Oncogenic signaling in the adult Drosophila prostate-like accessory gland leads to activation of a conserved pro-tumorigenic program, in the absence of proliferation.

Drosophila models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of Drosophila development, when tissues are highly mitotically active, or stem cells are abundant. Fewer Drosophila tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic. The Drosophila accessory glands are prostate-like tissues and a model for some aspects of prostate tumorigenesis using this tissue has been explored. In this model, oncogenic signaling was induced during the proliferative stage of accessory gland development, raising the question of how oncogenic activity would impact the terminally differentiated and postmitotic adult tissue. Here, we show that oncogenic signaling in the adult Drosophila accessory gland leads to activation of a conserved pro-tumorigenic program, similar to that observed in mitotic larval tissues, but in the absence of proliferation. Oncogenic signaling in the adult postmitotic gland leads to tissue hyperplasia with nuclear anaplasia and aneuploidy through endoreduplication, which increases polyploidy and occasionally results in non-mitotic neoplastic-like extrusions. We compare gene expression changes in our Drosophila model with that of endocycling prostate cancer cells induced by chemotherapy, which potentially mediate tumor recurrence after treatment. Similar signaling pathways are activated in the Drosophila gland and endocycling cancer cells, suggesting the adult accessory glands provide a useful model for aspects of prostate cancer progression that do not involve cellular proliferation.

Distinct spatial landscapes in clear-cell renal cell carcinoma as revealed by whole transcriptome analysis.

Background: Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of renal cancer and a paradigm of inter- and intratumor heterogeneity. We carried out an exploratory digital spatial profiling of the tumor interior and periphery of two ccRCC tumor specimens and mapped spatially the molecular and cellular composition of their tumor microenvironment and ecosystem. Materials and methods: Digital spatial profiling of the whole transcriptome of 19 regions of interest (ROIs) was carried out from two selected highly immunogenic stage pT3a/grade 3 (G3) and stage pT3a/grade 4 (G4) ccRCC. A total of 9-10 ROIs were selected from distinct areas from each tumor, including tumor interior and tumor periphery, and differences in gene expression were analyzed by RNA sequencing, pathway enrichment analysis, and cell deconvolution. Results: The distinct areas from the two locally advanced tumors displayed unique gene expression spatial patterns defining distinct biological pathways. Dimensional reduction analysis showed that the G3 ccRCC, compared to the G4 ccRCC, correlated with more variability between regions from the tumor interior and tumor periphery. Cell deconvolution analysis illustrated higher abundance of immune cells, including macrophages, myeloid dendritic cells, and CD4 T cells, and lower abundance of regulatory T cells in the tumor periphery compared to the tumor interior. Conclusions: Transcriptome spatial profiling revealed high inter- and intratumor heterogeneity in the analyzed tumors and provided information with potential clinical utility. This included the finding of less intratumor heterogeneity and more tumor-infiltrated T cells in the ccRCC tumor specimen with a higher grade.

Characterization of buried interfaces using Ga Kα hard X-ray photoelectron spectroscopy (HAXPES).

The extension of X-ray photoelectron spectroscopy (XPS) to measure layers and interfaces below the uppermost surface requires higher X-ray energies and electron energy analysers capable of measuring higher electron kinetic energies. This has been enabled at synchrotron radiation facilities and by using lab-based instruments which are now available with sufficient sensitivity for measurements to be performed on reasonable timescales. Here, we detail measurements on buried interfaces using a Ga Kα (9.25 keV) metal jet X-ray source and an EW4000 energy analyser (ScientaOmicron GmbH) in the Henry Royce Institute at the University of Manchester. Development of the technique has required the calculation of relative sensitivity factors (RSFs) to enable quantification analogous to Al Kα XPS, and here we provide further substantiation of the Ga Kα RSF library. Examples of buried interfaces include layers of memory and energy materials below top electrode layers, semiconductor heterostructures, ions implanted in graphite, oxide layers at metallic surfaces, and core-shell nanoparticles. The use of an angle-resolved mode enables depth profiling from the surface into the bulk, and is complemented with surface-sensitive XPS. Inelastic background modelling allows the extraction of information about buried layers at depths up to 20 times the photoelectron inelastic mean free path.

Segond fracture in an adult is not pathognomonic for ACL injury.

The Segond fracture is an avulsion fracture of the lateral tibial plateau and is considered pathognomonic for anterior cruciate ligament (ACL) injury. A case of a Segond fracture occurring with a clinically, radiologically and arthroscopically intact ACL is presented. This was associated with a serious injury to the posterolateral corner requiring surgical reconstruction. Relevant literature is discussed, and the suggestion is made that, whilst an ACL rupture may be the most commonly noted soft tissue component associated with a Segond fracture, the clinician should have a high level of suspicion for other serious soft tissue injuries. Level of evidence V.

