Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1ß, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-ß (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.

Smoking exposure trajectories and pulmonary function in early adulthood in a Brazilian cohort.

OBJECTIVES: To investigate smoking trajectories and their association with pulmonary function (PF) and respiratory symptoms at age 22. METHODS: Data from a population-based cohort study of 3350 individuals and their spirometries were analysed. The outcomes were: forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at the mid expiratory phase (FEF25-75 %), FEV1/FVC and FEF25-75/FVC ratio. Smoking data were collected at perinatal follow-up (gestational exposure) and 15, 18 and 22 years. Group-based trajectory model was applied. RESULTS: Four groups were identified: no exposure (NE), gestational (GE), gestational and adulthood (GAE) and continuous (CE) exposure. Both CE and GAE trajectories were associated with lower values of FEV1/FVC (-1.77pp; p = 0.01 and -1.58 pp; p<0.001 respectively) and FEF25-75/FVC ratio (-7.27pp; p = 0.019 and -6.04pp; p<0.001 respectively) compared to the NE trajectory. Lower FEV1 and FEF25-75 % values were also related to the GAE trajectory (-68 ml; p = 0.03 and -253 ml/s;p<0.001 respectively). Compared to those who never smoked, individuals who smoked 10 or more cigarettes daily presented a reduction in the FEV1/FVC ratio by 1.37pp (p<0.001), FEF25-75 % by 126 ml (p = 0.012) and FEF25-75 %/FVC ratio by 3.62pp (p = 0.011). CE trajectory showed higher odds of wheezing (OR 4.14; p<0.001) and cough (OR 2.39; p = 0.002) compared to the non-exposed group. CONCLUSIONS: The in-uterus exposure to maternal smoking reduces PF later in life. However, the perpetuation of smoking behaviour throughout adolescence and early adulthood is determinant for PF main reduction and the emergence of respiratory-related symptoms.

What makes community-based, multilevel physical activity promotion last? A systematic review with narrative synthesis on factors for sustainable implementation.

AIM: To follow the need for more research and strategies to enhance the knowledge of sustainable implementation, we examined cases of community-based, multilevel physical activity-related health promotion after initial funding has ceased and aimed to identify factors that influence their sustainable implementation. METHODS: Five scientific databases (PubMed; Scopus; Ebsco Host with CINAHL, PsychInfo, and Sportdiscus; ProQuest and Web of Science) were systematically searched for relevant literature in December 2021. Three reviewers performed a title/abstract screening and independently screened the full texts of the remaining papers, followed by a quality assessment. A narrative synthesis method, including qualitative text analysis, was used to synthesise retrieved articles. As starting point, the framework of Schell et al. containing nine domains for sustainability capacity was used and new emerging themes were inductively added. RESULTS: The search revealed 270 potentially eligible articles out of 27,652 hits. After the systematic review process, 14 studies were included. In the synthesis, 14 factors influencing the sustainablity of community-based, multilevel physical activity-related health promotion were identified of which six are new factors compared to Schell et al. In particular, our findings bring forth a novel understanding of the importance of the factors 'Participation and Partnerships', 'Empowerment and Capacity Building' and 'Community Support'. A dynamic interplay and high connectedness between factors were visible. CONCLUSION: The identified factors can help establish a better understanding of sustainability processes within whole-system approaches intervening on multiple levels in the community with the aim of systems change. They are relevant for practitioners, researchers and policy makers alike. Future research should more closely examine based on further theoretical elaboration how an interplay between the factors can promote sustainability and which interdependencies are of particular importance in facilitating sustainable and equitable change.

Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites.

BACKGROUND: Increasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites. OBJECTIVES: To identify factors contributing to therapy failure. METHODS: Sixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained. RESULTS: Sequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary. CONCLUSIONS: The kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.

[Stress fractures of the lower limbs]. / Stressfrakturen der unteren Extremität.

Stress reactions and fractures represent an important differential diagnostic entity, especially in patients active in sports. The lower extremities have predilection sites for stress fractures, which require special treatment in the context of the underlying risk factors. Clinically, patients usually complain of stress-dependent pain in the affected region and sport activities are mostly limited or even impossible. The detection of acute stress fractures is usually missed by conventional X­ray within the first 4-6 weeks. The gold standard diagnostic tool is magnetic resonance imaging (MRI). Depending on the location, a distinction must be made between low-risk and high-risk stress fractures. Low-risk fractures show a high healing rate after conservative treatment including load and stress reduction as well as avoiding risk factors. High-risk fractures can take a complicated course under conservative treatment measures and in some cases, surgical intervention is required.

