Population genomics of an outbreak of the potato late blight pathogen, Phytophthora infestans, reveals both clonality and high genotypic diversity.

An outbreak of the potato late blight pathogen Phytophthora infestans in Denmark was characterized in order to resolve the population structure and determine to what extent sexual reproduction was occurring. A standard set of microsatellite simple sequence repeats (SSRs) and single nucleotide polymorphism (SNP) markers generated using restriction site-associated DNA sequencing (RAD-seq) were employed in parallel. A total of 83 individuals, isolated from seven different potato fields in 2014, were analysed together with five Danish whole-genome sequenced isolates, as well as two Mexican individuals used as an outgroup. From a filtered dataset of 55 288 SNPs, population genomics analyses revealed no sign of recombination, implying clonality. In spite of this, multilocus genotypes were unique to individual potato fields, with little evidence of gene flow between fields. Ploidy analysis performed on the SNPs dataset indicated that the majority of isolates were diploid. These contradictory results with clonality and high genotypic diversity may suggest that rare sexual events likely still contribute to the population. Comparison of the results generated by SSRs vs SNPs data indicated that large marker sets, generated by RAD-seq, may be advised going forward, as it provides a higher level of genetic discrimination than SSRs.

The influence of timing the application of nitrogen fertilizer on early blight (Alternaria solani).

BACKGROUND: Field experiments were carried out in 2016 and 2017 to study the influence of timing the application of nitrogen fertilizer (N-fertilizer) on the susceptibility of potatoes to early blight. We hypothesized that potatoes that receive N-fertilizer as split applications or a one-time application at emergence will have a higher N content and be less susceptible to early blight than those that receive N-fertilizer as a one-time application before planting. N-fertilizer was applied either as a one-time application before planting or at emergence and as split applications. RESULTS: Potatoes that did not receive N-fertilizer were more susceptible to early blight [high area under the disease progress curve (AUDPC)] than those that did receive N-fertilizer (low AUDPC). The timing of N-fertilizer application had a significant effect on the susceptibility of potatoes to early blight. Potatoes that received the entire quantity of N-fertilizer at emergence or as split applications had higher N contents and were less susceptible to early blight than those that received the entire quantity of N-fertilizer before planting. Potatoes that did not receive N-fertilizer had a markedly lower starch yield than potatoes that received N-fertilizer. Potatoes that received the entire quantity of N-fertilizer before planting had a lower starch yield than potatoes that received the entire quantity of N-fertilizer at emergence or as split applications. CONCLUSION: N-fertilizer applied as a one-time application at emergence or as a split application was the best treatment to ensure both high N content and lower attack of early blight, which confirms our hypothesis. © 2018 Society of Chemical Industry.

The Effect of Special Diets on Weight and Nutritional Intake in Hematological Cancer Patients: A Randomized Study.

Major weight loss and taste changes are well documented in patients with hematological cancer during chemotherapy. We have previously documented, that such patients have preferences for much umami, a little sweet, sour and salt, and no bitter. We wanted to convert these results into real diets. Patients participated in two sensory pilot studies (n = 10), where dishes were tested for preferences before and after chemotherapy. From these results, four dishes were selected and tested on 32 patients in 30 days in a cross-over design. The diets resulted in a beneficial and statistically significant difference in weight development (p = 0.0008), with 1.2 ± 1.9 kg (+2%) in the intervention period and -2.8 ± 5.2 kg (-4%) in the control period. This difference persisted after sensitivity analysis (±10%) P = 0.005. However, the nutritional intake was still low in both periods, and the treatment with cytarabine turned out to be a major confounder as dosage was significantly higher in the control period.

Correction: Gas sensing performance at room temperature of nanogap interdigitated electrodes for detection of acetone at low concentration.

[This corrects the article DOI: 10.1039/C7RA09441H.].

End-Of-Life Medical Spending In Last Twelve Months Of Life Is Lower Than Previously Reported.

Although end-of-life medical spending is often viewed as a major component of aggregate medical expenditure, accurate measures of this type of medical spending are scarce. We used detailed health care data for the period 2009-11 from Denmark, England, France, Germany, Japan, the Netherlands, Taiwan, the United States, and the Canadian province of Quebec to measure the composition and magnitude of medical spending in the three years before death. In all nine countries, medical spending at the end of life was high relative to spending at other ages. Spending during the last twelve months of life made up a modest share of aggregate spending, ranging from 8.5 percent in the United States to 11.2 percent in Taiwan, but spending in the last three calendar years of life reached 24.5 percent in Taiwan. This suggests that high aggregate medical spending is due not to last-ditch efforts to save lives but to spending on people with chronic conditions, which are associated with shorter life expectancies.

The mesenteric defects in laparoscopic Roux-en-Y gastric bypass: 5 years follow-up of non-closure versus closure using the stapler technique.