Note: cryogenic microstripline-on-Kapton microwave interconnects.

Simple broadband microwave interconnects are needed for increasing the size of focal plane heterodyne radiometer arrays. We have measured loss and crosstalk for arrays of microstrip transmission lines in flex circuit technology at 297 and 77 K, finding good performance to at least 20 GHz. The dielectric constant of Kapton substrates changes very little from 297 to 77 K, and the electrical loss drops. The small cross-sectional area of metal in a printed circuit structure yields overall thermal conductivities similar to stainless steel coaxial cable. Operationally, the main performance tradeoffs are between crosstalk and thermal conductivity. We tested a patterned ground plane to reduce heat flux.

Pyogranulomatous lesion causing neurological signs localised to the sacral region in a horse.

This case report describes neurological signs associated with a pyogranulomatous lesion within the sacral vertebral canal of a horse. The clinical findings included urinary overflow incontinence and reduced anal, perianal and tail tone. The horse failed to respond to medical management and a guarded prognosis for return to athletic performance initiated the decision for euthanasia.

Effects of hyperimmune equine plasma on clinical and cellular responses in a low-dose endotoxaemia model in horses.

Endotoxaemia is a major cause of equine morbidity, and plasma from horses immunised against Escherichia coli is used in its treatment. The aim of this study was to determine the effects of hyperimmune plasma on the clinical and leukocyte responses, including production and activity of TNFα, in an in vivo endotoxin challenge model. Pre-treatment with hyperimmune equine plasma had no significant effect on peak total plasma TNFα concentration (occurring 90min after the administration of 30ng/kg LPS). However, the bioavailable (unbound) TNFα measured by bioassay was significantly reduced in plasma-treated horses (1044.44±193.93pg/ml at 90min) compared to saline treated controls (1373.92±107.63pg/ml; P=0.05). Therefore, although pre-treatment with hyperimmune equine plasma did not significantly modify the clinical signs of endotoxaemia in this model, there was some evidence of reduced TNF bioactivity, which may be due to factors in the plasma which bind and reduce the activity of this cytokine.

Acute myeloid leukaemia (M6B: pure acute erythroid leukaemia) in a Thoroughbred foal.

A 10-week-old Thoroughbred filly was referred for anaemia of 4 weeks' duration. Haematology revealed severe anaemia and panleucopenia. Cytological examination of bone marrow smears revealed a myeloid to erythroid ratio <0.02:1 (reference range 0.5-2.4:1.0) and an abundance of erythroid precursor cells. The erythroid cell population included rubriblasts, prorubricytes and rubricytes, with only scant numbers of metarubricytes present. There were numerous mitotic erythroid cells, some of which were atypical and megaloblastic. These cytomorphological changes are consistent with pure acute erythroid leukaemia. No treatment was instituted and the filly died three days after presentation. This case illustrates the need to consider both haematology and bone marrow findings to establish a diagnosis of pure erythroid leukaemia. To our knowledge, there is no documented case of acute myeloproliferative disease in horses involving cells of erythroid lineage, but this condition should be considered a differential diagnosis for horses presenting with anaemia.

Activin A as a novel biomarker of equine inflammatory abdominal disease: preliminary findings.

This study evaluated the inflammatory mediator activin A in horses with acute abdominal disease and compared this putative novel biomarker with serum amyloid A (SAA). Thirty-three adult horses referred for evaluation of acute abdominal disease were grouped into three lesion categories, non-strangulating, strangulating or inflammatory. Eleven healthy adult horses served as controls. Serum activin-A was significantly increased in animals with inflammatory or strangulating lesions compared with controls. Horses with non-strangulating, strangulating or inflammatory lesions had significantly elevated SAA concentrations. Activin A, along with other biomarkers, may be useful in monitoring inflammation in cases of acute abdominal disease in horses. Further validation is warranted to determine the utility of this biomarker in evaluating the effectiveness of novel anti-inflammatory treatments for equine colic and endotoxaemia.

Parity violation constraints using cosmic microwave background polarization spectra from 2006 and 2007 observations by the QUaD polarimeter.

We constrain parity-violating interactions to the surface of last scattering using spectra from the QUaD experiment's second and third seasons of observations by searching for a possible systematic rotation of the polarization directions of cosmic microwave background photons. We measure the rotation angle due to such a possible "cosmological birefringence" to be 0.55 degrees +/-0.82 degrees (random) +/-0.5 degrees (systematic) using QUaD's 100 and 150 GHz temperature-curl and gradient-curl spectra over the spectra over the multipole range 200

To what extent does Neisseria gonorrhoeae multiantigen sequence typing of gonococcal isolates support information derived from patient interviews?

