Implications of tree expansion in shrubland ecosystems for two generalist avian predators.

Shrublands globally have undergone structural changes due to plant invasions, including the expansion of native trees. Removal of native conifer trees, especially juniper (Juniperus spp.), is occurring across the Great Basin of the western U.S. to support declining sagebrush (Artemisia spp.) habitats and associated wildlife species, such as greater sage-grouse (Centrocercus urophasianus). One justification for conifer removal is that it may improve survival of sagebrush-associated wildlife by reducing the abundance of avian predators. However, the relationship between conifer expansion and predator distributions has not been explicitly evaluated. Further, although structural characteristics of habitat are important for generalist predators, overall prey abundance may also affect habitat use by predators. We examined habitat use of common ravens (Corvus corax) and red-tailed hawks (Buteo jamaicensis), two generalist predators whose populations are increasing in western North America, to variation in structural characteristics and prey distributions in sagebrush habitat that has experienced conifer expansion. Structural characteristics of habitat were important predictors of habitat use for both ravens and red-tailed hawks, whereas measures of prey abundance were unimportant for both species likely because generalist predators can use a wide variety of food resources. Ravens, but not red-tailed hawks, responded positively to increasing cover of juniper and the probability of habitat use was highest (> 0.95) where juniper cover within 100 m was > 20%. Habitat use by red-tailed hawks, but not ravens, was greater near cliffs but was not associated with juniper cover. Our study suggests that the removal of conifer in similar environments may lower the probability of habitat use for ravens, a common predator with significant impacts on many prey species. Therefore, we suggest conifer removal may improve sage-grouse reproductive success and survival depending on responses to conifer removal from other predators. Our results may be reflective of similar changes in rangeland ecosystems around the world undergoing expansion of conifer and other woody vegetation. Though species identities differ from sagebrush habitats, generalist avian predators in other habitats may have similar relationships with structural resources.

Successful treatment of a chronic oroantral fistula infected with extensively drug resistant bacteria using long-term oesophageal tube feeding and several non-conventional treatments in a horse.

BACKGROUND: Chronic oroantral fistulae (OAF) with secondary sinusitis can occur following repulsion of cheek teeth in horses. CASE REPORT: An 8-year-old Andalusian cross gelding presented with an iatrogenic clinical crown fracture of tooth 209, which underwent repulsion of its apical portion (day 0). The horse was treated with intramuscular penicillin and intravenous gentamicin (5 days), followed by oral trimethoprim-sulphonamide (10 days) and then oral doxycycline (14 days). The acute iatrogenic OAF created during the initial repulsion persisted; a chronic OAF was identified on day 24. On day 48, septic sinusitis with multidrug-resistant (MDR) Escherichia coli was confirmed. Although susceptible to enrofloxacin in vitro, 30 days of therapy was unsuccessful. Subsequent serial cultures grew multiple MDR and extensively drug-resistant (XDR) gram-negative microorganisms. Whole-genome sequencing (WGS) revealed multiple sequence types of E. coli, with a range of resistance and virulence genes. The orientation of the OAF, regional osteomyelitis and septic sinusitis were confirmed with computed tomography on day 70. On day 74, enteral nutrition was provided through a cervical oesophagostomy tube for 3 months for prevention of oral feed contamination. The OAF was treated with various alternative therapeutics, including apple cider vinegar, propolis and amikacin impregnated products, until resolution on day 116. CONCLUSION: These non-conventional therapeutics, antimicrobials and long-term oesophagostomy contributed to the successful treatment of a complicated OAF. In the future, WGS may be useful to inform antimicrobial selection when MDR or XDR organisms are identified.

Validation and clinical utility of the executive function performance test in persons with traumatic brain injury.

This study examined the relationships between the Executive Function Performance Test (EFPT), the NIH Toolbox Cognitive Function tests, and neuropsychological executive function measures in 182 persons with traumatic brain injury (TBI) and 46 controls to evaluate construct, discriminant, and predictive validity. Construct validity: There were moderate correlations between the EFPT and the NIH Toolbox Crystallized (r = -.479), Fluid Tests (r = -.420), and Total Composite Scores (r = -.496). Discriminant validity: Significant differences were found in the EFPT total and sequence scores across control, complicated mild/moderate, and severe TBI groups. We found differences in the organisation score between control and severe, and between mild and severe TBI groups. Both TBI groups had significantly lower scores in safety and judgement than controls. Compared to the controls, the severe TBI group demonstrated significantly lower performance on all instrumental activities of daily living (IADL) tasks. Compared to the mild TBI group, the controls performed better on the medication task, the severe TBI group performed worse in the cooking and telephone tasks. Predictive validity: The EFPT predicted the self-perception of independence measured by the TBI-QOL (beta = -0.49, p < .001) for the severe TBI group. Overall, these data support the validity of the EFPT for use in individuals with TBI.

miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis.

