Comparison of the efficacy of macrocyclic lactone anthelmintics, either singly or in combination with other anthelmintic(s), in nine beef herds in southern NSW.

Anthelmintic resistance (AR) is a well-recognized challenge in farmed ruminants. The use of anthelmintics in combination is one of the strategies recommended to slow the rate of AR development. Two studies were undertaken in 2017 and 2019 to assess the efficacy of single-dose macrocyclic lactone (ML) anthelmintic and ML combination drenches. In total, 11 Faecal Egg Count Reduction Trials (FECRTs) were set up in 10 different beef herds, with results available from 10 of those FECRTs (9 herds). AR to a single ML anthelmintic was detected in all 9 herds, with resistance to Cooperia and Haemonchus spp on 9 farms, and resistance to Ostertagia and Trichostrongylus spp on 2 farms. In contrast, for the ML combination anthelmintics, all FECRTs resulted in efficacies of 99%-100%. The results suggest that cattle producers should strongly consider using combination drenches in their herds in preference to single actives.

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1ß and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. RESULTS: The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. CONCLUSIONS: These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1ß and IL-6 suppression.

Lung cancer physicians' referral practices for palliative care consultation.

BACKGROUND: Integration of palliative care with standard oncologic care improves quality of life and survival of lung cancer patients. We surveyed physicians to identify factors influencing their decisions for referral to palliative care. METHODS: We provided a self-administered questionnaire to physicians caring for lung cancer patients at five medical centers. The questionnaire asked about practices and views with respect to palliative care referral. We used multiple regression analysis to identify predictors of low referral rates (<25%). RESULTS: Of 155 physicians who returned survey responses, 75 (48%) reported referring <25% of patients for palliative care consultation. Multivariate analysis, controlling for provider characteristics, found that low referral rates were associated with physicians' concerns that palliative care referral would alarm patients and families [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.21-0.98], while the belief that palliative care specialists have more time to discuss complex issues (OR 3.07, 95% CI 1.56-6.02) was associated with higher rates of referral. CONCLUSIONS: Although palliative care consultation is increasingly available and recommended throughout the trajectory of lung cancer, our data indicate it is underutilized. Understanding factors influencing decisions to refer can be used to improve integration of palliative care as part of lung cancer management.

Improving comfort and communication in the ICU: a practical new tool for palliative care performance measurement and feedback.

OBJECTIVE: To develop a practical set of measures for routine monitoring, performance feedback, and improvement in the quality of palliative care in the intensive care unit (ICU). DESIGN: Use of an interdisciplinary iterative process to create a prototype "bundle" of indicators within previously established domains of ICU palliative care quality; operationalization of indicators as specified measures; and pilot implementation to evaluate feasibility and baseline ICU performance. SETTING: The national Transformation of the Intensive Care Unit program developed in the United States by VHA Inc. PATIENTS: Critically ill patients in ICUs for 1, > 3, and > 5 days. MEASUREMENTS AND MAIN RESULTS: Palliative care processes including identification of patient preferences and decision making surrogates, communication between clinicians and patients/families, social and spiritual support, and pain assessment and management, as documented in medical records. Application is triggered by specified lengths of ICU stay. Pilot testing in 19 ICUs (review of > 100 patients' records) documented feasibility, while revealing opportunities for quality improvement in clinician-patient/family communication and other key components of ICU palliative care. CONCLUSIONS: The new bundle of measures is a prototype for routine measurement of the quality of palliative care in the ICU. Further investigation is needed to confirm associations between measured processes and outcomes of importance to patients and families, as well as other aspects of validity.

Long-term outcome of learning and memory in children following severe closed head injury.

Seventeen children aged 5-16 years old (M = 11.3, SD = 2.97, Range= 6.25-16.00) were assessed between 4-5 years post-severe closed head injury, using the Wide Range Assessment of Memory and Learning (WRAML). Compared to age and sex matched controls, this group demonstrated deficits in the ability to learn new information, particularly their rate of learning. Deficits were more apparent with verbal than visual material. There were no indications of differences in delayed recall as measured by the amount of information lost nor in recognition memory. Results indicate that retrieval deficits may be an important component of memory difficulties in severe closed head injury. Educational implications are considered.

A comparative analysis of relative brain size in waterfowl (Anseriformes).

