Characterization of New Races of Xanthomonas oryzae pv. oryzae in Mali Informs Resistance Gene Deployment.

Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae represents a severe threat to rice cultivation in Mali. Characterizing the pathotypic diversity of bacterial populations is key to the management of pathogen-resistant varieties. Forty-one X. oryzae pv. oryzae isolates were collected between 2010 and 2013 in the major rice growing regions in Mali. All isolates were virulent on the susceptible rice variety Azucena; evaluation of the isolates on 12 near isogenic rice lines, each carrying a single resistance gene, identified six new races (A4 to A9) and confirmed race A3 that was previously reported in Mali. Races A5 and A6, isolated in Office du Niger and Sélingué, were the most prevalent races in Mali. Race A9 was the most virulent, circumventing all of the resistance genes tested. Xa3 controlled six of seven races (i.e., 89% of the isolates tested). The expansion of race A9 represents a major risk to rice cultivation and highlights the urgent need to identify a local source of resistance. We selected 14 isolates of X. oryzae pv. oryzae representative of the most prevalent races to evaluate 29 rice varieties grown by farmers in Mali. Six isolates showed a high level of resistance to X. oryzae pv. oryzae and were then screened with a larger collection of isolates. Based on the interactions among the six varieties and the X. oryzae pv. oryzae isolates, we characterized eight different pathotypes (P1 to P8). Two rice varieties, SK20-28 and Gigante, effectively controlled all of the isolates tested. The low association observed among races and pathotypes of X. oryzae pv. oryzae suggests that the resistance observed in the local rice varieties does not simply rely on single known Xa genes. X. oryzae pv. oryzae is pathogenically and geographically diverse. Both the races of X. oryzae pv. oryzae characterized in this study and the identification of sources of resistance in local rice varieties provide useful information to inform the design of effective breeding programs for resistance to bacterial leaf blight in Mali.

Analysis of Xanthomonas oryzae pv. oryzicola population in Mali and Burkina Faso reveals a high level of genetic and pathogenic diversity.

Bacterial leaf streak (BLS) caused by Xanthomonas oryzae pv. oryzicola was first reported in Africa in the 1980s. Recently, a substantial reemergence of this disease was observed in West Africa. Samples were collected at various sites in five and three different rice-growing regions of Burkina Faso and Mali, respectively. Sixty-seven X. oryzae pv. oryzicola strains were isolated from cultivated and wild rice varieties and from weeds showing BLS symptoms. X. oryzae pv. oryzicola strains were evaluated for virulence on rice and showed high variation in lesion length on a susceptible cultivar. X. oryzae pv. oryzicola strains were further characterized by multilocus sequence analysis (MLSA) using six housekeeping genes. Inferred dendrograms clearly indicated different groups among X. oryzae pv. oryzicola strains. Restriction fragment length polymorphism analysis using the transcriptional activator like effector avrXa7 as probe resulted in the identification of 18 haplotypes. Polymerase chain reaction-based analyses of two conserved type III effector (T3E) genes (xopAJ and xopW) differentiated the strains into distinct groups, with xopAJ not detected in most African X. oryzae pv. oryzicola strains. XopAJ functionality was confirmed by leaf infiltration on 'Kitaake' rice Rxo1 lines. Sequence analysis of xopW revealed four groups among X. oryzae pv. oryzicola strains. Distribution of 43 T3E genes shows variation in a subset of X. oryzae pv. oryzicola strains. Together, our results show that African X. oryzae pv. oryzicola strains are diverse and rapidly evolving, with a group endemic to Africa and another one that may have evolved from an Asian strain.

Menopause or climacteric, just a semantic discussion or has it clinical implications?

Climacteric and menopause are two terms that are indistinctly used to name clinical expected events related to the decline in ovarian function. Thus, in the literature and in clinical settings we read and hear 'menopausal symptoms' or 'climacterics symptoms'. Globally, the term menopause is much more frequently used than climacteric but, before we use either one, we should consider that 'menopause' is referring to a specific event, the cessation of menses, and 'climacteric' to gradual changes of ovarian function that start before the menopause and continue thereafter for a while. In the premenopause period, hormonal changes will take place that are associated with symptoms, which deteriorate the quality of life, and with metabolic changes which increase the risk of chronic diseases. Therefore, the word climacteric ('steps' in Greek) seems more adequate to refer to the symptoms and chronic diseases associated with the gradual decrease of ovarian function, and we should leave the term 'menopause' only for naming the event of cessation of menstruation that will happen later as the consequence of the decline in ovarian activity. This differentiation has clinical importance, because it implies that, during the premenopausal period, the impact that the decrease in estrogen has on the health status of women must be assessed and, if it is pertinent, we should indicate lifestyle changes, hormonal therapy, hypolipidemic drugs, etc. It does not seem proper to wait for the cessation of menstrual bleeding before some intervention is started. The decay of women's health starts many years before menopause and prevention of its consequences is a must for us, the clinicians.

