The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

A Graded Approach to Intravenous Dextrose for Neonatal Hypoglycemia Decreases Blood Glucose Variability, Time in the Neonatal Intensive Care Unit, and Cost of Stay.

OBJECTIVE: To determine associations between a graded approach to intravenous (IV) dextrose treatment for neonatal hypoglycemia and changes in blood glucose (BG), length of stay (LOS), and cost of care. STUDY DESIGN: Retrospective cohort study of 277 infants born at ≥35 weeks of gestation in an urban academic delivery hospital, comparing the change in BG after IV dextrose initiation, neonatal intensive care unit (NICU) LOS, and cost of care in epochs before and after a hospital protocol change. During epoch 1, all infants who needed IV dextrose for hypoglycemia were given a bolus and started on IV dextrose at 60 mL/kg/day. During epoch 2, infants received IV dextrose at 30 or 60 mL/kg/day based on the degree of hypoglycemia. Differences in BG outcomes, LOS, and cost of hospital care between epochs were compared using adjusted median regression. RESULTS: In epoch 2, the median (IQR) rise in BG after initiating IV dextrose (19 [10, 31] mg/dL) was significantly lower than in epoch 1 (24 [14,37] mg/dL; adjusted ß = -6.0 mg/dL, 95% CI -11.2, -0.8). Time to normoglycemia did not differ significantly between epochs. NICU days decreased from a median (IQR) of 4.5 (2.1, 11.0) to 3.0 (1.5, 6.5) (adjusted ß = -1.9, 95% CI -3.0, -0.7). Costs associated with NICU hospitalization decreased from a median (IQR) $14 030 ($5847, $30 753) to $8470 ($5650, $19 019) (adjusted ß = -$4417, 95% CI -$571, -$8263) after guideline implementation. CONCLUSIONS: A graded approach to IV dextrose was associated with decreased BG lability and length and cost of NICU stay for infants with neonatal hypoglycemia.

Stevia rebaudiana Bertoni bioactive effects: From in vivo to clinical trials towards future therapeutic approaches.

Stevia rebaudiana Bertoni, a plant from South America and indigenous of Paraguay, has shown several biological effects and healthy properties, although it is especially used in South America and some Asiatic regions. In addition, it is a natural sweetener, almost 300 times sweeter than sucrose, being attributed to its phytoconstituents prominent antioxidant, antimicrobial, antidiabetic (antihyperglycemic, insulinotropic, and glucagonostatic), antiplatelet, anticariogenic, and antitumor effects. In this sense, this work aims to provide an extensive overview on the historical practices of stevia and its effects in human health based on its chemical composition and applications for both food and pharmaceutical industries.

Hedonic drinking engages a supraspinal inhibition of thermal nociception in adult rats.

The taste of sucrose is commonly used to provide pain relief in newborn humans and is innately analgesic to neonatal rodents. In adulthood, sucrose remains a strong motivator to feed, even in potentially hazardous circumstances (ie, threat of tissue damage). However, the neurobiological mechanisms of this endogenous reward-pain interaction are unclear. We have developed a simple model of sucrose drinking-induced analgesia in Sprague-Dawley rats (6-10 weeks old) and have undertaken a behavioral and pharmacological characterization using the Hargreaves' test of hind-paw thermal sensitivity. Our results reveal an acute, potent, and robust inhibitory effect of sucrose drinking on thermal nociceptive behaviour that unlike the phenomenon in neonates is independent of endogenous opioid signalling and does not seem to operate through classical descending inhibition of the spinal cord circuitry. Experience of sucrose drinking had a conditioning effect whereby the apparent expectancy of sucrose enabled water alone (in euvolemic animals) to elicit a short-lasting placebo-like analgesia. Sweet taste alone, however, was insufficient to elicit analgesia in adult rats intraorally perfused with sucrose. Instead, the sucrose analgesia phenomenon only appeared after conditioning by oral perfusion in chronically cannulated animals. This sucrose analgesia was completely prevented by systemic dosing of the endocannabinoid CB1 receptor antagonist rimonabant. These results indicate the presence of an endogenous supraspinal analgesic circuit that is recruited by the context of rewarding drinking and is dependent on endocannabinoid signalling. We propose that this hedonic sucrose-drinking model may be useful for further investigation of the supraspinal control of pain by appetite and reward.

Biofunctionalization of magnetite nanoparticles with stevioside: effect on the size and thermal behaviour for use in hyperthermia applications.

