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Background: Reflexive laboratory testing workflows can improve the assessment of patients receiving pain medications chronically, but complex workflows requiring pathologist input and interpretation may not be well-supported by traditional laboratory information systems. In this work, we describe the development of a web application that improves the efficiency of pathologists and laboratory staff in delivering actionable toxicology results., Method: Before designing the application, we set out to understand the entire workflow including the laboratory workflow and pathologist review. Additionally, we gathered requirements and specifications from stakeholders. Finally, to assess the performance of the implementation of the application, we surveyed stakeholders and documented the approximate amount of time that is required in each step of the workflow., Results: A web-based application was chosen for the ease of access for users. Relevant clinical data was routinely received and displayed in the application. The workflows in the laboratory and during the interpretation process served as the basis of the user interface. With the addition of auto-filing software, the return on investment was significant. The laboratory saved the equivalent of one full-time employee in time by automating file management and result entry., Discussion: Implementation of a purpose-built application to support reflex and interpretation workflows in a clinical pathology practice has led to a significant improvement in laboratory efficiency. Custom- and purpose-built applications can help reduce staff burnout, reduce transcription errors, and allow staff to focus on more critical issues around quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The inclusion level of dried Elaeis guineense supplementation on nitrogen and energy partitioning was evaluated using 12 two-year-old West African Dwarf (WAD) sheep fed a basal hay diet. Six of the sheep were fistulated ruminally and used for rumen pH, ammonia and volatile fatty acid determination in the fluid. Dried leaves of E. guineense were offered as supplement at two levels (25 and 50% of DMI, diets D25% and D50%, respectively) to a basal hay diet. Rumen liquor was sampled 1h before feeding and 1, 3 and 5h after the morning feeding. The sheep were also subjected to nitrogen and energy balance trials. The CP content of the control, D25% and D50% diets were (131.0, 121.0 and 111.0gkg-1), respectively, and their energy digestibility amounted to (0.625, 0.533 and 0.482), respectively. In the fermentation profile trial, rumen pH decreased (P < 0.05) with level of supplementation, with diet D50% having the lowest (P < 0.05) pH value. Diet D25% had a higher (P < 0.05) ruminal ammonia concentration than both the control and D50% diets, respectively. D25% had a superior (P < 0.05) volatile fatty acid (VFA) than the controls. Nitrogen intake decreased (P < 0.05) with supplementation level. Faecal-N increased (P < 0.05) with level of supplementation while N-digestibility decreased (P < 0.05). Organic matter digestibility (OMD), decreased (P < 0.05) with supplementation. Faecal energy increased (P < 0.05) with supplementation while methane energy decreased at the higher supplementation level (P < 0.05). The lowest (P < 0.05) heat loss of 709kJday-1 was observed on diet D50% and this was about 45% of the total energy intake. Animals in diet D50% lost 8.4% of the energy retained in fat and protein. Although E. guineense had a CT, CP and a relatively high GE content of (18gkg-1, 90gkg-1 and 19.8kJg-1 DM), respectively, dried leaves of E. guineense is of low fodder value and should be used sparingly. [Copyright &y& Elsevier]

In an earlier study [Hear. Res. 149 (2000) 55] velocity amplitudes of the outer Hensen''s cell (HC) and basilar membrane (BM) were measured before, and at different times, after, sacrificing the animal. The velocity amplitude changed in a way that was characteristic of a negative feedback amplifier. A simple negative feedback amplifier model was proposed to explain the magnitude of the HC and BM velocity changes at CF. In the experiment tuning changed as well, both at the HC and BM. The model has now been extended to include tuning changes. The model response is compared with the experimental observations. The model is able to account quantitatively for the following experimental observations: (i) At the HC the tuning broadens and velocity decreases slowly after sacrifice. (ii) At the BM tuning sharpens and velocity increases at a faster rate. (iii) The velocity increase at BM is much larger than the decrease at HC. [Copyright &y& Elsevier]

