Identifying gaps in the cascade of care for latent TB infection in a low-incidence setting.

BACKGROUND: The End TB Strategy calls for the global scale-up of treatment for latent TB infection (LTBI). We aimed to evaluate a nurse-led care programme for LTBI by identifying gaps in the care cascade in a low-incidence TB setting.METHODS: We included people at risk of TB over a 15-year period. We define three main outcomes in the LTBI care cascade: 1) attendance at the first appointment, 2) completion of the evaluation process, and 3) completion of treatment.RESULTS: We identified 6,126 individuals (2,369 TB contacts, 1,749 biological therapy candidates, and 2,008 transplant candidates). Overall, 5,938 (96.9%) attended, 5,872/5,938 (98.9%) completed the evaluation and 1,624/1,847 (87.9%) completed treatment. Pre-biological (aOR 2.32, 95% CI 1.54-3.49) and pre-transplant (aOR 1.82, 95% CI 1.20-2.76) candidates were more likely to attend the first appointment, while age was associated with completing the evaluation process (aOR 1.02, 95% CI 1.003-1.04). Female sex (aOR 1.47, 95% CI 1.08-1.99) was associated with completing the treatment.CONCLUSION: Successful assessment and treatment of LTBI is achievable when delivered as a part of a comprehensive, nurse-led, patient-centred programme in specialist TB clinics.

Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation.

Nanotechnology-based health products are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for quality and safety assessments of these innovative products prior to their translation into the clinic and for monitoring their performance when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work presented here explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs, as expressed by regulatory authorities, were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods, thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and excretion) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, (ii) method validation/standardisation and (iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work should raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing the development of a robust testing strategy for nanotechnology-based health products.

High-resolution ultrasound changes of the vagus nerve in idiopathic Parkinson's disease (IPD): a possible additional index of disease.

BACKGROUND AND RATIONALE: Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson's disease (IPD). Degeneration of VN axons should be detectable by high-resolution ultrasound (HRUS) as a thinning of the nerve trunk. In order to establish if the VN exhibits sonographic signs of atrophy in IPD, we examined patients with IPD compared with age-matched controls. MATERIAL AND METHODS: We measured the caliber (cross-sectional area, CSA) and perimeter of the VN in 20 outpatients with IPD (8 females and 12 males; mean age 73.0 + 8.6 years) and in age-matched controls using HRUS. Evaluation was performed by blinded raters using an Esaote MyLab Gamma device in conventional B-Mode with an 8-19 MHz probe. RESULTS: In both sides, the VN CSA was significantly smaller in IPD outpatients than in controls (right 2.37 + 0.91, left 1.87 + 1.35 mm2 versus 6.0 + 1.33, 5.6 + 1.26 mm2; p <0.001), as well as the perimeter (right 5.06 + 0.85, left 4.78 + 1.74 mm versus 8.87 + 0.86, 8.58 + 0.97 mm; p <0.001). There were no significant correlations between VN CSA and age, the Hoehn and Yahr scale, L-dopa therapy, and disease duration. CONCLUSION: Our findings provide evidence of atrophy of the VNs in IPD patients by HRUS. Moreover, HRUS of the VN represent a non-invasive easy imaging modality of screening in IPD patients independent of disease stage and duration and an interesting possible additional index of disease.

Why foodborne and waterborne parasites are important for veterinarians.

Parasites, including helminths and protists, are pathogens responsible for waterborne and foodborne illnesses in both developed and developing countries. Their global incidence is difficult to estimate, but the World Health Organization (WHO) has indicated the global disease burden of 11 waterborne and foodborne parasitic diseases, is responsible for causing over 407 million illnesses resulting in an estimated of 94 K deaths and 11 million disability-adjusted life years (DALYs). Nevertheless, compared with bacteria and viruses, parasites are often overlooked as etiological agents of foodborne or waterborne disease; this is due to a variety of reasons, including the difficulty of their identification in environmental matrices and because many have a prolonged period between infection and symptoms, making it difficult to implicate infection vehicles. This Special Issue comprises 17 articles that include the more significant waterborne and foodborne parasites of zoonotic importance due to their relevance, with all groups of parasites (protist, cestodes, trematodes, and nematodes) being represented. Each chapter covers relevant aspects regarding -the importance of the parasite in food and water, including an overview of outbreaks where relevant, information on fundamental epidemiological aspects such as transmission, lifecycle and host range, clinical aspects such as pathogenesis, diagnosis and treatment, a summary of prospects for control in water or the food chain, and, finally, providing the authors' opinions regarding future research or studies required to improve control of transmission to people via food or water.

