A Branchial Cyst in a Diamond Python (Morelia spilota).

A 9-year-old female diamond python (Morelia spilota) was presented with a submandibular swelling. The cytological, macroscopic and histological features of this lesion indicated a diagnosis of branchial (pharyngeal) cyst. Branchial cysts are benign lesions caused by anomalous development of the branchial apparatus and are described rarely in veterinary medicine. We suggest that possible persistence of branchial remnants should be included in the consideration of differential diagnoses for neck masses in adult snakes.

On the geometrically exact low-order modelling of a flexible beam: formulation and numerical tests.

This paper proposes a low-order geometrically exact flexible beam formulation based on the utilization of generic beam shape functions to approximate distributed kinematic properties of the deformed structure. The proposed nonlinear beam shapes approach is in contrast to the majority of geometrically nonlinear treatments in the literature in which element-based-and hence high-order-discretizations are adopted. The kinematic quantities approximated specifically pertain to shear and extensional gradients as well as local orientation parameters based on an arbitrary set of globally referenced attitude parameters. In developing the dynamic equations of motion, an Euler angle parametrization is selected as it is found to yield fast computational performance. The resulting dynamic formulation is closed using an example shape function set satisfying the single generic kinematic constraint. The formulation is demonstrated via its application to the modelling of a series of static and dynamic test cases of both simple and non-prismatic structures; the simulated results are verified using MSC Nastran and an element-based intrinsic beam formulation. Through these examples, it is shown that the nonlinear beam shapes approach is able to accurately capture the beam behaviour with a very minimal number of system states.

In vivo transplantation of fetal human gut-derived enteric neural crest cells.

The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75NTR were lentivirally labeled with either GFP or calcium-sensitive GCaMP and transplanted into the hindgut of Rag2- /γc- /C5- -immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut-derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections.

Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients.

Antibodies to donor-specific HLA antigens (donor-specific antibodies [DSA]) detected by single-antigen bead (SAB) analysis prior to kidney transplant have been associated with inferior graft outcomes. However, studies of pretransplant DSA, specifically in the setting of a negative flow cytometry crossmatch (FCXM) without desensitization therapy, are limited. Six hundred and sixty kidney and kidney-pancreas recipients with a negative pretransplant FCXM from September 2007 to August 2012 without desensitization therapy were analyzed with a median follow-up of 4.2 years. All patients underwent cell-based FCXM and SAB analysis on current and historic sera prior to transplantation. One hundred and sixty-two patients (24.5%) had DSA detected prior to transplant. One-year acute rejection rates were similar in DSA-positive versus DSA-negative patients (15.4% vs. 11.4%, respectively; p = 0.18) and were higher in those with DSA mean fluorescence intensity (MFI) greater than or equal to 3000 in multivariable analysis (p = 0.046). The estimated glomerular filtration rate (eGFR) at 3 and 4 years was lower in the DSA(+) versus the DSA(-) group (p = 0.050 at 3 years) without an impact on 5-year death-censored graft survival (89.0% vs. 90.6%, respectively; p = 0.53). Timing (current or historic) of DSA detection did not alter these findings. In conclusion, pretransplant DSA in the setting of a negative FCXM confers minimal immunologic risk in the intermediate term, does not necessitate desensitization therapy and should not represent a barrier to renal transplant.

APOL1 Polymorphisms in a Deceased Donor and Early Presentation of Collapsing Glomerulopathy and Focal Segmental Glomerulosclerosis in Two Recipients.

Two common polymorphisms in APOL1 (G1 and G2) are conserved in persons of African ancestry, and the presence of two polymorphisms (commonly referred to as risk variants) has been identified as a risk factor for chronic kidney disease and focal seg-mental glomerulosclerosis. In kidney transplantation, deceased donors with two APOL1 risk variants carry an increased risk of renal allograft failure in the recipient. An emerging question is whether these data should influence deceased donor assessment or be used to refine prediction of allograft survival. We present the first detailed report of two cases of recipient glomerular disease in the first year following transplant from a deceased donor later defined as carrying two APOL1 risk variants. A possible "second hit" predisposing to renal disease in these recipients is discussed, one with active cytomegalovirus infection concurrent with collapsing glomerulopathy and renal failure and the other with chronic, slowly healing wound infection and focal segmental glomeru-losclerosis but stable renal function. In retrospect, awareness of the donor APOL1 risk alleles would not have influenced donor selection and ultimately did not influence posttransplant management. These case reports inform further discussion of the value of APOL1 testing for deceased donors.

Novel immunosuppressive agents in kidney transplantation.

