Evaluation of incidence, predictive factors and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy.

INTRODUCTION AND OBJECTIVES: Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. PATIENTS AND METHODS: A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. RESULTS: Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation. CONCLUSIONS: Genitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

Evaluación de la incidencia, factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin / Evaluation of incidence and predictive factors, and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy

Introducción y objetivos Aunque las complicaciones de la terapia intravesical con el bacilo de Calmette-Guérin (BCG) están bien descritas, pocas veces se ha comunicado la formación posterior de granulomas genitourinarios asintomáticos, y su estrategia de tratamiento sigue siendo controvertida. El objetivo de este estudio es evaluar la tasa de incidencia de la formación de granulomas genitourinarios asintomáticos que imitan la recurrencia del cáncer de vejiga tras el tratamiento intravesical con el BCG, así como identificar las estrategias de diagnóstico y tratamiento según las características de los pacientes. Pacientes y métodos Se realizó una revisión retrospectiva de 162 pacientes sometidos a terapia intravesical con BCG. En los pacientes que desarrollaron granulomas, se evaluó el intervalo de tiempo entre la instilación de BCG y el desarrollo del granuloma, la presencia de bacterias acidorresistentes en las muestras de patología, los resultados del cultivo/reacción en cadena de la polimerasa, las estrategias de tratamiento de las lesiones y los resultados clínicos. Resultados Se desarrollaron masas genitourinarias asintomáticas en 14 pacientes, de los cuales 5 se sometieron a evaluaciones histológicas confirmando en todos los casos una inflamación granulomatosa. Los órganos afectados fueron el riñón, la vejiga, la próstata y el pene. Aunque 5 de los 5 pacientes no recibieron tratamiento para los granulomas, a uno de ellos se le administró medicación antituberculosa para evitar el empeoramiento de la lesión durante el periodo perioperatorio de la cistoprostatectomía programada. Ninguno de los pacientes experimentó empeoramiento o recurrencia de las lesiones granulomatosas. Los pacientes que desarrollaron masas asintomáticas (n=14) eran significativamente más jóvenes que ...(AU)

Introduction and objectives Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.Patients and methods A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. Results Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n=14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation...(AU)

Effects of oral administration of timothy hay and psyllium on the growth performance and fecal microbiota of preweaning calves.

The objective of this study was to evaluate the effects of oral administration of fiber from the first week of life on the growth and hindgut environment of preweaning calves. Twenty newborn female Holstein calves were divided into 2 groups as control and treatment. Calves in both groups were reared under the same feeding program except for oral fiber administration. Timothy hay and psyllium were mixed at a 50-to-6 ratio as a treatment diet for oral fiber administration. Calves in the treatment group were orally administered 50 g of fiber daily from 3 to 7 d of age and 100 g of fiber from 8 d of age until weaning. Feed intake and occurrence of diarrhea were recorded daily, and body weight (BW) was recorded weekly for the individual calf. Fresh feces were collected from calves at 7, 21, 35, 49, and 56 d of age to analyze fermentation parameters and microbiota to characterize the hindgut environment. Higher fiber intake in the treatment group due to oral administration of timothy and psyllium did not affect the starter intake and achieved higher BW at 21 d of age. The fecal pH, total volatile fatty acid, lactate, and ammonia nitrogen concentrations were not affected by oral fiber administration; meanwhile, the molar proportion of propionate was higher in the treatment group at 7 d of age. The difference in fecal microbiota in the calves subjected to the oral administration of fiber was observed within 21 d of life; Lactobacillus spp. and Prevotella spp. showed higher abundance, whereas that of Clostridium perfringens was decreased. These higher abundances of beneficial bacteria and lower abundance of pathogenic bacteria during early life may partly explain the higher BW of calves in the treatment group at 21 d of age. Furthermore, no adverse effect was observed for the BW and health status in the treatment group throughout the preweaning period. Therefore, early fiber feeding via oral administration potentially contributes to improving the hindgut environment in newborn calves, which leads to better growth of calves during the early stage of life.

Rumen microbiota and its relation to fermentation in lactose-fed calves.

