Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366

Folate and choline are methyl donor nutrients that may play a role in fetal brain development. Animal studies have reported that prenatal folate and choline supplementation are associated with better cognitive outcomes in offspring and that these nutrients may interact and affect brain development. Human studies that have investigated associations between maternal prenatal folate or choline levels and neurodevelopmental outcomes have reported contradictory findings and no human studies have examined the potential interactive effect of folate and choline on children’s neurodevelopment. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall in 309 women in the APrON cohort. At 3–5 years of age, their children’s neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence – Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children – Second Edition. Adjusted regressions revealed no associations between maternal folate and choline levels during pregnancy and most of the child outcomes. On the Dimensional Change Card Sort, an executive function task, there was an interaction effect; at high levels of choline intake (i.e., 1 SD above the mean; 223.03 mg/day), higher maternal folate status was associated with decreased odds of receiving a passing score (β = −0.44; 95%CI −0.81, −0.06). In conclusion, maternal folate status and choline intake during the second trimester of pregnancy were not associated with children’s intelligence, language, memory, or motor outcomes at 3–4 years of age; however, their interaction may have an influence children’s executive functions.

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here, we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, altered glucose tolerance, and coagulopathy; whereas male F1 offspring exhibited altered glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity (indicative of macrophage presence) and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in the offspring, and that the effects of inflammation may cross generations. Our findings provide evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation.

To assess the burden of respiratory virus coinfections with severe acute respiratory coronavirus virus 2 (SARS-CoV-2), this study reviewed 4,818 specimens positive for SARS-CoV-2 and tested using respiratory virus multiplex testing. Coinfections with SARS-CoV-2 were uncommon (2.8%), with enterovirus or rhinovirus as the most prevalent target (88.1%). Respiratory virus coinfection with SARS-CoV-2 remains low 1 year into the coronavirus disease 2019 (COVID-19) pandemic.

Whole-grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known about its health effects. The present study investigated the effect of a pearl millet porridge (PMP) compared with a well-known Scottish oats porridge (SOP) on glycaemic, gastrointestinal, hormonal and appetitive responses. In a randomised, two-way crossover trial, twenty-six healthy participants consumed two isoenergetic/isovolumetric PMP or SOP breakfast meals, served with a drink of water. Blood samples for glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY, gastric volumes and appetite ratings were collected 2 h postprandially, followed by an ad libitum meal and food intake records for the remainder of the day. The incremental AUC (iAUC2h) for blood glucose was not significantly different between the porridges (P > 0·05). The iAUC2h for gastric volume was larger for PMP compared with SOP (P = 0·045). The iAUC2h for GIP concentration was significantly lower for PMP compared with SOP (P = 0·001). Other hormones and appetite responses were similar between meals. In conclusion, the present study reports, for the first time, data on glycaemic and physiological responses to a pearl millet breakfast, showing that this ancient grain could represent a sustainable alternative with health-promoting characteristics comparable with oats. GIP is an incretin hormone linked to TAG absorption in adipose tissue; therefore, the lower GIP response for PMP may be an added health benefit.

Background: Gross total resection of pediatric posterior fossa tumors is paramount towards improving progression-free survival.

Fluorescein accumulates in tumoral tissue, where the blood-brain barrier is disrupted. It can therefore potentially aid in differentiating tumoral versus normal tissue. We aimed to evaluate the efficacy of fluorescent-guidance (using fluorescein) towards the resection of a pediatric cerebellar tumor, as the index case at our institution using this technique. Methods: 5 mg/kg of IV fluorescein sodium was injected upon induction of general anesthesia. During tumor resection, a yellow 560-nm filter (Kinevo microscope, Zeiss) was employed for fluorescent-guidance. The extent of resection was assessed via post-operative MRI. Results: There were no adverse side effects experienced by the patient. Tumoral material was clearly visualized under the yellow 560-nm filter, allowing for satisfactory gross total resection of the lesion (confirmed on post-operative MRI). Preliminary pathology was consistent with medulloblastoma. Conclusions: Fluorescent-guided resection of pediatric posterior fossa tumors appears to be a safe and useful adjunct for gross total resection of these lesions. To the best of our knowledge, this is the first reported case in Canada wherein IV fluorescein was used under a yellow 560-nm filter for resection of a posterior fossa medulloblastoma in a child.