The last several decades have seen a substantial decrease in the prevalence of acute allograft rejection in kidney transplant recipients, while equivalent improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use, improved side effect profiles, and reduced nephrotoxicity in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials primarily to replace the nephrotoxic but highly effective calcineurin inhibitors. ISA247 (voclosporine) is a cyclosporine (CsA) analog with reduced nephrotoxicity in Phase III study. AEB071 (sotrastaurin), a protein kinase C inhibitor, and CP-690550, a JAK3 inhibitor, are small molecules in Phase II studies. Everolimus is derived from the mTOR inhibitor sirolimus and is in Phase III study. Belatacept is a humanized antibody that inhibits T-cell costimulation and has shown encouraging results in multiple Phase II and III trials. Alefacept and Efaluzimab are humanized antibodies that inhibit T-cell adhesion and are in Phase I and II clinical trials. This article reviews the mechanisms of action as well as published and preliminary results of the Phase I-III clinical trials involving these novel immunosuppressive agents.

Is the incidence of psychotic disorder in decline? Epidemiological evidence from two decades of research.

BACKGROUND: It is unclear whether the incidence of first episode psychoses is in decline. We had the opportunity to determine whether incidence had changed over a 20-year period in a single setting, and test whether this could be explained by demographic or clinical changes. METHODS: The entire population at-risk aged 16-54 in Nottingham over three time periods (1978-80, 1993-95 and 1997-99) were followed up. All participants presenting with an ICD-9/10 first episode psychosis were included. The remainder of the population at-risk formed the denominator. Standardized incidence rates were calculated at each time period with possible change over time assessed via Poisson regression. We studied six outcomes: substance-induced psychoses, schizophrenia, other non-affective psychoses, manic psychoses, depressive psychoses and all psychotic disorders combined. RESULTS: Three hundred and forty-seven participants with a first episode psychosis during 1.2 million person-years of follow-up over three time periods were identified. The incidence of non-affective or affective psychoses had not changed over time following standardization for age, sex and ethnicity. We observed a linear increase in the incidence of substance-induced psychosis, per annum, over time (incidence rate ratios: 1.15; 95% CI 1.05-1.25). This could not be explained by longitudinal changes in the age, sex and ethnic structure of the population at-risk. CONCLUSIONS: Our findings suggest psychotic disorders are not in decline, though there has been a change in the syndromal presentation of non-affective disorders, away from schizophrenia towards other non-affective psychoses. The incidence of substance-induced psychosis has increased, consistent with increases in substance toxicity over time, rather than changes in the prevalence or vulnerability to substance misuse. Increased clinical and popular awareness of substance misuse could also not be excluded.

Early interactions between legumes and rhizobia: disclosing complexity in a molecular dialogue.

The exchange of chemical signals between soil bacteria (rhizobia) and legumes has been termed a molecular dialogue. As initially conceived in the early 1990s, it involved two main groups of molecules: nod gene-inducing flavonoids from plants and the mitogenic lipochito-oligosaccharide Nod factors of rhizobia. This review considers how subsequent research revealed the existence of a more complex set of interactions, featuring expanded roles for the original participants and contributions from additional plant and bacterial metabolites. Rhizobia respond to chemoattractants and growth-enhancing compounds in root exudates, and several plant nonflavonoids possess nod gene-inducing properties. Expression of non-nod genes is induced by flavonoids; these include encoders of a type I secreted protein and the entire type III, and possibly also type IV, secretion systems. Many other genes and proteins in rhizobia are flavonoid-inducible but their functions are largely unknown. Rhizobia produce far more Nod factor variants than was previously envisaged and their structures can be influenced by the pH of the environment. Other symbiotically active compounds or systems of rhizobia, some of them universally present, are: the surface polysaccharides, quorum-sensing N-acyl homoserine lactones, plant growth-promoting lumichrome and two-component regulatory systems.

Surgical resection of a primary tracheal fibrosarcoma in a dog.

A four-year-old, entire male Rottweiler was presented with a history of respiratory distress. A tracheal mass was diagnosed on thoracic radiographs and tracheoscopy. Surgical excision of three tracheal rings incorporating the tumour was performed. The mass was found to be a low-grade fibrosarcoma. Twenty-four months later, the owner reported that there was no recurrence of respiratory distress and the dog appeared to be doing well clinically. This case of primary tracheal fibrosarcoma suggests that this type of tumour should be listed in the differential diagnoses for tracheal neoplasia in dogs and that surgical treatment alone may be curative.

Diagnostic pathology of selected diseases in wildlife.

The prompt detection and effective management of infectious disease in wildlife rely greatly on field diagnosis. Although clinical work is sometimes of value, the cornerstone of diagnosis is pathological examination (gross necropsy with supporting laboratory investigations). The approach and rationale to gross post-mortem examination are common to all species, despite possible significant differences in technique. Likewise, the principles of sampling are usually comparable, with emphasis on standardisation, the correct use of equipment, and consistency in methods of storage and transportation of specimens. However, the type of sample taken and the laboratory tests required differ, depending upon the circumstances and possible diagnosis. Retention of material is always important. The principles of diagnostic pathology are discussed, with reference to selected diseases, namely: mycobacteriosis, Rift Valley fever, rabies, spongiform encephalopathies, morbillivirus and poxvirus infections, viral encephalitides, West Nile virus infection and chytridiomycosis. The importance of being able to perform certain investigations in the field, efficiently and safely, is emphasised.