In our previous studies, we revealed the effect of lactose inclusion in calf starters on the growth performance and gut development of calves. We conducted the present study as a follow-up study to identify the shift in rumen microbiota and its relation to rumen fermentation when calves are fed a lactose-containing starter. Thirty Holstein bull calves were divided into 2 calf starter treatment groups: texturized calf starter (i.e., control; n = 15) or calf starter in which starch was replaced with lactose at 10% (i.e., LAC10; n = 15) on a dry matter basis. All calves were fed their respective treatment calf starter ad libitum from d 7, and kleingrass hay from d 35. Rumen digesta were collected on d 80 (i.e., 3 wk after weaning) and used to analyze rumen microbiota and fermentation products. There was no apparent effect of lactose feeding on the α-diversity and overall composition of rumen microbiota. Amplicon sequencing and real-time PCR quantification of the 16S rRNA gene confirmed that the abundance of butyrate-producing bacteria (i.e., Butyrivibrio group and Megasphaera elsdenii) did not differ between the control and LAC10 groups. Conversely, the relative abundance of Mitsuokella spp., which produce lactate, succinate, and acetate, was significantly higher in the rumen of calves that were fed lactose, whereas the lactate concentration did not differ between the control and LAC10 groups. These findings suggest that the lactate production can be elevated by an increase of Mitsuokella spp. and then converted into butyrate, not propionate, since the proportion of propionate was lower in lactose-fed calves. In addition, we observed a higher abundance of Coriobacteriaceae and Pseudoramibacter-Eubacterium in the LAC10 group. Both these bacterial taxa include acetate-producing bacteria, and a positive correlation between the acetate-to-propionate ratio and the abundance of Pseudoramibacter-Eubacterium was observed. Therefore, the higher abundance of Coriobacteriaceae, Mitsuokella spp., and Pseudoramibacter-Eubacterium in the rumen of lactose-fed calves partially explains the increase in the proportion of rumen acetate that was observed in our previous study.

Retention among full-time occupational physicians in Japan.

BACKGROUND: To secure human resources for occupational medicine, it is important to analyse occupational physician retention trends and the factors associated with retention. However, little is currently known about this topic. AIMS: To identify occupational physician retention trends, to identify factors associated with this retention and to discuss the policy implications of the findings. METHODS: We analysed data from the biannual national physician census surveys conducted by the government of Japan from 2002 to 2014. In this study, those who chose 'working as an occupational physician' as their workplace/type of work from a pre-determined list in the survey questionnaire were considered full-time occupational physicians. We presented retention trends by calculating the annual retention rate for each set of two consecutive surveys. We then used logistic regression to identify factors associated with retention among occupational physicians. RESULTS: The annual retention rate of full-time occupational physicians from 2012 to 2014 was estimated as 76%, which represents a 6% improvement in retention over the study period. The odds of continuing to practise as an occupational physician were higher for occupational physicians working in cities compared with those working in towns or villages. CONCLUSIONS: Improving and facilitating smooth transitions between clinical practice and occupational medicine would help to secure human resources in occupational medicine, even if the current trend of low retention continues.

Cellulose acetate, a new candidate feed supplement for ruminant animals: In vitro evaluations.

Cellulose acetate (CA), a derivative of cellulose in which some hydroxyl groups are substituted with acetyl groups, was evaluated as a new cellulosic feed source for ruminants. In the present work, a series of in vitro studies was carried out to determine how CA supplementation affects rumen fermentation and microbiota. Batch culture studies were conducted to select the type of CA suitable for feed use and to define the optimal supplementation level. Rumen fluid from 2 Holstein cows was mixed with McDougall's buffer in test tubes into which grass hay and concentrate containing a fiber source [cellulose (control), water-soluble CA (WSCA), or insoluble CA] had been placed. Each fiber source was supplemented at 10% of total substrate. Tubes were incubated for 24 h to determine fermentation and microbial parameters. Then, the dose response of these parameters to different supplementation levels of WSCA (0, 7.5, 15, 22.5, and 30%) was tested in the same manner. We also operated a continuous culture system with WSCA supplementation and evaluated the effects on digestibility, fermentation, and microbial parameters. The supplementation level of WSCA was set at 15% of total feed. In batch culture studies, WSCA, but not insoluble CA, yielded dose-dependent increases in ruminal acetate levels. In the continuous culture system study, WSCA yielded increases in ruminal acetate levels and in the abundance of bacteria of the genus Prevotella, including Prevotella ruminicola. Dry matter digestibility and total gas production were not affected. These results suggest that WSCA supplementation at 15% of total feed yielded increased acetate levels without negatively affecting feed digestion; these effects may reflect activation of Prevotella species. As ruminal acetate is involved in milk fat synthesis, WSCA can be considered as a candidate feed additive suitable for dairy cattle.

