The Irish potato famine pathogen Phytophthora infestans originated in central Mexico rather than the Andes

Phytophthora infestans is a destructive plant pathogen best known for causing the disease that triggered the Irish potato famine and remains the most costly potato pathogen to manage worldwide. Identification of P. infestan’s elusive center of origin is critical to understanding the mechanisms of repeated global emergence of this pathogen. There are two competing theories, placing the origin in either South America or in central Mexico, both of which are centers of diversity of Solanum host plants. To test these competing hypotheses, we conducted detailed phylogeographic and approximate Bayesian computation analyses, which are suitable approaches to unraveling complex demographic histories. Our analyses used microsatellite markers and sequences of four nuclear genes sampled from populations in the Andes, Mexico, and elsewhere. To infer the ancestral state, we included the closest known relatives Phytophthora phaseoli, Phytophthora mirabilis, and Phytophthora ipomoeae, as well as the interspecific hybrid Phytophthora andina. We did not find support for an Andean origin of P. infestans; rather, the sequence data suggest a Mexican origin. Our findings support the hypothesis that populations found in the Andes are descendants of the Mexican populations and reconcile previous findings of ancestral variation in the Andes. Although centers of origin are well documented as centers of evolution and diversity for numerous crop plants, the number of plant pathogens with a known geographic origin are limited. This work has important implications for our understanding of the coevolution of hosts and pathogens, as well as the harnessing of plant disease resistance to manage late blight.Keywords: coalescent analysis, biological invasion, oomycete, population genetics, stramenopil

Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension

BACKGROUND: There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension. METHODS: Exosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed. RESULTS: Urinary miRNAs are highly enriched in exosome subpopulations compared to MVs, both in patients with or without increased albuminuria (p < 0.001), but not in the control group. High albuminuria was associated with 2.5-fold less miR-146a in exosomes (p = 0.017), whereas miR-146a levels in MV did not change. In addition, exosome miR-146a levels were inversely associated with albuminuria (r = 0.65, p < 0.0001), and discriminated the presence of urinary albumin excretion presence [area under the curve = 0.80, 95% confidence interval: 0.66-0.95; p = 0.0013]. CONCLUSIONS: Our results indicate that miRNAs were enriched in the urinary exosome subpopulation in hypertensive patients and that low miR-146a expression in exosomes was associated with the presence of albuminuria. Thus, urinary exosome miR-146a may be a potentially useful tool for studying early renal injury in hypertension

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Sydenham\u27s Chorea as a Presentation of Moyamoya Disease

A seven year-old male presented to his pediatrician with choreiform movements and a recent history of sore throat. He was diagnosed with Sydenham\u27s chorea based on clinical criteria and laboratory evidence. Worsening symptoms prompted a magnetic resonance imaging (MRI) of the brain which demonstrated evidence of Moyamoya disease. Sydenham\u27s chorea is a common and well-documented complication of post-streptococcal infection, but has not been previously reported in association with Moyamoya disease. This case raises the quandary of causality of chorea in this patient and the need for neuroimaging in children with movement disorders

Hemimegalencephaly in a Patient With a Neurocutaneous Syndrome

A 5-year-old girl with a history of hypomelanosis of Ito and intractable epilepsy was evaluated for possible resective surgery. Magnetic resonance imaging showed an enlarged right hemisphere, whereas electrographic seizures were arising from the right hemisphere or had a generalized onset. The patient was believed to be a good candidate for hemispherectomy, but the family was hesitant and started a modified Atkins diet. Her seizure control has improved, but she continues to have weekly seizures. Hypomelanosis of Ito is a well-known cause of hemimegalencephaly and is often associated with intractable epilepsy and hemiparesis. Hemispherectomy can often be an effective treatment in intractable cases

Osmotic Demyelination Syndrome as a Consequence of Treating Hyperammonemia in a Patient With Ornithine Transcarbamylase Deficiency

A 7-year-old female patient with a new diagnosis of ornithine transcarbamylase deficiency was treated for hyperammonemia with a standard protocol. Several days later, she developed ataxia, dysmetria, and dysarthria. Magnetic resonance imaging of the brain demonstrated pontine and extrapontine white matter changes consistent with osmotic demyelination. Classically described as a consequence of hyponatremia treatment, osmotic demyelination syndrome has rarely been associated with other entities. This case suggests a potentially serious complication of the standard therapy for hyperammonemia in patients with ornithine transcarbamylase deficiency

Compound Heterozygous Polymerase Gamma Gene Mutation in a Patient With Alpers Disease

Alpers disease is a mitochondrial depletion syndrome characterized by psychomotor retardation, intractable epilepsy, and liver failure. Polymerase gamma (POLG) gene mutations are a known cause of the disease. We describe a case in which a 14-month-old female presented with epilepsia partialis continua evolving into generalized status epilepticus. Treatment with multiple antiepileptic medications and the ketogenic diet eliminated her seizures, but she remained severely encephalopathic. Magnetic resonance imaging showed diffuse atrophy of gray-matter structures. She ultimately developed liver failure and died. Mitochondrial analysis revealed compound heterozygosity for 3 POLG gene mutations, 2 of which were previously unreported

Emergency Preparedness of Secondary School Athletic Programs in Arizona

Context: Schools that sponsor athletic programs have an obligation to provide a safe environment with appropriate policies for addressing emergencies. Objective: To describe the emergency preparedness of secondary schools in Arizona specific to emergency action plans (EAPs), cardiac arrest, concussion, and heat illness. Design: Cross-sectional study. Setting: Online survey. Patients or Other Participants: Athletic directors from 143 Arizona secondary schools (response rate ¼ 54%). Intervention(s): A 6-section survey that included questions related to athletic trainer (AT) access, EAPs, automated external defibrillators (AEDs), concussion, heat illness, and other policies. Main Outcome Measure(s): Descriptive statistics were reported. Comparisons of responses between schools with and without AT access were conducted with Mann-Whitney U tests. Results: Most respondents (81%, n ¼ 116) indicated their school had access to an AT, and 95% (n ¼ 125) of respondents reported their school had a written EAP. The AEDs were available at most (93%, n ¼ 121) schools. All respondents were familiar with the interscholastic concussion policy, and 98% (n ¼ 123) indicated they had a school-specific policy. Almost all respondents (99%, n ¼ 121) reported being familiar with the state heat-illness policy. Environmental measures were taken before practices at 48% (n ¼ 60) of schools. Schools with access to an AT were more likely to have an EAP, venue-specific EAPs, physician approval of EAPs, AEDs, heat-illness policies, and cold-water immersion tubs and to take environmental measures. Conclusions: Whereas the majority of schools reported AT access, not all schools had adequate EAPs in place. Schools would benefit from educational opportunities regarding best practices and policy development to improve emergency preparedness