To reduce the incidence of dysentery, cholera and other water-borne diseases and mortality of people drinking from surface contaminated sources of water, the World Bank and United Nations Children''s Fund began to sink tube wells into the underlying aquifers of Bangladesh and West Bengal, India, in the 1970s. Many of the tube wells were drilled into underground aquifers that provided microbiologically clean water that was later determined to contain arsenic (As). As contamination of drinking water is a problem of natural occurrence throughout the world and domestic water often exceeds the World Health Organization limit of 50 μg As/l in the countries of Bangladesh, West Bengal, India and Nepal as well as other areas occupying much of the Ganges–Brahmaputra delta. It is estimated that as many as one-half of these tube wells discharge water with sufficient amounts of As to produce arsenicosis, i.e. As toxicity in the human population. Access to clean As free water is the priority of most organized relief efforts. Where As free domestic water cannot be provided, an improved diet and/or dietary supplements may ameliorate As toxicity or prevent its toxicity all together. The dietary status of the essential human trace element, selenium (Se) may be adversely affected by a chronic excessive ingestion of As. As added to animal diets has been known to counteract Se toxicity in animals since the 1930s. It is reasoned therefore, that high levels of chronic As ingestion from well water by people within the delta will accelerate the excretion of Se lowering the body''s content of this essential trace element. Excessive Se excretion owing to Se/As complexation may add to the likelihood of As being more toxic and carcinogenic over time, due to the oxidative stress imposed by the excessive As and low Se ingestion. Because of the unique environment of the Ganges–Brahmaputra delta in which millions of people are presently exposed to As, we ask the question: are low dietary Se ingestion and accelerated Se depletion by As possible contributing factors to arsenicosis? [Copyright &y& Elsevier]

Typing of herpes simplex virus (HSV) into its serotypes plays a major role in epidemiology and management of reactivation. To develop and evaluate a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) was employed using Hae III and Taq I against neutralization test, allele-specific PCR and DNA sequencing for the detection of HSV serotypes. Neutralization test, allele-specific PCR, DNA sequencing and PCR-based RFLP were applied simultaneously to 2 standard strains (HSV-1 and HSV-2) and 23 clinical isolates. PCR-based RFLP was applied further to 20 culture negative PCR positive clinical specimens. The 179 bp product of the clinical isolates and specimens amplified using the type-common primers of HSV was subjected to DNA sequencing and PCR-based RFLP. Allele-specific PCR was absolutely specific and highly sensitive. All the typing methods differentiated concordantly 23 clinical isolates into 12 HSV-1 and 11 HSV-2. DNA sequencing did not reveal any nucleotide variations within the serotypes among the isolates sequenced. PCR-based RFLP typed a further 20 culture negative clinical specimens into 15 HSV-1 and 5 HSV-2. PCR-based RFLP was a reliable, less laborious and cost-effective molecular biological tool for the determination of HSV serotypes both for the clinical isolates and culture negative specimens. [Copyright &y& Elsevier]