[Avulsion injuries of the gluteus medius and gluteus minimus muscles]. / Avulsionsverletzungen des M. glutaeus medius und M. glutaeus minimus.

Avulsion injuries of the gluteus medius and gluteus minimus muscles represent a diagnostic and therapeutic challenge. Such injuries are rarely to be expected in high-energy trauma. Degenerative damage or iatrogenic injuries in the context of hip surgery are more frequently identified as the cause. Clinically, in addition to lateral hip pain, limping is an important finding and depends on the extent of the tendon damage. In addition to the medical history and clinical examination, imaging by means of sonography and, above all, magnetic resonance imaging (MRI, possibly with artifact-reduced sequences in the presence of an endoprosthesis) are diagnostically groundbreaking. Therapeutically, a stepwise approach is indicated according to the extent of rupture and quality of the gluteal tendon and muscle tissues. Specific conservative training regimens, mini-open/endoscopic anatomic reconstruction techniques in cases of gluteal muscle integrity and muscle transfer techniques as salvage option with chronic mass ruptures are available. The common goal is the restoration of everyday occupational and private activities to regain the quality of life.

Perilesional sun damage as a diagnostic clue for pigmented actinic keratosis and Bowen's disease.

BACKGROUND: Chronic sun damage in the background is common in pigmented actinic keratoses and Bowen's disease (pAK/BD). While explainable artificial intelligence (AI) demonstrated increased background attention for pAK/BD, humans frequently miss this clue in dermatoscopic images because they tend to focus on the lesion. AIM: To analyse whether perilesional sun damage is a robust diagnostic clue for pAK/BD and if teaching this clue to dermatoscopy users improves their diagnostic accuracy. METHODS: We assessed the interrater agreement and the frequency of perilesional sun damage in 220 dermatoscopic images and conducted a reader study with 124 dermatoscopy users. The readers were randomly assigned to one of two online tutorials; one tutorial pointed to perilesional sun damage as a clue to pAK/BD (group A) the other did not (group B). In both groups, we compared the frequencies of correct diagnoses before and after receiving the tutorial. RESULTS: The frequency of perilesional sun damage was higher in pAK/BD than in other types of pigmented skin lesions and interrater agreement was good (kappa = 0.675). The diagnostic accuracy for pAK/BD improved in both groups of readers (group A: +16.1%, 95%-CI: 9.5-22.7; group B: +13.1%; 95%-CI: 7.1-19.0; P for both <0.001), but the overall accuracy improved only in group A from (59.1% (95%-CI: 55.0-63.1) to 63.5% (95%-CI: 59.5-67.6); P = 0.002). CONCLUSION: Perilesional sun damage is a good clue to differentiate pAK/BD from other pigmented skin lesions in dermatoscopic images, which could be useful for teledermatology. Knowledge of this clue improves the accuracy of dermatoscopy users, which demonstrates that insights from explainable AI can be used to train humans.

[Maternal deaths due to haemorrhage in France 2013-2015]. / Mortalité maternelle par hémorragie en France 2013­2015.

Maternal death from haemorrhage is decreasing: in the last 15 years the number of deaths has been halved. This improvement demonstrates the progress made in hemorrhage management as a result of collective efforts. The number of deaths in this triennium is 22, representing 8.4% of maternal deaths and a maternal mortality ratio by haemorrhage of 1.0/100,000 live births. Nevertheless, there is a worrying proportion of deaths from occult haemorrhage. These occult haemorrhages most often occurred after caesarean sections. A lack of surveillance in the immediate follow-up was generally associated. One or more factors of sub-optimal care were present in 84% of the cases, and 88.9% of deaths were considered possibly or probably preventable. Delay in the diagnosis of haemorrhage, delay in surgical treatment, an insufficient transfusion strategy and inappropriate locations of care were the most frequently reported factors. The experts suggest that risk factors for haemorrhage should be identified in order to propose the most appropriate facility for childbirth. They encourage the strategies for early diagnosis of haemorrhage (attentive and regular monitoring, rapid haemoglobin measurement, abdominal ultrasound) and surgical intervention in case of hemoperitoneum.

