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Maize demand in Sub-Saharan Africa is expected to increase 2.3 times during the next 30 years driven by demographic and dietary changes. Over the past two decades, the area cropped with maize has expanded by 17 million hectares in the region, with limited yield increase. Following this trend could potentially result in further maize cropland expansion and the need for imports to satisfy domestic demand. Here, we use data collected from 14,773 smallholder fields in the region to identify agronomic practices that can improve farm yield gains. We find that agronomic practices related to cultivar selection, and nutrient, pest, and crop management can double on-farm yields and provide an additional 82 million tons of maize within current cropped area. Research and development investments should be oriented towards agricultural practices with proven capacity to raise maize yields in the region. Maize demand in Sub-Saharan Africa is expected to increase. Here, the authors use data collected by One Acre Fund on 14,773 smallholder fields in the region and determine that maize production can be increased with minimal cropland expansion by improving management practices. [ABSTRACT FROM AUTHOR]

Abstract The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient‐derived tumor organoids using CRISPR/Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer (CRC) organoids that carry EGFP and lineage‐tracing cassettes knocked in the LGR5 locus. Analysis of LGR5‐EGFP+ cells isolated from organoid‐derived xenografts demonstrated that these cells express a gene program similar to that of normal intestinal stem cells and that they propagate the disease to recipient mice very efficiently. Lineage‐tracing experiments showed that LGR5+ CRC cells self‐renew and generate progeny over long time periods that undergo differentiation toward mucosecreting‐ and absorptive‐like phenotypes. These genetic experiments confirm that human CRCs adopt a hierarchical organization reminiscent of that of the normal colonic epithelium. The strategy described herein may have broad applications to study cell heterogeneity in human tumors.

Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5–6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6. [ABSTRACT FROM AUTHOR]

Metallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses. [ABSTRACT FROM AUTHOR]

Purpose: Financial toxicity is a multidimensional side effect of cancer treatment. Yet, most relevant research has focused on individual-level determinants of financial toxicity and characterized only patient perspectives. This study examined the multilevel determinants of financial toxicity from the perspectives of Latina breast cancer survivors and healthcare professionals.Methods: We analyzed qualitative data from focus groups with 19 Latina breast cancer survivors and interviews with 10 healthcare professionals recruited through community partners and venues in Chicago.Results: At the individual-level, the lack of knowledge and prioritization regarding financial aspects of care (e.g., costs of treatment, insurance coverage) was identified as important determinants of financial toxicity. However, healthcare professionals emphasized the need for early financial planning, while survivors prioritized survival over financial concerns immediately after diagnosis. At the interpersonal-level, social networks were identified as important platforms for disseminating information on financial resources. At the community-level, community norms and dynamics were identified as important barriers to seeking financial assistance. Access to culturally astute community-based organizations was considered one potential solution to eliminate these barriers. At the organizational/healthcare policy-level, financial assistance programs' restrictive eligibility criteria, lack of coverage post-treatment, limited availability, and instability were identified as major determinants of financial toxicity.Conclusion: Our findings suggest that multilevel interventions at the individual-, interpersonal-, community-, and organizational/healthcare policy-levels are needed to adequately address financial toxicity among Latina and other survivors from disadvantaged communities. [ABSTRACT FROM AUTHOR]

