated oviposition and female fertility influence gamete limitation within females, we created two treatments of six mated female wasps, which each received a series of six hosts at intervals of 24 or 48 h. All females produced at least one mixed-sex brood (63 total broods; 3,696 offspring). As expected, if females became sperm-limited, in both treatments, brood sex ratios became increasingly male-biased with increasing host number. Interhost interval did not affect brood size, total offspring number, or sex ratio, indicating females did not become egg limited. Our results support earlier studies showing sperm depletion affects sex allocation in N. vitripennis¸ and could limit adaptive sex ratio manipulation in these parasitoid wasps.

Stroke Risk Factors, Subtype, and Outcomes in a Multi-Ethnic Stroke Population.

Aim We aim to describe differences in stroke risk factors, subtypes and outcomes in a multi-ethnic Irish Stroke population. Gaining an insight into prevalent risk factors and subtypes in ethnic groups may help target prevention efforts. Methods We retrospectively identified patients originally not of Irish ethnicity (ONIE) admitted to the acute stroke unit between 2016 and 2018 through surname recognition (N=44). Country of origin was confirmed on chart review. The presumed native Irish (PNI) patients admitted over the same time frame were used as a comparison group (N=437). Data was collected on stroke subtype, comorbidities, outcomes and socioeconomic factors. Results Patients ONIE made up 9.1% of all stroke unit admissions. Male gender was more common accounting for 33 of 44 (75%) patients ONIE and 251 of 437 (57.4%) PNI (p = 0.02). Overall ONIE were younger than PNI patients (mean age 57.5 [SD 13.0] vs 69.6yr [SD 13.2], p <0.001). Patients ONIE also recorded higher rates of intracranial haemorrhage(ICH) (N = 15 [34.1%] vs N=51 [11.7%], p <0.01). Conclusion Our study demonstrates that stroke patients ONIE have a different stroke subtype and demographic profile compared to Irish patients. Patients ONIE are more likely to be young, male with higher rates of ICH.

Reported rationales for HPV vaccination vs. Non-vaccination among undergraduate and medical students in South Carolina.

Objective: We sought to identify factors that influence Human Papillomavirus (HPV) vaccination rates in individuals at two higher education institutions in South Carolina (SC).Participants: We surveyed 1007 students with a mean age and standard deviation of 20.3 ± 3.3 from September 2018 to December 2018.Methods: Participants answered 13 questions, assessing HPV vaccination rates, demographics, and rationales for vaccination vs. non-vaccination.Results: Of 1007 respondents, 700 received HPV vaccination, 165 were unvaccinated, 75 received partial vaccination and 138 were uncertain. Commonalities in HPV vaccination existed between females (p = 0.037), individuals who received standard childhood vaccinations (p = 0.04), and those not native-born in SC (p < 0.001). Of non-vaccinated individuals, 37% "never thought about vaccination," 32% did not perceive a need for vaccination, and 31% reported vaccine safety as reasons for not receiving the vaccine.Conclusions: Promotion of HPV vaccination may benefit from targeting SC natives, males, and individuals who are under-vaccinated or unvaccinated.

Cottonmouth snake bites reported to the ToxIC North American snakebite registry 2013-2017.

Introduction: The majority of venomous snake exposures in the United States are due to snakes from the subfamily Crotalinae (pit vipers). There are three types of US pit vipers: rattlesnakes (Crotalus and Sisturus spp.) copperheads (Agkistrodon contortrix), and cottonmouths (Agkistrodon piscivorus) also known as water moccasins. Cottonmouth bites are reported less frequently than other pit viper envenomations, and data on cottonmouth envenomation are limited. Our objective was to describe the epidemiology, clinical manifestations, and management of cottonmouth envenomations using prospective data reported to the Toxicology Investigators Consortium's (ToxIC) North American Snakebite Registry (NASBR)Methods: Cottonmouth envenomation cases reported to NASBR for the period from January 1, 2013, through December 31, 2017 were reviewed. Variables collected included patient demographics, bite location, clinical manifestations, and management.Results: Thirty-one cottonmouth envenomations were reported. Most bites occurred in children aged 7-12 (39%). Most bites involved the lower extremity (72%). Intentional interaction with the snake occurred in three cases (10%). Swelling was the most reported clinical effect and occurred in all patients. Gastrointestinal symptoms were reported in 19% of patients, and 19% developed coagulopathy. Antivenom treatment was used in 84% of patients. Nineteen patients (61%) required hospital stays of >24 hours.Discussion: Our study represents the first systematic prospective data collection on cottonmouth bites. Our data demonstrate that cottonmouth envenomations cause primarily local effects and, occasionally, systemic toxicity. Our study also demonstrates that antivenom is often indicated for these envenomations per published guidelines and recommendations.Conclusions: Cottonmouth envenomations are relatively infrequent. However, they can cause significant local and systemic toxicity. Most cottonmouth envenomations in this series were treated with antivenom and were hospitalized beyond 24 hours.