[Maternal deaths due to hypertensive disorders in France 2013-2015]. / Morts maternelles par complications hypertensives en France 2013­2015.

Between 2013 and 2015, six maternal deaths were due to hypertensive disorders. During this period, the maternal mortality ratio was 0.2/100,000 live births. Hypertensive disorders were responsible for 2% of maternal deaths in France and for 5% of direct maternal mortality. All these deaths happened after the delivery. Mode of delivery was a cesarean section when the hypertensive complication started before the delivery (4/6; 67%). Three had DIC during the immediate post-partum. Five women were under 35 years old. Only one had a BMI over 30. Four out of six patients were primiparous. One woman was Afro-Caribbean. Medical care was estimated non-optimal in 100% of the cases. In three cases, it was prenatal care and in three cases it was obstetrical care during delivery; anesthesia and intensive care were suboptimal in five cases. Eighty percent of these deaths seemed to be preventable. The main causes of suboptimal management were inappropriate or insufficient obstetrical and/or anesthetic treatments, and delayed optimal treatment. The analysis of these maternal deaths offers the opportunity to stress major points to optimize medical management in case of hypertensive disorders during pregnancy such as management of eclampsia (use of magnesium sulfate) or recognition of DIC when HELLP syndrome is diagnosed.

Validation of maternal recall on exclusive breastfeeding 12 months after childbirth.

OBJECTIVE: We aimed to assess the validity of maternal recall of exclusive breastfeeding (EBF) at 3 months obtained 12 months after childbirth. DESIGN: A population-based birth cohort study. The gold standard is maternal report of EBF at the age of 3 months (yes or no) and age of introduction of other foods in the infant's diet. EBF was considered when the mother reported that no liquid, semi-solid or solid food was introduced up to that moment. The variable to be validated was obtained at 12 months after childbirth when the mother was asked about the age of food introduction. The prevalence of EBF at 3 months, and sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy of 12-month recall with 95 % CI were calculated. SETTING: Pelotas, Brazil. PARTICIPANTS: 3700 mothers of participants of the Pelotas 2004 Birth Cohort. RESULTS: The prevalence of EBF at 3 months was 27·8 % (95 % CI 26·4, 29·3) and 49·0 % (95 % CI 47·4, 50·6) according to gold standard and maternal recall, respectively. The sensitivity of maternal recall at 12 months was 98·3 % (95 % CI 97·4, 99·0), specificity 70·0 % (95 % CI 68·2, 71·7), PPV 55·8 % (95 % CI 53·4, 58·1), NPV 99·1 % (95 % CI 98·6, 99·5) and accuracy 77·9 % (95 % CI 76·6, 79·2). When the analyses were stratified by maternal and infant characteristics, the sensitivity remained around 98 %, and the specificity ranged from 64·4 to 81·8 %. CONCLUSIONS: EBF recalled at the end of the first year of infant's life is a valid measure to be used in epidemiological investigations.

The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction.

The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subångström length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.

Etiology-Specific Mineralization Patterns in Patients with Labyrinthitis Ossificans.

BACKGROUND AND PURPOSE: Our aim was to identify whether specific patterns of ossification in labyrinthitis ossificans are associated with the known risk factors. Labyrinthitis ossificans has been described as sequela of prior temporal bone trauma, prior infection, and other disorders including sickle cell disease. Specific patterns of mineralization in the membranous labyrinth associated with these risk factors has not been previously described. MATERIALS AND METHODS: This was a retrospective study evaluating temporal bone CT scans at our institution from November 2005 to May 2018 in patients with labyrinthitis ossificans. Membranous labyrinthine structures evaluated for ossification included the following: basal, middle, and apical cochlear turns; lateral, posterior, and superior semicircular canals; and the vestibule for both ears in all patients. These structures were assigned a severity score, 0-4, based on degree of mineralization. Clinical records were reviewed for potential labyrinthitis ossificans risk factors. Basic descriptive statistics and a mixed model were used to correlate the degree and patterns of ossification with clinical history. RESULTS: Forty-four patients (58 ears) with labyrinthitis ossificans were identified and evaluated. The most common risk factors were chronic otomastoiditis (n = 18), temporal bone surgery (n = 9), temporal bone trauma (n = 6), sickle cell disease (n = 5), and meningitis (n = 4). For all etiologies, the semicircular canals were most severely affected, and the vestibule was the least. In patients with prior temporal bone surgery, significantly greater mineralization was seen in the basal turn of the cochlea (P = .027), the vestibule (P = .001), and semicircular canals (P < .001-.008). No significant pattern was identified in patients with meningitis, sickle cell disease, or trauma. CONCLUSIONS: Significant patterns of mineralization in labyrinthitis ossificans were observed in patients with prior temporal bone surgery. For all etiologies, the semicircular canals were most severely affected. No significant mineralization pattern was observed in patients with chronic otomastoiditis, meningitis, sickle cell disease, or prior temporal bone trauma.