BACKGROUND: Internal hernia (IH) is a common complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Little large-volume data exist on how to handle the mesenteric defects during LRYGB. This study evaluated long-term follow-up (5.5 years) of 2443 patients with primary closure of the mesenteric defects with a stapling device at LRYGB, in comparison with a non-closed group from the same centre. METHODS: All patients (N = 4013) undergoing LRYGB over a 10-year period (2005-2015) at a single institution were evaluated. The mesenteric defects were routinely closed starting June 2010. In total, 1570 non-closure patients and 2443 patients with stapled closure of the defects were prospectively entered and the results analysed. RESULTS: Closure of the mesenteric defects increased surgical time by 4 min and did not affect the 30-day complication rate. IH incidence was significantly lower (2.5%) in the closure group compared with 11.7% in the non-closure group, at 60 months. The relative risk reduction by closing the mesenteric defects was 4.09-fold (95% CI = 2.97-5.62) as calculated using a survival model. CONCLUSIONS: Internal hernia after LRYGB occurs frequently if mesenteric defects are left unclosed. Primary closure with a hernia-stapling device is safe and significantly reduces the risk of internal hernia.

Mucosal glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide cell numbers in the super-obese human foregut after gastric bypass.

BACKGROUND: Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown. OBJECTIVE: To study the effects of laparoscopic RYGB on enteroendocrine cells. SETTING: University-affiliated, high-volume bariatric surgery center. METHODS: Eighteen nondiabetic patients were drawn from the present study (NCT 01514799), randomizing between biliopancreatic (BP) limbs of either 60 cm (BP60) or 200 cm (BP200). Demographic characteristics did not differ at baseline or 12 months. Pouch and jejunal biopsies were obtained intraoperatively and using endoscopy at 12 months. Mucosal height and density of hormone-producing cell populations were assessed and mRNA expression measured with real-time polymerase chain reaction. RESULTS: In perianastomotic jejunum, a 4.9-fold increase in GLP-1 cell density was evident 12 months after RYGB, most pronounced in the BP200-group. The densities of glucose-dependent insulinotropic polypeptide (GIP) cells and PYY immunoreactive cells were doubled after 12 months. GIP mRNA was unaffected, but GLP-1 and PYY mRNA were lower 12 months after RYGB. RYGB had no impact on villi length or density of ghrelin-, cholecystokinin-, neurotensin-, secretin-, or serotonin-producing cells after 12 months. Pouch mucosal height and cell densities of ghrelin-, histamine-, serotonin-, and somatostatin-producing cells remained unaffected by RYGB in both groups. CONCLUSIONS: RYGB selectively increased the density of incretin-producing cell populations in the jejunum. This may provide anatomic explanation for the observed increased plasma levels of incretins.

Enhanced seasonal exchange of CO2 by northern ecosystems since 1960.

Seasonal variations of atmospheric carbon dioxide (CO2) in the Northern Hemisphere have increased since the 1950s, but sparse observations have prevented a clear assessment of the patterns of long-term change and the underlying mechanisms. We compare recent aircraft-based observations of CO2 above the North Pacific and Arctic Oceans to earlier data from 1958 to 1961 and find that the seasonal amplitude at altitudes of 3 to 6 km increased by 50% for 45° to 90°N but by less than 25% for 10° to 45°N. An increase of 30 to 60% in the seasonal exchange of CO2 by northern extratropical land ecosystems, focused on boreal forests, is implicated, substantially more than simulated by current land ecosystem models. The observations appear to signal large ecological changes in northern forests and a major shift in the global carbon cycle.

Obstructive sleep apnea due to extrathoracic tracheomalacia.

We report obstructive sleep apnea in a 3-year-old boy with tracheomalacia secondary to tracheotomy that resolved after placement of a metallic stent in the region of tracheomalacia. The tracheal location of obstruction during sleep in this case contrasts with the usual location in the pharynx or, less often, the larynx. This case also demonstrates the utility of polysomnography in managing decannulation of tracheostomies.

Proceedings of the fifth Northern Region Paediatric Colloquium.

The disciplines of medicine, law and ethics frequently impinge upon each other in clinical practice but are seldom given the opportunity to come together in dialogue. It was with this aim that senior professionals from law and medicine met at the fifth Northern Region Paediatric Colloquium. An added dimension to the ethical viewpoint was brought to the meeting by the attendance of local religious leaders for the first time. We report the proceedings of the Colloquium, which adopted the usual format of clinical case presentation followed by discussion.

Characterization of a selective and potent antagonist of human P2X(7) receptors, AZ11645373.

