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Background: There are few published reports on the safety and efficacy of stereoelectroencephalography (SEEG) in the presurgical evaluation of pediatric drug-resistant epilepsy. Our objective was to describe institutional experience with pediatric SEEG in terms of (1) insertional complications, (2) identification of the epileptogenic zone and (3) seizure outcome following SEEG-tailored resections. Methods: Retrospective review of 29 patients pediatric drug resistant epilepsy patients who underwent presurgical SEEG between 2005 – 2018. Results: 29 pediatric SEEG patients (15 male; 12.4 ± 4.6 years old) were included in this study with mean follow-up of 6.0 ± 4.1 years. SEEG-related complications occurred in 1/29 (3%)—neurogenic pulmonary edema. A total of 190 multi-contact electrodes (mean of 7.0 ± 2.5per patient) were implanted across 30 insertions which captured 437 electrographic seizures (mean 17.5 ± 27.6 per patient). The most common rationale for SEEG was normal MRI with surface EEG that failed to identify the EZ (16/29; 55%). SEEG-tailored resections were performed in 24/29 (83%). Engel I outcome was achieved following resections in 19/24 cases (79%) with 5.9 ± 4.0 years of post-operative follow-up. Conclusions: Stereoelectroencephalography in presurgical evaluation of pediatric drug-resistant epilepsy is a safe and effective way to identify the epileptogenic zone permitting SEEG-tailored resection.
Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.
Background: Temporal lobe epilepsy (TLE) accounts for approximately 20% of pediatric epilepsy cases. Of those, many are considered medically intractable and require surgical interventions. In this study, we hypothesized that mesial temporal sclerosis (MTS) was less common in patients who had undergone surgery for intractable pediatric TLE than in adult series. We further hypothesized that there was a radiological and pathological discordance in identifying the cause of pediatric TLE. Methods: We retrospectively reviewed the charts of pediatric patients with TLE who had undergone surgical treatments as part of the University of Alberta’s Comprehensive Epilepsy Program between 1988 and 2018. Along with preoperative magnetic resonance imaging (MRI) reports, post-surgical pathology results and seizure outcomes were studied Results: Of the 83 pediatric patients who had undergone temporal lobe epilepsy surgery, 28% had tumors, 22% had dual pathologies, 18% had MTS, 11% had focal cortical dysplasia, and 22% had other pathologies. In addition, for 36% of these patients, discordance between their pre-surgical MRI reports and post-surgical pathology reports were found. Conclusions: This was one of the largest retrospective cohort studies of pediatric patients who had undergone surgery for intractable TLE. This study showed that tumors, and not MTS, were the most common pathology in surgical pediatric TLE.
Background: Selective amygdalohippocampectomy (SAH) is a surgical option in well-selected cases of pediatric medically refractory temporal lobe epilepsy (TLE). The objective of this study was to compare the surgical outcome and the rate of reoperation for ongoing or recurrent seizures between SAH and anterior temporal lobectomy (ATL) in pediatric TLE. Methods: Retrospective review of 78 pediatric intractable TLE patients referred to the Comprehensive Epilepsy Program at our institution between 1988 and 2015 treated initially with either a trans-middle temporal gyrus SAH (19) or ATL (59). Patients underwent baseline long-term video electroencephalography and 1.5-Tesla MRI. Neuropsychological testing was performed preoperatively and 12-months postoperatively (including reoperations). Results: The mean follow-up was 64 months (range, 12-186 months). The average age at initial surgery was 10.6±5 years with an average delay of 5.7±4 years between seizure onset and surgery. Ultimately 78% were seizure-free (61/78) at most recent follow-up. Seizure freedom after initial surgical treatment was achieved in 81% of patients who underwent ATL (48 patients) versus 42% in SAH (8 patients; p<0.001). Of patients with ongoing disabling seizures following SAH, reoperation (ATL) was offered in 8 resulting in seizure freedom in 63%, without interval neuropsychological decline. Conclusions: SAH amongst well-selected pediatric TLE results in significantly worse seizure control compared with ATL.