Functional modulation of caecal fermentation and microbiota in rat by feeding bean husk as a dietary fibre supplement.

A feeding study using rats was conducted to evaluate the utility of lablab bean husk and soya bean husk as sources of potential prebiotic fibre. Twenty 5-week-old Sprague Dawley rats were divided into 4 groups and fed one of the following diets for 3 weeks: purified diet (AIN93 G) containing 5% cellulose (CEL), or the same diet in which cellulose was replaced by corn starch (STA), lablab bean husk (LBH), or soya bean husk (SBH). Rats were sacrificed at 8 weeks of age and caecal digesta were collected. Feed intake, body weight, anatomical parameters, and caecal ammonia level did not differ significantly among diets. Rats on LBH and SBH showed higher concentrations of caecal short-chain fatty acid and lactate than those on CEL. Rats on CEL, SBH, and LBH exhibited lower caecal indole and skatole levels. LBH yielded increased caecal abundance of Akkermansia muciniphila and Oscillibacter relatives, as demonstrated by either qPCR, MiSeq, or clone library analysis. SBH favoured the growth of lactobacilli as assessed by both qPCR and MiSeq, and favoured the growth of bifidobacteria as assessed by MiSeq. In comparison with STA, LBH and SBH yielded lower caecal abundance of bacteria related to Dorea massiliensis, as demonstrated by qPCR, MiSeq, and clone library analysis. Both types of bean husk were found to contain oligosaccharides that might selectively stimulate the growth of beneficial bacteria. Based on these results, the two species of bean husk tested are considered potentially functional for promoting the gut health of monogastric animals.

Cognitive profiles in childhood and adolescence differ between adult psychotic and affective symptoms: a prospective birth cohort study.

BACKGROUND: Differences between verbal and non-verbal cognitive development from childhood to adulthood may differentiate between those with and without psychotic symptoms and affective symptoms in later life. However, there has been no study exploring this in a population-based cohort. METHOD: The sample was drawn from the MRC National Survey of Health and Development, and consisted of 2384 study members with self-reported psychotic experiences and affective symptoms at the age of 53 years, and with complete cognitive data at the ages of 8 and 15 years. The association between verbal and non-verbal cognition at age 8 years and relative developmental lag from age 8 to 15 years, and both adult outcomes were tested with the covariates adjusted, and mutually adjusted for verbal and non-verbal cognition. RESULTS: Those with psychotic experiences [thought interference (n = 433), strange experience (n = 296), hallucination (n = 88)] had lower cognition at both the ages of 8 and 15 years in both verbal and non-verbal domains. After mutual adjustment, lower verbal cognition at age 8 years and greater verbal developmental lag were associated with higher likelihood of psychotic experiences within individuals, whereas there was no association between non-verbal cognition and any psychotic experience. In contrast, those with case-level affective symptoms (n = 453) had lower non-verbal cognition at age 15 years, and greater developmental lag in the non-verbal domain. After adjustment, lower non-verbal cognition at age 8 years and greater non-verbal developmental lag were associated with higher risk of case-level affective symptoms within individuals. CONCLUSIONS: These results suggest that cognitive profiles in childhood and adolescence differentiate psychiatric disease spectra.

A randomised controlled trial of repeated filmed social contact on reducing mental illness-related stigma in young adults.