Variation in relative brain size was examined in 55 species of waterfowl (Anseriformes). Using both conventional statistics and phylogenetically based comparative methods, the extent of variation in relative brain size and possible relationships with mode of foraging and diet were examined. The results indicate that although brain size does vary considerably between closely related species of waterfowl, it is not reliably related to either foraging mode or diet. There are a number of possible reasons for the lack of relationships between brain size and foraging mode and diet. Firstly, subtle changes in foraging mode and diet may favor relatively large changes in brain size. Secondly, foraging mode and diet could be correlated with the expansion of an individual brain region without affecting overall brain size. Thirdly, other behavioral/ecological traits may be more important with respect to brain size evolution in waterfowl. For example, the relatively large brain of the musk duck (Biziura lobata) and altriciality of their young in comparison to other stiff-tailed ducks (Oxyura spp.) indicates that developmental rate plays a significant role in the evolution of brain size. Given the difference between our results and that reported in inter-order comparisons of brain size in birds, further research is required into other avian orders to assess how brain size and behavior might be related within orders as well as between them.

Do big-brained animals play more? Comparative analyses of play and relative brain size in mammals.

It has been hypothesized that play is more likely to be present in larger brained species. We tested this hypothesis in mammals using independent contrasts, a method that controls for phylogenetic relatedness. Comparisons across 15 orders revealed that the prevalence and complexity of play was significantly correlated with brain size, with larger brained orders having more playful species. Three orders, Rodentia, Marsupialia, and Primates, were used for within-order comparisons among species and, where possible, among families. The comparisons were not significant for rodents or primates, and those for marsupials yielded inconsistent results. Therefore, although a strong relationship is present at the highest taxonomic level of comparison, it diminishes or evaporates at lower level comparisons.

End-of-life care in the intensive care unit: where are we now?

A growing body of evidence and experience has effaced what were once thought to be clear distinctions between "critical illness" and "terminal illness" and has exposed the problems of postponing palliative care for intensive care patients until death is obviously imminent. Integration of palliative care as a component of comprehensive intensive care is now seen as more appropriate for all critically ill patients, including those pursuing aggressive treatments to prolong life. At present, however, data on which to base practice in this integrated model remain insufficient, and forces of the healthcare economy and other factors may constrain its application. The purpose of this article is to map where we are now in seeking to improve palliative care in the intensive care unit. We review existing evidence, which suggests that both symptom management and communication about preferences and goals of care warrant improvement and that prevailing practices for limitation of life-sustaining treatments are inconsistent and possibly irrational. We also address the need for assessment tools for research and quality improvement. We discuss recent initiatives and ongoing obstacles. Finally, we identify areas for further exploration and suggest guiding principles.

Self-reported symptom experience of critically ill cancer patients receiving intensive care.

OBJECTIVE: To characterize the symptom experience of a cohort of intensive care unit (ICU) patients at high risk for hospital death. DESIGN: Prospective analysis of patients with a present or past diagnosis of cancer who were consecutively admitted to a medical ICU during an 8-month period. SETTING: Academic, university-affiliated, tertiary-care, urban medical center. PATIENTS: One hundred cancer patients treated in a medical ICU. INTERVENTION: Assessment of symptoms. MEASUREMENTS: Patients' self-reports of symptoms using the Edmonton Symptom Assessment Scale (ESAS), and ratings of pain or discomfort associated with ICU diagnostic/therapeutic procedures and of stress associated with conditions in the ICU. MAIN RESULTS: Hospital mortality for the group was 56%. Fifty patients had the capacity to respond to the ESAS, among whom 100% provided symptom reports. Between 55% and 75% of ESAS responders reported experiencing pain, discomfort, anxiety, sleep disturbance, or unsatisfied hunger or thirst that they rated as moderate or severe, whereas depression and dyspnea at these levels were reported by approximately 40% and 33% of responders, respectively. Significant pain, discomfort, or both were associated with common ICU procedures, but most procedure-related symptoms were controlled adequately for a majority of patients. Inability to communicate, sleep disruption, and limitations on visiting were particularly stressful among ICU conditions studied. CONCLUSIONS: Among critically ill cancer patients, multiple distressing symptoms were common in the ICU, often at significant levels of severity. Symptom assessment may suggest more effective strategies for symptom control and may direct decisions about appropriate use of ICU therapies.

Energy, water balance and the roost microenvironment in three Australian cave-dwelling bats (Microchiroptera).

The ghost bat, Macroderma gigas, and the orange leaf-nosed bat, Rhinonycteris aurantius, occupy similar ranges across northern Australia and are often found in the same roost caves. Both species are considered rare and vulnerable to further population decline. A third small species, the large bent-wing bat, Miniopterus schreibersii, has a similar body mass to R. aurantius, but has one of the largest ranges of any Australian mammal. In the present study we examine the effect and sensitivity of the animals' roosting microclimates on their energy and water balance. M. schreibersii exhibits a basal metabolic rate about 40% greater than other bats of similar body mass, whereas the other two species are close to predicted levels. R. aurantius shows a decrease in body temperatures below thermoneutrality. R. aurantius has levels of pulmocutaneous water loss among the highest seen for a mammal, and calculations based on nasal tip temperatures suggest that most of this loss is across the skin. Calculated ambient temperatures at which metabolic water production is equal to pulmocutaneous water loss in dry air are -14.7 degrees C for R. aurantius, 9.8 degrees C for M. schreibersii and -0.3 degrees C for M. gigas. Exposing the animals to relative humidities of between 80% and 90% shifted these calculated temperatures to 5.6 degrees C, 25.2 degrees C, and 2.9 degrees C, respectively. For each species the ratio of metabolic water production to evaporative water loss has been treated as a joint function of humidity and ambient temperature. The resulting surface plot shows that under known roosting conditions in caves R. aurantius and M. schreibersii remain in positive water balance, whereas M. gigas does not.

