A Brief Informant Screening Instrument for Dementia in the ICU: The Diagnostic Accuracy of the AD8 in Critically Ill Adults Suspected of Having Pre-Existing Dementia.

BACKGROUND/AIM: The diagnostic accuracy of brief informant screening instruments to detect dementia in critically ill adults is unknown. We sought to determine the diagnostic accuracy of the 2- to 3-min Ascertain Dementia 8 (AD8) completed by surrogates in detecting dementia among critically ill adults suspected of having pre-existing dementia by comparing it to the Clinical Dementia Rating Scale (CDR). METHODS: This substudy of BRAIN-ICU included a subgroup of 75 critically ill medical/surgical patients determined to be at medium risk of having pre-existing dementia (Informant Questionnaire on Cognitive Decline in the Elderly [IQCODE] score ≥3.3). We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and AUC for the standard AD8 cutoff of ≥2 versus the reference standard CDR score of ≥1 for mild dementia. RESULTS: By the CDR, 38 patients had very mild or no dementia and 37 had mild dementia or greater. For diagnosing mild dementia, the AD8 had a sensitivity of 97% (95% CI 86-100), a specificity of 16% (6-31), a PPV of 53% (40-65), an NPV of 86% (42-100), and an AUC of 0.738 (0.626-0.850). CONCLUSIONS: Among critically ill patients judged at risk for pre-existing dementia, the 2- to 3-min AD8 is highly sensitive and has a high NPV. These data indicate that the brief tool can serve to rule out dementia in a specific patient population.

Enantioselective Synthesis of 3,3-Difluoropyrrolidin-4-ol, a Valuable Building Block in Medicinal Chemistry.

In this paper, we report for the first time two enantioselective routes to 4,4-difluoropyrrolidin-3-ol, a valuable building block in medicinal chemistry. In the first route, we took advantage of the C2 symmetry of (3R,4R)-3,4-dihydroxypyrrolidine in which the desired chirality was derived from the chiral pool (l-(+)-tartaric acid). In the second route, we efficiently assembled the pyrrolidine ring in the presence of a gem-difluoro moiety to avoid using potentially hazardous deoxofluorinating reagents and subsequently introduced the chirality by a stereoselective iridium-diamine-catalyzed asymmetric transfer hydrogenation reaction.

Can combined compost and biochar application improve the quality of a highly weathered coastal savanna soil?

Soil fertility decline is a major constraint to crop production in sub-Saharan Africa. The positive effect of biochar and compost applications on soil fertility has been reported by many authors. In this study, a 30-day laboratory incubation experiment was done using 120 g samples each of a Haplic acrisol amended with corn cob biochar (cbio), rice husk biochar (rbio), coconut husk biochar (coco300 and coco700) or poultry manure compost (compost); and co- composted rice husk biochar (rcocomp) or co-composted corn cob biochar (cococomp) at rates of 1 % w/w amendment: soil, respectively. Other treatments in the study were combined poultry manure compost and corn cob biochar or rice husk biochar (1 % compost + 1% biochar: 1% soil w/w), respectively, to examine their effects on basal soil respiration, soil pH; soil microbial carbon; cation exchange capacity; total organic carbon, total nitrogen and available nitrogen concentration. Biochar and compost applied solely or together, and composted biochar increased soil pH by 0.28-2.29 pH units compared to the un-amended control. Basal respiration from the sole compost or composted rice husk, or corn cob biochar or combined biochar and compost were higher than the un-amended control, which was similar to that from the biochar only treatments. TOC in the sole compost and combined corn cob biochar and compost treatments were up to 37% and 117% higher, respectively, than the control. Combined application of rice husk biochar and compost increased MBC by 132% while sole compost addition increased MBC by 247%, respectively, compared to the control. In conclusion, the study demonstrated that sole or combined application of compost and biochar, or composted biochar improved soil quality parameters such as soil pH and MBC, and promoted soil C stabilization through enhanced TOC and reduced soil C loss through basal respiration.

One-time application of biochar influenced crop yield across three cropping cycles on tropical sandy loam soil in Ghana.