Background: Cerebral palsy (CP) is a debilitating disorder (1). Based on neuromotor impairments it is divided to spastic, dyskinetic and ataxic types (2). Inborn Errors of Metabolism (IEMs), monogenic and chromosomal disorders mimic CP (3). We aimed to identify causal genetic variants in patients with atypical dyskinetic CP in whom known IEMs were ruled out. Timely diagnosis is essential for proper management, especially in conditions that mimic CP and are treatable. Methods: We enrolled 23 patients with unexplained atypical dyskinetic CP, for whole exome sequencing. Variants were filtered against public and in-house databases to identify variants predicted as damaging (in silico tools and ACMG criteria). We applied a virtual gene panel of known and suspected CP and movement disorder genes and investigated each sample. Results: The participants presented with symptoms including: spasticity, dystonia, choera-athetosis, ataxia and cognitive delays. We identified 23 diagnoses: 13 dominant,6 recessive and 4 X-linked. 12 patients had movement disorders. In 4, the diagnoses enabled targeted treatment (neurotransmitter supplements in Unverricht Lundborg diseases (CSTB) and PAK3 deficiency, deep brain stimulation in GNAO1 deficiency, medical diet in Glutaric Aciduria (GCDH). Conclusions: Whole Exome Sequencing contributes to establishing diagnosis in patients with atypical dyskinetic CP resulting in precision medicine and improved health outcomes.
The galactopoietic effect of growth hormone (GH) in lactating ruminants is well established; however the mechanisms that mediate these effects are not well understood. The first objective of this study was to determine the effect of GH on the synthesis of the major casein and whey proteins. The second objective was to identify the genes and pathways that may be involved in mediating the effect of GH on milk synthesis. A single subcutaneous injection of a commercially available slow release formulation of GH (Lactatropin®), or physiological saline solution (control) was administered to non-pregnant dairy cows (n=4/group) in mid-late lactation. Milk samples were collected for composition analysis and mammary lobulo-alveolar tissue was collected postmortem 6 days post injection. Gene expression profiles were evaluated using either a 22 000 bovine complementary DNA microarray or quantitative PCR (qPCR), and microarrays were validated by qPCR. The yield of all the major casein and whey proteins was increased 32% to 41% in GH-treated cows, with the exception of α-lactalbumin yield which was elevated by 70% relative to controls. Treatment with GH treatment tended to increase the concentration of α-lactalbumin but had no effect on the concentration of any of the major milk proteins. Messenger RNA (mRNA) abundance of the major whey and casein genes, with the exception of α-s2-casein, was increased in response to GH compared with controls, which is consistent with the positive effect of GH on milk production. Treatment with GH treatment influenced the mRNA abundance of genes involved in cell growth and proliferation, transcriptional and translational regulation, actin cytoskeleton signalling, lipid metabolism and cell death. This study has provided new insights into the cell signalling that may be involved in mediating the effect of GH on milk production in the mammary gland of lactating dairy cows.
Background: Dysembryoblastic neuroepithelial tumors (DNETs) are benign tumors of the cerebral cortex that most commonly occur in children or young adults. Seizures are a frequent presenting feature, with an incidence of 80-100%, and are often an indication for surgical resection. Methods: We performed a retrospective chart review of children with DNETs who underwent epilepsy surgery between 1998 and 2014. Results: A total of 12 subjects were identified (6 males, 6 females), all of whom had seizures prior to surgical resection. Of these patients, 1 had infantile spasms, 2 had simple partial seizures and 10 had complex partial seizures. Tumors were located in the temporal (n=7), frontal (n=3) or parietal (n=2) cortex. These patients went on to have surgery on average 15 months after seizure onset, 3 had incomplete resections. At an average follow up of 6 years 4 months, all patients were class 1 on Engel’s Classification. All but one subject with rare non-disabling seizures were seizure free, with only 6 on medication. Follow up MR imaging revealed tumor recurrence in 1 subject. Conclusions: Despite differing seizure seminology and tumor location, surgical resection of these low-grade tumors resulted in excellent seizure outcome even in the setting of incomplete tumor resection.
Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone. Reported effects of exposure include changes in organ weight and gross structure, histology and gene and protein expression but these changes are not reflected in changes in reproductive performance under the conditions tested. These results illustrate the complexity of the effects of endocrine disrupting compounds on the reproductive axis, which make it difficult to extrapolate between, or even within, species. Effects of pollutant exposure on the thyroid gland, immune, cardiovascular and obesogenic systems have not been shown explicitly, in ruminants, but work on other species suggests that these systems can also be perturbed. It is concluded that exposure to a mixture of anthropogenic pollutants has significant effects on a wide variety of physiological systems, including the reproductive system. Although this physiological insult has not yet been shown to lead to a reduction in ruminant gross performance, there are already reports indicating that anthropogenic pollutant exposure can compromise several physiological systems and may pose a significant threat to both reproductive performance and welfare in the longer term. At present, many potential mechanisms of action for individual chemicals have been identified but knowledge of factors affecting the rate of tissue exposure and of the effects of combinations of chemicals on physiological systems is poor. Nevertheless, both are vital for the identification of risks to animal productivity and welfare.