BACKGROUND: Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. METHODS: RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR. RESULTS: In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67. CONCLUSION: We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.

Magnetic resonance and radiographic diagnosis of osseous resorption of the flexor surface of the distal phalanx in the horse.

REASONS FOR PERFORMING STUDY: Osseous resorption of the flexor surface of the distal phalanx of the horse has been identified previously using magnetic resonance (MR) imaging; however, little is known about the prevalence and characteristics of this lesion. OBJECTIVES: To establish the MR prevalence of resorptive lesions in the flexor surface of the distal phalanx and identify concurrent lesions associated with this finding and associations between the MR and radiographic findings. METHODS: Horses with distal extremity MR and radiographs performed within 2 weeks of each other were included in the study. The flexor surface of the distal phalanx was graded independently on both modalities for the presence of osseous resorption. The sensitivity and specificity of radiography for identifying osseous resorption was calculated using MR as the gold standard. RESULTS: Eighty-two MR studies met the inclusion criteria, 8 of which included osseous resorption of the flexor surface of the distal phalanx. Concurrent injury to the deep digital flexor tendon and the navicular bone was a common finding. An association between MR and radiographic grades was identified. Radiography had a high specificity (0.96) but lower sensitivity (0.45-0.55) for detecting osseous resorption. CONCLUSIONS: Osseous resorption of the flexor surface of the distal phalanx can be observed both on MR and radiographic examinations of horses with lameness localised to the foot. This lesion is most often associated with other pathological changes in the podotrochlear apparatus. POTENTIAL RELEVANCE: Focal radiolucency of the flexor surface of the distal phalanx is a newly recognised radiographic sign associated with pathological changes of the podotrochlear apparatus.

Acute lameness associated with osseous metastasis of a peri-renal carcinoma in a horse.

We present a case of aggressive metastatic carcinoma in a horse that was initially presented for shoulder lameness. Although radiography and scintigraphy were useful for localising a lesion in the proximal humerus, subsequent development of non-specific signs of systemic disease prompted further evaluation. Haematology and blood biochemistry, urinalysis and ultrasonography were all instrumental in identifying renal involvement. A diagnosis of a peri-renal mass causing secondary renal failure prompted euthanasia of the horse because of the poor prognosis. Antemortem findings were supported by necropsy, with secondary lesions also identified in the spleen, liver, 8th left rib and proximal humerus. Histological examination yielded a diagnosis of undifferentiated metastatic carcinoma.

Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis.

BACKGROUND: The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg). METHODS: In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity. RESULTS: Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2. CONCLUSION: 6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.

Sarcoidosis and HTLV-1 infection.

An asymptomatic, homosexual, white man was found to have an abnormal chest x ray. A presumptive diagnosis of sarcoidosis was made, but pulmonary function tests and a transbronchial biopsy were normal. He then remained asymptomatic for 10 years until he developed a progressive spastic paraparesis. At this point, antibodies to human T cell lymphotropic virus type 1 (HTLV-1) were identified in the serum and cerebrospinal fluid, and the diagnosis of HTLV-1 associated myelopathy was made, the history suggesting sexual exposure to HTLV-1 many years previously. HTLV-1 is associated with a spectrum of immune related disorders, including a pulmonary sarcoid-like syndrome. Infection with this chronic proinflammatory retrovirus should be considered in the differential diagnosis of all immune disorders in at risk individuals.

Case report: Kaposi's sarcoma: an unusual presentation.

Kaposi's sarcoma (KS) is the most common tumor associated with HIV-1 infection, affecting 30% of HIV-infected homosexual men before the advent of highly active antiretroviral therapy (HAART). In the era of HAART, the incidence of KS has markedly declined. KS usually presents with cutaneous lesions, but it may involve other organs, most commonly the pulmonary and gastrointestinal systems. Isolated pulmonary KS without cutaneous involvement is rare, although intrathoracic KS is seen in up to 75% of patients with KS. We describe an unusual case of a patient with AIDS and isolated endobronchial KS despite a normal arterial pO2, normal pulmonary function tests, no cutaneous KS, and normal chest computed tomographic findings.

Binding of longer peptides to the H-2Kb heterodimer is restricted to peptides extended at their C terminus: refinement of the inherent MHC class I peptide binding criteria.