Gonococcal isolates from genitourinary (GU) medicine clinic attendees in Glasgow, Scotland were typed using Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST). Correlation between named partners (contacts) and NG-MAST type was sought and associations between specific NG-MAST types, and the social, epidemiological and geographical data were explored. We found NG-MAST typing to be a supportive and confirmatory tool for contact tracing. Specific NG-MAST types were found to be associated with distinct characteristics such as sexuality or chlamydial co-infection. An increased number of gonococcal infections were reported from those resident in deprived areas of Glasgow than from those resident in more affluent areas. However, there was no clear geographic clustering of specific NG-MAST types found within the city. Routinely observing the spread of common strains of gonorrhoea is likely best done from a larger geographical perspective unless a specific outbreak occurs.

Are general dental practitioners effective in the management of non-apnoeic snoring using mandibular advancement appliances?

OBJECTIVE: This study assessed the effectiveness of general dental practitioners (GDPs) in the management of subjects with non-apnoeic snoring using a mandibular advancement appliance (MAA), following a one day training course. SUBJECTS AND METHODS: Sixty subjects suffering from simple, non-apnoeic snoring were treated by 15 GDPs, in three hospital centres, using a monobloc mandibular advancement appliance design. All GDPs attended a one day training course prior to the study which covered theoretical and practical training in the use of mandibular advancement appliances. Snoring and level of disturbance were assessed using a questionnaire completed by their sleeping partner before and after a three month treatment period. Daytime sleepiness was assessed by the patients using the Epworth sleepiness scale questionnaire (ESS) before and after a three month treatment period. In addition, patients completed an outcome questionnaire, to assess side-effects experienced from the MAA. RESULTS: A success rate of 48% (95% CI 0.35, 0.61) was achieved in partner-assessed snoring and disturbance levels, following a three month period of MAA treatment. The median ESS score reduced from 9 to 7.5 (95% CI 0, 3). General dental practitioners experienced problems during protrusive bite registrations, with 10% being judged inadequate. CONCLUSION: GDPs were not effective in the management of non-apnoeic snoring using a monobloc appliance after a one day training course. Further training and/or selection of a different design of appliance should be considered for GDPs to become highly competent in this area.

Double-outlet right ventricle in a 10-month-old Friesian filly.

A 10-month-old Friesian filly had a presentation that was consistent with chronic left- and right-sided congestive heart failure. Clinical pathology findings included abnormal haematological and biochemical variables, abnormal blood gas values and increased serum concentration of cardiac troponin I. Echocardiography revealed cardiac chamber dilation and dextropositioning of the aorta. Radiography revealed a generally enlarged heart and pulmonary interstitial infiltration. These findings were supported at necropsy and the diagnosis of double-outlet right ventricle was confirmed. The pathological changes and physiological responses subsequent to double-outlet right ventricle have not previously been described in detail in horses. Clinical progression closely resembles that seen in humans, in whom antemortem diagnosis relies on echocardiography. In horses, complex cardiac disease presents a diagnostic challenge to the clinician. Appropriate therapy must be based on an accurate diagnosis.

Identifying opportunities for sexually transmitted infection prevention: analysis of critical points in the care pathways of patients with gonorrhoea.

We applied the principles of Hazard Analysis and Critical Control Points (HACCP) to systematically analyse the care pathway of patients diagnosed with gonorrhoea to identify potential intervention opportunities for preventive action. Data were collected on individuals with culture-positive gonococcal infection during 27 February 2003 to 08 January 2004. Qualitative data were gathered within individual semi-structured interviews. Two hundred and twenty-three gonorrhoea patient episodes were evaluated. The median interval between presentation and treatment was significantly longer in females and men having sex with men (MSM), compared with heterosexual men (P = 0.002). Females were significantly more likely to be in regular relationships at the timepoint of perceived infection acquisition than heterosexuals or MSM (P < 0.0001). Four major themes emerged from the interviews: life-stage and infection risk, determinants of risk perception around sexual encounters, attitudes to preventing re-infection and condom use. These informed three potential 'critical control points': health-related attitudes/behaviours preceding infection; access to appropriate care and optimizing health promotion to prevent further infection.

Changes in the four-strand hamstring graft in anterior cruciate ligament reconstruction in the skeletally-immature knee.

The potential harm to the growth plate following reconstruction of the anterior cruciate ligament in skeletally-immature patients is well documented, but we are not aware of literature on the subject of the fate of the graft itself. We have reviewed five adolescent males who underwent reconstruction of the ligament with four-strand hamstring grafts using MR images taken at a mean of 34.6 months (18 to 58) from the time of operation. The changes in dimension of the graft were measured and compared with those taken at the original operation. No growth arrest was seen on radiological or clinical measurement of leg-length discrepancy, nor was there any soft-tissue contracture. All the patients regained their pre-injury level of activity, including elite-level sport in three. The patients grew by a mean of 17.3 cm (14 to 24). The diameter of the grafts did not change despite large increases in length (mean 42%; 33% to 57%). Most of the gain in length was on the femoral side. Large changes in the length of the grafts were seen. There is a considerable increase in the size of the graft, so some neogenesis must occur; the graft must grow.

