Effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in gastrointestinal, adipose, and liver tissue of Holstein dairy calves.

The objective of this study was to evaluate the effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in Holstein dairy calves. A total of 70 1-d-old calves (38.8 ± 4.4 kg BW ± SD), blocked by sex and birth BW, were randomly assigned to a 2 × 2 factorial arrangement of treatments. The first factor was weaning age, which was either early (6 wk) or late (8 wk). The second factor was weaning pace, which was either abrupt (4 steps down over 3 d; the initial milk replacer was 7.6 L, which was reduced by 1.9 L in each step-down) or gradual (7 steps down over 14 d; the initial milk replacer was 7.6 L, which was reduced by 1.09 L in each step-down), generating early-abrupt (EA), early-gradual (EG), late-abrupt (LA), and late-gradual (LG) treatments. All treatments had 10 female and 8 male calves, except EA that had 1 fewer male calf. Milk replacer (24% CP, 17% fat) was bottle fed, up to 1,200 g/d, twice daily (0600 h and 1800 h). The EA and EG treatment calves received 46.2 kg of milk replacer, and the LA and LG treatment calves received 63 kg of milk replacer. The study had 2 cohorts (2020, n = 40; 2021, n = 31), and each cohort included all treatments. Blood was collected from the jugular vein at 0900 h at 3 and 7 d of age, and a day before starting and a day after weaning completion. Male calves were humanely killed a day after weaning. Rumen, jejunum, large intestine, liver, omental adipose and perirenal adipose tissues were sampled to determine the mRNA abundance of inflammation-related genes. Weaning pace, age, pace × age, birth BW, and sex were included as fixed and cohort was included as random effects in the model. Blood metabolites and cortisol were analyzed as repeated measures, and sampling day, pace × sampling day, and age × sampling day were also included as additional fixed effects. Significance was noted at P ≤ 0.05 and tendencies when 0.05

Effects of weaning strategies on health, hematology, and productivity in Holstein dairy calves.

Weaning strategies in dairy calves vary considerably, though the effect on animal health is unclear. This study examined the effects of calf weaning age (6 vs. 8 wk) and pace (abrupt vs. gradual) on performance, blood, and health parameters in dairy calves. The experiment consisted of a 2 × 2 factorial arrangement of treatments, where the factors included weaning age (early vs. late) and weaning pace (abrupt vs. gradual). Holstein calves (n = 72), blocked by sex and birth weight, were randomly assigned to one of 4 treatments (n = 18 per treatment): early-abrupt (EA), early-gradual (EG), late-abrupt (LA), and late-gradual (LG). Milk replacer (24% crude protein, 17% fat; up to 1,200 g/d) was fed twice daily; water, calf starter (18% crude protein), and chopped alfalfa hay were fed ad libitum. Daily intakes of milk replacer, calf starter, and forage were recorded from birth until end of weaning. Body weight, selected health measures, blood hematology, and fecal scores were obtained 1 d preweaning and 1 d postweaning. Calves were orally bolused with a rumen pH logger for the last 3 d of the weaning transition and rumen pH was measured continuously. Data were analyzed with age, pace, age × pace interaction, birthweight, and sex as fixed effects, and starting date as a random effect. Greater age at weaning increased respiration, whereas gradual-weaned calves had lower respiration rate. Heart rate was lower in gradual than in abrupt weaned groups. Fecal score had a marginal increase in late-weaned groups and significantly increased in gradually weaned groups. No difference was detected in body core temperature by age, pace, or interaction. During the weaning transition, average daily gain was lower in LA than EA and gradually weaned groups had an increased average daily gain. Change in grain intake, but not forage intake, was greater in gradually weaned groups. Mean rumen pH marginally increased from EG to LG and from LA to LG. No difference was detected among treatments in red or white blood cell counts, and hemoglobin. Procalcitonin was marginally highest in the LA group, while blood hematocrit increased in abruptly weaned groups. Overall, calf health is affected by both age and pace of weaning, though the health parameters affected by age and pace differ.

The human urobiome.