Rifabutin for treating tuberculosis in solid organ transplant recipients: A retrospective observational study and literature review.

BACKGROUND: The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. METHODS: A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin-containing regimens were compared and a literature review was conducted. RESULTS: We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50-20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non-rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P = .21), side effects (25%, 37.5%, and 20%, respectively; P = .74), or mortality (16.7%, 35.7%, and 0%, respectively; P = .21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin-containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. CONCLUSIONS: Rifabutin-containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients.

A simple novel approach for detecting blood-brain barrier permeability using GPCR internalization.

AIMS: Impairment of blood-brain barrier (BBB) is involved in numerous neurological diseases from developmental to aging stages. Reliable imaging of increased BBB permeability is therefore crucial for basic research and preclinical studies. Today, the analysis of extravasation of exogenous dyes is the principal method to study BBB leakage. However, these procedures are challenging to apply in pups and embryos and may appear difficult to interpret. Here we introduce a novel approach based on agonist-induced internalization of a neuronal G protein-coupled receptor widely distributed in the mammalian brain, the somatostatin receptor type 2 (SST2). METHODS: The clinically approved SST2 agonist octreotide (1 kDa), when injected intraperitoneally does not cross an intact BBB. At sites of BBB permeability, however, OCT extravasates and induces SST2 internalization from the neuronal membrane into perinuclear compartments. This allows an unambiguous localization of increased BBB permeability by classical immunohistochemical procedures using specific antibodies against the receptor. RESULTS: We first validated our approach in sensory circumventricular organs which display permissive vascular permeability. Through SST2 internalization, we next monitored BBB opening induced by magnetic resonance imaging-guided focused ultrasound in murine cerebral cortex. Finally, we proved that after intraperitoneal agonist injection in pregnant mice, SST2 receptor internalization permits analysis of BBB integrity in embryos during brain development. CONCLUSIONS: This approach provides an alternative and simple manner to assess BBB dysfunction and development in different physiological and pathological conditions.

A combined single-stage procedure to treat brain AVM.

Complete resection of brain arteriovenous malformation (AVM) is a surgical challenge, mainly due to risk of intraoperative rupture. The objective of this feasibility study was to analyze complete resection rate at 3 months and clinical outcome at 6 months after treatment of brain AVM by combined single-stage embolization and surgical resection. A retrospective observational study from July 2015 to February 2019 was conducted at the Department of Neurosurgery of Strasbourg University Hospital, France. Decision to treat was taken on the basis of history of AVM rupture, symptomatic AVM, or morphologic risk factors for rupture. Complete resection rate was assessed on postoperative cerebral subtraction angiography at 3 months and clinical outcome at 6 months was evaluated on the modified Rankin Scale (mRS). In the 16 patients treated for symptomatic brain AVM, the rate of complete resection was 75%, resection with residual shunt 18.7%, and incomplete resection with residual nidus 6.3%. Good clinical outcome (mRS=0 or 1) was achieved in 81.3% of patients at 6 months. The transfusion rate was 7.1%. There were procedural complications in 12.5% of patients but no intraoperative ruptures. This combined single-stage procedure allows extensive preoperative embolization of the AVM, facilitating surgical microdissection by identifying the dissection plane and perforating arteries and allowing the operator to work in close contact with the nidus without fear of intraoperative rupture.

Predictive factors of epilepsy in arteriovenous malformation.

OBJECTIVE: Structural epilepsy related to cerebral arteriovenous malformation (AVM) suggests different epileptogenic mechanisms. The aim of our study was to determine factors associated with epilepsy into a retrospective cohort of AVM patients. PATIENTS AND METHODS: Ruptured and unruptured AVM data retrieved from a prospective single center registry (2009-2016) were retrospectively assessed. Demographic, clinical and radiological features were identified in AVM patients with or without epilepsy according to the International League Against Epilepsy classification. RESULTS: Epilepsy concerned 22 out of 80 consecutive patients with AVM (27.5%). Univariate analysis comparing both groups revealed a significant association of different variables with the structural epilepsy: young age (P=0.02), large nidus size (P=0.02), venous dilation (P=0.02), posterior cerebral artery (PCA) feeder (P<0.001) and Spetzler-Martin grade (P=0.02). Based on multivariate analysis, only the PCA feeder was identified (OR=5.2 [95% CI 1.1-24,5], P=0.04). CONCLUSION: PCA feeder for cerebral AVM was significantly associated with structural epilepsy. The hypothesis of a vascular steal phenomenon to the detriment of internal temporal lobe vascularization could be related to the development of epilepsy.