The BfR MEAL Study aims to provide representative levels of chemical substances in foods consumed by the population in Germany for dietary exposure assessment. Calcium, potassium and phosphorus (Ca, K, P) are essential to obtain physiological functions in humans. Levels were investigated in 356 foods. Foods were purchased representatively, prepared as typically consumed and pooled before analysis. High mean levels were found in milk, dairy products, legumes, nuts, oilseeds and spices as well as chia seeds (Ca, K, P), chewing gum (Ca) and cocoa powder (K). Different levels comparing organically and conventionally produced foods were determined among others in cereal cracker (puffed), olives and tofu. Higher K levels were found in fried compared to boiled potatoes. Similar P levels were mainly found in regionally and seasonally sampled foods. These data provide a substantially improved basis to address dietary exposure assessment of the population in Germany for Ca, K and P., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical trauma, but this has not been studied in detail in this unique population. We aimed to quantify the impact of surgical interventions in patients awaiting liver transplantation on hepatic function and identify risk factors for decompensation., Methods: All surgeries between 2000 and 2018 in patients awaiting liver transplantation in a highvolume German liver transplant center were analyzed retrospectively. Change in liver function measured as indicated by MELD score was assessed and complication rates recorded. The primary endpoint was a composite of an increase in MELD score by > 5 points or death. A logistic regression model was used for multivariate analysis to identify risk factors., Results: In total, 177 surgical procedures in 148 patients were analyzed. The primary endpoint was reached in 42 cases (23.7%). The overall in-hospital complication rate (including death) was 44.1%. Multivariate analysis identified elevated leukocyte count, perioperative blood transfusion, preoperative presence of ascites, and preoperative circulatory support as independent risk factors for a decline in liver function or death., Conclusion: Surgery in patients awaiting liver transplantation carries a relevant risk of hepatic decompensation and death that needs to be considered when deciding whether to perform elective surgery prior to or defer until after liver transplantation., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase thus leading to a reduction in cholesterol synthesis. It has recently been demonstrated that ATO has different pharmacological actions, which are unrelated to its lipid-lowering effects and has the ability to treat chronic airway diseases. This paper reviews the potential of ATO as an anti-inflammatory, antioxidant, and anti-proliferative agent after oral or inhaled administration. This paper discusses the advantages and disadvantages of using ATO under conditions associated with those found in the airways. This treatment could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Background and Aim: Kaffir lime fruit peel oil and Kaffir lime leaf oil have been reported for their activities against respiratory tract pathogens. The purpose of the study was to develop clear oral sprays to be used as a first-defense oral spray., Experimental Procedure: Clear antibacterial oral sprays were prepared and analyzed for their respective active major compounds, using GC-MS. The sprays were tested against a Gr. A streptococcal clinical isolate and 3 standard respiratory tract pathogens, using Broth microdilution method. A 4-month stability test was carried out as well., Results and Conclusion: Six clear oral sprays, three formulae composed of Kaffir lime fruit peel oil (6, 10, 13%v/v KLO) and the other three formulae containing Kaffir lime leaf oil (4, 8, 12%v/v KLLO), were developed. The active compounds in KLO were α-terpineol and terpinene-4-ol whereas that in KLLO was citronellal. All oral sprays exhibited antibacterial activity against one Group A streptococcal clinical isolate and three respiratory pathogenic pathogens, Staphylococcus aureus ATCC 29213, Streptococcus pneumoniae ATCC 49619, and Haemophilus influenza e ATCC 49247, among which the strongest activity was against H. influenza e ATCC 49247. The antibacterial activity of all oral sprays remained unchanged in an accelerated stability test, at 4, 30, and 45 °C under 75% relative humidity, throughout the 4-month storage., (© 2019 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Aflatoxin B 1 (AFB 1 ) is a known human hepatocarcinogen and a recent study reported elevated AFB 1 levels, measured by serum albumin biomarkers, among Guatemalan adults. While AFB 1 can contaminate a variety of foodstuffs, including maize, Guatemala's main dietary staple, the relationship of maize intake to serum AFB 1 -albumin adducts levels in Guatemala has not been previously examined. As a result, a cross-sectional study was conducted among 461 Guatemalan adults living in five geographically distinct departments of the country. Participants provided a serum sample and completed a semi-quantitative food frequency questionnaire and a sociodemographic questionnaire. Multiple linear regression analysis was used to estimate the least square means (LSQ) and 95% confidence intervals (95% CI) of log-transformed AFB 1 -albumin adducts by quintiles of maize consumption in crude and adjusted models. Additionally, analyses of tortilla consumption and levels of maize processing were conducted. The median maize intake was 344.3 g per day [Interquartile Range (IQR): 252.2, 500.8], and the median serum AFB 1 -albumin adduct level was 8.4 pg/mg albumin (IQR: 3.8, 22.3). In adjusted analyses, there was no association between overall maize consumption and serum AFB 1 -albumin levels. However, there was a statistically significant association between tortilla consumption and AFB 1 -albumin levels (p trend  = 0.01). The LSM of AFB 1 -albumin was higher in the highest quintile of tortilla consumption compared to the lowest quintile [LSM:9.03 95%CI: 7.03,11.70 vs 6.23, 95%CI: 4.95,8.17, respectively]. These findings indicate that tortilla may be an important source of AFB 1 exposure in the Guatemalan population. Therefore, efforts to control or mitigate AFB 1 levels in contaminated maize used for tortillas may reduce overall exposure in this population.

The data present in this article is related to evaluation of standardized methanolic extract of Vernonia elaeagnifolia aerial parts [MEVE] , a species of Asteraceae family for antiulcer potential. Antiulcer activity of MEVE (200 and 400 mg/kg, b.w., p.o. ) was evaluated with ethanol and aspirin induced ulcer models and pylorus ligation induced gastric ulcer model. The antioxidant potential of MEVE was evaluated with nitric oxide radicals, hydroxyl radical and H 2 O 2 radical scavenging assay against standard ascorbic acid to correlate antioxidant and antiulcerogenic action. MEVE significantly protects the gastric mucosa against the ethanol and aspirin induced ulcer and pylorus ligation induced ulcer challenge. MEVE had shown significant [normal control: p < 0.0001, disease control: p < 0.0001, standard: p < 0.0001] decrease in the ulcer index produced by all three models in rats as compared to the standard drug omeprazole [20 mg/kg, b.w., p.o. ]. The present data suggest that aerial parts of Vernonia elaeagnifolia possess significant antiulcer activity, which may attributed to its antioxidant mechanism of action.