Traditionally, the healthy urinary bladder has been considered to be sterile. Several teams have used metagenomic (DNA-dependent) and metaculturomic (culture-dependent) methods to debunk this longstanding dogma. In fact, resident microbial communities (urobiome) have been detected in both adult females and males. Although the field is young, several observations have been made. For example, the urobiome differs between men and women, likely due to anatomical and hormonal differences. Importantly, the urobiome has been associated with a variety of lower urinary tract disorders, including overactive bladder and post-operative urinary tract infection, raising the possibility that clinicians might one day treat symptoms by modifying the urobiome instead of killing the suspected uropathogen. Little is known concerning the relationship between the urobiome and host genetics; so far, only a single paper has reported such a study. However, major efforts have gone into understanding the genomics of the urobiome itself, a process facilitated by the fact that many urobiome studies have used metaculturomic methods to detect and identify microbes. In this narrative review, we will introduce the urobiome with separate sections on the female and male urobiomes, discuss challenges specific to the urobiome, describe newly discovered associations between the urobiome and lower urinary tract symptoms, and highlight the one study that has attempted to relate host genetics and the urobiome. We will finish with a section on how metagenomic surveys and whole genome sequencing of bacterial isolates are improving our understanding of the urobiome and its relationship to lower urinary tract health and disorders.

Acute fasciolosis in an alpaca: a case report.

BACKGROUND: The popularity of new world camelids, particularly alpacas, is growing rapidly in Ireland, presenting a clinical challenge to veterinary practitioners who may not have worked with these species previously. To the authors' knowledge, the clinical course of a case of acute fasciolosis in an alpaca has not previously been reported, and fasciolosis has not been reported at all in alpacas in Ireland, making this case report a valuable addition to the current literature. CASE PRESENTATION: A three-year-old male castrated huacaya alpaca was admitted to UCD Veterinary Hospital with a two-day history of colic and tenesmus. He had been treated with albendazole, dexamethasone and potentiated amoxycillin by the referring veterinary practitioner with no response. On initial clinical exam, sensitivity to abdominal palpation was the only abnormality. However, the alpaca proceeded to show abnormal lying positions, tenesmus and reduced faecal output over the next 24 h. A general blood panel demonstrated moderate anaemia, marked hyperglobulinaemia and moderately increased hepatocellular and hepatobiliary enzyme activity. Abdominal radiography revealed enlargement of the first forestomach compartment without evidence of gastrointestinal obstruction or peritonitis. An abdominal ultrasound exam revealed an elongated, heterogenous mass in the caudoventral abdomen that appeared to be contiguous with the liver. FNA of this mass revealed that it was in fact a liver lobe with biliary stasis and inflammation. Faecal sedimentation demonstrated Fasciola hepatica eggs. In spite of treatment with triclabendazole and supportive treatment including blood transfusion, the alpaca's condition continued to deteriorate and he was euthanised. On post-mortem exam, acute fasciolosis was diagnosed. CONCLUSIONS: The clinical presentation and course of a case of acute fasciolosis in an individual alpaca is described, including the results of a range of diagnostic tests that were carried out. The final diagnosis is supported by a description of post-mortem findings. This information will serve as a resource for veterinary practitioners involved in the diagnosis and treatment of similar cases.

The urobiome of continent adult women: a cross-sectional study.

OBJECTIVE: To characterise the bladder microbiota of continent adult women. DESIGN: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data. SETTING: US academic medical centre. POPULATION: Well-characterised continent adult women. METHODS: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing. MAIN OUTCOME MEASURES: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen). RESULTS: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively. CONCLUSIONS: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged. TWEETABLE ABSTRACT: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice.

Myxoma Virus M083 Is a Virulence Factor Which Mediates Systemic Dissemination.