A reassessment of the epidemiology of Rice yellow mottle virus following recent advances in field and molecular studies.

The available knowledge on the epidemiology of Rice yellow mottle virus (RYMV) is reassessed in the light of major advances in field and molecular studies of the disease it causes in rice. Previously un-described means of transmission by mammals and through leaf contact have been discovered recently. Several agricultural practices, including the use of seedbed nurseries, have also contributed to a massive build-up of RYMV inoculum. Phytosanitation is now known to be critical to reduce disease incidence in rice. A new model of the ecology of RYMV in which man plays a central role has emerged. Furthermore, estimates of the evolutionary rate of change of RYMV provided a time-frame for its epidemiology, the first attempt for a plant virus. Earlier interpretations of the patterns of virus diversity which assumed a long-term evolution, and assigned a major role to adaptive events had to be discarded. In contrast, a wave-like model of dispersal of RYMV, which postulates its initial diversification in East Africa, followed by westward spread across the continent, was developed, refined and dated. The most salient -- and largely unexpected -- finding is that RYMV emerged recently and subsequently spread rapidly throughout Africa in the last two centuries. Diversification and spread of RYMV has been concomitant with an extension of rice cultivation in Africa since the 19th century. This major agro-ecological change increased the encounters between primary hosts of RYMV and cultivated rice. It also modified the landscape ecology in ways that facilitated virus spread.

Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction.

AIM: To evaluate with validated instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy (AHT). DESIGN: Randomised, double-blind, double-dummy study with two parallel treatment arms. PATIENTS AND METHODS: Forty-seven healthy post-menopausal women, aged 45-64 years, were evaluated using the Female Sexual Function Index (FSFI) and the menopause-specific quality of life questionnaire (MENQOL). Of them, 40 diagnosed with sexual dysfunction were randomised (1:1) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo. After 3 months follow-up, FSFI and MENQOL questionnaires were administered for a second time. RESULTS: Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor, psychological, physical and sexual symptoms. As expected, FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly. In addition, at the end of the study, 68.7% of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI (p < 0.0001). CONCLUSIONS: Adding methyl-testosterone to hormone therapy improves quality of life and sexuality in post-menopausal women with sexual dysfunction.

No effect of atypical antipsychotic drugs on weight gain and risk of developing type II diabetes or lipid abnormalities among nursing home elderly patients with Alzheimer's disease.

AIM: Weight gain and the risk of developing alterations in lipid and glucose metabolism are possible side effects of atypical antipsychotic therapy in young and adult patients. The objective of this study was to examine whether elderly patients with Alzheimer's disease (AD) gain weight or develop disturbances in lipid and glucose metabolism while being treated with atypical antipsychotic drugs. METHODS: This retrospective study identified 36 out of 99 patients (mean age: 75.4+/-7.1, 27 female, 9 males) who were taking risperidone (N=9, mean dosage: 1.42+/-0.49 mg/day), olanzapine (N=17: 4.42+/-1.10 mg/day), and quetiapine (N=10: 75+/-27 mg/day) over a 12 months period. Anthropometric parameters, mini nutritional assessment (MNA), total, HDL and LDL cholesterol, triglycerides, glycaemia were assessed at baseline (T0) and 12 (T1) months. RESULTS: Body weight (BMI=23+/-5 vs 23+/-5), MNA score (21+/-4 vs 21+/-4), blood glucose (5.7+/-2 vs 4.9+/-0.9 mmol/L) or total cholesterol (4.9+/-1.1 vs 4.3+/-0.7 mmol/L), HDL cholesterol (1.3+/-0.3 vs 1.1+/-0.3 mmol/L), LDL cholesterol (3.3+/-0.7 vs 3 +/- 0.4 mmol/L), triglycerides (1.1+/-0 vs 1+/-0.3 mmol/L) did not reveal treatment-induced changes in the patients evaluated (T0 vs T1). CONCLUSION: These results suggest that the treatment with low-dose of atypical antipsychotic drugs is not associated with weight gain or increase the risk of developing type II diabetes or abnormalities of lipid metabolism among elderly patients with AD, who were residing in long-term nursing home.

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

Epirubicin versus CMF as adjuvant therapy for stage I and II breast cancer: a prospective randomised study.