Controlling the magnetic properties of a nanoparticle efficiently via its particle size to achieve optimized heat under alternating magnetic field is the central point for magnetic hyperthermia-mediated cancer therapy (MHCT). Here, we have shown the successful use of stevioside (a natural plant-based glycoside) as a promising biosurfactant to control the magnetic properties of Fe3O4 nanoparticles by controlling the particle size. The biocompatibility and cellular uptake efficiency by rat C6 glioma cells and calorimetric magnetic hyperthermia profile of the nanoparticles were further examined. Our finding suggests superior properties of stevioside-coated magnetite nanoparticles in comparison to polysorbate-80 and oleic acid coated nanomagnets as far as particle size reduction, biocompatibility, hyperthermic effect, and cellular uptake by the glioblastoma cancer cells are concerned. The stevioside-coated nanomagnets exhibiting the maximum temperature rise were further investigated as heating agents in in vitro magnetic hyperthermia experiments (405 kHz, 168 Oe), showing their efficacy to induce cell death of rat C6 glioma cells after 30 min at a target temperature T = 43 °C.

Pain Experience in a US Children's Hospital: A Point Prevalence Survey Undertaken After the Implementation of a System-Wide Protocol to Eliminate or Decrease Pain Caused by Needles.

OBJECTIVES: Pain in hospitalized children remains under-assessed and undertreated. With this study, we aim to describe results from a repeat single-day, hospital-wide survey of children's pain and its treatment after the initiation of a hospital-wide quality improvement initiative used to reduce or eliminate pain caused by needle procedures. METHODS: All patients and parents listed on the inpatient morning census, in emergency department and outpatient surgery registration lists, were invited to participate in a brief single-day point prevalence survey of their experience with pain and its management in the hospital setting. Results were compared with a survey conducted 2 years earlier, before implementation of a system-wide Children's Comfort Promise needle pain treatment and prevention protocol. RESULTS: A total of 194 children and their parents participated in the current survey. A higher percentage of children reported having no pain compared with the previous survey (33% vs 24%; P = .07; not significant) and fewer experienced severe pain (score ≥7 out of 10). Fewer children identified pain caused by needles as the cause of the worst pain (21% vs 30%), although it remained the highest reported cause of the most painful experience overall. The number of pain management strategies administered and offered to children with needle pain (distraction, positioning, numbing cream, and sucrose and/or breastfeeding for infants) increased. CONCLUSIONS: The implementation of a mandatory Comfort Promise protocol used to minimize or prevent pain caused by elective needle procedures was associated with a significant reduction in overall pain prevalence and improved use of evidence-based practices for needle pain management.

Nursing care to patients with diabetes based on King's Theory / Cuidado de enfermería al paciente con diabetes justificado en la Teoría de King / Cuidado de enfermagem ao paciente com diabetes fundamentado na Teoria de King

ABSTRACT Objective: To verify the effectiveness of nursing interventions based on the Imogene King's Theory of Goal Attainment, on improving care for people with diabetes and adherence to treatment. Method: Quasi-experimental, longitudinal, randomized, simple study in a Primary Health Care Unit, in the city of Fortaleza, Ceará state, Brazil. The sample consisted of 60 people with diabetes, divided into intervention and control groups, whose collection occurred from February to August 2013. Results: In the intervention group, a significant adherence of the patients to the goals defined in the study was found. In the control, there was improvement in some aspects of the treatment. Conclusion: With these results, it was possible to conclude the feasibility of using Theory of Goal Attainment in the positive aspects for adherence to diabetes treatment and improvement of quality of life.

RESUMEN Objetivo: Comprobar la efectividad de intervenciones en enfermería, justificada en la Teoría del Alcance de Metas de Imogene King, en el perfeccionamiento del cuidado a la persona con diabetes y en la adhesión al tratamiento. Método: Estudio cuasi experimental, de naturaleza longitudinal, aleatorizado simple, en una Unidad de Atención Primaria a la Salud, en el municipio de Fortaleza, Ceará, Brasil. La muestra incluyó 60 personas con diabetes, divididas en los grupos de intervención y control, cuya recolección ocurrió de febrero a agosto de 2013. Resultados: En el grupo de intervención, se encontró una adhesión significativa de los pacientes a las metas definidas en el estudio. En el control, hubo una mejora en algunos aspectos del tratamiento. Conclusión: Con estos resultados se pudo concluir la viabilidad del empleo de la Teoría del Alcance de Metas en los aspectos positivos para la adhesión al tratamiento de la diabetes y mejora de la calidad de vida.