Poxviruses are large, DNA viruses whose protein capsid is surrounded by one or more lipid envelopes. Embedded into these lipid envelopes are three conserved viral proteins which are thought to mediate binding of virions to target cells. While the function of these proteins has been studied in vitro, their specific roles during the pathogenesis of poxviral disease remain largely unclear. Here we present data demonstrating that the putative chondroitin binding protein M083 from the leporipoxvirus myxoma virus is a significant virulence factor during infection of susceptible Oryctolagus rabbits. Removal of M083 results in a reduced capacity of virus to spread beyond the regional lymph nodes and completely eliminates infection-mediated mortality. In vitro, removal of M083 results in only minor intracellular replication defects but causes a significant reduction in the ability of myxoma virus to spread from infected epithelial cells onto primary lymphocytes. We hypothesize that the physiological role of M083 is therefore to mediate the spread of myxoma virus onto rabbit lymphocytes, allowing these cells to disseminate virus throughout infected rabbits.IMPORTANCE Poxviruses represent both a class of human pathogens and potential therapeutic agents for the treatment of human malignancy. Understanding the basic biology of these agents is therefore significant to human health in a variety of ways. While the mechanisms mediating poxviral binding have been well studied in vitro, how these mechanisms impact poxviral pathogenesis in vivo remains unclear. The current study advances our understanding of how poxviral binding impacts viral pathogenesis by demonstrating that the putative chondroitin binding protein M083 plays a critical role during the pathogenesis of myxoma virus in susceptible Oryctolagus rabbits by impacting viral dissemination through changes in the transfer of virions onto primary splenocytes.

Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes.

Objective: Thermosensitive liposomal doxorubicin (TSL-Dox) is a promising stimuli-responsive nanoparticle drug delivery system that rapidly releases the contained drug in response to hyperthermia (HT) (>40 °C). Combined with localized heating, TSL-Dox allows highly localized delivery. The goals of this study were to demonstrate that real-time fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake. Methods: Nude mice carrying subcutaneous tumors (Lewis lung carcinoma) were anesthetized and injected with TSL-Dox (5 mg/kg dose). Localized HT was induced by heating tumors for 15, 30 or 60 min via a custom-designed HT probe placed superficially at the tumor location. In vivo fluorescence imaging (excitation 523 nm, emission 610 nm) was performed before, during, and for 5 min following HT. After imaging, tumors were extracted, drug uptake was quantified by high-performance liquid chromatography, and correlated with in vivo fluorescence. Plasma samples were obtained before and after HT to measure TSL-Dox pharmacokinetics. Results: Local drug uptake could be visualized in real-time during HT. Compared to unheated control tumors, fluorescence of heated tumors increased by 4.6-fold (15 min HT), 9.3-fold (30 min HT), and 13.2-fold (60 min HT). HT duration predicted tumor drug uptake (p = .02), with tumor drug concentrations of 4.2 ± 1.3 µg/g (no HT), 7.1 ± 5.9 µg/g (15 min HT), 14.1 ± 6.7 µg/g (30 min HT) and 21.4 ± 12.6 µg/g (60 min HT). There was good correlation (R2 = 0.67) between fluorescence of the tumor region and tumor drug uptake. Conclusions: Real-time in vivo fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake.

[Therapeutic Use of Botulinum Toxin to Correct Misalignment of the Eyes]. / Therapeutische Anwendung von Botulinumtoxin zur Korrektur von Augenfehlstellungen.

BACKGROUND/PURPOSE: There are no concrete guidelines for the therapeutic use of botulinum toxin in strabismus. The 2012 Cochrane Analysis concluded that it was controversial, but included only 4 prospective randomized controlled trials. However, many retrospective studies suggest that botulinum toxin treatment is a viable alternative to surgical treatment. We have now retrospectively evaluated the outcomes of our patients treated with botulinum toxin. PATIENTS AND METHODS: We retrospectively reviewed the charts of the patients treated with Botox® for strabismus. The period covered was between 2003 and 2015, with a follow-up of at least 6 months. Successful outcome was defined as alignment within ≤ 10 prism dioptres, with stereopsis at the final follow-up. RESULTS: 16 patients were included, including 11 children. The mean follow-up was 19 months. All 11 children were initially esotropic; 9 exhibited lasting angle reduction (mean 25.5 prism dioptres) at the final follow-up, and 6 of these (54.5 %) achieved a successful outcome. Only one adult patient achieved a lasting angle reduction. Other benefits were: Psychological relief due to reduced nystagmus (n = 1), relief of headaches from decompensating exophoria (n = 1), and renewed ability to read, due to less adduction of the dominant eye in a patient with bilateral sixth nerve palsy. Transient ptosis without obstruction of the visual axis was seen in 4 (36 %) of the children, but in none of the adults. CONCLUSIONS: Botulinum toxin has a lasting effect, especially in children with esotropia. It is minimally invasive and can prevent surgery. If there is subsequent surgery, the dosage may be reduced. Ptosis rates were comparable to those in the literature.