Introduction Advances in systemic chemotherapy, molecular targeted therapy and immunotherapy have extended and improved the quality of life of patients with cancer. However, the central nervous system is very susceptible to complications of systemic cancer and its treatment. Posterior reversible encephalopathy syndrome (PRES) is a rare clinical and neuroradiologic entity which has garnered increasing recognition in the past two decades. Cancer patients are generally treated with cytotoxic agents, immunotherapy, molecular targeted therapies or glucosteroids which are more frequently associated with PRES. Case presentation A 59-year old female, known with a relapse of her lung adenocarcinoma, had been treated with 4 cycles of cisplatin (75 mg/m²) and pemetrexed (500 mg/m²). Six weeks after this combination chemotherapy and within 28 h after the administration of pemetrexed maintenance therapy, she developed a generalised epileptic insult. Magnetic resonance imaging (MRI) of the brain showed bilateral areas of increased signal intensity in the subcortical parietal and frontal white matter. She was treated with a broad spectrum antiseizure drug, levetiracetam 750 mg twice daily and strict control of blood pressure. Discussion Diagnosis of PRES should be considered in all patients with neurologic symptoms who are at risk to develop PRES. It is crucial to establish the diagnosis as soon as possible since there is no specific treatment of PRES other than correction of the underlying risk factors and preventing seizure recurrence. Administration of pemetrexed is a possible risk factor for the development of PRES.

Hypertension is a becoming a major threat to the world. Angiotensin converting enzyme (ACE) is a key part in the renin angiotensin aldosterone system (RAAS) which control blood pressure. Over expression of RAAS is related with vascular hypertension, ACE inhibition has turned into a noteworthy target for controlling hypertension. In the search of lead molecules from plant origin as a substitute for toxic synthetic drugs, 25 Indian medicinal plants and foods were screened for their ACE inhibitory activity. IC 50 (50% inhibition of ACE) values of hydroalcoholic crude extracts and fraction were determined by a colorimetric method. Active fractions were further screened to determine the enzyme kinetics, mode, specificity and mechanism of inhibition. Standardization was done by determining total phenolics and flavonoids as gallic acid and quercetin equivalents/mg of extract respectively. Among 25 crude extracts, Cynara scolymus extract showed the best activity, IC 50 value 356.62 μg/mL. ACE inhibition resulting from protein precipitation was highest in Coscinium fenestratum . Lineweaver-Burk plots revealed a competitive mode of inhibition for Punica granatum ethyl acetate fraction. Fractions of Cassia occidentalis , Cynara scolymus and Embelia ribes were found to be non-specific inhibitors of ACE. Embelia ribes, Cassia occidentalis and Coscinium fenestratum fractions inhibited the ACE by Zn 2+ ion chelation. Research revealed the potential of tested plants fractions as ACE inhibitors along with their inhibition kinetics and mechanism of inhibition. These active plant fractions might find importance in the development of potential antihypertensive agents after further investigations using preclinical and clinical trials.

Microalgae are increasingly being utilized as food ingredients for a variety of applications, including as sources of protein, egg and dairy substitutes, and cooking oils. The dietary safety of a new structuring fat produced using a heterotrophic fermentation process by a strain of Prototheca moriformis was evaluated in a 13-week dietary toxicity study and compared with kokum fat, a structuring fat of similar composition used in the food industry and derived from Garcinia indica seeds. The algal structuring fat was evaluated for its genotoxic potential using both in vitro and in vivo assays. No treatment-related adverse events occurred in rats consuming algal structuring fat or kokum fat in the 13-week study; no treatment-related effects were reported for body weight, food consumption, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, or histopathology. While statistically significant effects occurred in some parameters, none were dose-related or considered adverse. Overall, the NOAELs for the algal structuring fat and the kokum fat were 100 000 ppm, the highest concentrations tested. The algal structuring fat was not mutagenic in the bacterial reverse mutation assay in the Salmonella typhimurium or Escherichia coli strains tested and was not clastogenic in the in vivo mouse bone marrow chromosome aberration assay.

Despite a major improvement in the treatment of advanced kidney cancer by the recent introduction of targeted agents such as multi-kinase inhibitors, long-term benefits are still limited and a significant unmet medical need remains for this disease. Cancer immunotherapy has shown its potential by the induction of long-lasting responses in a small subset of patients, however, the unspecific immune interventions with (high dose) cytokines used so far are associated with significant side effects. Specific cancer immunotherapy may circumvent these problems by attacking tumor cells while sparing normal tissue with the use of multi-peptide vaccination being one of the most promising strategies. We here summarize the clinical and translational data from phase I and II trials investigating IMA901. Significant associations of clinical benefit with detectable T cell responses against the IMA901 peptides and encouraging survival data in treated patients has prompted the start of a randomized, controlled phase III trial in 1st line advanced RCC with survival results expected toward the end of 2015. Potential combination strategies with the recently discovered so-called checkpoint inhibitors are also discussed.

Although rare, atrial myxoma is the most common primary tumour of the heart. Its relation to immunosuppression in solid organ transplant is presently debateable. We report the case of a 71-year-old male patient who underwent renal transplant 17 years prior. Since that time he continued high dose immunosuppression without physician consultation and presented to us with atrial myxoma and its complications raising the question of any association between immunosuppression and the development of atrial myxoma.