Introduction: Although acute gastroenteritis is an extremely common childhood illness, there is a paucity of literature characterizing the associated pain and its management. Our primary objective was to quantify the pain experienced by children with acute gastroenteritis in the 24-hours prior to emergency department (ED) presentation. Secondary objectives included describing maximum pain, analgesic use, discharge recommendations, and factors that influenced analgesic use in the ED. Methods: Study participants were recruited into this prospective cohort study by the Alberta Provincial Pediatric EnTeric Infection TEam between January 2014 and September 2017. This study was conducted at two Canadian pediatric EDs; the Alberta Children's Hospital (Calgary) and the Stollery Children's Hospital (Edmonton). Eligibility criteria included < 18 years of age, acute gastroenteritis (□ 3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration □ 7 days. The primary study outcome, caregiver-reported maximum pain in the 24-hours prior to presentation, was assessed using the 11-point Verbal Numerical Rating Scale. Results: We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4); 45.8% (979/2136) female. In the 24-hours prior to enrolment, 28.6% (610/2136) of caregivers reported that their child experienced moderate (4-6) and 46.2% (986/2136) severe (7-10) pain in the preceding 24-hours. During the emergency visit, 31.1% (664/2136) described pain as moderate and 26.7% (571/2136) as severe. In the ED, analgesia was provided to 21.2% (452/2131) of children. The most commonly administered analgesics in the ED were ibuprofen (68.1%, 308/452) and acetaminophen (43.4%, 196/452); at home, acetaminophen was most commonly administered (77.7%, 700/901), followed by ibuprofen (37.5%, 338/901). Factors associated with analgesia use in the ED were greater pain scores during the visit, having a primary-care physician, shorter illness duration, fewer diarrheal episodes, presence of fever and hospitalization. Conclusion: Although children presenting to the ED with acute gastroenteritis experience moderate to severe pain, both prior to and during their emergency visit, analgesic use is limited. Future research should focus on appropriate pain management through the development of effective and safe pain treatment plans.

A novel laboratory experimental design is described that will investigate the processing of dust grains in astrophysical shocks. Dust is a ubiquitous ingredient in the interstellar medium (ISM) of galaxies; however, its evolutionary cycle is still poorly understood. Especially shrouded in mystery is the efficiency of grain destruction by astrophysical shocks generated by expanding supernova remnants. While the evolution of these remnants is fairly well understood, the grain destruction efficiency in these shocks is largely unknown. The experiments described herein will fill this knowledge gap by studying the dust destruction efficiencies for shock velocities in the range ${\sim}10{-}30~\text{km}/\text{s}$ ($\unicode[STIX]{x03BC}\text{m}/\text{ns}$), at which most of the grain destruction and processing in the ISM takes place. The experiments focus on the study of grain–grain collisions by accelerating small (${\sim}1~\unicode[STIX]{x03BC}\text{m}$) dust particles into a large (${\sim}5{-}10~\unicode[STIX]{x03BC}\text{m}$ diameter) population; this simulates the astrophysical system well in that the more numerous, small grains impact and collide with the large population. Facilities that combine the versatility of high-power optical lasers with the diagnostic capabilities of X-ray free-electron lasers, e.g., the Matter in Extreme Conditions instrument at the SLAC National Accelerator Laboratory, provide an ideal laboratory environment to create and diagnose dust destruction by astrophysically relevant shocks at the micron scale.

The 2 km × 5 m Newmains Dyke in the Scottish Southern Uplands consists mainly of primitive (mg number > 70), at least partly mantle-derived lamprophyre (vogesite spessartite, SiO2 50–60%), with hornblende-pyroxene-rich cumulates (SiO2 < 50%) and small amounts of quartz syenitic to granite residua (60–73% SiO2). The lamprophyres and cumulates yield an Rb-Sr whole-rock isochron age of 395±9 Ma (MSWD 2.0), and (87Sr/86Sr)i 0.70514±5—identical values to the nearby Criffell granitic pluton. After some 65% hornblende + clinopyroxene fractionation of parent lamprophyre magma, a volatile phase separated and metasomatically enriched the country rock greywackes in K, Ba, and Rb. The remaining quartz syenitic liquids became contaminated by 87Sr from these greywackes, which have a mean (87Sr/86Sr)395 value of 0.70789±114. Further fractionation of the contaminated syenitic liquids gave the granitic rocks, which have (87Sr/86Sr)395 values of 0.7056–64. The dyke appears to demonstrate in situ some of the hidden processes previously invoked to explain the evolution of the Criffell pluton itself.