BACKGROUND AND PURPOSE: The ATP-gated P2X(7) receptor has been shown to play a role in several inflammatory processes, making it an attractive target for anti-inflammatory drug discovery. We have recently identified a novel set of cyclic imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human macrophage THP-1 cells. In this study the actions and selectivity of one of these compounds, AZ11645373, were characterized. EXPERIMENTAL APPROACH: We measured membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP). KEY RESULTS: AZ11645373 up to 10 microM, had no agonist or antagonist actions on membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2), human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in HEK cells. AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean values not significantly different between assays. K (B) values were not altered by removing extracellular calcium and magnesium. ATP-evoked IL-1beta release from lipopolysaccharide-activated THP-1 cells was inhibited by AZ11645373, IC(50) = 90 nM. AZ11645373 was > 500-fold less effective at inhibiting rat P2X(7) receptor-mediated currents with less than 50% inhibition occurring at 10 microM. CONCLUSIONS AND IMPLICATIONS: AZ11645373 is a highly selective and potent antagonist at human but not rat P2X(7) receptors and will have much practical value in studies of human cells.

Novel P2X7 receptor antagonists.

The synthesis and pharmacological evaluation of a new series of potent P2X(7) receptor antagonists is disclosed. The compounds inhibit BzATP-mediated pore formation in THP-1 cells. The distribution of the P2X(7) receptor in inflammatory cells, most notably the macrophage, mast cell and lymphocyte, suggests that P2X(7) antagonists have a significant role to play in the treatment of inflammatory disease.

Neutron-mapping polymer flow: scattering, flow visualization, and molecular theory.

Flows of complex fluids need to be understood at both macroscopic and molecular scales, because it is the macroscopic response that controls the fluid behavior, but the molecular scale that ultimately gives rise to rheological and solid-state properties. Here the flow field of an entangled polymer melt through an extended contraction, typical of many polymer processes, is imaged optically and by small-angle neutron scattering. The dual-probe technique samples both the macroscopic stress field in the flow and the microscopic configuration of the polymer molecules at selected points. The results are compared with a recent "tube model" molecular theory of entangled melt flow that is able to calculate both the stress and the single-chain structure factor from first principles. The combined action of the three fundamental entangled processes of reptation, contour length fluctuation, and convective constraint release is essential to account quantitatively for the rich rheological behavior. The multiscale approach unearths a new feature: Orientation at the length scale of the entire chain decays considerably more slowly than at the smaller entanglement length.

A comparison of cortisporin and ciprofloxacin otic drops as prophylaxis against post-tympanostomy otorrhea.

Myringotomy and tube insertion, a common pediatric surgical procedure, is frequently complicated by purulent otorrhea. Many otolaryngologists routinely use topical antibiotics as prophylaxis against post-tympanostomy otorrhea. The aminoglycosides (neomycin sulfate, tobramycin and gentamicin) contained in commonly used topical antibiotics as well as components of the solutions have been shown to be ototoxic in animal studies. Although little reported evidence of ototoxicity in humans exists, sporadic reports of sensorineural hearing loss linked to topical antibiotic use do exist, and the potential for sensorineural hearing loss must be considered. The purpose of this study is to compare the rate of post-tympanostomy otorrhea in a double-blinded randomized trial using either topical Ciprofloxacin, with no reported ototoxicity, or Cortisporin as prophylaxis. One hundred patients (200 ears) between ages 7 months and 11 years with a diagnosis of recurrent otitis media or chronic otitis media undergoing tympanostomy tube insertion were randomized into two equal groups. Three drops of either drop A or B were placed into each ear at the time of tube insertion and then three times daily for 3 days. Patients were examined at 3 weeks and details of otorrhea were obtained. The rate of otorrhea was analyzed using chi-square. The overall rate of otorrhea was 39 ears (19.5%), 17 (17%) ears for the Cortisporin group and 22 (22%) for the Ciprofloxacin group. The difference in rate of otorrhea was not statistically significant (P=0.372, 95% confidence interval equals -6-16%). Our data suggest that topical Cortisporin offers no benefit over Ciprofloxacin for post-operative otorrhea prophylaxis. Therefore we recommend topical quinolone prophylaxis, which should eliminate concerns about ototoxicity, without sacrificing efficacy.

Congenital nasal pyriform aperture stenosis: non-surgical management and long-term analysis.

Congenital nasal pyriform aperture stenosis is a rare cause of airway obstruction in the newborn. Immediate recognition and therapy are essential for this potentially life-threatening condition. After initial management, which includes establishment of an oral airway, surgical repair of the stenotic bony inlet has been traditionally considered. We present a long-term follow-up of two patients with congenital pyriform aperture stenosis, who were managed expectantly. Pertinent embryology, clinical presentation, and general treatment strategies for these patients are also discussed.

Atypical indications for OtoScan laser-assisted myringotomy.