Customised multiphasic nucleus/annulus scaffold for intervertebral disc repair/regeneration.

Background: In the case of a degenerated intervertebral disc (IVD), even though spinal fusion has provided good short-term clinical results, an alteration of the spine stability has been demonstrated by long-term studies. In this context, different designs of IVD prostheses have been proposed as alternative to spinal fusion. However, over the past few years, much of the recent research has been devoted to IVD tissue engineering, even if several limitations related to the complex structure of IVD are still presented.Purpose/Aim: Accordingly, the aim of the current paper was to develop a strategy in designing customised multiphasic nucleus/annulus scaffolds for IVD tissue engineering, benefiting from the great potential of reverse engineering, additive manufacturing and gels technology.Materials and Methods: The device consisted of a customised additive-manufactured poly(ε-caprolactone) scaffold with tailored architectural features as annulus and a cell-laden collagen-low molecular weight hyaluronic acid-based material as nucleus with specific rheological and functional properties. To this aim, injectability and viscoelastic properties of the hydrogel were analyzed. Furthermore, a mechanical and biological characterization of cell-laden multiphasic nucleus/annulus scaffold was performed.Results and Conclusions: Analyses on the developed devices demonstrated appropriate viscoelastic and mechanical properties. As evidenced by rheological tests, the hydrogel showed a shear-thinning behaviour, supporting the possibility to inject the material. The mechanical characterization highlighted a compressive modulus which falls in the range of lumbar discs, with the typical initial J-shaped stress-strain curve of natural IVDs. Furthermore, preliminary biological tests showed that human mesenchymal stem cells were viable over the culture period.

Detecting abnormal thyroid cartilages on CT using deep learning.

PURPOSE: The purpose of this study was to evaluate the performance of a deep learning algorithm in detecting abnormalities of thyroid cartilage from computed tomography (CT) examination. MATERIALS AND METHODS: A database of 515 harmonized thyroid CT examinations was used, of which information regarding cartilage abnormality was provided for 326. The process consisted of determining image abnormality and, from these preprocessed images, finding the best learning algorithm to appropriately characterize thyroid cartilage as normal or abnormal. CT images were cropped to be centered around the cartilage in order to focus on the relevant area. New images were generated from the originals by applying simple transformations in order to augment the database. Characterizations of cartilage abnormalities were made using transfer learning, by using the architecture of a pre-trained neural network called VGG16 and adapting the final layers to a binary classification problem. RESULTS: The best algorithm yielded an area under the receiving operator characteristic curve (AUC) of 0.72 on a sample of 82 thyroid test images. The sensitivity and specificity of the abnormality detection were 83% and 64% at the best threshold, respectively. Applying the model on another independent sample of 189 new thyroid images resulted in an AUC of 0.70. CONCLUSION: This study demonstrates the feasibility of using a deep learning-based abnormality detection system to evaluate thyroid cartilage from CT examinations. However, although promising results, the model is not yet able to match an expert's diagnosis.

A Josephson relation for fractionally charged anyons.

Anyons occur in two-dimensional electron systems as excitations with fractional charge in the topologically ordered states of the fractional quantum Hall effect (FQHE). Their dynamics are of utmost importance for topological quantum phases and possible decoherence-free quantum information approaches, but observing these dynamics experimentally is challenging. Here, we report on a dynamical property of anyons: the long-predicted Josephson relation f J = e*V/h for charges e* = e/3 and e/5, where e is the charge of the electron and h is Planck's constant. The relation manifests itself as marked signatures in the dependence of photo-assisted shot noise (PASN) on voltage V when irradiating contacts at microwaves frequency f J The validation of FQHE PASN models indicates a path toward realizing time-resolved anyon sources based on levitons.

Preweaned heifer management on US dairy operations: Part III. Factors associated with Cryptosporidium and Giardia in preweaned dairy heifer calves.