Sex differences in obesity prevalence and cardiometabolic factors among Western Alaska Native people.

BACKGROUND AND AIMS: Obesity is associated with increased risks of cardiovascular disease, type 2 diabetes, and other chronic diseases. Prevalence estimates for metabolic disorders are well documented in many populations, but Alaska Native groups are understudied. The Western Alaska Tribal Collaborative for Health Study combines data from three Alaska Native study cohorts to assess differences in obesity prevalence and associations with cardiometabolic risk factors by sex. METHODS AND RESULTS: Analyses were based upon a sample of 3985 adult Yup'ik and Inupiat participants with a mean age of 40 years. Prevalence of obesity and metabolic risk factors was assessed according to nationally recognized guidelines. Regression analysis was used to evaluate the association between obesity and cardiometabolic risk factors, including lipids, blood pressure and glucose. The prevalence of obesity (BMI ≥ 30) was significantly higher in women (40%) than men (20%). Only 18.6% of men had a waist circumference (WC) > 102 cm, while 58% of women had a WC > 88 cm (p < 0.001). Women had higher mean HDL-C and triglyceride levels compared to men, while systolic and diastolic blood pressure, LDL-C, and glucose means were higher in men than in women. In multivariate analyses, BMI and WC were significantly associated with all of the cardiometabolic risk factors, although these associations were more pronounced in men than women. CONCLUSION: The high prevalence of obesity and central adiposity among AN women is an important public health concern. Differences in associations between obesity and cardiometabolic risk factors by sex warrants further investigation to develop effective intervention programs.

Tendinous muscle insertions (scleromuscular junctions of the recti muscles) in patients with ocular alignment problems.

BACKGROUND: The purpose of this study was to prove the hypothesis whether the scleromuscular junction of extraocular recti muscle is tendinous. PATIENTS AND METHODS: Muscle samples of the 41 extraocular recti muscles of 33 patients and 4 muscle-/eye-matched samples from 2 postmortem eyes, were processed for light/electron microscopy and immunohistochemistry with antibodies against desmin, smooth-muscle actin and muscle regulating proteins like myf3 and myf4 (myogenin), tenascin C and for 8 samples against collagens I to IV. RESULTS: Histological examination of the muscle samples confirmed a thick collagen-structured tissue, specific for muscle tendon; without appearance of muscle tissue. This was confirmed by immunohistochemistry with antibodies against desmin, smooth-muscle actin, myf3 and myf4 (myogenin) and for eight samples with collagens I to IV. Anti-tenascin C marker was only strongly positive in the connective tissue of the blood vessel walls. Electron microscopy demonstrated collagen bundles composed of parallel oriented fibrils with a moderate amount of ground substance. CONCLUSIONS: The absence of contractile fibers at the sclerotendinous junction is an entirely normal finding in humans and cannot be related to ocular alignment pathogenesis.

The 2-global flash mfERG in glaucoma: attempting to increase sensitivity by reducing the focal flash luminance and changing filter settings.

PURPOSE: To test a new 2-flash multifocal electroretinogram (mfERG) paradigm in glaucoma using a reduced light intensity of the m-frame flash as opposed to the global flash, as it has been suggested that this may increase the responses induced by the global flash, which has been the part of the mfERG response where most changes have been noted in glaucoma. METHODS: A mfERG was recorded from one eye of 22 primary open angle glaucoma (POAG) patients [16 normal tension glaucoma (NTG), 6 high tension glaucoma (HTG)] and 20 control subjects. A binary m-sequence (2^13-1, Lmax 100 cd/m2, Lmin<1 cd/m2), followed by two global flashes (Lmax 200 cd/m2) at an interval of 26 ms (VERIS 6.0™, FMSIII), was used. The stimulus array consisted of 103 hexagons. Retinal signals were amplified (gain=50 K) and bandpass filtered at 1-300 Hz. For each focal response, the root mean square was calculated. We analyzed 5 larger response averages (central 15° and 4 adjoining quadrants) as well as 8 smaller response averages (central 10° and 7 surrounding response averages of approximately 7° radius each). Three epochs were analyzed: the direct component at 15-45 ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75 ms (IC-1) and at 75-105 ms (IC-2). Statistical analysis was performed using linear mixed effects models adjusted for age. RESULTS: Responses differed significantly between POAG patients and controls in all central response averages. This difference was larger for the central 10° than for the response average of the central 15°. While these observations held true for all response epochs analyzed, the DC differed least and the IC-1 most when POAG was compared to control. For POAG, the most sensitive differential measure was IC-1 of the central 10° with an area under the ROC curve of 0.78. With a cutoff value of 12.52 nV/deg2, 80% of the POAG patients (100% HTG, 69% NTG) were correctly classified as abnormal, while 77% of the control subjects were correctly classified as normal. When the results of the mfERG were compared to the visual fields, there was a tendency for the mfERG to decrease as the mean defect increased. However, this correlation was only significant in the superior nasal quadrant when the IC-1 of the mfERG was compared to the corresponding area of the visual field. CONCLUSION: When compared to findings from previous studies, reducing the luminance of the m-frame flash in the 2-global flash paradigm did not increase the sensitivity and specificity of the mfERG to detect glaucoma further.