AIMS: Public stigma alters attitudes towards people with mental illness, and is a particular concern for young people since most mental health problems occur in adolescence and young adulthood. However, little is known about the long-term effects of repeated filmed social contact (FSC) on reducing mental health-related stigma among young adults in the general population, compared with self-instructional Internet search (INS) and control interventions. METHODS: This study is a parallel-group randomised controlled trial over 12 months conducted in Tokyo, Japan. A total of 259 university students (male n = 150, mean age = 20.0 years, s.d. = 1.2) were recruited from 20 colleges and universities between November 2013 and July 2014, without being provided information about the mental health-related survey or trial. Participants were assigned to one of three groups before completion of the baseline survey (FSC/INS/control = 89/83/87). The FSC group received a computer-based 30-min social contact film with general mental health education and five follow-up web-based FSCs at 2-month intervals. The INS group undertook a 30-min search for mental health-related information with five follow-up web-based reminders for self-instructional searches at 2-month intervals. The control group played PC games and had no follow-up intervention. The main outcome measures were the future (intended behaviour) domain of the Reported and Intended Behaviour Scale at 12 months after the intervention. Analysis was conducted in September 2015. RESULTS: At the 12-month follow-up, 218 participants completed the survey (84.1%, 75:70:73). The FSC group showed the greatest change at the 12-month follow-up (FSC: mean change 2.11 [95% CI 1.49, 2.73], INS: 1.04 [0.29, 1.80], control: 0.71 [0.09, 1.33]; FSC v. INS p = 0.037, FSC v. controls p = 0.004). No adverse events were reported during the follow-up period. CONCLUSIONS: FSC was more successful in reducing stigma at 12 months after intervention than INS or control interventions. FSC could be used to reduce stigma in educational lectures and anti-stigma campaigns targeted at young people. STUDY REGISTRATION: This study is registered at UMIN-CTR (No. UMIN000012239).

Japan health system review

The Asia Pacific Observatory on Health Systems and Policies (the APO) is a collaborative partnership of interested governments, international agencies, foundations, and researchers that promotes evidence-informed health systems policy regionally and in all countries in the Asia Pacific region. The APO collaboratively identifies priority health system issues across the Asia Pacific region; develops and synthesizes relevant research to support and inform countries' evidence-based policy development; and builds country and regional health systems research and evidence-informed policy capacity.

Plasma concentrations of glucagon-like peptide 1 and 2 in calves fed calf starters containing lactose.

The objective of this study was to evaluate the effects of lactose inclusion in calf starters on plasma glucagon-like peptide (GLP)-1 and GLP-2 concentrations and gastrointestinal tract development in calves. Holstein bull calves (n = 45) were raised on an intensified nursing program using milk replacer containing 28.0% CP and 15.0% fat, and were fed a texturized calf starter containing 0 (control), 5.0 (LAC5), or 10.0% (LAC10; n = 15 for each treatment) lactose on a DM basis. Lactose was included in the starter by partially replacing dry ground corn in pelleted portion of the starter. All calf starters were formulated with 23.1% CP. The ethanol-soluble carbohydrate concentrations of the control, LAC5, and LAC10 starters were 7.3, 12.3, and 16.8% on a DM basis, respectively. Starch concentrations of the control, LAC5, and LAC10 starters were 29.7, 27.0, and 21.4% on a DM basis, respectively. All calves were fed treatment calf starters ad libitum. Blood samples were obtained weekly from 1 to 11 wk of age, and used to measure plasma GLP-1, GLP-2, and insulin concentrations, serum ß-hydroxybutyrate (BHB) concentration, and blood glucose concentration. At 80 d of age, calves were euthanized, and weights of the reticulorumen, omasum, abomasum, small intestine, and large intestine tissue were measured. Serum BHB concentration was higher for calves fed the LAC10 (171 µmol/L) starter than for those fed the control (151 µmol/L) and LAC5 (145 µmol/L) starters. Plasma GLP-1 and GLP-2 concentrations did not differ between treatments. However, relative to the baseline (1 wk of age), the plasma GLP-1 concentration was higher for the LAC10 (125.9%) than for the LAC5 (68.2%) and control (36.8%), and for the LAC5 than for the control (36.8%). Moreover, similar differences between treatments were observed for GLP-2 concentration relative to the baseline (88.2, 76.9, and 74.9% for LAC10, LAC5, and control treatments, respectively). The serum BHB concentration was positively correlated with the plasma GLP-1 concentration (r = 0.428). Furthermore, the plasma GLP-1 concentration was positively correlated with the insulin concentration (r = 0.793). The weights of the reticulorumen, omasum, abomasum, small intestine, and large intestine were not affected by the treatments. In conclusion, inclusion of lactose in calf starters resulted in higher plasma GLP-1 and GLP-2 concentrations, and BHB might be associated with higher plasma GLP-1 concentration.

Identification of an argpyrimidine-modified protein in human red blood cells from schizophrenic patients: A possible biomarker for diseases involving carbonyl stress.

