Meta-analysis: Intestinal ultrasound to evaluate colonic contents and constipation.

BACKGROUND: Constipation can be diagnosed clinically using the Rome criteria. Ultrasound (US), which lacks the radiation exposure of conventional X-ray, holds promise as a non-invasive tool to evaluate colonic contents and constipation. AIM: To examine the role of US in the assessment of constipation. METHODS: We performed a systematic search of Embase (OVID, 1984), Medline (Ovid, 1946), Cochrane Central, ClinicalTrials.gov and Australia New Zealand Clinical Trials Registry from database inception to 26 January 2024 according to PRISMA guidelines and prospectively registered with PROSPERO. All studies using US to assess constipation or colonic contents in either adults or children were included. Rectal diameter measurements were pooled in meta-analysis. Risk of bias was assessed using the Newcastle Ottawa Scales and Joanna Briggs Institute checklists. RESULTS: Of 12,232 studies screened, 51 articles (6084 patients; 3422 children) describing US to assess symptoms in patients with constipation were included. Most studies used Rome criteria to diagnose constipation. Rectal diameter was associated with clinical constipation in 29 paediatric studies (3331 patients). Meta-analysis showed the mean rectal diameter of constipated patients was significantly higher than controls (mean difference 12 mm, 95% confidence intervals (CI): 6.48, 17.93, p < 0.0001, n = 16 studies). Other features of constipation on US included posterior acoustic shadowing and echogenicity of luminal contents. CONCLUSION: US is an appealing imaging modality to assess luminal contents and constipation. Further well-designed studies are required to validate US metrics that accurately identify constipation.

Metal-Organic Framework Glass as a Functional Filler Enables Enhanced Performance of Solid-State Polymer Electrolytes for Lithium Metal Batteries.

Polymers are promising candidates as solid-state electrolytes due to their performance and processability, but fillers play a critical role in adjusting the polymer network structure and electrochemical, thermal, and mechanical properties. Most fillers studied so far are anisotropic, limiting the possibility of homogeneous ion transport. Here, applying metal-organic framework (MOF) glass as an isotropic functional filler, solid-state polyethylene oxide (PEO) electrolytes are prepared. Calorimetric and diffusion kinetics tests show that the MOF glass addition reduces the glass transition temperature of the polymer phase, improving the mobility of the polymer chains, and thereby facilitating lithium (Li) ion transport. By also incorporating the lithium salt and ionic liquid (IL), Li-Li symmetric cell tests of the PEO-lithium salt-MOF glass-IL electrolyte reveal low overpotential, indicating low interfacial impedance. Simulations show that the isotropic structure of the MOF glass facilitates the wettability of the IL by enhancing interfacial interactions, leading to a less confined IL structure that promotes Li-ion mobility. Finally, the obtained electrolyte is used to construct Li-lithium iron phosphate full batteries that feature high cycle stability and rate capability. This work therefore demonstrates how an isotropic functional filler can be used to enhance the electrochemical performance of solid-state polymer electrolytes.

Fundamental Limits in Bayesian Thermometry and Attainability via Adaptive Strategies.

We investigate the limits of thermometry using quantum probes at thermal equilibrium within the Bayesian approach. We consider the possibility of engineering interactions between the probes in order to enhance their sensitivity, as well as feedback during the measurement process, i.e., adaptive protocols. On the one hand, we obtain an ultimate bound on thermometry precision in the Bayesian setting, valid for arbitrary interactions and measurement schemes, which lower bounds the error with a quadratic (Heisenberg-like) scaling with the number of probes. We develop a simple adaptive strategy that can saturate this limit. On the other hand, we derive a no-go theorem for nonadaptive protocols that does not allow for better than linear (shot-noise-like) scaling even if one has unlimited control over the probes, namely, access to arbitrary many-body interactions.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion

ABSTRACT: The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.

