We report the discovery of a bow-shock pulsar wind nebula (PWN), named Potoroo, and the detection of a young pulsar J1638$-$4713 that powers the nebula. We present a radio continuum study of the PWN based on 20-cm observations obtained from the Australian Square Kilometre Array Pathfinder (ASKAP) and MeerKAT. PSR J1638$-$4713 was identified using Parkes radio telescope observations at frequencies above 3 GHz. The pulsar has the second-highest dispersion measure of all known radio pulsars (1 553 pc cm$^{-3}$), a spin period of 65.74 ms and a spin-down luminosity of $\dot{E}=6.1\times10^{36}$ erg s$^{-1}$. The PWN has a cometary morphology and one of the greatest projected lengths among all the observed pulsar radio tails, measuring over 21 pc for an assumed distance of 10 kpc. The remarkably long tail and atypically steep radio spectral index are attributed to the interplay of a supernova reverse shock and the PWN. The originating supernova remnant is not known so far. We estimated the pulsar kick velocity to be in the range of 1 000–2 000 km s$^{-1}$ for ages between 23 and 10 kyr. The X-ray counterpart found in Chandra data, CXOU J163802.6$-$471358, shows the same tail morphology as the radio source but is shorter by a factor of 10. The peak of the X-ray emission is offset from the peak of the radio total intensity (Stokes $\rm I$) emission by approximately 4.7$^{\prime\prime}$, but coincides well with circularly polarised (Stokes $\rm V$) emission. No infrared counterpart was found.

Background: The advent of real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD) facilitating earlier recognition of affected patients. Recognizing this, we evaluated the performance of clinical features and diagnostic tests for CJD in the modern era. Methods: Clinical data were extracted from the electronic medical records of 115 patients with probable or definite CJD assessed at Mayo Clinic from 2014-2021. Clinical features and diagnostic tests were evaluated at presentation, and associations with diagnosis and prognosis determined. Results: Mean age-at-symptom onset was 64.8±9.4 years; 68 patients were female (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (stereotyped EEG abnormalities, 16%; CSF 14-3-3, 60%). Conversely, RT-QuIC (93%), t-tau >1149 pg/mL (88%), and characteristic signal abnormalities on MRI (77%) identified most patients. Multivariable linear regression confirmed shorter days-to-death in patients with myoclonus (125.9, CI95% 23.3-15.5, p=0.026), visual/cerebellar signs (180.19, CI95% 282.2-78.2, p<0.001), positive 14-3-3 (193, CI95% 304.9-82.9; p<0.001), and elevated t-tau (9.0, CI95% 1.0-18.0, for every 1000 pg/ml elevation; p=0.041). Conclusions: CSF RT-QuIC and elevated t-tau, and stereotyped MRI abnormalities were consistently detected in CJD patients. Myoclonus, EEG findings, and CSF protein 14-3-3 were less useful in the modern era.

Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.

Cucumber powdery mildew is a destructive foliar disease caused by Podosphaera xanthii (formerly known as Sphaerotheca fuliginea) that substantially damages the yield and quality of crops. The control of this disease primarily involves the use of chemical pesticides that cause serious environmental problems. Currently, numerous studies have indicated that some plant extracts or products potentially have the ability to act as natural pesticides to control plant diseases. It has been reported that turmeric (Curcuma longa L.) and its extract can be used in agriculture due to their insecticidal and fungicidal properties. However, the most effective fungicidal component of this plant is still unknown. In the current study, the crude extract of C. longa L. was found to have a fungicidal effect against P. xanthii. Afterwards, eight fractions (Fr.1–Fr.8) were gradually separated from the crude extract by column chromatography. Fraction 1 had the highest fungicidal effect against this pathogen among the eight fractions. The active compound, (+)-(S)-ar-turmerone, was separated from Fr 1 by semi-preparative high-performance liquid chromatography and identified based on its 1H nuclear magnetic resonance (NMR) and 13C NMR spectrum data. The EC50 value of (+)-(S)-ar-turmerone was found to be 28.7 µg/ml. The compound also proved to have a curative effect. This is the first study to report that the compound (+)-(S)-ar-turmerone has an effect on controlling this disease. These results provide a basis for developing a new phytochemical fungicide from C. longa L. extract.

Background: Ataluren is the first drug to treat the underlying cause of nmDMD. Methods: Phase 2 and 3 studies of ataluren in nmDMD were reviewed, with efficacy and safety/tolerability findings summarized. Results: Ataluren nmDMD trials include: a Phase 2a proof-of-concept study (N=38); a Phase 2b randomized controlled trial (RCT) (N=174); an ongoing US-based open-label safety extension study (N=108); an ongoing non-US-based open-label safety/efficacy extension study (N=94); and a Phase 3 RCT, ACT DMD (N=228), whose primary endpoint was change in six-minute walk distance (6MWD) over 48 weeks. The proof-of-concept study demonstrated increased dystrophin production in post-treatment muscle biopsies from ataluren-treated patients with nmDMD. The Phase 2b results demonstrated an ataluren treatment effect in 6MWD, timed function tests, and other measures of physical functioning, The Phase 3 ACT DMD results demonstrated an ataluren treatment effect in patients with nmDMD in both primary and secondary endpoints, particularly in those with a baseline 6MWD of 300-400m. Ataluren was consistently well-tolerated in all three trials, as well as in the ongoing extension studies. Trial findings will be presented in detail. Conclusions: The totality of the results demonstrates that ataluren enables nonsense mutation readthrough in the dystrophin mRNA, producing functional dystrophin and slowing disease progression.