RESUMO Objetivo: Verificar a efetividade de intervenções em enfermagem, fundamentada na Teoria do Alcance de Metas de Imogene King, na melhoria do cuidado à pessoa com diabetes e na adesão ao tratamento. Método: Estudo quase-experimental, do tipo longitudinal, randomizado simples, numa Unidade de Atenção Primária à Saúde, no município de Fortaleza, Ceará, Brasill. A amostra contou com 60 pessoas com diabetes, divididas nos grupos de intervenção e controle, cuja coleta ocorreu de fevereiro a agosto de 2013. Resultados: No grupo de intervenção, encontrou-se uma adesão significativa dos pacientes às metas definidas no estudo. No controle, houve melhora em alguns aspectos do tratamento. Conclusão: Com esses resultados pôde-se concluir a viabilidade do emprego da Teoria do Alcance de Metas nos aspectos positivos para a adesão ao tratamento do diabetes e melhoria da qualidade de vida.

Sugarcane Molasses - A Potential Dietary Supplement in the Management of Iron Deficiency Anemia.

Iron deficiency anemia (IDA) is a serious public health problem that debilitates ∼1.6 billion people globally every year, the majority being pregnant women and children from developing countries. In India, for example, in spite of several operational programs at the national level using iron-folic acid and other allopathic interventions, IDA is still prevalent. Traditional medicines, such as Ayurveda, prescribe herbal formulations containing sugarcane derivatives for the management of pandu, a condition similar to IDA. This article reviews molasses, a sugar industry by-product, as a potential raw material to develop nutraceutical products for IDA. Molasses contains iron and its absorption enhancers, such as sulfur, fructose, and copper, which make it a potential dietary supplement for IDA. More research, product development, and evidence of safety and efficacy of molasses in IDA management can provide a tasty and cost-effective dietary supplement, particularly for children. However, there are challenges, such as competition for raw material from refined sugar manufacturers, quality control, etc., that need to be overcome.

Xylitol for preventing acute otitis media in children up to 12 years of age.

BACKGROUND: Acute otitis media (AOM) is the most common bacterial infection among young children in the United States. There are limitations and concerns over its treatment with antibiotics and surgery and so effective preventative measures are attractive. A potential preventative measure is xylitol, a natural sugar substitute that reduces the risk of dental decay. Xylitol can reduce the adherence of Streptococcus pneumoniae (S pneumoniae) and Haemophilus influenzae (H influenzae) to nasopharyngeal cells in vitro. This is an update of a review first published in 2011. OBJECTIVES: To assess the efficacy and safety of xylitol to prevent AOM in children aged up to 12 years. SEARCH METHODS: We searched CENTRAL (to Issue 12, 2015), MEDLINE (1950 to January 2016), Embase (1974 to January 2016), CINAHL (1981 to January 2016), LILACS (1982 to January 2016), Web of Science (2011 to January 2016) and International Pharmaceutical Abstracts (2000 to January 2016). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of children aged 12 years or younger where xylitol supplementation was compared with placebo or no treatment to prevent AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed and rated study quality and extracted relevant data for inclusion in the review. We contacted trial authors to request missing data. We noted data on any adverse events of xylitol. We extracted data on relevant outcomes and estimated the effect size by calculating risk ratio (RR), risk difference (RD) and associated 95% confidence intervals (CI). MAIN RESULTS: We identified five clinical trials that involved 3405 children for inclusion. For this 2016 update, we identified one new trial for inclusion. This trial was systematically reviewed but due to several sources of heterogeneity, was not included in the meta-analysis. The remaining four trials were of adequate methodological quality. In three RCTs that involved a total of 1826 healthy Finnish children attending daycare, there is moderate quality evidence that xylitol (in any form) can reduce the risk of AOM from 30% to around 22% compared with the control group (RR 0.75, 95% CI 0.65 to 0.88). Among the reasons for dropouts, there were no significant differences in abdominal discomfort and rash between the xylitol and the control groups. Xylitol was not effective in reducing AOM among healthy children during a respiratory infection (RR 1.13, 95% CI 0.83 to 1.53; moderate quality evidence) or among otitis-prone healthy children (RR 0.90, 95% CI 0.67 to 1.21; low-quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence showing that the prophylactic administration of xylitol among healthy children attending daycare centres can reduce the occurrence of AOM. There is inconclusive evidence with regard to the efficacy of xylitol in preventing AOM among children with respiratory infection, or among otitis-prone children. The meta-analysis was limited because data came from a small number of studies, and most were from the same research group.

Prevention and Management of Procedural Pain in the Neonate: An Update.

The prevention of pain in neonates should be the goal of all pediatricians and health care professionals who work with neonates, not only because it is ethical but also because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor, yet painful procedures. Therefore, every health care facility caring for neonates should implement (1) a pain-prevention program that includes strategies for minimizing the number of painful procedures performed and (2) a pain assessment and management plan that includes routine assessment of pain, pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and measures for minimizing pain associated with surgery and other major procedures.