Bacteria living in biofilms exhibit altered growth phenotypes, while the biofilm provides benefits, the foremost of which is a certain protection against both immune system and killing effect by antimicrobials. Laser-activated irrigation (LAI) and passive ultrasonic irrigation (PUI) have been proposed as alternative methods for cleaning and disinfecting the root canal, as an adjuvant to conventional chemo-mechanical preparation in order to improve debridement and disinfection. Nevertheless, the potential antibacterial effect of LAI using 0.5% of sodium hypochlorite (NaOCl) has received little attention. Glass Pasteur pipettes were used to mimic single-tooth root canal and to build Enterococcus faecalis biofilm. Several irrigants and treatments were assayed for 60 s including (I) Saline, (II) NaOCl 0.5%, (III) NaOCl 5%, (IV) Er,Cr:YSGG, (V) Saline + LAI, (VI) NaOCl 0.5% + LAI, (VII) Saline + PUI, and (VIII) NaOCl 0.5% + PUI. Bacterial reduction was measured by counting the colony-forming units (CFUs). Additionally, AFM visualization and measurement of nano-roughness parameters were used to evaluate LAI effect on bacteria. NaOCl 5% unpowered and NaOCl 0.5% + LAI were capable of eliminating all bacteria, whereas non-activated saline solution and NaOCl 0.5% failed to eliminate E. faecalis. Lower efficiencies were achieved by PUI. Surface analysis by AFM revealed apparent alterations in NaOCl + LAI-treated cells. The Er,Cr:YSGG laser-activated irrigation (LAI) increased the bactericidal efficiency of 0.5% NaOCl against E. faecalis biofilm. [ABSTRACT FROM AUTHOR]

The glutamate N-methyl-D-aspartate receptor (NMDAR) plays an essential role in the excitotoxic neural damage that follows ischaemic stroke. Because the sigma-1 receptor (σ1R) can regulate NMDAR transmission, exogenous and putative endogenous regulators of σ1R have been investigated using animal models of ischaemic stroke. As both agonists and antagonists provide some neural protection, the selective involvement of σ1Rs in these effects has been questioned. The availability of S1RA (E-52862/MR309), a highly selective σ1R antagonist, prompted us to explore its therapeutic potential in an animal model of focal cerebral ischaemia. Mice were subjected to right middle cerebral artery occlusion (MCAO), and post-ischaemic infarct volume and neurological deficits were determined across a range of intervals after the stroke-inducing surgery. Intracerebroventricular or intravenous treatment with S1RA significantly reduced the cerebral infarct size and neurological deficits caused by permanent MCAO (pMCAO). Compared with the control/sham-operated mice, the neuroprotective effects of S1RA were observed when delivered up to 5 h prior to surgery and 3 h after ischaemic onset. Interestingly, neither mice with the genetic deletion of σ1R nor wild-type mice that were pre-treated with the σ1R agonist PRE084 showed beneficial effects after S1RA administration with regard to stroke infarction. S1RA-treated mice showed faster behavioural recovery from stroke; this finding complements the significant decreases in matrix metalloproteinase-9 (MMP-9) expression and reactive astrogliosis surrounding the infarcted cortex. Our data indicate that S1RA, via σ1R, holds promising potential for clinical application as a therapeutic agent for ischaemic stroke. [ABSTRACT FROM AUTHOR]

Eu(III) and Tb(III) Schiff base complexes are applicable in various fields such as sensing, assays, screening protocols in vitro, and imaging studies in vitro or in vivo. Fluorescent europium and terbium complexes and their interaction with cell penetrating peptide (KKKRKC) can represent an excellent key for understanding pathway of peptide transportation though cell membrane and the application of Schiff base complexes as potential antibacterial drugs. The Schiff base-metal complexes and its conjugates with peptide were tested for their antibacterial activity against Pseudomonas aeruginosa and Salmonella typhimurium. Schiff base-metal complexes conjugated with peptide show minor toxicity in normal human PNT1A cells and high antibacterial activity against P. aeruginosa and S. typhimurium, where IC50 down to 125.9 and/or 36.1 µM were found for P. aeruginosa and S. typhimurium, respectively. Our results strongly suggest that Schiff base-metal complexes conjugated with peptide have great potential to be developed into highly effective antibacterial drug. [ABSTRACT FROM AUTHOR]

Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis. [ABSTRACT FROM AUTHOR]

