Objective:  To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. Methods:  In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of ≥1 previous manic or mixed episodes, and ≥20 Young Mania Rating Scale (YMRS) score were randomized to double‐blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9‐week double‐blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3‐week study. Results:  Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, −5.1 to −8.4). Mean YMRS reductions in lithium‐treated groups were significantly greater (p ≤ 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double‐blind treatment in studies with double‐blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. Conclusions:  These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment‐emergent depression. Lithium was confirmed as an effective therapy in this population.

The concentrations of heavy metals such as Cd, Cr, Cu, Mn, Ni, Pb and Zn were investigated in drinking water sources (surface and groundwater) collected from Swat valley, Khyber Pakhtunkhwa, Pakistan. The potential health risks of heavy metals to the local population and their possible source apportionment were also studied. Heavy metal concentrations were analysed using atomic absorption spectrometer and compared with permissible limits set by Pakistan Environmental Protection Agency and World Health Organization. The concentrations of Cd, Cr, Ni and Pb were higher than their respective permissible limits, while Cu, Mn and Zn concentrations were observed within their respective limits. Health risk indicators such as chronic daily intake (CDI) and health risk index (HRI) were calculated for adults and children separately. CDIs and HRIs of heavy metals were found in the order of Cr > Mn > Ni > Zn > Cd > Cu > Pb and Cd > Ni > Mn > Cr > Cu > Pb > Zn, respectively. HRIs of selected heavy metals in the drinking water were less than 1, indicating no health risk to the local people. Multivariate and univariate statistical analyses showed that geologic and anthropogenic activities were the possible sources of water contamination with heavy metals in the study area.

Both treatments were efficacious and well tolerated.

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Thus, ischemic ST-segment changes developing during recovery from treadmill exercise in apparently healthy individuals have adverse prognostic significance similar to those appearing during exercise.

BACKGROUND In contrast to benign meningiomas, malignant meningiomas (MM) are rare and associated with an unfavourable prognosis. Reports on MM concern fairly small cohorts, often comprising less than 30 cases. OBJECTIVE To describe the outcome MM and identify factors that may influence survival. METHODS Pathology reports and clinical data of 178 patients treated between 1989 and 2017 for a MM at 6 different international institutions were retrospectively reviewed. Seventy-six patients (42.7%) had a previous history of grade I or grade II meningioma. The patients underwent a total of 380 surgical resections and 72.5% received radiotherapy. Median follow-up was 4.5 yr. RESULTS At data collection, 111 patients were deceased (63.4%) and only 23 patients (13.7%) were alive without any residual tumor on the most recent scan. Median overall survival was 2.9 yr, 95% confidence interval [CI; 2.4, 4.5]. Overall survival rates at 1, 5, and 10 yr, respectively, were: 77.7%, 95% CI [71.6, 84.3], 40%, 95% CI [32.7, 49], and 27.9%, 95% CI [20.9, 37.3]. In the multivariable analysis, age at MM surgery <65 yr (hazard ratio [HR] = 0.44, 95% CI [0.29, 0.67], P < .001), previous benign or atypical meningioma surgery (HR = 1.9, 95% CI [1.23, 2.92], P = .004), completeness of resection (HR = 0.51, 95% CI [0.34, 0.78], P = .002), and adjuvant radiotherapy (HR = 0.64, 95% CI [0.42, 0.98], P = .039) were established as independent prognostic factors for survival. CONCLUSION This large series confirms the poor prognosis associated with MM, the treatment of which remains challenging. Patients under 65-yr-old with primary MM may live longer after complete resection and postoperative radiotherapy. Even with aggressive treatments, local control remains difficult to achieve.

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Beauveria bassiana (Balsamo Á Crivelli) Vuillemin based mycoinsecticides are used against agricultural, veterinary and medical insect pests. The fungus has a very diverse and extensive host range. Variation in virulence among isolates of B. bassiana to different insect species has been abundantly documented. Given the effect of multiple factors on virulence, it is not certain whether the observed difference in virulence can be labelled as host specificity. Environmental conditions and susceptibility of the insect population are two main factors that affect successful fungal infection. Keeping the environmental factors constant, if virulence of an isolate to different insect species and different populations within an insect species is compared, the scale of difference between the two responses can be estimated. If differences in virulence of an isolate to different insect species are greater than the difference in virulence to different insect populations within an insect species, then, the isolate can be considered as exhibiting specific preference to those insect species towards which it exhibits high virulence. To examine this feature, a worldwide sample of B. bassiana was bioassayed on nine insect species and two different populations within two insect species. Laboratory bioassays were done on: Bombyx mori (Lepidoptera), Spodoptera litura (Lepidoptera), Chilo partellus (Lepidoptera), Helicoverpa armigera (Lepidoptera), Epilachna vigintioctopunctata (Coleoptera), Mylabris pustulata (Coleoptera), Aphis craccivora (Homoptera), Maconellicoccus hirsutus (Hemiptera) and Oecophylla smaragdina (Hymenoptera). The range of variation in virulence of a B. bassiana isolate to different insect species was not more than that observed with different populations within a single insect species. B. bassiana is thus a generalist with no strict host preference. B. bassiana based biopesticide can be used as a broad spectrum insecticide against a myriad of insect pests.