Insulin plays an important role in regulating the partitioning of nutrients to the mammary gland, particularly in lactating ruminants fed concentrate-based diets. There is evidence that the nutritional status of the animals might also affect their response to insulin. This is largely untested in early lactating ruminants fed fresh forage. To investigate nutritional effects on insulin response, 12 lactating sheep, housed indoors, were allocated to one of two treatment groups (hyperinsulinaemic euglycaemic clamp (HEC) or control) in a randomised block design and fed perennial ryegrass (Lolium perenne)/white clover (Trifolium repens) pasture. Mammary amino acid (AA) net uptake from plasma and utilisation for milk protein synthesis was measured during the 4th day of the HEC using arterio–venous concentration differences, and 1-13C-leucine was used to estimate whole body and mammary gland leucine kinetics. There was no change in feed intake, milk protein output and mammary blood flow during the HEC (P > 0.1). The HEC decreased (P < 0.1) the arterial concentrations of all essential AA (EAA) except histidine. The mammary net uptake of some EAA (isoleucine, leucine, methionine and phenylalanine) was reduced by the HEC (P < 0.1). Leucine oxidation in the mammary gland was not altered during the HEC (P > 0.1) but mammary protein synthesis was reduced by the HEC (P < 0.05). These results show that sheep mammary gland can adapt to changing AA precursor supply to maintain milk protein production during early lactation, when fed fresh forage. How this occurs remains unclear, and this area deserves further study.
The effects of an established Trichostrongylus colubriformis infection on amino acid (AA) absorption from the small intestine and their availability to other tissues were determined in lambs 48 days post infection. The lambs were fed fresh Lucerne (Medicago sativa; ∼800 g dry matter (DM)/day) and dosed with 6000 L3 T. colubriformis larvae for 6 days (n = 5) or kept as parasite free controls (n = 6). Faecal egg production was monitored every second day from day 22 to day 48. A nitrogen (N) balance was conducted on days 35 to 43 after infection, and digesta flow and AA concentration measurements were made on day 44. On day 48 after infection, blood was continuously collected from the mesenteric artery and vein, plasma harvested and AA concentrations measured. Faecal egg production peaked on the 26th day after infection (P < 0.001) and intestinal worm burdens on day 48 were greater (P < 0.001) in the infected lambs. Feed intake and liveweight gain were similar (P > 0.10) between control and infected lambs. Digestibility and flow of DM and N through the digestive tract were also unaffected (P > 0.10) by parasite infection. Despite a trend towards higher abomasal AA flux in the parasitised lambs (P < 0.10), apparent AA absorption from the small intestine and AA availability to other tissues were unaffected (P > 0.10) by infection. These results suggest that an established parasite infection had little effect on the intestinal absorption and availability of AA to other tissues in lambs fed fresh Lucerne.
Trans-10, cis-12 CLA is produced as an intermediary during the biohydrogenation of linoleic acid (C18:2 n-6) in the rumen and has been shown to be a potent inhibitor of milk fat synthesis in ruminants. The production of trans-10, cis-12 CLA in the rumen is affected by dietary concentrate: forage ratio (Kucuk et al., 2001), rumen pH and the amount and source of linoleic acid in the diet. However, the interaction between oil source, carbohydrate source and pH on the production of trans-10, cis-12 CLA is unclear (Beam et al., 2000). The objectives of the current study were to determine the effects of oil source, carbohydrate source and pH on the biohydrogenation of linoleic acid and production of trans-10, cis-12 CLA in vitro.