Control of LMP7 expression in human endothelial cells by cytokines regulating cellular and humoral immunity.

Formation of antigenic peptides by the multicatalytic proteinase complex (MPC, proteasome) is facilitated by incorporation of three subunits (LMP2, LMP7 and LMP10) that are inducible by IFN-gamma and TNF-alpha. These cytokines, or their functional homologues (e.g. TNF-beta), are released from many cells including Th(1)lymphocytes. To learn more about the relationship between control of cellular immunity and expression of LMP subunits, we measured LMP7 levels in human umbilical vein endothelial cells of cytokines promoting cellular immunity (IL-12, IFN-gamma, TNF-alpha) or humoral immunity (IL-10, IL-6). Little or no effect was seen when cells were exposed to IL-6, IL-10 or IL-12 alone. IFN-gamma upregulated LMP7 levels, as did TNF-alpha to a lesser extent. IL-10 downregulated IFN-gamma-induced increases in LMP7 levels, as did IL-12. The findings indicate that regulation of levels of LMP7 is similar to and may be coupled with that of other molecules required for MHC class I-dependent immunity, and depends primarily on cytokines released by Th(1)helper lymphocytes.

Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure.

OBJECTIVE: Although childhood-onset schizophrenia is rare, children with brief psychotic symptoms and prominent emotional disturbances commonly present diagnostic and treatment problems. Quantitative anatomic brain magnetic resonance images (MRIs) of a subgroup of children with psychotic disorder not otherwise specified were compared with those of children with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Anatomic MRIs were obtained for 71 patients (44 with childhood-onset schizophrenia and 27 with psychotic disorder not otherwise specified) and 106 healthy volunteers. Most patients had been treated with neuroleptics. Volumetric measurements for the cerebrum, anterior frontal region, lateral ventricles, corpus callosum, caudate, putamen, globus pallidus, and midsagittal thalamic area were obtained. RESULTS: Patients had a smaller total cerebral volume than healthy comparison subjects. Analysis of covariance for total cerebral volume and age found that lateral ventricles were larger in both patient groups than in healthy comparison subjects and that schizophrenia patients had a smaller midsagittal thalamic area than both subjects with psychotic disorder not otherwise specified and healthy comparison subjects. CONCLUSIONS: Pediatric patients with psychotic disorder not otherwise specified showed a pattern of brain volumes similar to those found in childhood-onset schizophrenia. Neither group showed a decrease in volumes of temporal lobe structures. Prospective longitudinal magnetic resonance imaging and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders.

Finger motion, wrist motion and tendon travel as a function of keyboard angles.

OBJECTIVE: This study assessed the impact of keyboard angles (in terms of Pitch, Roll and Yaw) on tendon travel and wrist and finger joint kinematics for the flexor digitorum profundus and flexor digitorum superficialis.DESIGN. A repeated measures, laboratory study was conducted. Independent variables were three Pitch angles, three Roll angles, three Yaw angles, and three keyboard separation distances. Dependent variables were tendon travel, wrist deviation, wrist and finger joint kinematics, and Borg comfort rating. BACKGROUND: The increased usage of computers and the risk of cumulative trauma disorders have led to the development of alternate keyboards. This study is a biomechanical assessment of several keyboard designs.METHODS. Lightweight wrist and finger goniometers were used to measure motion of the wrist in three planes, and for three finger joints. Fifteen experienced typists (eight women, seven men) typed a standard text on 30 keyboard conditions. Regression equations were used to calculate tendon travel from joint positions. RESULTS: Tendon travel is sensitive to changes in Pitch, Roll and Yaw angles with approximately 13% difference between the minimal and maximal tendon travel. A flat keyboard produced more tendon travel than keyboards with greater Pitch and Roll angles.CONCLUSIONS. There is a trade-off between wrist and finger positions; as the wrist extends more, the finger joints flex more to compensate. Keyboards imposed different trade-offs between the wrist and finger positions, affecting the overall tendon travel. Relevance Alternate keyboard designs can significantly affect tendon travel and may address reduced repetitiveness in typing by reducing the amount of tendon travel.