The objective of this study was to evaluate management practices and environmental factors associated with cryptosporidiosis and giardiasis in preweaned heifer calves on US dairy operations. This study was conducted as part of the calf component of the National Animal Health Monitoring System's Dairy 2014 study. The calf component included 104 dairy operations in 13 states and was an 18-mo longitudinal study focused on dairy heifer calves from birth to weaning. Fecal samples were collected from 2,249 calves: 839 calves in the West region (California, Colorado, and Washington) and 1,410 calves in the East region (Iowa, Michigan, Minnesota, Missouri, New York, Ohio, Pennsylvania, Vermont, Virginia, and Wisconsin). Fecal samples were collected only once from calves during the preweaning period. Samples were collected from calves 3 to 66 d of age, with a mean of 22 d. Overall, Cryptosporidium and Giardia were detected in 43.1 and 30.5% of fecal samples, respectively. Backward elimination logistic model selection was used after univariate screening to determine which management practices and environmental factors significantly affected the presence of Cryptosporidium or Giardia. The final Cryptosporidium model included herd size, days of age at fecal collection, and average temperature-humidity index for the month of fecal collection (fTHI). Cryptosporidium was found on a higher percentage of large operations (≥500 cows) than small operations (30 to 99 cows). Younger calves were more likely to have a fecal sample positive for Cryptosporidium than samples from older calves. Fecal samples from calves during the warmer parts of the year (fTHI >70) were more likely to be positive for Cryptosporidium than samples collected in colder months (fTHI <20). The final Giardia model included herd size, days of age at fecal collection, average fTHI, failure of passive transfer status, and average daily gain (kg/d) during the preweaning period. Giardia was isolated more frequently from calves on small operations than on large operations and from calves that were older compared with younger calves. Giardia was more frequently isolated in warmer months. Samples from calves with failure of passive transfer were more likely to have Giardia than calves with adequate passive transfer (>10 g/L IgG). Average daily gain during the preweaning period was lower in calves from which Giardia was isolated. These results highlight the factors associated with the presence of Cryptosporidium and Giardia in preweaned dairy heifer calves.

Preweaned heifer management on US dairy operations: Part VI. Factors associated with average daily gain in preweaned dairy heifer calves.

The study objective was to evaluate average daily gain (ADG) in dairy heifer calves based on health, feeding, management practices, and environmental factors. This study included 102 operations in 13 states that participated in the calf component of the National Animal Health Monitoring System's Dairy 2014 study. This 18-mo longitudinal study included 1,410 Holstein heifer calves monitored from birth to weaning. The mean ADG from birth to final weight was 0.74 kg/d. Backward elimination model selection in Proc Mixed after univariate screening determined factors that significantly affected ADG. The final model included dam lactation number, singleton versus twin birth, bedding type, Giardia and Cryptosporidium fecal shedding, disease events, a categorized average temperature-humidity index for the preweaning period (pTHI), amount of protein in the liquid diet (kg/d), milk pasteurization, direct-fed microbials, and the interaction between milk pasteurization and direct-fed microbials. After controlling for other independent variables in the model, calves born to first-lactation dams gained less (0.60 kg/d) than calves from second- (0.65 kg/d) or third- or greater-lactation (0.64 kg/d) dams. Singleton calves gained 0.07 kg/d more than twins. Calves bedded with sand or no bedding gained less (0.49 kg/d) than calves on all other bedding types. Calves negative for Cryptosporidium or Giardia at the time of sampling gained 0.03 or 0.02 kg/d more, respectively, than calves that were positive for Cryptosporidium or Giardia. Calves with no disease events gained 0.07 kg/d more than calves with one or more disease events. Calves experiencing an average pTHI <50 gained more (0.67 kg/d) than calves experiencing an average pTHI from 50 to 69 (0.62 kg/d), or ≥70 (0.59 kg/d). Within the range of observed kilograms of protein fed per day in the liquid diet, every additional 0.1 kg of protein fed per day equated to 0.02 kg/d of gain. Calves fed milk replacer with a direct-fed microbial gained less (0.44 kg/d) than calves fed milk replacer without a direct-fed microbial (0.60 kg/d) and calves fed pasteurized or unpasteurized milk regardless of direct-fed microbial use. These results highlight the importance of feeding a quantity and quality of a liquid diet to achieve optimal growth, keeping calves free of disease, the type or status of bedding, and mitigating the effects of temperature and humidity on preweaning ADG.

The Grisel's syndrome: A non-traumatic subluxation of the atlantoaxial joint.