TP53 mutations in canine brain tumors.

The p53 tumor suppressor gene (TP53) is the most frequently altered gene in human cancer. Mutation of the gene has been shown to be an important mechanism of p53 pathway inactivation in a variety of human brain tumors, particularly those of astrocytic origin. Genomic DNA from a series of 37 glial and 51 nonglial canine brain tumors was sequenced to determine the frequency of TP53 gene mutations involving exons 3-9. Exonic mutations were found in 3 of 88 tumors (3.4%) and specifically in 1 of 18 astrocytic tumors (5.5%). This is markedly lower than that reported in comparable human tumors, suggesting that alternative mechanisms of p53 inactivation are likely to be present if p53 function contributes significantly to oncogenesis in canine brain tumors.

Complications with hot, cold and altitude environments in disaster management.

INTRODUCTION: Disaster management is the process of preparing, responding and recovering to an emergency whether that be natural or man-made. It is a time-consuming, resource-heavy process with the aim of reducing the risk of certain events and, where not possible, reducing the impact of said disaster, ensuring that the risks have been identified and appropriate rescue and recovery plan is in place. METHODS: We carried out a thorough literature search on the complications of hot, cold and altitude environments in disaster management and distilled the learnings into this article. RESULTS: The incidence of disasters of natural, man-made and complex origin is likely to continue increasing as global temperatures continue to rise. CONCLUSION: Disaster management in the extreme environments of hot, cold and high altitude is fraught with unique challenges, especially around the physiological response of rescuers, resource constraints and logistics. Recognising these challenges is an important aspect of planning and preparation for disaster management in these environments.

Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities.

Thermosensitive liposomal doxorubicin (TSL-Dox) combined with localized hyperthermia enables targeted drug delivery. Tumor drug uptake occurs only during hyperthermia. We developed a novel method for removal of systemic TSL-Dox remaining after hyperthermia-triggered delivery to reduce toxicities. The carotid artery and jugular vein of Norway brown rats carrying two subcutaneous BN-175 tumors were catheterized. After allowing the animals to recover, TSL-Dox was infused at 7 mg/kg dose. Drug delivery to one of the tumors was performed by inducing 15 min microwave hyperthermia (43 °C). At the end of hyperthermia, an extracorporeal circuit (ECC) comprising a heating module to release drug from TSL-Dox followed by an activated carbon filter to remove free drug was established for 1 h (n = 3). A computational model simulated TSL-Dox pharmacokinetics, including ECC filtration, and predicted cardiac Dox uptake. In animals receiving ECC, we were able to remove 576 ± 65 mg of Dox (29.7 ± 3.7% of the infused dose) within 1 h, with a 2.9-fold reduction of plasma AUC. Fluorescent monitoring enabled real-time quantification of blood concentration and removed drug. Computational modeling predicted that up to 59% of drug could be removed with an ideal filter, and that cardiac uptake can be reduced up to 7×. We demonstrated removal of drug remaining after tumor delivery, reduced plasma AUC, and reduced cardiac uptake, suggesting reduced toxicity.

Unilateral granulomatous orchitis in a harbour porpoise (Phocoena phocoena): a case report.

