Clinical standards for drug-susceptible TB in children and adolescents

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents. METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document. RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent. CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.National Institutes of HealthRevisión por pare

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

DIE ONTWIKKELING VAN 'N GEBRUIKERSVRIENDELIKE TRANSSKEPINGSPAKKET VIR IBM-AANPASBARE PERSOONLIKE REKENAARS.

&lt;p&gt;ENGLISH ABSTRACT: This article reports the implementation of a userfriendly transshipment computer program, NETl, written in Turbo Pascal for IBM-compatible personal computers. The program is based on an existing computer program based on the out-of-kilter algorithm. The validation of the program as well as time tests and applications are discussed.&lt;/p&gt;&lt;p&gt;AFRIKAANSE OPSOMMING: Die artikel beskryf die implementering van 'n gebruikersvriendelike transskepingspakket, NETl, geskryf in Turbo Pascal vir IBMaanpasbare persoonlike rekenaars. Die pakket is gebaseer op 'n reeds best.aande rekenaarprogram wat op die "out-of-kilter"algoritme gebaseer is. Die validering van die program asook tydtoetse en moontlike toepassings word bespreek.&lt;/p&gt

The effect of medium composition and ethanol toxicity on the growth of Saccharomyces cerevisiae strain W303-1A(a).

Published ArticleThe growth of Saccharomyces cerevisiae strain W303-1A(a) was evaluated in complex and chemically defined media. The use of chemically defined medium allowed the complete utilisation of glucose within 20 h. as well as all of the produced ethanol within 45 h. Maximum specific growth rates (µmax) were increased from 0.28 h-1 to 0.42 h-1 and the volumetric rate of ethanol production increased from 0.204 g l-1 h-1 to 0.597 g l-1 h-1. However, when the ethanol concentration exceeded a threshold value of 10 g l-1, the µmax value was significantly decreased. These observations suggest that ethanol metabolism related growth experiments for the relevant strain should be carried out in chemically defined medium with ethanol concentrations below 10 g l-1

The effect of runoff on spray deposition and control of Alternaria brown spot of mandarins

Alternaria alternata pv. citri is the causal agent of Alternaria brown spot on tangerines and their hybrids and infects young leaves and fruit of all ages. In South Africa, repeated high volume (∼9000 L/ha) fungicide sprays on susceptible cultivars are the only effective control measure of this disease. The effect of runoff on spray deposition and biological efficacy was largely unknown. The aims of this study were first to characterise spray deposition and runoff on fruit and leaves, and second to determine the effect of runoff on biological efficacy. Mature Nova mandarin leaves (upper and lower leaf surfaces), Valencia Late oranges and Eureka lemons were sprayed with different volumes of, or dipped in, a mixture of water and a yellow fluorescent pigment. Sprayed parts were illuminated under black light, visualised under a stereomicroscope and digitally photographed at 10 magnification. Quantitative and qualitative deposition assessment of the spray deposition was performed by means of digital image analyses. Hoerl regression curves were fitted to quantitative and qualitative deposition values on upper and lower leaf surfaces over spray volume (R2-values &gt;0.95) and trends clearly indicated that deposition on young or mature leaves and fruit improved as spray volume increased, but only until the point of runoff was reached, thereafter deposition quantity and quality decreased. Deposition values following dip treatments were in all cases significantly subordinate to those of the best spray volumes. Mature upper leaf surfaces and Eureka lemon fruit generally retained less spray deposits than lower leaf surfaces and Valencia Late orange fruit, respectively. In order to determine the effect of runoff on biological efficacy of copper hydroxide against Alternaria brown spot, young Nova leaves were treated in a similar fashion and subsequently drop-inoculated with a virulent strain of A. alternata pv. citri and incubated for 3.5 days in moist chambers at 25C. Biological efficacy of sprays followed a quadratic trend over spray volume and clearly demonstrated the detrimental effect of runoff on biological efficacy of fungicide sprays. Sigmoidal regression analyses of mean infection percentages against quantitative and qualitative deposition on upper and lower surfaces of young Nova leaves yielded very good fits indicating the correlation between biological and deposition data. © Australasian Plant Pathology Society 2009.Articl

The production of hemicellulases by Thermomyces lanuginosus strain SSBP: Influence of agitation and dissolved oxygen tension

Shake-flask cultivation of T. lanuginosus strain SSBP on coarse corn cobs yielded β-xylanase levels of 56,500 nkat/ml at 50 °C, whereas other hemicellulases (β-xylosidase, β-glucosidase, and α-L-arabinofuranosidase) were produced at levels less than 7 nkat/ml. Cultivation on D-xylose yielded much lower levels of xylanase (350 nkat/ml), although other hemicellulase levels were similar to those produced on corn cobs. The influence of agitation rate and dissolved oxygen tension (DOT) on hemicellulase production was studied further in a bioreactor. On xylose, xylanase activities of 4,330 nkat/ml and 4,900 nkat/ml were obtained at stirrer speeds up to 1,400 rpm to control DOT. At a constant stirrer speed of 400 rpm, xylanase activities of 10,930 nkat/ml and 15,630 nkat/ml were obtained when cultivated on xylose and beechwood xylan respectively, despite DOT levels below 5% for the duration of fermentation. The results indicate that there is an interaction between agitation rate and DOT, impacting on xylanase and accessory enzyme production. Higher agitation rates favoured the production of xylosidase, arabinofuranosidase and glucosidase by T. lanuginosus strain SSBP, whereas the lower agitation rates favoured xylanase production. Rheological difficulties precluded cultivation on corn cobs in the bioreactor. Volumetric xylanase productivities of 1,060,000 nkat/l·h and 589,000 nkat/l·h obtained on beechwood xylan and xylose indicate that T. lanuginosus strain SSBP is a hyperxylanase producer with considerable industrial potential.Articl

Development and validation of a HPLC electrochemical detection method to measure COMT activity as a tool in drug development

The determination of catechol-O-methyltransferase (COMT) activity is considered valuable for various pharmaceutical and biomedical research projects. A specific high performance liquid chromatography-coulometric electrochemical detection method, for the assay of COMT activity was developed by measuring the formation of normetanephrine from norepinephrine. The chromatographic separation was achieved on a C18 reversed phase column with a mobile phase consisting of 10 mM sodium dihydrogen phosphate buffer, 4 mM sodium 1-octanesulfonate, 0.17 mM ethylenediaminetetra-acetic acid disodium salt, 6 % methanol and 4 % acetonitrile (pH ± 4.0). The detection of normetanephrine was achieved through electrochemical detection, with a coulometric cell potential setting of +450 mV. The flow rate was at 1 ml/min and the total run time was 45 min. The method was validated according to validation guidelines (Shabir 2006; European Medicines Agency 2011; US FDA 2018). The method was found to be linear (R2 > 0.99) over the analytical range (100 to 2500 ng/ml) for all the analytes. All the other validation parameters (sensitivity, precision, accuracy, recovery and stability) were acceptable and within range. The method was applied for the determination of COMT activity in rat liver homogenate test samples. The known selective COMT inhibitor entacapone was used as test inhibitor. The results confirmed the ability of entacapone to inhibit COMT activity by decreasing the production of all the metabolites of norepinephrin