Professional oral care in end-of-life patients with advanced cancers in a hospice ward: improvement of oral conditions.

BACKGROUND: In end-of-life patients with advanced cancers, oral examination, oral care, and oral re-examination are crucial. Although oral symptoms are among the major complaints of end-of-life patients, few studies have focused on oral care in these patients. In this study, the association between oral symptoms and oral dryness among end-of-life patients was examined, and improvement of oral conditions after oral care interventions by a professional dentist was quantified. METHODS: This prospective intervention study included 27 terminally ill patients with advanced cancers in a hospice ward. Professional oral care was administered every morning, and the improvement of oral conditions was assessed by comparing oral conditions before and after the intervention. Oral assessment was performed using the Oral Health Assessment Tool (OHAT) and Oral Assessment Guide. Oral dryness was evaluated through Clinical Diagnosis Classification of oral dryness and an oral moisture device. Oral cleanliness was evaluated using a bacterial counter, and tongue smears were collected for Candida examination; furthermore, oral function was recorded. RESULTS: The presence of oral mucositis was closely associated with severe oral dryness (odds ratio [OR] = 14.93; 95% confidence interval [CI]: 1.95-114.38). The level of oral debris retention was significantly related to the degree of oral dryness (OR = 15.97; 95% CI: 2.06-123.72). The group with higher scores (OHAT > 8), which represent poor oral conditions, showed severe oral dryness (OR = 17.97; 95% CI: 1.45-223.46). Total OHAT scores (median: 7 vs 2) and those of other subgroups (lip, tongue, gums and tissues, saliva, and oral cleanliness showed a significant decrease after the intervention. Furthermore, the occurrence of mucositis (47.1% vs 0%), candidiasis rate (68.8% vs 43.8%), oral dryness self-sensation (63.6% vs 9.1%), and severe oral debris (52.9% vs 11.8%) decreased significantly. CONCLUSIONS: Proper oral care can improve oral health and hygiene, reduce the rate of mucositis, reduce the sensation of oral dryness, increase oral moisture, and reduce the chances of oral infections among end-of-life patients. Daily oral care is necessary and can alleviate oral discomfort, increase food intake, and increase the chances of communication between end-of-life patients and their families.

Targeting intracellular transport combined with efficient uptake and storage significantly increases grain iron and zinc levels in rice.

Rice, a staple food for more than half of the world population, is an important target for iron and zinc biofortification. Current strategies mainly focus on the expression of genes for efficient uptake, long-distance transport and storage. Targeting intracellular iron mobilization to increase grain iron levels has not been reported. Vacuole is an important cell compartment for iron storage and the NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN (NRAMP) family of transporters export iron from vacuoles to cytosol when needed. We developed transgenic Nipponbare rice lines expressing AtNRAMP3 under the control of the UBIQUITIN or rice embryo/aleurone-specific 18-kDa Oleosin (Ole18) promoter together with NICOTIANAMINE SYNTHASE (AtNAS1) and FERRITIN (PvFER), or expressing only AtNRAMP3 and PvFER together. Iron and zinc were increased close to recommended levels in polished grains of the transformed lines, with maximum levels when AtNRAMP3, AtNAS1 and PvFER were expressed together (12.67 µg/g DW iron and 45.60 µg/g DW zinc in polished grains of line NFON16). Similar high iron and zinc levels were obtained in transgenic Indica IR64 lines expressing the AtNRAMP3, AtNAS1 and PvFER cassette (13.65 µg/g DW iron and 48.18 µg/g DW zinc in polished grains of line IR64_1), equalling more than 90% of the recommended iron increase in rice endosperm. Our results demonstrate that targeting intracellular iron stores in combination with iron and zinc transport and endosperm storage is an effective strategy for iron biofortification. The increases achieved in polished IR64 grains are of dietary relevance for human health and a valuable nutrition trait for breeding programmes.

Facilitated citrate-dependent iron translocation increases rice endosperm iron and zinc concentrations.

Iron deficiency affects one third of the world population. Most iron biofortification strategies have focused on genes involved in iron uptake and storage but facilitating internal long-distance iron translocation has been understudied for increasing grain iron concentrations. Citrate is a primary iron chelator, and the transporter FERRIC REDUCTASE DEFECTIVE 3 (FRD3) loads citrate into the xylem. We have expressed AtFRD3 in combination with AtNAS1 (NICOTIANAMINE SYNTHASE 1) and PvFER (FERRITIN) or with PvFER alone to facilitate long-distance iron transport together with efficient iron uptake and storage in the rice endosperm. The citrate and iron concentrations in the xylem sap of transgenic plants increased two-fold compared to control plants. Iron and zinc levels increased significantly in polished and unpolished rice grains to more than 70% of the recommended estimated average requirement (EAR) for iron and 140% of the recommended EAR for zinc in polished rice grains. Furthermore, the transformed lines showed normal phenotypic growth, were tolerant to iron deficiency and aluminum toxicity, and had grain cadmium levels similar to control plants. Together, our results demonstrate that deploying FRD for iron biofortification has no obvious anti-nutritive effects and should be considered as an effective strategy for reducing human iron deficiency anemia.

Enhanced Grain Iron Levels in Rice Expressing an IRON-REGULATED METAL TRANSPORTER, NICOTIANAMINE SYNTHASE, and FERRITIN Gene Cassette.

Micronutrient malnutrition is widespread, especially in poor populations across the globe, and iron deficiency anemia is one of the most prevalent forms of micronutrient deficiencies. Iron deficiency anemia has severe consequences for human health, working ability, and quality of life. Several interventions including iron supplementation and food fortification have been attempted and met with varied degrees of success. Rice, which is a staple food for over half of the world's population, is an important target crop for iron biofortification. The genetic variability of iron content in the rice germplasm is very narrow, and thus, conventional breeding has not been successful in developing high iron rice varieties. Therefore, genetic engineering approaches have targeted at increasing iron uptake, translocation, and storage in the rice endosperm. We previously reported that AtIRT1, when expressed together with AtNAS1 and PvFERRITIN (PvFER) in high-iron (NFP) rice, has a synergistic effect of further increasing the iron concentration of polished rice grains. We have now engineered rice expressing AtIRT1, AtNAS1, and PvFER as a single locus gene cassette and compared the resulting lines with transgenic lines expressing AtIRT1 and PvFER gene cassettes. We also evaluated the efficacies of the MsENOD12B and native AtIRT1 promoters for the expression of AtIRT1 in rice in both types of gene cassettes, and found the native AtIRT1 promoter to be a better choice for driving the AtIRT1 expression in our biofortification strategy. All the single insertion transgenic lines have significant increases of iron concentration, both in polished and unpolished grains, but the concerted expression of AtIRT1, AtNAS1, and PvFER resulted to be a more effective strategy in achieving the highest iron increases of up to 10.46 µg/g dry weight. Furthermore, the transformed high iron lines grew better under iron deficiency growth conditions and also have significantly increased grain zinc concentration. Together, these rice lines have nutritionally relevant increases in polished grain iron and zinc concentration necessary to support human health.