The preparation and application of biochar by smallholder farmers is labour intensive hence an effective one-time application for multiple cropping seasons would be desirable by farmers and researchers. In this study, one-time biochar application as a soil amendment and its interaction with compost and NPK on yield performances of different crops was investigated across three cropping seasons. Treatments included biochar applied alone or together with compost, inorganic NPK fertilizer or both. Maize, okra and cassava were planted in succession and data was collected on their shoot N, P and K concentrations, yields as well as selected soil parameters (pH, exchangeable acidity, total exchangeable bases, effective cation exchange capacity, total N, total organic carbon, available phosphorus). Data was analyzed with GenSTAT and results were presented in tables and bar graph. Corn cob biochar applied solely did not significantly improve maize and okra yield in the first and second cropping season but increased yield of cassava significantly at the third cropping season. Yield increased in sole NPK, compost and NPK + compost treatments for all cropping cycles, but yields obtained from these treatments in the presence of biochar were greater than their corresponding treatments without biochar. The study also showed that biochar application together with compost, NPK or both, improved total organic carbon, total nitrogen, available phosphorus, total exchangeable bases, exchangeable acidity, effective cation exchange capacity and pH as well as tissue N, P and K of all crops. Our findings demonstrated that a single application of biochar, particularly in the presence of compost, inorganic NPK fertilizer or both can increase yields across three cropping seasons and improve soil fertility.

Application of biochar and inorganic phosphorus fertilizer influenced rhizosphere soil characteristics, nodule formation and phytoconstituents of cowpea grown on tropical soil.

The effect of biochar alone or co-applied with triple superphosphate on rhizosphere soil characteristics, nodule formation, phytoconstituents and antioxidant property of cowpea (Vigna uguiculata) is yet to be adequately examined in sub Saharan Africa. A field experiment was conducted where cowpea (Vigna unguiculata) was grown in a tropical sandy loam soil amended with biochar at 1.5 t ha-1 and 2.5 t ha-1 solely or together with inorganic phosphate fertilizer (Triple superphosphate), applied at a rate of 60 kg P ha -1. At 50% flowering, changes in selected rhizosphere soil properties (pH, total nitrogen, available phosphorus, soil organic carbon, cation exchange capacity), nodule count, phytochemicals (phenols, flavonoids, alkaloids, tannins, saponins) and antioxidant property of cowpea roots and leaves were determined by standard laboratory procedures. Differences between means of the measured parameters were established using ANOVA, and relationships among the parameters were explored using Pearson correlation (p < 0.05). Addition of biochar solely or in combination with TSP significantly (p < 0.05) increased soil pH, total nitrogen, available phosphorus, soil organic carbon, cation exchange capacity and root nodule count. Flavonoids, phenols, alkaloids, saponin, tannin contents and antioxidant activity in the roots and leaves were significantly (p < 0.05) higher in the amended soils compared with the unamended soil. Similarly, soil flavonoids, phenols, alkaloids and antioxidant activity were significantly higher in amended soils compared with control. Significant, positive inter and intra correlation with varying strength was found between soil properties, nodule number and phytoconstituents. This is an indication that biochar can be co-applied with triple superphosphate to sustain soil fertility, improve nodulation and enhance concentrations of phytoconstituents in soil, cowpea roots and leaves.

Antibiotics utilization and farmers' knowledge of its effects on soil ecosystem in the coastal drylands of Ghana.

BACKGROUND: There is paucity of information on antibiotics utilization amongst farmers, factors associated with administration of antibiotics and farmers' knowledge of the effects of antibiotics on the soil ecosystem in Ghana. METHODS: A cross sectional quantitative survey across three coastal regions of Ghana was undertaken amongst poultry and livestock farmers. Six hundred respondents were selected from five districts each across the three regions. Pretested and structured questionnaire were used to collect data through face to face interview. Data were summarized using descriptive statistics and regression analysis. Factors associated with antibiotic administration were determined using binary multiple logistic regression at p ≤ 0.05. RESULTS: Out of the 600 farmers, 95% administered antibiotics and 84% bought antibiotics over-the-counter without prescription. Approximately 9% of antibiotic administration was carried out by veterinary officers, and the remaining, 91% based on farmer's experience. Approximately 93% had access to antibiotics without any difficulty. Withdrawal period was always observed by only 16% of farmers. Majority (74%) of farmers never had education on antibiotics and none of the farmers screened manure for the antibiotic residuals. Years of farming, income status, level of education of farmers, type of animal kept, access to extension services, registration with farmers' association, employing veterinary services, location of farm, system of production, education on antibiotics and access to antibiotics positively and significantly predicted the administration of antibiotics by farmers. Majority of farmers had inadequate knowledge of the effects of antibiotics on soil ecosystem with mean score ranging between 2.87±0.60 and 2.98 ± 0.7 on a scale of 5.0. CONCLUSION: The study exposed the poor practices regarding antibiotic use and also inadequate knowledge on its effect on the soil ecosystem amongst farmers in Ghana. This calls for development of strategies to increase awareness on antibiotics because its misuse can negatively impact human, animals, environment and impact food security.