Spontaneous neoplasms in captive African cane rats (Thryonomys swinderianus Temminck, 1827).

Despite the increasing importance of cane rat (Thryonomys swinderianus) farming in Africa, diseases of these animals in captivity are not well known. A survey of a colony in Gabon averaging 235 cane rats over a period of 36 months allowed the observation of several suspected tumors and the confirmation of three cases of neoplasms. Within a period of 8 months, a chondroma in an adult female, a hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female were diagnosed. This incidence (1.3%) of neoplasms in the cane rat colony in such a short period is uncommon. Neoplasms in rodents might be induced by such factors as a high inbreeding coefficient, an oncogenic virus, or chemical agent intoxication. Although the etiology remains undetermined, these cases are described to provide baseline data on the pathology of this species in captivity.

A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.

STUDY DESIGN: Randomized controlled trial (RCT). OBJECTIVES: To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital. SUMMARY OF BACKGROUND DATA: Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear. METHODS: This three-armed RCT consisted of a "control arm," a "safe lifting" arm, and a "no strenuous lifting" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the "safe lifting" arm used improved patient handling techniques using manual equipment, whereas the "no strenuous lifting" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment. RESULTS: Frequency of manual patient handling tasks was significantly decreased on the "no strenuous lifting" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered. CONCLUSIONS: The "no strenuous lifting" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.

Cross-cultural implementation of a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) in Taiwan.

BACKGROUND: There are no published reports of cross-cultural equivalence and interrater reliability at the level of individual symptom items assessed by a semi-structured clinical interview employing operationalised clinician ratings. AIMS: To assess the cross-cultural clinical equivalence and reliability of a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry (SCAN). METHOD: UK-US and Taiwanese groups of psychiatrists used Chinese and English transcripts of videotape interviews of Taiwanese patients to discuss cross-cultural issues and ratings of SCAN items. Item ratings were compared quantitatively individually and pooled by SCAN section. RESULTS: Chinese equivalents were found for all SCAN items. No between-group differences were found for most individual items, but there were differences for some scaled items. Average agreement between the two groups was 69-100%. CONCLUSIONS: Cross-cultural implementation based on SCAN in Taiwan appears valid.

Biomechanical analysis of peak and cumulative spinal loads during simulated patient-handling activities: a substudy of a randomized controlled trial to prevent lift and transfer injury of health care workers.

Back injuries are a serious problem for nursing personnel who perform frequent patient-handling activities. Common prevention strategies include body mechanics education, technique training, and ergonomic interventions such as the introduction of assistive equipment. This investigation assessed and compared the effectiveness of two patient-handling approaches to reducing injury risk. One strategy involved using improved patient-handling technique with existing equipment, and the other approach aimed at eliminating manual patient handling through the use of additional mechanical and other assistive equipment. Both intervention arms received training in back care, patient assessment, and use of the equipment available on their particular wards. An analysis of compliance with interventions and the effects of patient-handling methods on both peak and cumulative spinal compression and shear during various tasks was conducted. Results showed greater compliance with interventions that incorporated new assistive patient-handling equipment, as opposed to those consisting of education and technique training alone. In several tasks, subjects who were untrained or non-compliant with interventions experienced significantly higher peak spinal loading. However, patient-handling tasks conducted with the aid of assistive equipment took substantially longer than those performed manually. This, along with variations in techniques, led to increases in cumulative spinal loading with the use of patient-handling equipment on some tasks. Thus, the use of mechanical assistive devices may not always be the best approach to reducing back injuries in all situations. No single intervention can be recommended; instead all patient-handling tasks should be examined separately to determine which methods maximize reductions in both peak and cumulative lumbar forces during a manoeuver.

Postmortem findings in captive cane rats (Thryonomys swinderianus) in Gabon.

The causes of morbidity and mortality in a population of cane rats (Thryonomys swinderianus) on an experimental farm in Gabon were monitored for 21 months; 94 of 546 animals (17.2 per cent) died and were examined postmortem, and complementary laboratory examinations were carried out on 23 of the cases together with samples from 13 other animals kept elsewhere in similar conditions. Twenty-six (28 per cent) of the deaths occurred in preweaned kits, 40 (42 per cent) in subadults and 28 (30 per cent) in adults. The average monthly mortality was 2.5 per cent. Trauma was responsible for 29 of the deaths, 12 were due to septicaemia, 10 to primary respiratory lesions, five to digestive disorders, four to urinary lesions, three to reproductive problems and three to other causes; no diagnosis could be reached in 28 cases.