Early Cenozoic Decoupling of Climate and Carbonate Compensation Depth Trends.

Our understanding of the long-term evolution of the Earth system is based on the assumption that terrestrial weathering rates should respond to, and hence help regulate, atmospheric CO2 and climate. Increased terrestrial weathering requires increased carbonate accumulation in marine sediments, which in turn is expected to result in a long-term deepening of the carbonate compensation depth (CCD). Here, we critically assess this long-term relationship between climate and carbon cycling. We generate a record of marine deep-sea carbonate abundance from selected late Paleocene through early Eocene time slices to reconstruct the position of the CCD. Although our data set allows for a modest CCD deepening, we find no statistically significant change in the CCD despite >3 °C global warming, highlighting the need for additional deep-sea constraints on carbonate accumulation. Using an Earth system model, we show that the impact of warming and increased weathering on the CCD can be obscured by the opposing influences of ocean circulation patterns and sedimentary respiration of organic matter. From our data synthesis and modeling, we suggest that observations of warming, declining δ13C and a relatively stable CCD can be broadly reproduced by mid-Paleogene increases in volcanic CO2 outgassing and weathering. However, remaining data-model discrepancies hint at missing processes in our model, most likely involving the preservation and burial of organic carbon. Our finding of a decoupling between the CCD and global marine carbonate burial rates means that considerable care is needed in attempting to use the CCD to directly gauge global carbonate burial rates and hence weathering rates.

Loneliness and perceived social support in pregnancy and early postpartum of mothers living with HIV in Ontario, Canada.

The HIV Mothering Study (n = 72) was a prospective, observational, cohort study exploring psychosocial experiences and needs of WLWHIV in pregnancy and postpartum. We performed quantitative analysis of determinants of loneliness (UCLA Loneliness Scale) and lower perceived social support (SS) (Medical Outcomes Study-Social Support Survey). The hypothesized determinants included: age, years with HIV, racism (Everyday Discrimination Scale), depression (Edinburgh Postnatal Depression Scale [EPDS]), nadir CD4 (<200 cells/µL), tertiary vs. community HIV care, and marital status. The median age was 33 (IQR = 30-37); 65.3% were African/Caribbean/Black. Multivariable analyses revealed associations between marital status and perceived social support (ß = -16.48, p < 0.0001), and this association was also seen with change over time (p = 0.02). Variables associated with SS that did not change over time were: income, EDS racism, EPDS score. Significant associations with loneliness were seen with the same variables associated with SS. Variables associated with loneliness that also changed over time were: EDS Racism (ß = 0.22, p = 0.0005, and over time p = 0.003), and EPDS score (ß = 0.74, p < 0.0001), and over time (p = 0.0211). Variables associated with loneliness but that did not change over time were: marital status and income. This analysis provides clinicians with prenatal risk factors which may be associated with increase loneliness and lower SS during pregnancy and postpartum: marital status, income, racism and depression.

Patterns of mortality in modern stroke care

Background Stroke is a leading cause of death. We looked at the causes (direct and indirect) of in-hospital mortality in a modern stroke unit over a two-year period. Methods We reviewed medical charts of stroke deaths in hospital from 2014-2015 inclusive. Data on stroke type, aetiology, age, length of stay, comorbidities, and documented cause of death were recorded. All patients were included. Results 518 patients were admitted acutely to the stroke service. Overall death rate was 7.5% (n=39). Of fatal strokes 29 (74%) were ischaemic. Average age 78.6 years. Mean survival was 26.4 days (range 1-154). 19 (49%) patients had atrial fibrillation. Forty-nine percent of deaths were due to pneumonia, and 33% were due to raised intracranial pressure. Discussion Mortality rate in our stroke service has decreased from 15% in 1997, and now appears dichotomised into early Secondary Stroke Related Cerebral Events (SSRCEs) and later infections.

Simulation of Legionnaires' disease prospective spatiotemporal cluster detection, Allegheny County, Pennsylvania, USA.

Legionnaires' disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014-2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.

Sampling considerations for a potential Zika virus urosurvey in New York City.