RESUMO: O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion / A necessidade de opioide na analgesia pós-operatória de cães submetidos à hemilaminectomia devido à extrusão do disco intervertebral

The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.(AU)

O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.(AU)

Clinical management of dogs with presumptive diagnosis of cervical intervertebral disc disease: 78 cases (2006-2017) / Tratamento clínico de cães com diagnóstico presuntivo de doença do disco intervertebral cervical: 78 casos (2006-2017)

This study aimed to identify dogs with a presumptive diagnosis of cervical intervertebral disc disease (IVDD; C1-C5 or C6-T2) submitted to clinical management and evaluate the outcome. This study also aimed to demonstrate the age, sex, and treatment response according to the neurological degree, and verify whether those factors could potentially influence the outcome. The data were obtained from patients with a neurological dysfunction, admitted at the Veterinary Hospital from January 2006 to March 2017. In addition to patient records, the tutors answered a questionnaire related to the success of therapy. A hundred and seventy-seven neurological records were evaluated, and 78 were included in the study according to the inclusion criteria. The most frequent breeds were Dachshunds, followed by mixed-breed dogs. Regarding the neurological dysfunction degree, 58.97% presented grade I (only neck pain), 25.64% were grade II (ambulatory tetraparesis), and 15.38% grade III (nonambulatory tetraparesis). Absolute and partial space rest were performed in 75.64% and 24.36% of the cases, respectively. The minimum rest time was one week and could come up to four weeks. Most dogs were small-sized (≤15kg). The recovery was satisfactory in 87.17% of dogs and unsatisfactory in 12.83%. Regarding recurrence, we observed that 10.3% of dogs presented satisfactory recovery. The clinical treatment for dogs with cervical IVDD can be indicated with adequate clinical response to dysfunction degrees ranging from I to III, either at rest or in restricted space and with a low rate of relapse.(AU)

O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de doença do disco intervertebral cervical (DDIV; C1-C5 ou C6-T2) submetidos ao tratamento clínico e avaliar a resposta a terapia instituída e o índice de recidiva. Esse estudo também visou demonstrar a idade, o gênero e a resposta ao tratamento de acordo com o grau neurológico, a fim de verificar se esses parâmetros podem ser utilizados como fatores prognósticos para a evolução clínica desses pacientes. Foram revisados os registros neurológicos do Hospital Veterinário Universitário de janeiro de 2006 a março de 2017. Realizaram coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Avaliaram 177 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 78 delas. As raças mais frequentes foram Dachshunds, seguido dos cães sem raça definida. Quanto ao grau de disfunção neurológica, 58,97% apresentavam grau I (somente dor), 25,64% estavam em grau II (tetraparesia ambulatória) e 15,38% em grau III (tetraparesia não ambulatória). O repouso absoluto e em espaço restrito foram realizados em 75,64% e 24,36% dos casos, respectivamente e com duração de no mínimo uma semana, podendo chegar a mais de quatro semanas. A maioria dos animais era de pequeno porte (≤15kg). A recuperação foi satisfatória em 87,17% dos cães e insatisfatória em 12,83%. Quanto à recidiva, esta foi observada em 10,3% dos pacientes com recuperação satisfatória. O tratamento clínico para cães com DDIV cervical pode ser indicado com adequada resposta clínica para graus de disfunção que variam de I a III, seja em repouso absoluto ou em espaço restrito e com baixo índice de recidiva.(AU)

Specific effect of hypobaria on cerebrovascular hypercapnic responses in hypoxia.