We compared a relatively short regimen of monochemotherapy with epirubicin versus polychemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as adjuvant treatment for stage I and II breast cancer patients. 348 patients with oestrogen receptor negative (ER-) node negative and ER- or ER+ node-positive with <10 nodes were accrued. CMF was given intravenously (i.v.) on days 1 and 8, every 4 weeks, for six courses; epirubicin was given weekly for 4 months. Postmenopausal patients received tamoxifen for 3 years. The primary endpoints were overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS). Outcome evaluation was performed both in eligible patients and in all randomised patients according to the intention-to-treat principle. 8 randomised patients were considered ineligible. At a median follow-up of 8 years, there was no difference in OS (Hazard Ratio (HR)=1.11, 95% Confidence Interval (CI): 0.77-1.61, P=0.58), EFS (HR=1.14, 95% CI: 0.78-1.64, P=0.48), and RFS (HR=1.14, 95% CI: 0.8-1.64, P=0.48) between the two arms for all of the patients. At 8 years, the RFS percentages (+/-Standard Error (S.E.)) were 65.4% (+/-4%) in the CMF arm and 62.7% (+/-4%) in the epirubicin arm; for EFS these were 64.2% (+/-4%) for CMF and 60.8% (+/-4%) for epirubicin, respectively. A significant difference in RFS (P=0.015) was observed in patients with 4-9 positive nodes in favour of the CMF arm. Toxicity in the two arms was superimposable except for more frequent grade 3 alopecia in the epirubicin-treated patients (P=0.001). Overall, at a median follow-up of 8 years, there were no differences between the two arms in terms of OS, EFS and RFS.

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen, or vindesine plus tamoxifen: a prospective randomized study.

This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1-5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.

Different types of smiles and laughter in preschool children.

The relationship among morphologically different forms of smiling and laughter was examined. The participants were 19 Brazilian preschool children. Each child was observed a total of 60 min. in three 10-min. sessions on the playground and three 10-min. sessions in the classroom. Analysis suggests that the various forms of smiling do not simply express different intensities of a single emotion. A two-dimensional structure was indicated by factorial analysis. The first dimension, which could be called playfulness-mock aggression, consisted of a broad smile and laughter. The second dimension, which could be called friendliness-appeasement, consisted of a closed and upper smile. The pattern of correlation found between expressive behaviors and both teacher's and peers' evaluations gives further support to the interpretation that smiling is an heterogeneous category.

Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: a prospective study.

BACKGROUND: The conventional treatment of brain metastases not amenable to surgery is most often radiotherapy. Until now, pharmacologic issues related to the blood brain barrier (BBB) prevented a wide evaluation of chemotherapy. The authors previously reported that the combination of cisplatin (P) and etoposide (E) had strikingly high activity in patients with brain metastases from breast carcinoma. The purpose of this study was to assess, in a larger prospective study, the front-line activity of that combination against brain metastases from breast carcinoma (BC), nonsmall cell lung carcinoma (NSCLC), and malignant melanoma (MM) in patients previously untreated with radiotherapy. METHODS: From December 1986 to July 1993, 116 patients received P 100 mg/m2 on Day 1 and E 100 mg/m2 on Days 1, 3, and 5 or on Days 4, 6, and 8 every 3 weeks. An insignificant change in the E schedule using the same dose on a random basis assured the prospective enrollment and the registration of all cases. Six patients were not eligible and three patients were excluded from the analysis because they were lost to follow-up shortly after the date of registration. One-hundred seven patients were considered for analysis. The distribution according to the primary tumor site was BC in 56 patients (52%), NSCLC in 43 (40%), and MM in 8 (8%). The first evaluation of response was performed after two cycles. In cases of no disease progression, chemotherapy was continued to a maximum of six cycles. RESULTS: Among the 56 patients with BC, 7 achieved complete response (CR) (13%), 14 achieved partial response (PR), 12 had no change (NC), 15 had progressive disease (PD), and 8 had insufficient treatment or response was not assessed. The CR plus rate was 38%. Among the 43 patients with NSCLC, 3 achieved CR (7%), 10 achieved PR, 15 had SD, 7 had PD, and 8 had insufficient treatment or response was not assessed. The CR plus PR rate was 30%. None of the eight patients with MM achieved an objective response. The median survival was 31 weeks for patients with BC (range, 0-287), 32 for patients with NSCLC (0-392+), and 17 for patients with MM (2-48). CONCLUSIONS: The combination of P and E is effective for patients with brain metastases from BC and NSCLC. In this study, the response rate was of the same order as that reported for disseminated disease without central nervous system involvement. The survival figures compare favorably with some others reported in the literature for patients given radiotherapy. A randomized study is warranted to compare this chemotherapy followed by radiotherapy with radiotherapy alone for patients with brain metastases from BC or NSCLC not amenable to surgery or radiosurgery.