The distribution and abundance of free-living arthropods from soil and under stones were surveyed at the Cape Hallett ice-free area (ASPA No. 106), North Victoria Land, Antarctica. A total of 327 samples from 67 plots yielded 11 species of arthropods comprised of three Collembola: Cryptopygus cisantarcticus, Friesea grisea and Isotoma klovstadi and eight mites: Coccorhagidia gressitti, Eupodes wisei, Maudheimia petronia, Nanorchestes sp., Stereotydeus belli, S. punctatus, Tydeus setsukoae and T. wadei. Arthropods were absent from areas occupied by the large Adélie penguin colony. There was some distinction among arthropod communities of different habitats, with water and a lichen species (indicative of scree slope habitats) ranking as significant community predictors alongside spatial variables in a Canonical Correspondence Analysis. Recent changes to the management plan for ASPA No. 106 may need to be revisited as the recommended campsite is close to the area of greatest arthropod diversity.
The fly, Philornis downsi Dodge & Aitken, was first collected in 1964 on the Galápagos Islands and is now widespread across the archipelago. Virtually nothing is known about the behaviour and ecology of the fly as well as for the genus in general. Here, we describe all larval instars for the first time, and discuss infection intensity and impacts of parasitism on nestling survival of Darwin's finches. Adult P. downsi are non-parasitic free-living flies, whereas the larvae are obligate blood-feeding parasites on nestling birds. The larvae show a marked shift in their host site specificity – a novel finding for the genus Philornis: the first and early second larval instars live as agents of myiasis in finch nostrils and other tissues, while the older second and third instar larvae reside in the nest material and feed externally on the blood of nestlings, leading to blood losses in nestlings of 18–55%. Pupation occurs in the bottom layer of the nest. The combined effects of tissue damage by the endoparasitic instar larvae and anaemia by nest-dwelling haematophagous instar larvae account for the high nestling mortality (76%) due to Philornis parasitism. This represents the highest mortality by Philornis reported in the literature and emphasizes the extremely serious threat this parasite poses for the endemic passerine fauna of the Galápagos Islands.
Trans- 10, cis- 12 conjugated linoleic acid (CLA), a biohydrogenation intermediate produced in the rumen, is a potent inhibitor of milk fat synthesis. Data from a number of studies where various doses of trans -10, cis -12 CLA have been abomasally infused demonstrate a curvilinear relationship between the percent reduction in milk fat yield and both the dose of trans- 10, cis- 12 CLA infused and the milk fat content of trans- 10, cis- 12 CLA. In addition to a reduction in milk fat output, under some circumstances an increase in milk yield and milk protein output are observed. To date, there has been no examination of the effects of trans- 10, cis- 12 CLA on milk fat synthesis in lactating sheep. The current study was therefore designed to determine if trans- 10, cis- 12 CLA would inhibit milk fat synthesis in lactating sheep. In order to test the effectiveness of trans- 10, cis- 12 CLA in inhibiting milk fat synthesis we used a lipid-encapsulated trans- 10, cis- 12 CLA supplement (LE-CLA) as a means to provide the trans- 10, cis- 12 CLA isomer post-ruminally.
Few studies have assessed risk factors for sporadic cryptosporidiosis in industrialized countries, even though it may be numerically more common than outbreaks of disease. We carried out case-control studies assessing risk factors for sporadic disease in Melbourne and Adelaide, which have water supplies from different ends of the raw water spectrum. In addition to examining drinking water, we assessed several other exposures. 201 cases and 795 controls were recruited for Melbourne and 134 cases and 536 controls were recruited for Adelaide. Risk factors were similar for the two cities, with swimming in public pools and contact with a person with diarrhoea being most important. The consumption of plain tap water was not found to be associated with disease. This study emphasizes the need for regular public health messages to the public and swimming pool managers in an attempt to prevent sporadic cryptosporidiosis, as well as outbreaks of disease.
The effects of space allowance during transportation and duration of a mid-journey lairage period on measurements of stress, injury, dehydration, food restriction and rest in young calves were assessed during and after transport. Groups of calves were transported for two 9-h journeys (at a space allowance of either 0·375 or 0·475 m2 per calf) separated by a mid-journey lairage period of either 1 or 12 h. Non-transported calves were offered milk replacer and drinking water either at the usual times or only at the same times as the transported calves.
During transport, transported calves spent significantly less time lying down and had a greater plasma cortisol concentration than control calves. Under the driving conditions used, increased space allowance was not associated with greater injury or loss of stability. The duration of the mid-journey lairage was not an important factor; the shorter lairage time, giving the calves sufficient time to receive milk replacer but little opportunity to rest, had no major detrimental effects on the variables used to assess welfare. Although there was little evidence that transport affected immunological variables, there was some evidence that it adversely affected the health of the calves post transport.