It remains unknown whether hypobaria plays a role on cerebrovascular reactivity to CO2 (CVR). The present study evaluated the putative effect of hypobaria on CVR and its influence on cerebral oxygen delivery (cDO2 ) in five randomized conditions (i.e., normobaric normoxia, NN, altitude level of 440 m; hypobaric hypoxia, HH at altitude levels of 3,000 m and 5,500 m; normobaric hypoxia, NH, altitude simulation of 5,500 m; and hypobaric normoxia, HN). CVR was assessed in nine healthy participants (either students in aviation or pilots) during a hypercapnic test (i.e., 5% CO2 ). We obtained CVR by plotting middle cerebral artery velocity versus end-tidal CO2 pressure (PET CO2 ) using a sigmoid model. Hypobaria induced an increased slope in HH (0.66 ± 0.33) compared to NH (0.35 ± 0.19) with a trend in HN (0.46 ± 0.12) compared to NN (0.23 ± 0.12, p = .069). PET CO2 was decreased (22.3 ± 2.4 vs. 34.5 ± 2.8 mmHg and 19.9 ± 1.3 vs. 30.8 ± 2.2 mmHg, for HN vs. NN and HH vs. NH, respectively, p < .05) in hypobaric conditions when compared to normobaric conditions with comparable inspired oxygen pressure (141 ± 1 vs. 133 ± 3 mmHg and 74 ± 1 vs. 70 ± 2 mmHg, for NN vs. HN and NH vs. HH, respectively) During hypercapnia, cDO2 was decreased in 5,500 m HH (p = .046), but maintained in NH when compared to NN. To conclude, CVR seems more sensitive (i.e., slope increase) in hypobaric than in normobaric conditions. Moreover, hypobaria potentially affected vasodilation reserve (i.e., MCAv autoregulation) and brain oxygen delivery during hypercapnia. These results are relevant for populations (i.e., aviation pilots; high-altitude residents as miners; mountaineers) occasionally exposed to hypobaric normoxia.

Clinical management of dogs with presumptive diagnosis of thoracolumbar intervertebral disc disease: 164 cases (2006-2017) / Tratamento clínico de cães com diagnóstico presuntivo de doença do disco intervertebral toracolombar: 164 casos (2006-2017)

This study aimed to identify dogs with presumptive diagnosis of cervical intervertebral disc disease (IVDD) submitted to clinical management and to evaluate the outcomes. Data were obtained from the medical records of patients with neurological dysfunction assisted at a University Veterinary Hospital from 2006 to 2017. In addition to the patients' records, dog owners responded to a questionnaire on the success of therapy. Four hundred and thirteen neurological records were evaluated, and 164 met the inclusion criteria of the study. The most common breed was Dachshund, followed by mongrels. Classification of neurological dysfunction in the study sample was as follows: 15.9% with grade I, 25.6% with grade II, 26.8% with grade III, 8.5% with grade IV, and 23.2% with grade V. Outcome was satisfactory in 71.6% of the dogs and unsatisfactory in 28.4% of them. Recurrence was observed in 27.7% of those with satisfactory outcomes. The clinical treatment of dogs with thoracolumbar IVDD is satisfactory, particularly for animals with milder disease grades (I, II, and III). There is possibility of recurrence with conservative therapy and clinical signs may be more severe.(AU)

O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar submetidos ao tratamento clínico, a fim de avaliar a resposta à terapia instituída. Foram revisados os registros neurológicos de cães atendidos pelo Serviço de Neurologia e Neurocirurgia Veterinária no período de 2006 a 2017 de um Hospital Veterinário Universitário. Foi realizada coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Foram avaliadas 413 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 164 delas. As raças mais frequentes foram dachshunds, seguido de cães sem raça definida. Quanto ao grau de disfunção neurológica foi definido como grau I para 15,9% dos cães, grau II para 25,6%, grau III para 26,8%, grau IV para 8,5% e grau V para 23,2%. A recuperação foi satisfatória em 71,6% dos cães e insatisfatória em 28,4%. Dos que se recuperaram satisfatoriamente, 27,7% tiveram recidivas. Com base nos resultados obtidos pode-se concluir que o tratamento clínico em repouso absoluto e administração de anti-inflamatórios e analgésicos opióides para cães com DDIV toracolombar é efetivo, principalmente para cães em graus mais leves da doença (grau I, II e III). Há possibilidade de recidiva com esse tipo de terapia cujos sinais clínicos poderão ser mais graves.(AU)

Active Preconditioning With Blood Flow Restriction or/and Systemic Hypoxic Exposure Does Not Improve Repeated Sprint Cycling Performance.