Falls in anaemic and non-anaemic hospitalized elderly patients in 2012-2016 - mutual relationships.

Although falls are more prevalent as ageing proceeds, it cannot be assumed that they happen due to ageing alone. The retrospective cohort study of data was targeted to make an analysis of prevalence of falls in anaemic patients in comparison to the non-anaemic elderly admitted to the acute geriatric department and evaluation of pertinent influence of age, gender and immobility on occurrence of falls. During the considered period of four years (2012-2016) the authors treated 9 363 elderly patients aged 79,9±8,6 years (in the majority of them 65+ years). Among them there were 8 809 non-anaemic and subgroup of 551 old anaemic patients (aged 81±7 years) with decreased haemoglobin (<110 g/l). Falls at hospital admission in average was present in 1 766 non-anaemic persons (20%) in comparison to 380 falls among anaemic patients (68,6%). Prevalence in anaemic subgroup is statistically significant higher (p<0,005). Also relation between falls and age, ADL and MMSE test and mobility is highly statistically significant (p<0,001). Meaningfully higher is occurrence of repeated falls in the anaemic subgroup in comparison to the non-anaemic one (41,2 vs 1,7%). The occurrence of falls in female gender in comparison to men is statistically significant higher in non-anaemic patients, not in anaemic group. Authors emphasize that anaemia appears to us as significant risk factor for falls in the elderly.

[Modified Salter innominate osteotomy in adults]. / Modifizierte Salter-Innominatum-Osteotomie für Erwachsene.

OBJECTIVE: The dysplastic acetabulum is shifted three-dimensionally outwards and forwards. INDICATIONS: Symptomatic residual hip dysplasias and hip subluxations in skeletally mature patients up to the age of 50 years. Sharp's acetabular up to 60°, as an exception above 60°. CONTRAINDICATIONS: Acetabular retroversion. Radiographic joint space at the lateral acetabular edge that is less than half the normal thickness for the patient's age. Relative contraindication: Elongated leg on the affected side. SURGICAL TECHNIQUE: Ilioinguinal approach in a supine position. Division of the innominate bone. Pivoting the distal osteotomy fragment outwards and forwards with the aid of the Salter maneuver. Fixing the fragments with a guide wire. Final correction of the osteotomy fragments. Force fitting of a dovetail grooved, wedge-shaped bone graft. Insertion of a cannulated compression screw and two further threaded rods. Wound closure. POSTOPERATIVE MANAGEMENT: Unloaded 3­point walking for 4 weeks. Increasing weight bearing from week 4. Full weight bearing from week 10-12. RESULTS: A total of 45 consecutive patients (7 men, 38 women, 49 hips) underwent surgery. Average age at surgery was 27.6 years. The Sharp acetabular angle improved from preoperatively 45.7°â€¯± 4.2° by 13.8° to 32.0°â€¯± 6.4°; the Wiberg (LCE) angle increased from 15.4°â€¯± 9.3° by 19.5° to 34.9°â€¯± 10° postoperatively. The anterior center edge (ACE) angle increased from 28.9°â€¯± 10.4° by 8.6°â€¯± 2.3° to 37.5°â€¯± 8.1°. Complications requiring surgical intervention occurred in 7 patients.

Automatic microscopic detection of mycobacteria in sputum: a proof-of-concept.