Proteasome from cytokine-treated human cells shows stimulated BrAAP activity and depressed PGPH activity.

The branched chain amino acid-preferring (BrAAP) activity of multicatalytic proteinase complex isolated from human umbilical vein endothelial cells and treated with interferon-gamma was increased more than 2-fold, which was associated with a marked increase in LMP7 expression and decreased peptidylglutamyl peptide-hydrolyzing activity. Increases in BrAAP activity in supernatants from cells treated with interferon-gamma, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, or lipopolysaccharide paralleled the increases in LMP7 expression. These findings are consistent with the conclusion that the increased BrAAP activity of LMP-containing multicatalytic proteinase complex results from incorporation of LMP7 or other LMP subunits.

Up-regulation of the proteasome subunit LMP7 in tissues of endotoxemic rats.

The proteasome has been implicated in systemic responses to infection or inflammatory stimuli including catabolism of skeletal muscle. Cytokines including tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are known to be elevated systemically and locally under these conditions. They are also known to be potent inducers of three peptide subunits of the proteasome, including LMP7, that replace constitutively expressed subunits and change enzymatic properties. To determine whether endotoxemia alters the expression of inducible proteasome subunits, we examined the levels of LMP7 in tissues from rats 3 days after the injection of lipopolysaccharide (LPS) or normal saline solution (NS). By both immunoblotting and immunohistochemistry, significant increases in levels of LMP7 were observed in the heart, kidney, and lung of animals given LPS as compared with results in NS-treated animals, whereas immunoblotting revealed no changes in LMP7 levels in skeletal muscle or brain. Increased expression of LMP7 was limited to certain subpopulations of cells and was further localized at the subcellular level. Decreases in organ weight were also documented for organs in which the expression of LMP7 was up-regulated. Systemic or local release of cytokines or other proinflammatory mediators is suggested as the most likely mechanism for changes in LMP7 expression during endotoxemia. Changes in LMP7 expression may have functional consequences that contribute to organ dysfunction during systemic responses to infection and inflammatory stimuli.

Inverse association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs): results of a case-control study.

We examined the association of prostate cancer and non-steroidal anti-inflammatory drugs (NSAIDs) in a case control study of 417 prostate cancer patients and 420 group-matched control subjects. Regular daily use of over the counter NSAIDs, ibuprofen or aspirin, was associated with a 66% reduction in prostate cancer risk (odds ratio = 0.34, 95% confidence interval = 0.23-0.58, p<0.01). The risk of prostate cancer was also significantly reduced in men who reported taking prescription NSAIDs (odds ratio = 0.35, 95% confidence interval = 0.15-0.84, p<0.05). These results suggest that NSAIDs may have value in the chemoprevention of prostate cancer.

Organization of visual cortex in the northern quoll, Dasyurus hallucatus: evidence for a homologue of the second visual area in marsupials.

Two visual areas, V1 and V2 (first and second visual areas), appear to be present in the posterior neocortex of all eutherian mammals investigated so far. However, previous studies have not established whether an area homologous to V2 also exists in metatherian mammals (marsupials). Using electrophysiological techniques, we mapped the visual receptive fields of neurons in the striate and peristriate cortices of the northern quoll, an Australian marsupial. We found that neurons in a 2-mm-wide strip of cortex rostrolateral to V1 form a single, relatively simple representation of the complete contralateral hemifield. This area resembles V2 of eutherians in several respects: (i) neurons in the medial half of the peristriate area represent the lower visual quadrant, whereas those in the lateral half represent the upper visual quadrant; (ii) the vertical meridian of the visual field is represented adjacent to V1, while the visual field periphery is represented along the lateral and rostrolateral borders of the peristriate area; (iii) there is a marked anisotropy in the representation, with a larger magnification factor parallel to the V1 border than perpendicular to this border; and (iv) receptive fields of multiunit clusters in the peristriate cortex are much larger than those of cells in V1 at comparable eccentricities. The cortex immediately rostral and lateral to V2 did not respond to visual stimulation under our recording conditions. These results suggest that V1 and V2 together form a 'core' of homologous visual areas, likely to exist in all therian mammals.

Imported yellow fever in a United States citizen.

The last imported case of yellow fever seen in this country was in 1924. We report a case of yellow fever acquired by an American tourist who visited the jungles of Brazil along the Rio Negro and Amazon Rivers. The patient died 6 days after hospital admission and 10 days after his first symptoms appeared. Yellow fever virus was recovered from clinical specimens, and the isolate was genetically similar to the E genotype IIB of South American yellow fever viruses. This patient's illness represents a case of vaccine-preventable death since he failed to be immunized with a recommended preexposure yellow fever vaccine.