PURPOSE: The aim of this study was to evaluate the effects of active preconditioning techniques using blood flow restriction or/and systemic hypoxic exposure on repeated sprint cycling performance and oxygenation responses. METHODS: Participants were 17 men; 8 were cycle trained (T: 21 ± 6 h/week) and 9 were untrained but physically active (UT). Each participant completed 4 cycles of 5 min stages of cycling at 1.5 W⋅kg-1 in four conditions [Control; IPC (ischemic preconditioning) with partial blood flow restriction (60% of relative total occlusion pressure); HPC (hypoxic preconditioning) in normobaric systemic hypoxia (FIO2 13.6%); and HIPC (hypoxic and ischemic preconditioning combined)]. Following a 40 min rest period, a repeated sprint exercise (RSE: 8 × 10 s sprints; 20 s of recovery) was performed. Near-infrared spectroscopy parameters [for each sprint, change in deoxyhemoglobin (Δ[HHb]), total hemoglobin (Δ[tHb]), and tissue saturation index (ΔTSI%)] were measured. RESULTS: Trained participants achieved higher power outputs (+10-16%) than UT in all conditions, yet RSE performance did not differ between active preconditioning techniques in the two groups. All conditions induced similar sprint decrement scores during RSE in both T and UT (16 ± 2 vs. 23 ± 9% in CON; 17 ± 3 vs. 19 ± 6% in IPC; 18 ± 5 vs. 20 ± 10% in HPC; and 17 ± 3 vs. 21 ± 5% in HIPC, for T and UT, respectively). During the sprints, Δ[HHb] was larger after IPC than both HPC and CON in T (p < 0.001). The Δ[tHb] was greater after HPC than all other conditions in T, whereas IPC, HPC, and HIPC induced higher Δ[tHb] than CON in UT. CONCLUSION: None of the active preconditioning methods had an ergogenic effect on repeated sprint cycling performance, despite some specific hemodynamic responses (e.g., greater oxygen extraction and changes in blood volume), which were emphasized in the trained cyclists.

Cardiovascular and Cerebral Responses During a Vasovagal Reaction Without Syncope.

This clinical case report presents synchronous physiological data from an individual in whom a spontaneous vasovagal reaction occurred without syncope. The physiological data are presented for three main phases: Baseline (0-200 s), vasovagal reaction (200-600 s), and recovery period (600-1200 s). The first physiological changes occurred at around 200 s, with a decrease in blood pressure, peak in heart rate and vastus lateralis tissue oxygenation, and a drop in alpha power. The vasovagal reaction was associated with a progressive decrease in blood pressure, heart rate and cerebral oxygenation, whilst the mean middle cerebral artery blood flow velocity and blood oxygen saturation remained unchanged. Heart rate variability parameters indicated significant parasympathetic activation with a decrease in sympathetic tone and increased baroreflex sensitivity. The total blood volume and tissue oxygenation index (TOI) dropped in the brain but slightly increased in the vastus lateralis, suggesting cerebral hypoperfusion with blood volume pooling in the lower body part. Cerebral hypoperfusion during the vasovagal reaction was associated with electroencephalography (EEG) flattening (i.e., decreased power in beta and theta activity) followed by an EEG high-amplitude "slow" phase (i.e., increased power in theta activity). The subject developed signs and symptoms of pre-syncope with EEG flattening and slowing during prolonged periods of symptomatic hypotension, but did not lose consciousness.

Exploiting the Causal Tensor Network Structure of Quantum Processes to Efficiently Simulate Non-Markovian Path Integrals.

In the path integral formulation of the evolution of an open quantum system coupled to a Gaussian, noninteracting environment, the dynamical contribution of the latter is encoded in an object called the influence functional. Here, we relate the influence functional to the process tensor-a more general representation of a quantum stochastic process-describing the evolution. Then, we use this connection to motivate a tensor network algorithm for the simulation of multitime correlations in open systems, building on recent work where the influence functional is represented in terms of time evolving matrix product operators. By exploiting the symmetries of the influence functional, we are able to use our algorithm to achieve orders-of-magnitude improvement in the efficiency of the resulting numerical simulation. Our improved algorithm is then applied to compute exact phonon emission spectra for the spin-boson model with strong coupling, demonstrating a significant divergence from spectra derived under commonly used assumptions of memorylessness.