OBJECTIVE: To describe the role of OtoScan laser-assisted myringotomy (OtoLAM) for indications other than chronic otitis media or recurrent acute otitis media. STUDY DESIGN: Cross-sectional review. METHODS: Twenty-seven office-based OtoLAM procedures were performed in 21 patients for "atypical" reasons. The indications included middle ear dysfunction with necessary air travel (n = 10) or hyperbaric oxygen treatment (n = 6), mastoiditis with postauricular cellulitis (n = 2), canal exostosis prohibiting tympanostomy (n = 1), acute otitis media accompanied by seizures (n = 1), and chronic middle ear effusion in a patient with hemophilia (n = 1). RESULTS: In each of the 20 cases available for follow-up, middle ear disease resolved with closure of the laser-assisted myringotomy. At a later date, two patients (10%) underwent another OtoLAM in the opposite ear and four patients (20%) required repeat OtoLAM in the same or both ears. Three patients (15%) ultimately underwent myringotomy tube placement because of recurrent middle ear dysfunction. CONCLUSIONS: Although this report contains preliminary data, the data suggest that OtoLAM may provide an additional option in the care of certain patients who have previously been treated with myringotomy tubes.

Is tracheotomy decannulation possible in oxygen-dependent children?

OBJECTIVE: The goal was to determine whether decannulation can be safely achieved in children with persistent oxygen requirements. DESIGN: The study was a prospective evaluation of 12 oxygen-dependent children at a tertiary care academic children's medical center. METHODS: Twelve tracheotomy-dependent children with persistent oxygen requirements were evaluated for decannulation. Patients requiring more than 35% FiO(2) were not considered. Direct laryngoscopy and bronchoscopy were performed in all patients. Two required single-stage laryngotracheoplasty to correct subglottic stenosis, 1 required tracheal resection, and 7 required removal of suprastomal granulation tissue. Oxygen was administered after decannulation through a nasal cannula. RESULTS: Decannulation was successful in 92% (11 of 12) of patients. At final follow-up, oxygen requirements decreased in 58% of patients after decannulation. CONCLUSIONS: Decannulation can be successful in children who remain oxygen dependent; conversion to a more physiologic airway may be an adjunct to reducing or eliminating their oxygen demand.

Nasally inhaled dornase alfa in the postoperative management of chronic sinusitis due to cystic fibrosis.

OBJECTIVE: To determine the benefit of nasally inhaled dornase alfa in cystic fibrosis (CF) sinusitis. DESIGN: Retrospective chart review comparing postsurgical course, radiographic studies, and pulmonary function test results in patients who were treated with nasally inhaled dornase alfa with those in patients who were not treated with dornase alfa. PATIENTS: Twenty consecutive patients with CF who underwent functional endoscopic sinus surgery from 1993 to 1997 were included in the study. Treatment with nasally inhaled dornase alfa was initiated in 5 of the 20 patients after they underwent functional endoscopic sinus surgery. SETTING: Tertiary care academic center. RESULTS: The dornase alfa-treated patients had less mucosal edema and no polyps at serial endoscopy over 3 years compared with the non-dornase alfa-treated patients. The patients who received nasally inhaled dornase alfa also underwent fewer revision functional endoscopic sinus surgical procedures (1.6 vs 3.2), even though there was essentially no change in pulmonary function test results in these patients. CONCLUSIONS: Sinusitis continues to be a major cause of morbidity in patients with CF. Symptomatic patients frequently require multiple drug regimens, including long-term systemic antibiotic therapy, topical and systemic steroid therapy, and antibiotic nasal irrigations. This preliminary study indicates the potential impact of nasally inhaled dornase alfa in controlling postoperative symptoms in CF sinusitis.

Tympanostomy tubes and otic suspensions: do they reach the middle ear space?

The treatment of patients with tympanostomy tubes (TTs) and otorrhea with medicated otic suspensions is well known, but confirmation of penetration into the middle ear is difficult. To address this question, we created an in vitro model of the human head and ear and then tested it with 5 different types of liquid exposure: tap water, soapy water, polymyxin B sulfate (Cortisporin), tobramycin and dexamethasone (TobraDex), and ciprofloxacin (Cipro) suspensions. A positive test result corresponded to liquids entering the middle ear through the TT. No positive test result was elicited with tap water (0/20), but soapy water did enter the middle ear (10/40) and was statistically significant (P = 0.0112). Without the use of slight tragal pressure, Cortisporin, TobraDex, and Cipro drops did not consistently pass through the TT (0/20, 1/25, 1/25). By placing the drops with the addition of tragal pressure, a statistically significant difference was obtained for each solution (20/20, 20/20, and 20/20, respectively [P < 0.0001]). We conclude that with a clean external auditory canal, patent TT, and no middle ear fluid, medicated otic suspensions enter the middle ear only when combined with slight tragal pressure.