INTRODUCTION: Grisel's syndrome consists in rotational subluxation of C1-C2 following ENT infection or surgery. There is no consensus on management. We present 2 cases requiring surgical treatment in our center. CASE REPORTS: Two 10-year-old patients presented torticollis with cervical pain resistant to medical treatment, with onset a few months after tonsillectomy. In both cases, radiological assessment, comprising CT scan and MRI, showed Fielding-Hawkins type-3 C1-C2 rotational subluxation, without ligament lesion. After failure of conservative treatment, posterior reaming, realignment, C1-C2 arthrodesis using lateral masses and pars interarticularis screws and bone graft achieved good fusion and immediate spinal stability in all planes of the atlantoaxial complex. DISCUSSION: Grisel's syndrome consists in non-traumatic subluxation of the atlantoaxial joint with intact atlantoaxial ligaments. Initial pharyngeal inflammation spreads to the prevertebral fascia via direct connections between the periodontoidal venous plexus and pharyngovertebral veins, inducing fasciitis that leads to abnormal relaxation of the atlantoaxial ligaments and reactional muscle contraction with ankylosis. This phenomenon, appearing gradually and insidiously over a period of a few weeks, creates a frozen joint with ankylosis. Medical treatment with NSAIDs, muscle relaxants, and immobilization is usually sufficient; cervical traction may be needed. Surgical treatment by C1-C2 arthrodesis is indicated in case of failure of medical management or onset of neurologic signs. CONCLUSION: Close collaboration between pediatricians, ENT surgeons and neurosurgeons is essential for early diagnosis and management, which is the main prognostic factor for successful medical treatment, avoiding surgery.

Subclinical haemorrhage in non-functional adenomas.

AIM: The prevalence and risk factors of subclinical haemorrhage on non-functional adenomas (NFA) remain controversial. The primary aim of our study was to assess the incidence of subclinical haemorrhage (SH) and the secondary objectives were to evaluate the risk factors of SH and the impact of SH on pituitary function at diagnosis. PATIENTS AND METHODS: This retrospective transversal analysis included 95 patients between January 2012 and December 2014. The patients included in this series were all adults (>18 years of age), who presented a non-functional adenoma confirmed by an endocrinological evaluation and on dedicated MRI pituitary imaging. Sixty-four patients were eligible for this study. Subclinical haemorrhage was defined by the presence of haemorrhage within pituitary adenoma confirmed by pituitary MRI with no clinical symptoms. A senior neuroradiologist blinded to the diagnosis reviewed all MRI. The population was prospectively divided into two groups based on MRI results (SH group vs. group control) to determine risk factors. RESULTS: SH was diagnosed in 22 patients (34.38%). No risk factors (age, sex, tumor size, chronic hypertension, diabetes mellitus, malignant disease, the use of anticoagulation or antithrombotic medication or Cabergoline treatment) were involved as regards the SH. At the diagnosis, pituitary deficiency was statistically significantly more frequent in the SH group (45.45%) than in the control group (19.04%) (P=0.04). CONCLUSION: The SH within NFA was observed in 34.38% of cases without an association of risk factors.

Diagnosis and suggested treatment against an isolated unilateral rupture of the alar ligament - Concerning one case.

BACKGROUND: An isolated rupture of the alar ligament is a rare occurrence with only a few cases reported in the literature. CASE REPORT: The objective was to report the case of a young man with a unilateral rupture of the alar ligament that we closely monitored, clinically and radiologically, in order to describe the evolution of the alar ligament lesions. CONCLUSION: Radiological diagnosis using cervical MRI and duration of the conservative treatment remain debated and we proposed a close radiological follow-up in order to best understand the nature of these ligament lesions and their evolution following specific treatment.

Increasing isolation of rapidly growing mycobacteria in a low-incidence setting of environmental mycobacteria, 1994-2015.

To determine trends in incidence and clinical relevance of rapidly growing mycobacteria (RGM) in a low-prevalence region of non-tuberculous mycobacteria. We retrospectively identified all patients with RGM-positive cultures between January 1994 and December 2015. Trends in incidence, clinical significance, and outcomes were assessed. One hundred and forty patients had RGM-positive cultures (116 respiratory and 24 extra-respiratory sources). The incidence of RGM isolates increased steadily from 2003 (0.34 per 100,000) to 2015 (1.73 per 100,000), with an average annual increase of 8.3%. Thirty-two patients (22.9%) had clinical disease, which trended to cluster in the second half of the study period. A positive acid-fast bacilli smear (odds ratio [OR] 97.7, 95 % CI 13.8-689.4), the presence of extra-respiratory isolates (OR 19.4, 95 % CI 5.2-72.7), and female gender (OR 5.9, 95 % CI 1.9-19.1) were independently associated with clinical disease. Cure rates were 73.3 and 87.5% for pulmonary and extra-pulmonary disease respectively. Although the burden of disease remains low, the presence of RGM isolates is increasing in our geographical setting. Whether this rise will be sustained over time and will coincide with an increase in clinical disease, or whether it is merely a cycle in the poorly understood epidemiological behaviour of environmental mycobacteria, will be seen in the near future.