Use of N-methylformamide as a solvent in indium-promoted Barbier reactions en route to enediyne and epoxy diyne formation: comparison of rate and stereoselectivity in C-C bond-forming reactions with water.

Indium-promoted coupling reactions between propargyl aldehydes (1) and alpha-chloropropargylphenyl sulfide are reported. Although water has been shown to accelerate indium metal promoted reactions, the reverse pattern was observed in this series. Use of N-methylformamide (NMF), which has not previously been a solvent known for use in indium-promoted reactions, afforded an acceleration of these Barbier-style reactions compared to water. Indium-promoted reactions in this study also showed excellent regiocontrol and good stereocontrol, allowing for easy entry into the formation of epoxydiyne and enediyne skeletal structures. This paper also describes use of the Barbier Coupled product (2) as a new, and easy, entry into the formation of enediyne and epoxydiyne skeletal structures.

Fertilizer produced from abattoir waste can contribute to phosphorus sustainability, and biofortify crops with minerals.

Our food security depends on finding a sustainable alternative to rock phosphate for fertilizer production. Furthermore, over 2 billion people worldwide are currently affected by micronutrient deficiencies, and crop concentrations of essential minerals are declining. This paper examines whether a novel multi-element fertilizer, Thallo®, can produce crop yields comparable to conventional rock phosphate derived fertilizers, and have an additional benefit of increasing essential mineral concentrations. Thallo®, produced from abattoir and recycled industrial by-products, was tested against conventional mineral fertilizers in a pot trial with wheat and grass. In soil, yields were comparable between the fertilizer types, but, in a low-nutrient substrate, Thallo® showed a yield benefit. Elemental concentrations in the plant material typically reflected the relative concentrations in the fertilizer, and Thallo® fertilized plants contained significantly more of some essential elements, such as selenium and zinc. Furthermore, concentrations of the toxic element cadmium were significantly lower in Thallo® fertilized crops. Among the fertilizers, manganese concentrations were greatest in the Thallo®, but within the fertilized plants, they were greatest under the mineral fertilizer, showing the complexity of assessing whether nutrients will be taken up by crops. In summary, fertilizers from livestock waste have the potential to improve wheat and grass concentrations of essential elements while maintaining yields.

Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models.

AICARFT is a folate dependent catalytic site within the ATIC gene, part of the purine biosynthetic pathway, a pathway frequently upregulated in cancers. LSN3213128 is a potent (16 nM) anti-folate inhibitor of AICARFT and selective relative to TS, SHMT1, MTHFD1, MTHFD2 and MTHFD2L. Increases in ZMP, accompanied by activation of AMPK and cell growth inhibition, were observed with treatment of LY3213128. These effects on ZMP and proliferation were dependent on folate levels. In human breast MDA-MB-231met2 and lung NCI-H460 cell lines, growth inhibition was rescued by hypoxanthine, but not in the A9 murine cell line which is deficient in purine salvage. In athymic nude mice, LSN3213128 robustly elevates ZMP in MDA-MB-231met2, NCI-H460 and A9 tumors in a time and dose dependent manner. Significant tumor growth inhibition in human breast MDA-MB231met2 and lung NCI-H460 xenografts and in the syngeneic A9 tumor model were observed with oral administration of LSN3213128. Strikingly, AMPK appeared activated within the tumors and did not change even at high levels of intratumoral ZMP after weeks of dosing. These results support the evaluation of LSN3213128 as an antineoplastic agent.

Discovery of N-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model.

A hallmark of cancer is unbridled proliferation that can result in increased demand for de novo synthesis of purine and pyrimidine bases required for DNA and RNA biosynthesis. These synthetic pathways are frequently upregulated in cancer and involve various folate-dependent enzymes. Antifolates have a proven record as clinically used oncolytic agents. Our recent research efforts have produced LSN 3213128 (compound 28a), a novel, selective, nonclassical, orally bioavailable antifolate with potent and specific inhibitory activity for aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), an enzyme in the purine biosynthetic pathway. Inhibition of AICARFT with compound 28a results in dramatic elevation of 5-aminoimidazole 4-carboxamide ribonucleotide (ZMP) and growth inhibition in NCI-H460 and MDA-MB-231met2 cancer cell lines. Treatment with this inhibitor in a murine based xenograft model of triple negative breast cancer (TNBC) resulted in tumor growth inhibition.