Development and Validation of an Analytical Method to Quantitate Tris(chloroisopropyl)phosphate in Rat and Mouse Plasma using Gas Chromatography with Flame Photometric Detection.

Tris(chloropropyl)phosphate (TCPP) is an organophosphorus flame retardant (OPFR) and plasticizer increasingly used in consumer products and as a replacement for brominated flame retardants. Commercially available TCPP is a mixture of four structural isomers the most abundant of which is tris(1-chloro-2-propyl)phosphate (TCPP-1). Although there is a widespread use of TCPP and potential for human exposure, there is limited data on the safety or toxicity of TCPP. The National Toxicology Program is conducting long-term studies to examine the toxicity of the TCPP in rats after lifetime exposure, including perinatal oral exposure. Quantitative estimates of internal dose are essential to interpret toxicological findings in rodents. To aid in this, a method was fully validated to quantitate the most abundant isomer, TCPP-1, in female Harlan Sprague Dawley (HSD) rat and B6C3F1 mouse plasma with partial validation in male rat plasma, and male and female mouse plasma. The method used protein precipitation using trichloroacetic acid followed by the extraction with toluene, and analysis by gas chromatography with flame photometric detection. The performance of the method was evaluated over 5-70 ng TCPP-1/mL plasma. The method was linear (r ≥ 0.99), accurate (inter-day relative error: ≤ ± -7.2) and precise (inter-batch relative standard deviation: ≤27.5%). The validated method has lower limits of quantitation and detection of ~5 and 0.9 ng/mL, respectively, in female HSD rat plasma and can be used on samples as small as 50 µL demonstrating the applicability to plasma samples from toxicology studies.

Análise do líquido cérebro-espinhal de três doenças do sistema nervoso central de cães / Analysis of cerebral-spinal fluid of three central nervous system diseases of dogs

Foi realizado um estudo retrospectivo do líquido cérebro-espinhal de cães (LCE), atendidos pelo Serviço de Neurologia do Hospital Veterinário da Instituição, de 2004 a 2015, com o objetivo de analisar os resultados de cães com sinais neurológicos, comparar as alterações encontradas em dois locais de colheita no mesmo paciente e verificar se esse exame auxiliou o clínico em reforçar a suspeita clínica das principais doenças do sistema nervoso central. A pleocitose linfocítica esteve presente em 78,3% (29/37) das amostras de cães com cinomose e em 23,2% (10/43) de cães com DDIV. Houve dissociação albuminocitológica (DAC) em 73% (19/26) das amostras de cães com tumores IC e em 64,3% (9/14) de cães com tumores envolvendo a ME. Em cães com DDIV, houve significância estatística (p<0,05) entre o grau de disfunção neurológica e o total de células nucleadas (TCN) e total de proteínas (TP). Em 29 cães, houve a colheita do LCE da cisterna magna e da cisterna lombar e em 12 (41,4%) os resultados foram diferentes entre as duas amostras colhidas do mesmo cão, onde dois (6,9%) apresentaram alteração na amostra colhida cranial à lesão. Pode-se concluir que a pleocitose linfocítica foi a principal alteração encontrada no LCE de cães com cinomose e DDIV e DAC nas neoplasias, IC e ME, cães acometidos pela DDIV apresentaram sinais neurológicos mais severos conforme o TCN e o TP aumentaram e o LCE sofreu alteração, mesmo colhido cranial ao local da lesão e auxiliou o clínico em reforçar a suspeita clínica, mas não confirmou, as principais doenças neurológicas em cães.(AU)