Argpyrimidine (ARP) is an advanced glycation end product thought to be generated from a reaction between methylglyoxal and arginine residues in proteins. In this study, we observed marked accumulation of an approximately 56 kD protein, reactive to anti-ARP antibodies, in the red blood cells (RBCs) of some patients with refractory schizophrenia. This ARP-modified protein was purified from the blood of schizophrenic patients and identified as selenium binding protein 1 (SBP1) by LC-MS/MS. This is the first report of ARP-modified proteins accumulating in RBCs of patients with diseases involving carbonyl stress. We also observed high accumulation of ARP-modified SBP1 in the RBCs of patients with chronic kidney disease. Therefore, this modified protein may be a novel marker of carbonyl stress.

Effects of partial replacement of corn grain with lactose in calf starters on ruminal fermentation and growth performance.

The objective of this study was to evaluate effects of partial replacement of dry ground corn with lactose in calf starters on dry matter intake, growth rate, ruminal pH, and volatile fatty acid profile. Sixty Holstein bull calves were raised on a high plane of nutrition program until 55 d of age. Calves were fed texturized calf starters containing 30.1% steam-flaked grains and lactose at 0 (control), 5, or 10% (n = 20 for each treatment) on a dry matter basis. All calves were fed treatment calf starters ad libitum from d 7 and kleingrass hay from d 35. Ruminal pH was measured continuously immediately after weaning (d 55-62) for 15 calves (n = 5 per treatment), and 3 wk after weaning (d 77 to 80) for the other 45 calves (n = 15 per treatment). Dry matter intake, growth performance, and ruminal pH variables were not affected by treatment. However, according to Spearman's correlation coefficient (rs) analyses, lactose intake was positively correlated with dairy minimum ruminal pH (rs = 0.306) for the data collected from d 77 to 80. Similarly, hay intake was not affected by treatment, but positively correlated with daily mean (rs = 0.338) and maximum ruminal pH (rs = 0.408) and negatively correlated with duration pH <5.8 (rs = -0.329) and area pH <5.8 (rs = -0.325), indicating that the variation in hay intake among animals might have masked treatment effects on ruminal pH. Ruminal molar ratio of acetate was higher (45.2 vs. 40.6%), and that of propionate was lower in 10% lactose than control (35.3 vs. 40.2%) for ruminal fluid collected on d 80; however, molar ratio of butyrate was not affected by treatment. These results indicate that lactose inclusion in calf starters up to 10% of dry matter might not affect dry matter intake and growth performance of calves, but that greater lactose and hay intake might be associated with higher ruminal pH.

Ginkgo fruit extract as an additive to modify rumen microbiota and fermentation and to mitigate methane production.

Ginkgo fruit, an unused byproduct of the ginkgo nut industry, contains antimicrobial compounds known as anacardic acids. Two major cultivars of ginkgo, Kyuju (K) and Tokuro (T), were evaluated for their potential as a feed additive for ruminants. In batch culture, we incubated a mixture of hay and concentrate in diluted rumen fluid with or without 1.6% (fruit equivalent) ginkgo fruit extract. We conducted another series of batch culture studies to determine the dose response of fermentation. We also conducted continuous culture using the rumen simulation technique (RUSITEC) with cultivar K and carried out a pure culture study to monitor the sensitivity of 17 representative rumen bacterial species to ginkgo extract and component phenolics. Although both K and T extracts led to decreased methane and increased propionate production, changes were more apparent with K extract, and were dose-dependent. Total gas production was depressed at doses ≥3.2%, suggesting that 1.6% was the optimal supplementation level. In RUSITEC fermentation supplemented with 1.6% ginkgo K, methane decreased by 53% without affecting total gas or total VFA production, but with decreased acetate and increased propionate. Disappearance of dry matter, neutral detergent fiber, and acid detergent fiber were not affected by ginkgo, but ammonia levels were decreased. Quantitative PCR indicated that the abundance of protozoa, fungi, methanogens, and bacteria related to hydrogen and formate production decreased, but the abundance of bacteria related to propionate production increased. MiSeq analysis (Illumina Inc., San Diego, CA) confirmed these bacterial changes and identified archaeal community changes, including a decrease in Methanobrevibacter and Methanomassiliicoccaceae and an increase in Methanoplanus. Pure culture study results supported the findings for the above bacterial community changes. These results demonstrate that ginkgo fruit can modulate rumen fermentation toward methane mitigation and propionate enhancement via microbial selection.

The Population of Fusarium oxysporum f. sp. fragariae, Cause of Fusarium Wilt of Strawberry, in California.