MHC class I molecules usually bind short peptides of 8-10 amino acids, and binding is dependent on allele-specific anchor residues. However, in a number of cellular systems, class I molecules have been found containing peptides longer than the canonical size. To understand the structural requirements for MHC binding of longer peptides, we used an in vitro class I MHC folding assay to examine peptide variants of the antigenic VSV 8 mer core peptide containing length extensions at either their N or C terminus. This approach allowed us to determine the ability of each peptide to productively form Kb/beta2-microglobulin/peptide complexes. We found that H-2Kb molecules can accommodate extended peptides, but only if the extension occurs at the C-terminal peptide end, and that hydrophobic flanking regions are preferred. Peptides extended at their N terminus did not promote productive formation of the trimolecular complex. A structural basis for such findings comes from molecular modeling of a H-2Kb/12 mer complex and comparative analysis of MHC class I structures. These analyses revealed that structural constraints in the A pocket of the class I peptide binding groove hinder the binding of N-terminal-extended peptides, whereas structural features at the C-terminal peptide residue pocket allow C-terminal peptide extensions to reach out of the cleft. These findings broaden our understanding of the inherent peptide binding and epitope selection criteria of the MHC class I molecule. Core peptides extended at their N terminus cannot bind, but peptide extensions at the C terminus are tolerated.

Time-efficiency of nondermatologists compared with dermatologists in the care of skin disease.

BACKGROUND: It has been suggested that using an established primary care doctor potentially could be a more efficient use of physician time than a new visit to a dermatologist for patients seeking care for skin diseases. OBJECTIVE: We test the hypothesis that seeing an established primary care doctor for a skin problem is a more efficient use of physician-time resources than a new visit to a dermatologist. METHODS: The duration (in minutes) of outpatient visits for dermatologic conditions was obtained from the National Ambulatory Medical Care Survey from 1990 to 1994. To control for the complexity of visits, the analysis was limited to the 62% of these visits in which a single dermatologic condition was the only condition being treated. RESULTS: For all outpatient dermatologic visits combined, dermatologist visits for patients 18 years old or younger were 1.5 minutes (12%) shorter than nondermatologist visits, and dermatologist visits for patients older than 18 years were 3.1 minutes (20%) shorter than nondermatologist visits. Compared with nondermatologists, dermatologists have a shorter average visit duration for new, first-time patient encounters and for encounters with established patients. A significant difference in outpatient visit duration does not exist when comparing new, first-time visits for dermatologists to established visits for nondermatologists (P = .3). CONCLUSION: A visit to an established primary care provider for treatment of a skin problem is not a more efficient use of physician resources than a new or return visit to a dermatologist.

Point mutations in the beta chain CDR3 can alter the T cell receptor recognition pattern on an MHC class I/peptide complex over a broad interface area.

To study how the T cell receptor interacts with its cognate ligand, the MHC/peptide complex, we used site directed mutagenesis to generate single point mutants that alter amino acids in the CDR3beta loop of a H-2Kb restricted TCR (N30.7) specific for an immunodominant peptide N52-N59 (VSV8) derived from the vesicular stomatitis virus nucleocapsid. The effect of each mutation on antigen recognition was analyzed using wild type H-2Kb and VSV8 peptide, as well as H-2Kb and VSV8 variants carrying single replacements at residues known to be exposed to the TCR. These analyses revealed that point mutations at some positions in the CDR3beta loop abrogated recognition entirely, while mutations at other CDR3beta positions caused an altered pattern of antigen recognition over a broad area on the MHC/peptide surface. This area included the N-terminus of the peptide, as well as residues of the MHC alpha1 and alpha2 helices flanking this region. Assuming that the N30 TCR docks on the MHC/peptide with an orientation similar to that recently observed in two different TCR-MHC/peptide crystal structures, our findings would suggest that single amino acid alterations within CDR3beta can affect the interaction of the TCR with an MHC surface region distal from the predicted CDR3beta-Kb/VSV8 interface. Such unique recognition capabilities are generated with minimal alterations in the CDR3 loops of the TCR. These observations suggest the hypothesis that extensive changes in the recognition pattern due to small perturbations in the CDR3 structure appears to be a structural strategy for generating a highly diversified TCR repertoire with specificity for a wide variety of antigens.

The use of percutaneous endoscopic gastrostomy (PEG) feeding tubes in patients with neurological disease.

Percutaneous endoscopic gastrostomy (PEG) is being used increasingly in the treatment of patients with neurogenic dysphagia to improve nutrition and prevent choking and aspiration pneumonia. PEG is used in a wide range of general medical conditions, but its role in clinical neurology is sometimes controversial. This paper reviews the place of PEG in the management of 32 patients with a variety of chronic and progressive neurological disorders. All the patients found it to be an effective and acceptable method of feeding that prevented weight loss, reduced chest infections, facilitated nursing care and improved their quality of life. PEG has an important role in neurological rehabilitation.