Reducing gut effects from Cryptosporidium parvum infection in dairy calves through prophylactic glucagon-like peptide 2 therapy or feeding of an artificial sweetener.

Glucagon-like peptide 2 (GLP-2) therapy was shown previously to reduce inflammation-related gut damage from coccidiosis in dairy calves, and feeding of artificial sweetener stimulates GLP-2 secretion from intestinal L cells. The purpose of this study was to determine whether GLP-2 treatment or artificial sweetener feeding beginning 1 wk before an experimental inoculation with the coccidian parasite Cryptosporidium parvum can reduce infection-related intestinal damage in Holstein bull calves. Newborn calves were assigned to 1 of 4 treatment groups of 6 calves each, including noninfected control calves injected s.c. every 12 h with control buffer (CON), infected control calves injected s.c. every 12 h with control buffer (INF), infected calves injected s.c. every 12 h with 50 µg/kg of body weight of GLP-2 (GLP2), and infected calves injected s.c. every 12 h with control buffer and supplemented in the diet with Sucram (Pancosma, Geneva, Switzerland) at 400 mg/kg of dry matter of milk replacer (SUC). Treatments were initiated on d 1, and calves in INF, GLP2, and SUC were orally dosed on d 8 with 12,500 C. parvum oocysts. Fecal scores were recorded daily, plasma was collected on d 1, 8, 12, 15, and 18 to evaluate markers of inflammation, and fecal samples were collected on d 1, 8, and every other day thereafter to determine the presence of oocysts. Calves were euthanized on d 18 for collection of intestinal tissues and histological and gene expression analyses. Relative to CON, calves in INF exhibited an increase in diarrhea severity, increased plasma serum amyloid A concentration on d 15 and 18, reduced intestinal villus height, increased villus apoptosis and crypt cell proliferation, and increased intestinal mRNA expression of MARVELD2 and GPX2. However, calves in SUC and GLP2 had reduced diarrhea severity and fecal C. parvum oocyst shedding, reduced plasma serum amyloid A concentration on d 15 and 18, and, depending on the intestinal segment, increased villus height, reduced crypt cell proliferation, and reduced mRNA expression of MARVELD2, GPX2, and other tight junction proteins relative to INF. Lastly, GLP2 and SUC exhibited increased intestinal mass-to-length ratio and decreased length-to-empty body weight ratio relative to INF. Our findings suggest that GLP-2 and Sucram treatments administered before a low-level C. parvum exposure may contribute to fewer effects on intestinal integrity, morphology, and inflammation in response to infection, and shorter, denser intestines.

Reproducibility of R2 * and quantitative susceptibility mapping (QSM) reconstruction methods in the basal ganglia of healthy subjects.

The basal ganglia are key structures for motor, cognitive and behavioral functions. They undergo several changes with aging and disease, such as Parkinson's or Huntington's disease, for example. Iron accumulation in basal ganglia is often related to these diseases, which is conventionally monitored by the transverse relaxation rate (R2 *). Quantitative susceptibility mapping (QSM) is a novel contrast mechanism in MRI produced by adding information taken from the phase of the MR signal to its magnitude. It has been shown to be more sensitive to subtle changes in Parkinson's disease. In order to be applied widely to various pathologies, its reproducibility must be evaluated in order to assess intra-subject variability and to disseminate into clinical and pharmaceutical studies. In this work, we studied the reproducibility and sensitivity of several QSM techniques. Fourteen subjects were scanned four times, and QSM and R2 * images were reconstructed and registered. An atlas of the basal ganglia was used to automatically define regions of interest. We found that QSM measurements are indeed reproducible in the basal ganglia of healthy subjects and can be widely used as a replacement for R2 * mapping in iron-rich regions. This reproducibility study could lead to several lines of research in relaxometry and susceptibility measurements, in vivo iron load evaluation as well as pharmacological assessment and biomarker development. Copyright © 2016 John Wiley & Sons, Ltd.