Due to the considerable stability of green fluorescent proteins and their capacity to be readily permutated or mutated, they may be exploited in multiple ways to enhance the functionality of in vitro biosensors. Many possibilities, such as the formation of chimeras with other proteins or antibodies, as well as Förster resonance emission transfer performance, may be used for the highly sensitive and specific detection of the target molecules. This review considers the great potential of green fluorescent proteins as the fluorescent probing or recognition biomolecule in various in vitro biosensors applications, as well as obstacles associated with their use. [ABSTRACT FROM AUTHOR]

Invasive pulmonary aspergillosis (IPA) is a fungal infection that is seen with particular frequency in immunocompromised patients, and associated with high rates of mortality. To combat or prevent IPA, triazoles such as voriconazole or itraconazole and posaconazole have become accepted as first- and second-line therapy, respectively. However, triazoles are associated with issues of oral bioavailability, high liver metabolism, and/or drug-drug interactions, increasing the variability of systemic concentrations. As a way to overcome these issues, inhalation appears to be a promising route for delivery of triazoles for prophylactic or curative therapy in IPA. Indeed, pulmonary drug delivery drastically increases the drug in situ while decreasing the systemic exposure, thereby limiting drug metabolization, side effects, and drug-drug interactions. The development of triazoles for inhalation has focused on voriconazole and itraconazole, drugs which are both highly permeable but with significant different solubility. In this review, we describe the most advanced and promising pharmaceutical developments for voriconazole and itraconazole. [ABSTRACT FROM AUTHOR]

Arbuscular mycorrhizal (AM) symbioses are mutualistic associations between soil fungi and most vascular plants. Modulation of the hormonal and transcriptional profiles, including changes related to defense signalling, has been reported in many host plants during AM symbioses. These changes have been often related to the improved stress tolerance common in mycorrhizal plants. However, results on the alterations in phytohormones content and their role on the symbiosis are controversial. Here, an integrative analysis of the response of phylogenetically diverse plants (i.e., tomato, soybean, and maize) to two mycorrhizal fungi - Funneliformis mosseae and Rhizophagus irregularis- was performed. The analysis of the defense-related hormones salicylic acid, abscisic acid, and jasmonates, and the expression of marker genes of the pathways they regulate, revealed significant changes in the roots of mycorrhizal plants. These changes depended on both the plant and the AM fungus (AMF) involved. However, general trends can be identified: roots associated with the most effective colonizer R. irregularis showed fewer changes in these defense-related traits, while the colonization by F. mosseae led to significant modifications in all plants tested. The up-regulation of the jasmonate pathway by F. mosseae was found to be highly conserved among the different plant species, suggesting an important role of jasmonates during this AM interaction. Our study evidences a strong influence of the AMF genotype on the modulation of host defense signalling, and offers hints on the role of these changes in the symbiosis. [ABSTRACT FROM AUTHOR]

Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis. [ABSTRACT FROM AUTHOR]

To compare a quantitative assessment of contrast cardiovascular magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) with visual analysis for predicting depressed ejection fraction (dEF) and major adverse cardiac events (MACE). 192 patients underwent CMR at 1 week and 6 months after STEMI. Three quantitative (initial slope, maximal signal intensity and contrast delay in first-pass imaging) and 2 visual perfusion indexes (hypoenhancement in first-pass and microvascular obstruction in late enhancement imaging (LE)) were determined. Quantification of infarct mass and visual assessment of the extent of transmural necrosis (ETN) were also performed. At 6 months, 69 patients displayed dEF. During follow-up (mean 655 days) 20 MACE (death, re-infarction, re-admission for heart failure) occurred. Perfusion quantification took longer ( P < 0.001) and, in ROC curve analyses and the C-statistic, was not superior to visual perfusion analysis for predicting late EF or MACE ( P = ns). Similarly, infarct size quantification was not superior to visual assessment of ETN ( P = ns). In multivariate analyses, only visual assessment of ETN (per segment) predicted dEF (OR 1.30 95%CI [1.04-1.61], P = 0.02) and MACE (HR 1.38 95%CI [1.19-1.60], P < 0.001). Visual analysis of CMR after STEMI is not time consuming and predicts dEF and MACE comparable to quantification. ETN was the strongest parameter. [ABSTRACT FROM AUTHOR]