The laboratory diagnosis of lung mycobacterioses including tuberculosis comprises the microscopic examination of sputum smear after appropriate staining such as Ziehl-Neelsen staining to observe acid-fast bacilli. This standard procedure is operator-dependant and its sensitivity depends on the duration of observation. We developed and evaluated an operator-independent microscopic examination of sputum smears for the automated detection and enumeration of acid-fast bacilli using a ZEISS Axio Scan.Z1 microscope. The sensitivity, specificity, positive predictive value, negative predictive values and accuracy were calculated using standard formulations by comparison with standard microscopic examination. After in-house parameterization of the automatic microscope and counting software, the limit of detection evaluated by seeding negative sputa with Mycobacterium bovis BCG or Mycobacterium tuberculosis H37Rv (100-105 bacilli/mL) was of 102 bacilli/mL of sputum with a 100% positivity rate. Then, the evaluation of 93 sputum specimens including 34 smear-positive and 59 smear-negative specimens yielded a sensitivity of 97.06% [84.67-99.93%], a specificity of 86.44% [73.01-92.78%]. Up to 100 smear slides could be stocked for reading in the microscope magazine and results are exportable into the laboratory information system. Based on these preliminary results, we are implanting this automatic protocol in the routine workflow so that only smears detected positive by automatic microscopy are confirmed by standard microscopic examination.

Next generation sequencing reveals packaging of host RNAs by brome mosaic virus.

Although RNA viruses evolved the mechanisms of specific encapsidation, miss-packaging of cellular RNAs has been reported in such RNA virus systems as flock house virus or cucumber necrosis virus. To find out if brome mosaic virus (BMV), a tripartite RNA virus, can package cellular RNAs, BMV was propagated in barley and in Nicotiana benthamiana hosts, purified by cesium chloride (CsCl) gradient ultracentrifugation followed by nuclease treatment to remove any contaminating cellular (host) RNAs. The extracted virion RNA was then sequenced by using next-generation sequencing (NGS RNA-Seq) with the Illumina protocol. Bioinformatic analysis revealed the content of host RNAs ranging from 0.07% for BMV extracted from barley to 0.10% for the virus extracted from N. benthamiana. The viruses from two sources appeared to co-encapsidate different patterns of host-RNAs, including ribosomal RNAs (rRNAs), messenger RNAs (mRNAs) but also mitochondrial and plastid RNAs and, interestingly, transposable elements, both transposons and retrotransposons. Our data reveal that BMV virions can carry host RNAs, having a potential to mediate horizontal gene transfer (HGT) in plants.

Effect of age and dietary carbohydrate profiles on glucose and insulin dynamics in horses.

BACKGROUND: Glucose and insulin dynamics may be different in adult and aged horses. OBJECTIVES: To determine the effects of age and dietary carbohydrates on glucose and insulin dynamics in healthy horses. STUDY DESIGN: Balanced Latin square with four isocaloric diets: CONTROL (hay plus restricted-starch-and-sugar fortified pellets), STARCH (control plus kibbled corn), FIBER (control plus unmolassed sugar beet pulp/soybean hull pellets) and SUGAR (control plus dextrose powder). METHODS: A total of 16 healthy Thoroughbreds and Standardbreds divided into two age groups: ADULT (8.8 ± 2.9 years; n = 8) and AGED (20.6 ± 2.1 years; n = 8). Following dietary adaptation, horses underwent an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT), modified oral sugar test (OST) and dietary meal challenge. Outcome variables included: insulin sensitivity (SI), disposition index (DI), glucose effectiveness (Sg) and acute insulin response to glucose (AIRg) from the FSIGTT; peak glucose, peak insulin, time to peak, area under the curve for glucose (AUCg) and insulin (AUCi) from the OST and dietary meal challenge. Data were analyzed using multivariable linear mixed regression modelling. RESULTS: AIRg was higher in AGED (mean [95% confidence interval]; 582.0 [455.0-709.0]) vs. ADULT (358.0 [224.0-491.0]; P = 0.03). ADULT and AGED horses had a higher SI on STARCH (adult: 3.3 [2.3-4.2]; aged: 2.8 [1.9-3.7]) and SUGAR (adult: 3.4 [2.5-4.3]; aged: 4.0 [3.1-4.9]) diets compared with CONTROL (adult: 2.0 [1.1-2.9], P = 0.029 (starch), P = 0.009 (sugar); aged: 1.4 [0.5-2.2], P = 0.009 (starch), P < 0.001 (sugar)). Feeding a STARCH (adult: 21581.0 [15029.0-28133.0]; aged: 35205.0 [29194.0-41216.0]) or SUGAR (adult: 26050.0 [19885.0-32215.0]; aged: 25720.0 [19770.0-31670.0]) meal resulted in postprandial hyperinsulinaemia (AUCi). MAIN LIMITATIONS: Study cohort contained two insulin-sensitive breeds and no insulin-resistant breeds. CONCLUSIONS: Age and diet should be considered when evaluating glucose and insulin dynamics.