The objectives of this study were to investigate the structure of the population of Fusarium oxysporum f. sp. fragariae in California and to evaluate methods for its detection. Fifty-nine isolates of F. oxysporum f. sp. fragariae were obtained from diseased strawberry plants and their identity was confirmed by pathogenicity testing. The full nuclear ribosomal intergenic spacer (IGS) and elongation factor 1-α gene (EF-1α) were amplified by polymerase chain reaction (PCR) and sequenced to elucidate phylogenetic relationships among isolates. IGS and EF-1α sequences revealed three main lineages, which corresponded to three somatic compatibility groups. Primers designed to detect F. oxysporum f. sp. fragariae in Japan amplified a 239-bp product from 55 of 59 California isolates of F. oxysporum f. sp. fragariae and from no nonpathogenic isolates of F. oxysporum. The sequence of this PCR product was identical to the sequence obtained from F. oxysporum f. sp. fragariae isolates in Japan. Intensive sampling at two locations in California showed results of tests based on PCR and somatic compatibility to be in agreement for 97% (257 of 264) of isolates tested. Our findings revealed considerable diversity in the California population of F. oxysporum f. sp. fragariae, and indications that horizontal gene transfer may have occurred.

Spatiotemporal Patterns in the Airborne Dispersal of Spinach Downy Mildew.

Downy mildew is the most devastating disease threatening sustainable spinach production, particularly in the organic sector. The disease is caused by the biotrophic oomycete pathogen Peronospora effusa, and the disease results in yellow lesions that render the crop unmarketable. In this study, the levels of DNA from airborne spores of P. effusa were assessed near a field of susceptible plants in Salinas, CA during the winter months of 2013-14 and 2014/15 using rotating-arm impaction spore-trap samplers that were assessed with a species-specific quantitative polymerase chain reaction (qPCR) assay. Low levels of P. effusa DNA were detectable from December through February in both winters but increased during January in both years, in correlation with observed disease incidence; sharp peaks in P. effusa DNA detection were associated with the onset of disease incidence. The incidence of downy mildew in the susceptible field displayed logistic-like dynamics but with considerable interseason variation. Analysis of the area under the disease progress curves suggested that the 2013-14 epidemic was significantly more severe than the 2014-15 epidemic. Spatial analyses indicated that disease incidence was dependent within an average range of 5.6 m, approximately equivalent to the width of three planted beds in a typical production field. The spatial distribution of spores captured during an active epidemic most closely fit a power-law distribution but could also be fit with an exponential distribution. These studies revealed two important results in the epidemiology of spinach downy mildew in California. First, they demonstrated the potential of impaction spore-trap samplers linked with a qPCR assay for indicating periods of high disease risk, as well as the detection of long-distance dispersal of P. effusa spores. Second, at the scale of individual crops, a high degree of spatial aggregation in disease incidence was revealed.

Season-Long Dynamics of Spinach Downy Mildew Determined by Spore Trapping and Disease Incidence.

Peronospora effusa is an obligate oomycete that causes downy mildew of spinach. Downy mildew threatens sustainable production of fresh market organic spinach in California, and routine fungicide sprays are often necessary for conventional production. In this study, airborne P. effusa spores were collected using rotating arm impaction spore trap samplers at four sites in the Salinas Valley between late January and early June in 2013 and 2014. Levels of P. effusa DNA were determined by a species-specific quantitative polymerase chain reaction assay. Peronospora effusa was detected prior to and during the growing season in both years. Nonlinear time series analyses on the data suggested that the within-season dynamics of P. effusa airborne inoculum are characterized by a mixture of chaotic, deterministic, and stochastic features, with successive data points somewhat predictable from the previous values in the series. Analyses of concentrations of airborne P. effusa suggest both an exponential increase in concentration over the course of the season and oscillations around the increasing average value that had season-specific periodicity around 30, 45, and 75 days, values that are close to whole multiples of the combined pathogen latent and infectious periods. Each unit increase in temperature was correlated with 1.7 to 6% increased odds of an increase in DNA copy numbers, while each unit decrease in wind speed was correlated with 4 to 12.7% increased odds of an increase in DNA copy numbers. Disease incidence was correlated with airborne P. effusa levels and weather variables, and a receiver operating characteristic curve analysis suggested that P. effusa DNA copy numbers determined from the spore traps nine days prior to disease rating could predict disease incidence.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.