This case report describes orchitis in a stranded adult sexually mature free-living harbour porpoise (Phocoena phocoena). Orchitis, with or without epididymitis, is a rare finding in harbour porpoises and has been reported to be associated with infection with Brucella species or fungi. This porpoise was examined as part of an ongoing investigation into causes of death in harbour porpoises stranded on the Dutch coast. At necropsy, the animal was in very poor body condition and the most significant pathological change encountered was unilateral chronic granulomatous orchitis. Histologically, the seminiferous tubules were multifocally severely distended by large numbers of macrophages and fewer neutrophils that often showed central necrosis, with intra- and extracellular rod-shaped bacteria that stained negatively with Gram stain. No acid-fast bacteria, fungal elements, or spirochetes were detected when the lesions were stained with Ziehl-Neelsen, Fite-Faraco, Warthin-Starry, and Periodic acid-Schiff stains. Culture of samples taken from the testis revealed a pure culture of a bacterium of the Alcaligenaceae family. Further analysis by biochemistry, fatty acid profiling, and 16S rRNA gene sequencing techniques identified the bacterium as a Castellaniella species. The association of this bacterium with the observed lesions remains uncertain.

A Mouse Model for Chronic Pancreatitis via Bile Duct TNBS Infusion.

Chronic pancreatitis (CP) is a complex disease involving pancreatic inflammation and fibrosis, glandular atrophy, abdominal pain and other symptoms. Several rodent models have been developed to study CP, of which the bile duct 2,4,6 -trinitrobenzene sulfonic acid (TNBS) infusion model replicates the features of neuropathic pain seen in CP. However, bile duct drug infusion in mice is technically challenging. This protocol demonstrates the procedure of bile duct TNBS infusion for generation of a CP mouse model. TNBS was infused into the pancreas through the ampulla of Vater in the duodenum. This protocol optimized drug volume, surgical techniques, and drug handling during the procedure. TNBS-treated mice showed features of CP as reflected by bodyweight and pancreas weight reductions, changes in pain-associated behaviors, and abnormal pancreatic morphology. With these improvements, mortality associated with TNBS injection was minimal. This procedure is not only critical in generating pancreatic disease models but is also useful in local pancreatic drug delivery.

Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes.

GOAL: The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. METHODS: We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (TSL-DOX) delivery in mouse tumors with three HT methods (thermistor probe (T), laser (L) and water bath (WB), at 15 min and 60 min HT duration), with corroborating in vivo studies. RESULTS: Average computer model-predicted tumor drug concentrations (µg/g) were 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 min), and 8.7(WB, 60 min). Tumor fluorescence was increased by 2.6 × (T) and 1.6 × (L) when HT duration was extended from 15 to 60 min (p < 0.05), with no increase for WB HT. Pharmacokinetic analysis confirmed that water bath HT causes rapid depletion of encapsulated TSL-DOX in systemic circulation due to the large heated tissue volume. CONCLUSIONS: Untargeted large volume HT causes poor tumor drug uptake from TSL.

Comparison of storage phosphor computed radiography with conventional film-screen radiography in the recognition of pneumoconiosis.

Traditional film-screen radiography (FSR) has been useful in the recognition and evaluation of interstitial lung diseases, but is becoming increasingly obsolete. To evaluate the applicability of storage phosphor digital computed radiography (CR) images in the recognition of small lung opacities, we compared image quality and the profusion of small opacities between FSR and CR radiographs. We screened 1,388 working coal miners during the course of the study with FSR and CR images obtained on the same day from all participants. Each traditional chest film was independently interpreted by two of eight experienced readers using the International Labour Office (ILO) classification of radiographs of pneumoconiosis, as were CR images displayed on medical-grade computer monitors. The prevalence of small opacities (ILO category 1/0 or greater) did not differ between the two imaging modalities (5.2% for FSR and 4.8% for soft copy CR; p>0.50). Inter-reader agreement was also similar between FSR and CR. Significant differences between image modalities were observed in the shape of small opacities, and in the proportion of miners demonstrating high opacity profusion (category 2/1 and above). Our results indicate that, with appropriate attention to image acquisition and soft copy display, CR digital radiography can be equivalent to FSR in the identification of small interstitial lung opacities.