Background: Epilepsy/seizure awareness is improving across Canada. With the formation of a Comprehensive Epilepsy Program in Manitoba (including a new Pediatric Epilepsy Monitoring Unit), a provincial strategy has been proposed outlining a path towards improved access to epilepsy care. We now sought to qualify the current state of clinician knowledge and comfort towards diagnosis and management of this condition. Methods: A qualitative online survey, comprised of 36 short-answer questions, was delivered to primary care and specialist physicians in Manitoba. Results:108 subjects responded, across varying medical disciplines. 101 (93.5%) have previously managed epilepsy patients, and 87 (80.6%) have previously ordered an EEG. A total of 63 (59.4%) have referred to a neurologist, with a lower proportion (30, 28.3%) referring specifically to an epileptologist. 36 respondents (33.3%) have heard of the ILAE guidelines, with 43 (63.2%) reporting refractory epilepsy to be -defined by the failure of 3 (or more) medications. 61 (56.5%) were unaware of invasive EEG techniques. Most (85, 78.7%) understood a role for surgery in treating epilepsy, with 12 (11.1%) unaware of surgical therapies beyond VNS. Conclusions: SESAME successfully identified strong awareness towards epilepsy, with small lapses in knowledge that will benefit from a formal provincial-wide educational curriculum.

Weed scientists regularly attend conferences, symposiums, and workshops to communicate with colleagues about their current weed research programs. Communication of research can be hindered by poor visual aids. Computer programs, film recorders, and color printers have greatly increased the ease of visual aid production but have also increased the opportunity to prepare incomprehensible presentations. The size of the text, the amount of information presented, and the contrast between the text color and background color are the most important factors that affect the legibility of visual aids. Text, tables, and graphs should be short, simple, and legible. Computers and film recorders are not essential to produce good visual aids. The greatest assets in the production of visual aids are common sense, familiarity with the production equipment, sufficient preparation time, and critical assessment of the visual aids well in advance of the presentation date.

Dodder is a serious parasitic weed in the crops in which it is a problem (particularly citrus). Alternaria destruens is the active ingredient in a registered bioherbicide for control of dodder species. In greenhouse studies, the treatments applied to citrus parasitized with field dodder were a nontreated control; oil at 7.5% v/v in water; ammonium sulfate at 0.125% w/v in water; glyphosate at 0.02 kg ae/L; A. destruens at 1.8 × 1010 spores/L; A. destruens (1.8 × 1010 spores/L) + oil at 7.5% v/v in water; and a mixture of A. destruens (1.8 × 1010 spores/L) + oil at 7.5% v/v in water + glyphosate at 0.02 kg ae/L + ammonium sulfate 0.125% w/v (the mixture treatment). The highest disease or damage severity rating out of all treatments, measured as the area under the disease or damage progress curve (AUDPC), was obtained for the mixture treatment. By 35 d after treatment, all field dodder plants that received the mixture treatment were dead but the host plant, citrus, was not. These results indicate the feasibility of integrating glyphosate, ammonium sulfate, and A. destruens to manage dodder.

The importance of PRE herbicide applications in cotton has increased since the evolution of glyphosate-resistant (GR) Palmer amaranth. Cotton producers are relying on residual herbicides for control of Palmer amaranth, as POST options are limited or ineffective. S-Metolachlor, acetochlor, fomesafen, and dicamba all provide PRE control of Palmer amaranth; however, little is known about the effect of irrigation rate on incorporation and herbicidal efficacy. In 2015, an experiment was conducted on fine sand and loamy sand soils to evaluate the influence of irrigation volume (0.0 to 12.7 mm ha−1) on Palmer amaranth control with PRE herbicides. Irrigation volume after herbicide application was significant for both S-metolachlor and acetochlor. Efficacy of S-metolachlor was greatest in plots receiving 6.4 and 12.7 mm of irrigation where Palmer amaranth biomass was reduced to 4 and 2% of a nontreated control (NTC), respectively, compared with 61% in plots with the 0-mm irrigation treatment. Palmer amaranth control by acetochlor incorporated at 3.2- to 12.7-mm irrigation did not differ but did reduce Palmer amaranth biomass compared with the 1.6-mm irrigation rate. Irrigation volume was not significant for the soil incorporation of fomesafen or dicamba. Across all herbicides, fomesafen-treated plots provided the most consistent control of Palmer amaranth, reducing its biomass to < 3% of NTC at all irrigation rates. Dicamba provided the least and most inconsistent control of Palmer amaranth, producing 17 to 51% of NTC biomass.