Is Stevia rebaudiana Bertoni a Non Cariogenic Sweetener? A Review.

Stevia rebaudiana Bertoni is a small perennial shrub of the Asteraceae (Compositae) family that is native to South America, particularly Brazil and Paraguay, where it is known as "stevia" or "honey leaf" for its powerful sweetness. Several studies have suggested that in addition to their sweetness, steviosides and their related compounds, including rebaudioside A and isosteviol, may offer additional therapeutic benefits. These benefits include anti-hyperglycaemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. Additionally, critical analysis of the literature supports the anti-bacterial role of steviosides on oral bacteria flora. The aim of this review is to show the emerging results regarding the anti-cariogenic properties of S. rebaudiana Bertoni. Data shown in the present paper provide evidence that stevioside extracts from S. rebaudiana are not cariogenic. Future research should be focused on in vivo studies to evaluate the effects on dental caries of regular consumption of S. rebaudiana extract-based products.

Comparative evaluation of in vitro and in vivo high glucose-induced alterations in voltage-gated tetrodotoxin-resistant sodium channel: Effects attenuated by sodium channel blockers.

Glucose uptake in neurons depends on their cellular/physiological activity and the extracellular concentration of glucose around the cell. High concentration of extra-cellular glucose, as under hyperglycemic conditions or pathological condition in diabetes, may persist for extended periods of time in neurons and trigger cellular damage by altering voltage-gated sodium channels (VGSCs), the exact mechanism of which remains unclear. Therefore, we hypothesized that high glucose may directly affect kinetics of the VGSCs in the dorsal root ganglion (DRG) neurons. DRG neurons were exposed to normal glucose (NG: 5.5 mM) and high glucose (HG: 30 mM) for 24 h. In another set of experiments, diabetic DRG neurons were also isolated from streptozotocin-induced diabetic rats. Effects of sodium channel blockers on nociceptive parameters and tetrodotoxin-resistant (TTX-R) Na(+) channel kinetics were elucidated by whole-cell patch-clamp in HG exposure and diabetes-induced rat DRG neurons. HG exposure and diabetes-induced DRG neurons demonstrated significant increase in TTX-R Na(+) current (INa) densities in comparison to the control. Both HG-exposed and diabetic DRG neurons demonstrated similar biophysical characteristics of INa. Lidocaine and tetracaine significantly decreased TTX-R INa density in a concentration- and voltage-dependent manner. Steady-state fast inactivation of INa was shifted in the hyperpolarizing direction whereas voltage-dependent activation was shifted in the rightward direction. Diabetic rats treated with lidocaine and tetracaine (3 mg/kg, i.p.) significantly improved thermal hyperalgesia, mechanical allodynia and motor nerve conduction velocity with a significant inhibition of TTX-R INa density as compared to the diabetic control. These results suggest that HG exposure increases the TTX-R Na(+) channel activity sensitive to Na(+) channel blockers, lidocaine and tetracaine.

D-Xylose suppresses adipogenesis and regulates lipid metabolism genes in high-fat diet-induced obese mice.

D-Xylose, a natural pentose, has been reported to reduce postprandial glucose levels, although its effect on lipid metabolism has not been investigated. Therefore, this study hypothesized that d-xylose, as an alternative sweetener, suppresses adipogenesis and lipid metabolism by regulating blood lipid profiles, blood glucose levels, and related gene expression in high-fat diet (HFD)-induced obese mice. Mice were fed a normal diet, a 60% HFD diet, or an HFD with 5% or 10% of the total sucrose content supplemented with d-xylose (Xylo 5 and Xylo 10 diets, respectively). Weight gain, food intake, and serum lipid levels for each group were measured. After 12 weeks, histopathology of liver sections and assays of gene expression related to adipogenesis and lipid metabolism in visceral fat and liver tissues were analyzed. Body weight gain; fasting blood glucose levels; weights of subcutaneous and visceral adipose tissues; and serum biochemical markers, including total cholesterol and low-density lipoprotein cholesterol, low-/high-density lipoprotein, and total cholesterol/high-density lipoprotein, were significantly lowered in the Xylo 5 and Xylo 10 groups. In addition, d-xylose supplementation resulted in the down-regulation of adipogenesis-related genes, including sterol regulatory element-binding protein 1C, fatty acid synthase, adipocyte protein 2, and CCAAT/enhancer-binding protein α in visceral adipose tissues. Histopathologically, Xylo 5 and Xylo 10 supplementation reduced HFD-induced fat accumulation in the liver and decreased expressions of fatty acid synthase and peroxisome proliferator-activated receptor γ. D-Xylose supplementation also enhanced lipid oxidation by increasing expressions of carnitine palmitoyltransferase 1A; cytochrome P450, family 4, subfamily a, polypeptide 10; and acyl-CoA oxidase. In conclusion, our finding suggests that d-xylose may help prevent or attenuate the progression of obesity-related metabolic disorders by alleviating adipogenesis and dyslipidemia and improving lipid oxidation.