Effect of dietary carbohydrates and time of year on ACTH and cortisol concentrations in adult and aged horses.

Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20.6 ± 2.1 yr; n = 8). None of the horses showed clinical signs (hypertrichosis, regional adiposity, skeletal muscle atrophy, lethargy) of pituitary pars intermedia dysfunction. Horses were randomly assigned to groups of 4, blocked for age, and fed grass hay plus 4 isocaloric concentrate diets (control, starch-rich, fiber-rich, and sugar-rich) using a balanced Latin square design. Data were analyzed using a multivariable linear mixed regression model. Baseline ACTH was significantly higher in aged horses (mean ± standard error of the mean; 60.0 ± 10.7 pg/mL) adapted to the starch-rich diet compared to adult horses (15.7 ± 12.0 pg/mL) on the same diet (P = 0.017). After controlling for age and diet, baseline ACTH concentrations were significantly increased in October (57.7 ± 7.1 pg/mL) compared to March (13.2 ± 7.1 pg/mL; P < 0.001), May (12.4 ± 7.1 pg/mL; P < 0.001), and August (24.2 ± 7.1 pg/mL; P < 0.001), whereas post-TRH ACTH was higher in August (376.6 ± 57.6 pg/mL) and October (370.9 ± 57.5 pg/mL) compared to March (101.9 ± 57.3 pg/mL; P < 0.001) and May (74.5 ± 57.1 pg/mL; P < 0.001). Aged horses had significantly higher post-dexamethasone cortisol on the starch-rich diet (0.6 ± 0.1 µg/dL) compared to the sugar-rich diet (0.2 ± 0.1 µg/dL; P = 0.021). Post-dexamethasone cortisol was significantly higher in October (0.6 ± 0.1 µg/dL) compared to March (0.3 ± 0.1 µg/dL; P = 0.005), May (0.2 ± 0.1 µg/dL; P < 0.001), and August (0.3 ± 0.1 µg/dL; P = 0.004). Breed did not influence ACTH or cortisol measurements. In conclusion, in addition to age and time of year, diet is a potential confounder as animals on a starch-rich diet may be incorrectly diagnosed with pituitary pars intermedia dysfunction.

Pediatric stroke related to Lyme neuroborreliosis: Data from the Swiss NeuroPaediatric Stroke Registry and literature review.

BACKGROUND: Cerebrovascular complications of Lyme neuroborreliosis (LNB) are poorly documented in the paediatric population. METHODS: We performed a retrospective analysis from prospectively registered cases of acute ischemic stroke (AIS) from the Swiss NeuroPaediatric Stroke Registry (SNPSR) from 2000 to 2015. Only cases with serologically confirmed LNB were included. In addition, a literature review on paediatric stroke cases secondary to Lyme neuroborreliosis in the same time frame was performed. RESULTS: 4 children out of 229 children with arterial ischemic childhood stroke and serologically confirmed LNB were identified in the SNPSR giving a global incidence of 1.7%. Median age was 9.9 years. A prior history of tick bites or erythema migrans (EM) was reported in two cases. Clinical presenting signs were suggestive of acute cerebellar/brainstem dysfunction. On imaging, three children demonstrated a stroke in the distribution of the posterior inferior cerebellar artery. The remaining fourth child had a "stroke-like" picture with scattered white matter lesions and a multifocal vasculitis with prominent basilar artery involvement. Lymphocytic pleocytosis as well as intrathecal synthesis of Borrelia burgdorferi antibodies were typical biological features. Acute intravenous third generation cephalosporins proved to be effective with rapid improvement in all patients. No child had recurrent stroke. Data from the literature concerning eight patients gave similar results, with prominent posterior circulation stroke, multifocal vasculitis and abnormal CSF as distinctive features. CONCLUSIONS: Lyme Neuroborreliosis accounts for a small proportion of paediatric stroke even in an endemic country. The strong predilection towards posterior cerebral circulation with clinical occurrence of brainstem signs associated with meningeal symptoms and CSF lymphocytosis are suggestive features that should rapidly point to the diagnosis. This can be confirmed by appropriate serological testing in the serum and CSF. Clinicians must be aware of this rare neurological complication of Lyme disease that demands specific antibiotic treatment.