Suspected primary scapulohumeral osteoarthritis in two Miniature ponies.

Two cases of severe scapulohumeral osteoarthritis in Miniature ponies are described, one bilateral and the other unilateral. The condition is thought to occur in miniature breeds as a result of scapulohumeral dysplasia. The presentation in one of the ponies was unusal: it refused to pick up either fore limb, with progression to a uniquely bizarre gait with narrow forelimb placement, an arched back and widely placed hindlimbs camped well forward under the body. The other pony was presented for an acute unilateral non-weight bearing forelimb lameness. Response to analgesia in both cases was poor and both ponies were euthanased. A pathological fracture was evident in one affected glenoid cavity.

The EPIC nutrient database project (ENDB): a first attempt to standardize nutrient databases across the 10 European countries participating in the EPIC study.

OBJECTIVE: This paper describes the ad hoc methodological concepts and procedures developed to improve the comparability of Nutrient databases (NDBs) across the 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). This was required because there is currently no European reference NDB available. DESIGN: A large network involving national compilers, nutritionists and experts on food chemistry and computer science was set up for the 'EPIC Nutrient DataBase' (ENDB) project. A total of 550-1500 foods derived from about 37,000 standardized EPIC 24-h dietary recalls (24-HDRS) were matched as closely as possible to foods available in the 10 national NDBs. The resulting national data sets (NDS) were then successively documented, standardized and evaluated according to common guidelines and using a DataBase Management System specifically designed for this project. The nutrient values of foods unavailable or not readily available in NDSs were approximated by recipe calculation, weighted averaging or adjustment for weight changes and vitamin/mineral losses, using common algorithms. RESULTS: The final ENDB contains about 550-1500 foods depending on the country and 26 common components. Each component value was documented and standardized for unit, mode of expression, definition and chemical method of analysis, as far as possible. Furthermore, the overall completeness of NDSs was improved (>or=99%), particularly for beta-carotene and vitamin E. CONCLUSION: The ENDB constitutes a first real attempt to improve the comparability of NDBs across European countries. This methodological work will provide a useful tool for nutritional research as well as end-user recommendations to improve NDBs in the future.

Experimental inoculation of wild turkeys (Meleagris gallopavo) with Mycobacterium bovis.

Although avian species are known to be susceptible to infection with Mycobacterium spp. organisms, much remains unknown about the susceptibility of birds to infection with M. bovis. The objective of this current study was to determine if wild turkeys (Meleagris gallopavo) can be infected with M. bovis when inoculated by the oral or intratracheal route. Six turkeys were orally inoculated and another six were inoculated via the trachea with a high dose of M. bovis, 1 x 10(5) CFU/ml. Six turkeys were sham-inoculated controls. Two turkeys from each treatment group were sacrificed on days 30, 60, and 90 postinoculation. There were no gross or microscopic lesions consistent with mycobacteriosis in the 23 inoculated turkeys over the 90-day duration of this study. Fecal cultures were also consistently negative for M. bovis when sampled before inoculation and on days 1, 30, and 60 postinoculation. Two intratracheally inoculated turkeys were positive for M. bovis in visceral tissues at 30 days postinoculation. However, this finding was only indicative of passive persistence of mycobacteria in the tissues and not of infection, as there were no attendant lesions or clinical compromise to support infection. Thus, it can be concluded that young wild turkeys are resistant to infection with M. bovis and, therefore, pose minimal threat as reservoir or spillover hosts for this organism.

Reconstruction of the anterior cruciate ligament: timing of surgery and the incidence of meniscal tears and degenerative change.

We reviewed 183 patients who had undergone reconstruction of the anterior cruciate ligament. The incidence of meniscal tears and degenerative change was assessed and related to the timing from injury to surgery. Degenerative change was scored using the French Society of Arthroscopy system. The patients were divided into an early (surgery within 12 months of injury) and a late group (surgery more than 12 months from injury). The late group was also subdivided into four groups of 12-month periods ranging from one year to more than four years after injury. There was a significantly higher incidence of meniscal tears in patients undergoing reconstruction after 12 months compared with those in the early group (71.2% vs 41.7%; p < 0.001). This was due to a large increase in medial meniscal tears in the late group. An increased incidence of degenerative change was also found in the late group (31.3% vs 10.7%; p < 0.001). Analysis of the subgroups showed that the incidence of meniscal tears and degenerative change did not differ significantly when surgery was performed after 12 months from injury. We conclude that reconstruction of the anterior cruciate ligament should be carried out within 12 months of injury to minimise the risk of meniscal tears and degenerative change.