In 2016, imported Zika virus (ZIKV) infections and the presence of a potentially competent mosquito vector (Aedes albopictus) implied that ZIKV transmission in New York City (NYC) was possible. The NYC Department of Health and Mental Hygiene developed contingency plans for a urosurvey to rule out ongoing local transmission as quickly as possible if a locally acquired case of confirmed ZIKV infection was suspected. We identified tools to (1) rapidly estimate the population living in any given 150-m radius (i.e. within the typical flight distance of an Aedes mosquito) and (2) calculate the sample size needed to test and rule out the further local transmission. As we expected near-zero ZIKV prevalence, methods relying on the normal approximation to the binomial distribution were inappropriate. Instead, we assumed a hypergeometric distribution, 10 missed cases at maximum, a urine assay sensitivity of 92.6% and 100% specificity. Three suspected example risk areas were evaluated with estimated population sizes of 479-4,453, corresponding to a minimum of 133-1244 urine samples. This planning exercise improved our capacity for ruling out local transmission of an emerging infection in a dense, urban environment where all residents in a suspected risk area cannot be feasibly sampled.

Estimating the prevalence of chronic hepatitis C virus infection in New York City, 2015.

Chronic hepatitis C virus (HCV) infection is the most common blood-borne infection in the USA. Estimating prevalence is critical for monitoring diagnosis, treatment, and cure and for allocating resources. Surveillance data reported to the New York City (NYC) Health Department, 2000-2015, were used to estimate HCV prevalence in NYC in 2015. The numbers who died, out-migrated or whose last RNA test was negative were removed from the count of people reported with HCV. A simulation model was used to remove estimates of people whose infection spontaneously cleared or was cured and to add an estimate of people unaware of infection. The surveillance-based HCV prevalence in NYC in 2015 overall was 1.4% (95% certainty level (CL) 1.2-1.6%; n ≈ 116 000, 95% CL ≈99 000-135 000) and among adults aged ⩾20 years was 1.8% (95% CL 1.5-2.0%, n ≈ 115 000, 95% CL ≈99 000-134 000), lower than the 2010 estimate among adults aged ⩾20 years of 2.4% (n ≈ 147 000). Contributors to the decrease in HCV prevalence from 2010 to 2015 include both the availability of highly effective treatment and also deaths among an ageing population. The 2015 estimate can be used to set NYC-specific HCV screening and treatment targets and monitor progress towards HCV elimination.

Outbreak of non-tuberculous mycobacteria skin or soft tissue infections associated with handling fish - New York City, 2013-2014.

Mycobacterium marinum, a bacterium found in freshwater and saltwater, can infect persons with direct exposure to fish or aquariums. During December 2013, the New York City Department of Health and Mental Hygiene learned of four suspected or confirmed M. marinum skin or soft tissue infections (SSTIs) among persons who purchased whole fish from Chinese markets. Ninety-eight case-patients with non-tuberculous mycobacteria (NTM) SSTIs were identified with onset June 2013-March 2014. Of these, 77 (79%) were female. The median age was 62 years (range 30-91). Whole genome sequencing of clinical isolates revealed two main clusters and marked genetic diversity. Environmental samples from distributors yielded NTM though not M. marinum. We compared 56 case-patients with 185 control subjects who shopped in Chinese markets, frequency-matched by age group and sex. Risk factors for infection included skin injury to the finger or hand (odds ratio [OR]: 15·5; 95% confidence interval [CI]: 6·9-37·3), hand injury while preparing fish or seafood (OR 8·3; 95% CI 3·8-19·1), and purchasing tilapia (OR 3·6; 95% CI 1·1-13·9) or whiting (OR 2·7; 95% CI 1·1-6·6). A definitive environmental outbreak source was not identified.

Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

Expression of miR-200c in claudin-low breast cancer alters stem cell functionality, enhances chemosensitivity and reduces metastatic potential.

Claudin-low tumors are a highly aggressive breast cancer subtype with no targeted treatments and a clinically documented resistance to chemotherapy. They are significantly enriched in cancer stem cells (CSCs), which makes claudin-low tumor models particularly attractive for studying CSC behavior and developing novel approaches to minimize CSC therapy resistance. One proposed mechanism by which CSCs arise is via an epithelial-mesenchymal transition (EMT), and reversal of this process may provide a potential therapeutic approach for increasing tumor chemosensitivity. Therefore, we investigated the role of known EMT regulators, miR-200 family of microRNAs in controlling the epithelial state, stem-like properties and therapeutic response in an in vivo primary, syngeneic p53(null) claudin-low tumor model that is normally deficient in miR-200 expression. Using an inducible lentiviral approach, we expressed the miR-200c cluster in this model and found that it changed the epithelial state, and consequently, impeded CSC behavior in these mesenchymal tumors. Moreover, these state changes were accompanied by a decrease in proliferation and an increase in the differentiation status. miR-200c expression also forced a significant reorganization of tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion and motility. Accordingly, induced miR200c expression significantly enhanced the chemosensitivity and decreased the metastatic potential of this p53(null) claudin-low tumor model. Collectively, our data suggest that miR-200c expression in claudin-low tumors offers a potential therapeutic application to disrupt the EMT program on multiple fronts in this mesenchymal tumor subtype, by altering tumor growth, chemosensitivity and metastatic potential in vivo.