Supported by: PTC Therapeutics Inc.

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropatho-logical diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a cliniconeuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neu-rohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and postnatal influences. Dentition patterns were recorded at ages 1 and 2 years in 2915 children born to women in the Southampton Women’s Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages 1 and 2 years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age 2 years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child’s primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity.

The model diatom Thalassiosira pseudonana is believed to be a single species with a global distribution, but it has not been confirmed previously whether isolates from different environmental and geographic origins are genotypically and phenotypically identical. In the present study, a polyphasic approach was employed to characterize nine clonal isolates, plus an additional replicate of one of the isolates, of the diatom T. pseudonana from culture collections to investigate whether there was any cryptic speciation in the publicly available strains of this species. Morphological analysis using scanning electron microscopy concluded that the strains were indistinguishable. Furthermore, conventional DNA barcoding genes (SSU rDNA, ITS1 and ITS2 rDNA and rbcL), revealed no nucleotide variation among the strains tested. On employing a whole genome fingerprinting technique, Amplified Fragment Length Polymorphism (AFLP), three clusters were revealed, although the level of variation between the clusters was surprisingly low. These findings indicate a low level of diversity among these cultured T. pseudonana strains, despite their wide spatial and temporal distribution and the salinity range of their original habitats. Based on the limited number of available strains, this suggests that T. pseudonana is a highly conserved diatom that nevertheless has an ability to tolerate wide ranges of salinity and populate varied geographic locations.

To determine risk factors for sporadic Vibrio parahaemolyticus gastroenteritis, we conducted a population-based case-control study in sentinel hospital surveillance areas of Shanghai and Jiangsu province, China. Seventy-one patients with diarrhoea and confirmed V. parahaemolyticus infections were enrolled, and they were matched with 142 controls for gender, age and residential area. From the multivariable analysis, V. parahaemolyticus infections were associated with antibiotics taken during the 4 weeks prior to illness [odds ratio (OR) 8·1, 95% confidence interval (CI) 1·2–56·4)], frequent eating out (OR 3·3, 95% CI 1·1–10·1), and shellfish consumption (OR 3·2, 95% CI 1·0–9·9), with population-attributable fractions of 0·09, 0·25, and 0·14, respectively. Protective factors included keeping the aquatic products refrigerated (OR 0·4, 95% CI 0·1–0·9) and pork consumption (OR 0·2, 95% CI 0·1–0·8). Further study of the association of V. parahaemolyticus gastroenteritis with prior antibiotic use and shellfish consumption is needed.

To determine the burden and distribution of acute gastrointestinal illness (AGI) in the population, a cross-sectional, monthly face-to-face survey of 10 959 residents was conducted in Jiangsu province between July 2010 and June 2011. The adjusted monthly prevalence was 4·7% with 0·63 AGI episodes/person per year. The prevalence was the highest in children aged <5 years and lowest in persons aged ⩾65 years. A bimodal seasonal distribution was observed with peaks in summer and winter. Regional difference of AGI prevalence was substantial [lowest 0·5% in Taicang, highest 15·1% in Xinqu (Wuxi prefecture)]. Healthcare was sought by 38·4% of the ill respondents. The use of antibiotics was reported by 65·2% of the ill respondents and 38·9% took antidiarrhoeals. In the multivariable model, gender, education, season, sentinel site and travel were significant risk factors of being a case of AGI. These results highlight the substantial burden of AGI and the risk factors associated with AGI in Jiangsu province, China.

Preliminary evidence suggests that consumption of Porphyridium cruentum (PC) biomass results in hypocholesterolaemic effects; however, mechanisms responsible have not been elucidated. The aim of the present study was to determine whether PC biomass lowers circulating cholesterol concentrations, dose dependently, in hamsters fed hypercholesterolaemic diets for 28 d and determine whether cholesterol biosynthesis is affected. Biomass added to diets at 2·5, 5 and 10 % resulted in 14, 38 and 53 % reductions (P < 0·001) in total plasma cholesterol, respectively, compared with a control diet. Similarly, non-HDL-cholesterol concentrations in the 5 and 10 % PC groups were reduced (P < 0·001) 28 and 45 %, respectively, v. controls. These effects were unrelated to cholesterol fractional synthesis rate (FSR), as this did not differ between either treatment or control animals. PC consumption had no effect on food intake, plasma glucose concentrations or energy expenditure, but percentage of body fat was lower (P < 0·001) in the 5 and 10 % PC groups compared with controls. These data show that PC reduces total plasma cholesterol and non-HDL-cholesterol when incorporated into the diet at levels as low as 2·5 %. The mechanism of action for this reduction may be related to increased excretion since food intakes and cholesterol FSR were not reduced in the animals receiving the PC. In conclusion, the use of PC biomass reduces circulating cholesterol, dose dependently, in hypercholesterolaemic hamsters but not via reductions in cholesterol FSR. There is potential for the use of this biomass as a functional ingredient to aid in the management of blood cholesterol concentrations.