The use of sugar free chewing gum as a supplement in the prevention of dental caries. Narrative Review / Uso del chicle libre de azúcar como complemento en la prevención de la caries dental: revisión narrativa

Dental caries is one of the most prevalent diseases. The WHO has classified it as one of the major public health problems worldwide. That is why a special emphasis has been paid to developing new preventive methods and the use of gum without sugar has been included as one of them. This strategy has significant benefits on oral health due to: (1) saliva stimulation, which favors teeth clearance and regulates the pH; (2) remineralization promotion as a result of the above and incorporation of minerals to the gum;(3) mechanical control of the bacterial plaque; (4) replacement of sugar by sweeteners which are harmful for bacteria (the most commonly used is xylitol) and (5) incorporation of active agents such as bicarbonate, casein, urea, chlorhexidine and chitosan, among others. Despite these benefits, the effect of the gum is considered to be weak for dental caries prevention when used instead of brushing. Therefore, its implementation must be proposed as a complement to oral hygiene routines and not as a preventive measure by itself. It is necessary to carry out a greater amount of clinical trials to evaluate its effectiveness in a context of high biological variability in the short and long term and including patients of different sex, age, socio-economic status and systemic health...

La caries dental constituye una de las enfermedades de mayor prevalencia, siendo catalogada por la OMS como uno de los principales problemas de saludpública a nivel mundial. Por ésta razón se ha enfatizado en el desarrollo de nuevos métodos preventivos a los que se ha incorporado el uso del chicle sin azúcar. Con esta estrategia es posible obtener importantes beneficios para la salud oral producto de: (1) estimulación de la salivación, lo que favorece el aclaramiento y regula el pH; (2) promoción de la remineralización como consecuencia de lo anterior y de la incorporación de minerales a la goma de mascar; (3) control mecánico de la placa bacteriana; (4) sustitucióndel azúcar por edulcorantes nocivos para las bacterias, de los cuales el más utilizado es el xilitol; e (5) incorporaciónde agentes activos tales como bicarbonato, caseína, urea, clorhexidina y quitosano, entre otros. Pese a proporcionar ésta serie de beneficios se considera que el efecto del chiclees débil en la prevención de caries cuando éste propósito se busca en ausencia de cepillado dental y por lo tanto debe proponerse su implementación como complemento a las rutinas de higiene oral y no como una medida preventiva por sí sola, siendo necesario realizar una mayor cantidad de ensayos clínicos, a corto y largo plazo, que evalúen laefectividad en un contexto de alta variabilidad biológica, incluyendo pacientes de distinto sexo, edad, situación socioeconómica y salud sistémica...

Management of patients with active caries.

This paper reports on a mechanism to manage caries as a disease and to medically intervene in the disease process to halt progression. The goal of this paper is to provide this alternative to a surgical-only approach. The management of caries begins with assessing lesion activity and the potential for arrest. This requires a clinical and radiological assessment and evaluation of risk. Hopeless teeth are extracted and large cavities filled to reduce infection. Risk reduction strategies are employed so efforts to arrest lesions can be successful. Teeth with lesions in the enamel or outer third of the dentin should be sealed, not restored, as restorations can weaken teeth and can be traumatic to pulps.

Congenital hyperinsulinism: exclusive human milk and breastfeeding.

Congenital hyperinsulinism is a genetic condition causing dysregulation of insulin and results in persistent hypoglycemia. The most common types are sulfonylurea receptor (SUR1), potassium inward rectifying channel (Kir6.2), glutamate dehydrogenase (GDH), and glucokinase (GK), with SUR1 and Kir6.2 being the most prevalent. It is imperative that these infants undergo diagnostic testing, which includes genetic, neonatal fasting study to induce hypoglycemia, glucagon stimulation, and imaging. Once a diagnosis has been made, surgical intervention may be needed to help regulate blood glucose levels. During this diagnostic process and as the infant is undergoing treatment, there may be little concern for the mother's feeding plan. Because human milk is the preferred form of nutrition for all infants, these mothers should receive prenatal counseling regarding the initiation and maintenance of milk supply. Parenteral nutrition may be necessary to maintain blood glucose to support human milk administration and breastfeeding.