Using winter 2009-2010 to assess the accuracy of methods which estimate influenza-related morbidity and mortality.

We used the winter of 2009-2010, which had minimal influenza circulation due to the earlier 2009 influenza A(H1N1) pandemic, to test the accuracy of ecological trend methods used to estimate influenza-related deaths and hospitalizations. We aggregated weekly counts of person-time, all-cause deaths, and hospitalizations for pneumonia/influenza and respiratory/circulatory conditions from seven healthcare systems. We predicted the incidence of the outcomes during the winter of 2009-2010 using three different methods: a cyclic (Serfling) regression model, a cyclic regression model with viral circulation data (virological regression), and an autoregressive, integrated moving average model with viral circulation data (ARIMAX). We compared predicted non-influenza incidence with actual winter incidence. All three models generally displayed high accuracy, with prediction errors for death ranging from -5% to -2%. For hospitalizations, errors ranged from -10% to -2% for pneumonia/influenza and from -3% to 0% for respiratory/circulatory. The Serfling and virological models consistently outperformed the ARIMAX model. The three methods tested could predict incidence of non-influenza deaths and hospitalizations during a winter with negligible influenza circulation. However, meaningful mis-estimation of the burden of influenza can still result with outcomes for which the contribution of influenza is low, such as all-cause mortality.

Reported ingested dose of paracetamol as a predictor of risk following paracetamol overdose.

PURPOSE: To evaluate reported ingested dose of paracetamol as a risk assessment tool in acute paracetamol overdose. METHODS: Data was retrospectively obtained from a clinical toxicology database linked to one Australian and two United Kingdom hospitals. Plasma paracetamol concentrations (PPCs) of adult patients presenting with acute single ingestion, non-staggered paracetamol deliberate self-poisoning between 2006 and 2012 were recorded and plotted on a treatment nomogram to determine accuracy of reported dose ingested as an indicator for antidotal treatment. PPC plotted on a treatment nomogram with a line intersecting a 4-h concentration of 100 mg/L [667 µmol/L] was considered an indication for antidotal treatment in the UK; the corresponding Australasian population utilised a line intersecting 150 mg/L [1000 µmol/L]. RESULTS: Of 1246 patients, 65.7 % were female and 88 % were from the UK. Fifty-two percent of patients reporting ingestion of ≥8 g paracetamol had a PPC above the 100 mg/L treatment line; PPV 52 % [95 % confidence interval (CI) 49 %, 55 %], sensitivity 81 % [95 %CI 78 %, 85 %]. Forty-four of patients reporting percent ingestion of ≥10 g had a PPC above the 150 mg/L treatment line; PPV 44 % [95 % CI 41 %, 49 %], sensitivity 85 % [95 % CI 78 %, 89 %], 72 % of patients reporting ingestion of ≥16 g had a PPC above the 100 mg/L treatment line; PPV 72 % [95% CI 67 %, 77 %], sensitivity 50 % [95 % CI 45 %, 54 %]. Overall, there was moderate correlation (R = 0.58) between reported paracetamol dose ingested and extrapolated 4-h PPC. CONCLUSIONS: There is a positive correlation between reported ingested dose of paracetamol and subsequent chance of a PPC being above a defined treatment line; however, ingested dose of paracetamol alone is a poor risk assessment tool in accurately determining need for treatment with an antidote.

The Kuwait-Scotland eHealth Innovation Network (KSeHIN): a sustainable approach to quality improvement in healthcare.