Passage of Proposition 227 has almost effectively eliminated bilingual education in California public schools, tying the hands of teachers who still have to educate students not fluent in the English language. The intent of bilingual education has been to educate the child first in the native language before immersion into the English language. One principal idea behind this philosophy is that a person who can read and write in his or her native tongue will transition less stressfully to a second language. Proposition 227 has virtually eliminated any chance for this to take place. As teachers, we ask if our English language learners (ELLs) may learn to read and write, but will they comprehend and become fluent in English without the basic knowledge in their primary language? We, as numerous other bilingual education supporters, don't believe so. Our study looked at how 10 practicing educators were impacted by the passage of Proposition 227. Our research team was interested in how Proposition 227 changed their teaching styles, their beliefs regarding the proposition, and whether they believed it to be working or not. We concluded that our teacher interviewees were impacted by the passage of Proposition 227 for several reasons. The first reason is that teaching strategies had to be changed to accommodate the new curriculum. Second, sufficient training was not provided to assist the teachers on the immediate implementation of the English-only initiative. Furthermore, teaching resources such as textbooks, curriculum guides, and new state standards were not received until the following school year, thus creating an unproductive teaching environment for both students and educators. [ABSTRACT FROM AUTHOR]

Objective and design: To examine the inhibitory potential of rupatadine, a new H1-antihistamine and anti-PAF agent, on histamine and TNF- α release. Comparison with an H1-antihistamine (loratadine) and a PAF-antagonist (SR-27417A).¶ Material: Dispersed canine skin mast cells were used to assess the effect of the drugs tested on Fc εRI-dependent and -independent histamine release; the human HMC-1 cell line was used to study TNF- α release.¶ Treatment and methods: Before stimulation mast cell populations were treated with increasing concentrations of rupatadine, loratadine and SR-27417A. Histamine and TNF- α release were measured following 15-30 min and 3 h activation, respectively.¶ Results: The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7 ± 0.4 μM, 3.2 ± 0.7μM and 1.5 ± 0.4 μM, respectively whereas for loratadine the IC50 was 2.1 ± 0.9 μM, 4.0 ± 1.3 M and 1.7 ± 0.5 μM. SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A inhibited TNF- α release with IC50 2.0 ± 0.9 μM, 2.1 ± 1.1 M and 4.3 ± 0.6 μM, respectively.¶ Conclusions: Rupatadine and loratadine showed similar inhibitory effect on histamine and TNF- α release, whereas SR-27417A only exhibited inhibitory effect against TNF- α. [ABSTRACT FROM AUTHOR]

Electrothermal atomic absorption procedures for the rapid determination of cobalt, nickel and copper in soil and sediment samples are presented. The samples are suspended in a hydrofluoric acid solution before being injected into the electrothermal atomizer. Prior mild heating in a microwave oven is recommended for nickel and copper determination. No modifier other than hydrofluoric acid is required. The conventional ashing step is unnecessary since the fast-heating programmes lead to well defined atomization profiles with low background levels that can be corrected using a common deuterium device. Calibration is performed directly using aqueous standards. The results obtained for six certified reference materials confirm the reliability of the procedures. [ABSTRACT FROM AUTHOR]

The three mutator strains ana-8, ana-14, and diu-301 were shown to produce respiratory deficient mutants at different rates. The frequency of respiratory deficient mutants in a culture could be increased by adding ethidium bromide. According to their cytochrome spectra and enzymatic activities they form three classes, namely mutants defective in cytochrome oxidase, in cytochrome b, and in both cytochromes. By restriction enzyme analysis of mitochondrial DNA from about 100 mutants, 22 deletion mutants were identified. The deletions, ranging from 50 to 1,500 base pairs were physically mapped. Deletions were localized in the genes coding for subunit 1 of cytochrome oxidase with its two introns, within the cytochrome b gene and its intron, and within the genes for subunits 2 and 3 of cytochrome oxidase. In several cases, where the physical mapping yielded ambiguous results, pairwise genetic crosses ruled out an overlap between two neighbouring deletions. Using these mitochondrial deletion mutants as tester strains, it was shown that only tetrad analysis and chemical haploidization, but not mitotic segregation analysis, allows a decision between chromosomal and mitochondrial inheritance of respiratory deficiency in Schizosaccharomyces pombe. [ABSTRACT FROM AUTHOR]

The topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal, have been evaluated. Flutrimazole inhibited mouse ear oedema induced by arachidonic acid, tetradecanoylphorbolacetate and dithranol, with IC values of 3.32, 0.55 and 2.42 μmols/ear, respectively. Ketoconazole showed similar potency in arachidonic acid and dithranol models (IC=3.76 and 2.41 μmols/ear) whereas it was less active against tetradecanoylphorbol acetate (IC=1.96 μmols/ear). The standard anti-inflammatory sodium diclofenac was overall slightly more potent than antifungals (IC=2.23, 0.57 and 0.57 μmols/ear against arachidonic acid, tetradecanoylphorbol acetate and dithranol, respectively). Both 2% flutrimazole and 2% ketoconazole creams, applied topically, inhibited carrageenan-induced rat paw oedema by about 40%. Under the same conditions, 1% flutrimazole and diclofenac creams inhibited by 26 and 54%, respectively. Flutrimazole may work through the inhibition of 5-lipoxygenase, as it inhibited LTB production by human granulocytes with an IC value of 11 μM (IC value for ketoconazole was 17 μM), whereas ram seminal vesicle cyclooxygenase was only inhibited by 16% at a concentration of 25 μM. Drugs such as flutrimazole, with dual anti-inflammatory/antifungal activity, may be advantageous in the treatment of topical fungal infections with an inflammatory component. [ABSTRACT FROM AUTHOR]

The inhibitory potencies of different flavonoids for rat liver cytosolic glutathione S-transferase activity varied over 30-fold, depending on the pattern of hydroxylation, the presence of a C-2, C-3 double bond and the substitution of a hydroxyl group with a sugar moiety. Kinetic inactivation studies of the enzyme with the inhibitor quercetin revealed a non-competitive profile versus both glutathione and 1-chloro-2,4-dinitrobenzene. [ABSTRACT FROM AUTHOR]

Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic cells with the longest telomeres and elevated expression of intestinal stem cell (ISC) marker genes. Moreover, using culturing conditions that recreate the ISC niche, a substantial proportion of EPHB2-high cells can be expanded in vitro as an undifferentiated and multipotent population. [ABSTRACT FROM AUTHOR]

The article discusses UR-60427, a novel H4 receptor-inverse agonist investigated at Palau Pharma and found to show good efficacy in the rat asthma model. It details that the effects of histamine as full agonist and thioperamide as inverse agonist were compared. The article concludes that the rat asthma model showed increased airway hyperactivity indicating pulmonary resistance in sensitised animals that was reduced by all doses of UR-60427.

The attachment of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 28213 onto six different materials used to manufacture dental implant abutments was quantitatively determined after 2 and 24 h of contact between the materials and the bacterial cultures. The materials were topographically characterized and their wettability determined, with both parameters subsequently related to bacterial adhesion. Atomic force microscopy, interferometry, and contact angle measurement were used to characterize the materials' surfaces. The results showed that neither roughness nor nano-roughness greatly influenced bacterial attachment whereas wettability strongly correlated with adhesion. After 2 h the degree of E. coli attachment markedly differed depending on the material whereas similar differences were not observed for S. aureus, which yielded consistently higher counts of adhered cells. Nevertheless, after 24 h the adhesion of the two species to the different test materials no longer significantly differed, although on all surfaces the numbers of finally adhered E. coli were higher than those of S. aureus. [ABSTRACT FROM AUTHOR]