Agricultural Machinery Corrosion

Agricultural machinery expose to wear and corrosion. This damage results from dealing with varying conditions, such as plant moisture, density of plants, soil types, and environmental condition in the field; therefore, this damage leads to an increase in energy consumption, production losses, and a decrease in the lifetime service of reciprocating mower knives. There are many studies that have identified solutions that can be used to increase the life span of agricultural machinery by reducing the chemical corrosion of agricultural machinery. The methods used to reduce chemical corrosion in agricultural machinery can be summarized by selecting new resistant materials, using paint, and using corrosion inhibitors

SCREENING OF SOME EGYPTIAN PLANT EXTRACTS FOR BIOLOGICAL ACTIVITY AGAINST SOME PATHOGENIC BACTERIA

Plants and plant by-products are now gaining attractiveness in treatment of bacterial infections and food preservation. The objective of this study was to assess antibacterial activity of some Egyptian plant and plant by-products against the locally pathogenic isolates from patients having infectious diseases in our country. Screening of antibacterial activity of ethanol, methanol and hexane extracts of some plants: grape leaves (Vitis vinifera), mulberry leaves (Morus alba), mallow leaves (Corchorus olitorius) and lemon leaves (Citrus limon) toward Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella sp., were investigated. Antibacterial activity was performed by the agar disc diffusion method. The ethanol and methanol extract of tested plant leaves showed promising antibacterial activities against both Gram-positive and Gram-negative tested bacterial isolates due to its great ability to extract those polyphenolic and biological active compounds from natural sources which effectively act against broad spectrum bacteria. Ethanol followed by methanol were found to be the best solvents of choice to extract natural products to get maximum health and medicinal benefits. The results revealed that the extraction efficiency increase with polarity increasing of the solvents, hence the highest extraction done with ethanol and methanol and the lowest extraction with nonpolar solvent n-hexanedid not exhibit any activity against all the tested bacteria. Irradiation at 5 and 10 kGy did not significantly affect the antibacterial activity of all tested plant leaves. Results indicate the potential of these plants for further work on isolation and characterization of the active compounds responsible for antibacterial activity and its exploitation as therapeutic agent

Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014

Sinteza i biološko djelovanje novih supstituiranih derivata tiazolin-kinolina

5-Acyl-8-hydroxyquinoline-2-(3\u27-substituted-4\u27-aryl-2,3-dihydrothiazol-2\u27-ylide- ne)hydrazones, 5a-e to 10a-c, were prepared by the reaction of the appropriate 5-acyl-8-hydroxyquinoline-4-substituted thiosemicarbazones 3a-e and phenacyl bromides 4a-e. Structures of the new compounds were verified on the basis of spectral and elemental analyses. Twenty-eight new compounds were tested for their possible antimicrobial activities. Most of the tested compounds showed weak to moderate antibacterial activity against most of the bacterial strains used in comparison with gatifloxacin as a reference drug. The test compounds showed weak to moderate antifungal activity against tested fungi in comparison with ketoconazole as a reference drug. On the other hand, the newly synthesized compounds were tested for their anti-inflammatory effects and most of them showed good to excellent anti-inflammatory activity compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD50) of the most active anti-inflammatory compounds 6b and 9e were determined in mice; they were non-toxic at doses up to 400 mg kg-1 after i.p. administration.5-Acil-8-hidroksikinolin-2-(3\u27-supstituirani-4\u27-aril-2,3-dihidrotiazol-2\u27-ilid- ne)hidrazoni 5a-e do 10a-c pripravljeni su reakcijom odgovarajućih 5-acil-8-hidroksikinolin-4-supstituiranih tiosemikarbazona 3a-e i fenacil bromida 4a-e. Strukture novih spojeva potvrđene su na temelju spektralnih i elementarnih analiza. Dvadeset osam novih spojeva testirano je na potencijalno antimikrobno djelovanje. Većina spojeva pokazuje slabo do umjereno antibakterijsko djelovanje protiv većine testiranih bakterijskih sojeva u usporedbi s gatifloksacinom kao referentim lijekom, te slabo do umjereno antifungalno djelovanje protiv gljivica u usporedbi s ketokonazolom kao referentnim lijekom. Testovi na protuupalno djelovanje pokazuju da većina spojeva posjeduje dobro ili snažno protuupalno djelovanje u usporedbi s indometacinom. Ulcerogeno djelovanje i srednje letalne doze (LD50) najaktivnijih spojeva 6b i 9e određeni su na miševima. Rezultati pokazuju da su netoksični u dozama do 400 mg kg-1 nakon i.p. primjene

Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab

Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the DMD gene that results in a lack of functional dystrophin protein. Herein, we report the use of quantitative magnetic resonance imaging (MRI) measures as biomarkers in the context of a multicenter phase 2, randomized, placebo-controlled clinical trial evaluating the myostatin inhibitor domagrozumab in ambulatory boys with DMD (n = 120 aged 6 to < 16 years). MRI scans of the thigh to measure muscle volume, muscle volume index (MVI), fat fraction, and T2 relaxation time were obtained at baseline and at weeks 17, 33, 49, and 97 as per protocol. These quantitative MRI measurements appeared to be sensitive and objective biomarkers for evaluating disease progression, with significant changes observed in muscle volume, MVI, and T2 mapping measures over time. To further explore the utility of quantitative MRI measures as biomarkers to inform longer term functional changes in this cohort, a regression analysis was performed and demonstrated that muscle volume, MVI, T2 mapping measures, and fat fraction assessment were significantly correlated with longer term changes in four-stair climb times and North Star Ambulatory Assessment functional scores. Finally, less favorable baseline measures of MVI, fat fraction of the muscle bundle, and fat fraction of lean muscle were significant risk factors for loss of ambulation over a 2-year monitoring period. These analyses suggest that MRI can be a valuable tool for use in clinical trials and may help inform future functional changes in DMD.Trial registration: ClinicalTrials.gov identifier, NCT02310763; registered December 2014

Homozygous missense WIPI2 variants cause a congenital disorder of autophagy with neurodevelopmental impairments of variable clinical severity and disease course.

WIPI2 is a member of the human WIPI protein family (seven-bladed b-propeller proteins binding phosphatidylinositols, PROPPINs), which play a pivotal role in autophagy and has been implicated in the pathogenesis of several neurological conditions. The homozygous WIPI2 variant c.745G>A; p.(Val249Met) (NM_015610.4) has recently been associated with a neurodevelopmental disorder in a single family. Using exome sequencing and Sanger segregation analysis, here, two novel homozygous WIPI2 variants [c.551T>G; p.(Val184Gly) and c.724C>T; p.(Arg242Trp) (NM_015610.4)] were identified in four individuals of two consanguineous families. Additionally, follow-up clinical data were sought from the previously reported family. Three non-ambulant affected siblings of the first family harbouring the p.(Val184Gly) missense variant presented with microcephaly, profound global developmental delay/intellectual disability, refractory infantile/childhood-onset epilepsy, progressive tetraplegia with joint contractures and dyskinesia. In contrast, the proband of the second family carrying the p.(Arg242Trp) missense variant, similar to the initially reported WIPI2 cases, presented with a milder phenotype, encompassing moderate intellectual disability, speech and visual impairment, autistic features, and an ataxic gait. Brain MR imaging in five patients showed prominent white matter involvement with a global reduction in volume, posterior corpus callosum hypoplasia, abnormal dentate nuclei and hypoplasia of the inferior cerebellar vermis. To investigate the functional impact of these novel WIPI2 variants, we overexpressed both in WIPI2-knockout HEK293A cells. In comparison to wildtype, expression of the Val166Gly WIPI2b mutant resulted in a deficient rescue of LC3 lipidation whereas Arg224Trp mutant increased LC3 lipidation, in line with the previously reported Val231Met variant. These findings support a dysregulation of the early steps of the autophagy pathway. Collectively, our findings provide evidence that biallelic WIPI2 variants cause a neurodevelopmental disorder of variable severity and disease course. Our report expands the clinical spectrum and establishes WIPI2-related disorder as a congenital disorders of autophagy

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy.

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to \u3c16 \u3eyears) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619