BACKGROUND: The rising prevalence of obesity and diabetes in Kuwait represents a significant challenge for the country's healthcare system. Diabetes care in Scotland has improved by adopting a system of managed clinical networks supported by a national informatics platform. In 2010, a Kuwait-Dundee collaboration was established with a view to transforming diabetes care in Kuwait. This paper describes the significant progress that has been made to date. METHODS: The Kuwait-Scotland eHealth Innovation Network (KSeHIN) is a partnership among health, education, industry and government. KSeHIN aims to deliver a package of clinical service development, education (including a formal postgraduate programme and continuing professional development) and research underpinned by a comprehensive informatics system. RESULTS: The informatics system includes a disease registry for children and adults with diabetes. At the patient level, the system provides an overview of clinical and operational data. At the population level, users view key performance indicators based on national standards of diabetes care established by KSeHIN. The national childhood registry (CODeR) accumulates approximately 300 children a year. The adult registry (KHN), implemented in four primary healthcare centres in 2013, has approximately 4000 registered patients, most of whom are not yet meeting national clinical targets. A credit-bearing postgraduate educational programme provides module-based teaching and workplace-based projects. In addition, a new clinical skills centre provides simulator-based training. Over 150 masters students from throughout Kuwait are enrolled and over 400 work-based projects have been completed to date. CONCLUSION: KSeHIN represents a successful collaboration between multiple stakeholders working across traditional boundaries. It is targeting patient outcomes, system performance and professional development to provide a sustainable transformation in the quality of diabetes healthcare for the growing population of Kuwaitis with diabetes in Kuwait.

Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.

INTRODUCTION: Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. CASE REPORT: A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 µg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. DISCUSSION: Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.

Filamentous sulfur bacteria preserved in modern and ancient phosphatic sediments: implications for the role of oxygen and bacteria in phosphogenesis.

Marine phosphate-rich sedimentary deposits (phosphorites) are important geological reservoirs for the biologically essential nutrient phosphorous. Phosphorites first appear in abundance approximately 600 million years ago, but their proliferation at that time is poorly understood. Recent marine phosphorites spatially correlate with the habitats of vacuolated sulfide-oxidizing bacteria that store polyphosphates under oxic conditions to be utilized under sulfidic conditions. Hydrolysis of the stored polyphosphate results in the rapid precipitation of the phosphate-rich mineral apatite-providing a mechanism to explain the association between modern phosphorites and these bacteria. Whether sulfur bacteria were important to the formation of ancient phosphorites has been unresolved. Here, we present the remains of modern sulfide-oxidizing bacteria that are partially encrusted in apatite, providing evidence that bacterially mediated phosphogenesis can rapidly permineralize sulfide-oxidizing bacteria and perhaps other types of organic remains. We also describe filamentous microfossils that resemble modern sulfide-oxidizing bacteria from two major phosphogenic episodes in the geologic record. These microfossils contain sulfur-rich inclusions that may represent relict sulfur globules, a diagnostic feature of modern sulfide-oxidizing bacteria. These findings suggest that sulfur bacteria, which are known to mediate the precipitation of apatite in modern sediments, were also present in certain phosphogenic settings for at least the last 600 million years. If polyphosphate-utilizing sulfide-oxidizing bacteria also played a role in the formation of ancient phosphorites, their requirements for oxygen, or oxygen-requiring metabolites such as nitrate, might explain the temporal correlation between the first appearance of globally distributed marine phosphorites and increasing oxygenation of Neoproterozoic oceans.

Randomized trial of cisplatin versus firocoxib versus cisplatin/firocoxib in dogs with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Cisplatin combined with a nonselective cyclooxygenase (cox) inhibitor has potent antitumor activity against transitional cell carcinoma (TCC) in dogs, but this treatment is limited by renal toxicosis. Cox-2 is expressed in TCC, but only in limited sites within the kidney. A cox-2 inhibitor could enhance the antitumor activity of cisplatin with potentially fewer adverse effects on the kidney. HYPOTHESIS: Cisplatin/cox-2 inhibitor treatment will have greater antitumor activity but no more renal toxicosis than cisplatin alone in dogs with TCC. ANIMALS: Forty-four dogs with naturally occurring urinary bladder TCC. METHODS: Dogs were randomized to receive cisplatin (60 mg/m(2) IV q21d), firocoxib (5 mg/kg PO q24h), or the combination. Tumor measurements were determined before and at 6-week intervals during treatment. Renal function was monitored by serum creatinine concentration, iohexol clearance, and urine specific gravity. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. RESULTS: The remission rate with cisplatin/firocoxib (57%) was significantly (P = .021) higher than that with cisplatin alone (13%). Renal and gastrointestinal toxicoses were common in dogs receiving cisplatin, but there were no significant differences between dogs receiving cisplatin or cisplatin/firocoxib. Firocoxib alone induced partial remission or stable disease in 20 and 33% of dogs, respectively. CONCLUSIONS: Firocoxib significantly enhanced the antitumor activity of cisplatin resulting in partial remission in more than half of the cases. The toxicoses inherent to cisplatin, however, were noted in dogs receiving this combination. Firocoxib had antitumor effects as a single agent and can be considered a palliative treatment for dogs with TCC.