A retrospective study including the analysis of the cerebrospinal fluid (CSF) of dogs neurologically affected was conducted by the Neurology Service of the Veterinary Hospital at the Institution, between 2004 and 2015. The aim of this study was to analyze the results of the CSF of dogs with neurological signs, and compare the changes in the CSF in two sampling sites in the same patient and see if this test helped the clinician to strengthen clinical suspicion of the major diseases of the central nervous system. Lymphocytic pleocytosis was present in 78.3% (29/37) of samples from dogs with distemper and in 23.2% (10/43) of samples from dogs with IVDD. The albumin cytologic dissociation (ACD) was found in 73% (19/26) of samples from dogs with IC tumors and in 64.3% (9/14) from dogs with tumors involving the SC. For dogs with IVDD, there was statistical significance (p<0.05) between the degree of neurological dysfunction and the total nucleated cells (TNC) and total protein (TP). In 29 dogs, CSF was collected from the cistern magna and the lumbar and in 12 (41.4%) the results were different between the samples of the same dog, where two cases (6,9%) showed alterations in the sample collected cranial to the injury. It can be concluded that the lymphocytic pleocytosis was the main alteration found in the CSF of dogs with distemper and IVDD and ACD in tumors. Dogs affected by IVDD had more severe neurological signs as TNC and TP increased and the CSF was altered even collected cranial to the lesion site and helped the clinician to strengthen the clinical suspicion, but not confirm, the major neurological diseases in dogs.(AU)

Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells.

BACKGROUND: The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. OBJECTIVES: The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. MATERIALS AND METHODS: In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). RESULTS: We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). CONCLUSIONS: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.

A peripheral blood diagnostic test for acute rejection in renal transplantation.

Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.

Subclinical inflammation and chronic renal allograft injury in a randomized trial on steroid avoidance in pediatric kidney transplantation.

Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.

Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up.

To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years posttransplant. Standardized height Z-score change after 3 years follow-up was -0.99 ± 2.20 in SF versus -0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z-score at 3 years -0.43 ± 1.15 vs. -1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow-up. Over the 3 year follow-up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.

CD14, a key candidate gene associated with a specific immune response to cockroach.

BACKGROUND: Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans. OBJECTIVE: Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen. METHODS: We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4+ T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells. RESULTS: We observed significantly elevated levels of IL-13, IL-10, and TNF-alpha, but undetectable levels of IL-12p70 and IFN-alpha, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14-260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway. CONCLUSION: Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.

Transgenic expression of AQP1 in the fiber cells of AQP0 knockout mouse: effects on lens transparency.

Mutations and knockout of aquaporin 0 (AQP0) result in dominant lens cataract. To date, several functions have been proposed for AQP0; however, two functions, water permeability and cell-to-cell adhesion have been supported by several investigators and only water channel function has been readily authenticated by in vitro and ex vivo studies. Lens shifts protein expression from the more efficient AQP1 in the equatorial epithelial cells to the less efficient water channel, AQP0, in the differentiating secondary fiber cells; perhaps, AQP0 performs a distinctive function. If AQP0 has only water permeability function, can the more efficient water channel AQP1 transgenically expressed in the fiber cells compensate and restore lens transparency in the AQP0 knockout (AQP0(-/-)) mouse? To investigate, we generated a transgenic wild-type mouse line expressing AQP1 in the fiber cells using alphaA-crystallin promoter. These transgenic mice (TgAQP1(+/+)) showed increase in fiber cell membrane water permeability without any morphological, anatomical or physiological defects compared to the wild type indicating that the main purpose of the shift in expression from AQP1 to AQP0 may not be to lessen the membrane water permeability. Further, we transgenically expressed AQP1 in the lens fiber cells of AQP0 knockout mouse (TgAQP1(+/+)/AQP0(-/-)) to determine whether AQP1 could restore AQP0 water channel function and regain lens transparency. Fiber cells of these mice showed 2.6 times more water permeability than the wild type. Transgene AQP1 reduced the severity of lens cataract and prevented dramatic acceleration of cataractogenesis. However, lens fiber cells showed deformities and lack of compact cellular architecture. Loss of lens transparency due to the absence of AQP0 was not completely restored indicating an additional function for AQP0. In vitro studies showed that AQP0 is capable of cell-to-cell adhesion while AQP1 is not. To our knowledge, this is the first report which uses an animal model to demonstrate that AQP0 may have an additional function, possibly cell-to-cell adhesion.