In vivo and in vitro disappearance of energy and nutrients in novel carbohydrates and cereal grains by pigs

In vivo and in vitro experiments were conducted to determine digestibility of GE and nutrients, as well as DE and ME of carbohydrates fed to growing pigs. The objective of Exp. 1 was to determine the DE and ME of 4 novel carbohydrates fed to pigs. The 4 novel carbohydrates were 2 sources of resistant starch (RS 60 and RS 70), soluble corn fiber (SCF), and pullulan. These carbohydrates were produced to increase total dietary fiber (TDF) intake by humans. Maltodextrin (MD) was used as a highly digestible control carbohydrate. The DE and ME for RS 60 (1,779 and 1,903 kcal/kg, respectively), RS 75(1,784 and 1,677 kcal/kg, respectively), and SCF (1,936 and 1,712 kcal/kg, respectively) were less (P < 0.05) than for MD (3,465 and 3,344 kcal/kg, respectively) and pullulan (2,755 and 2,766 kcal/kg, respectively), and pullulan contained less (P < 0.05) DE and ME than MD. However, there was no difference in the DE and ME for RS 60, RS 75, and SCF. The varying degrees of small intestinal digestibility and differences in fermentability among these novel carbohydrates may explain the differences in the DE and ME among carbohydrates. Therefore, the objectives of Exp. 2 were to determine the effect of these 4 novel carbohydrates and cellulose on apparent ileal (AID) and apparent total tract (ATTD) disappearance, and hindgut disappearance (HGD) of GE, TDF, and nutrients when added to diets fed to ileal-cannulated pigs. The second objective was to measure the endogenous flow of TDF to be able to calculate the standardized ileal disappearance (SID) and standardized total tract (STTD) disappearance of TDF in the 4 novel fibers fed to pigs. Results of the experiment indicated that the AID of GE and DM in diets containing cellulose or the novel fibers was less (P < 0.05) than of the maltodextrin diet, but the ATTD of GE and DM was not different among diets. The addition of RS 60, RS 75, and SCF did not affect the AID of acid hydrolysed ether extract (AEE), CP, or ash, but the addition of cellulose and pullulan reduced (P < 0.01) the AID of CP. The average ileal and total tract endogenous losses of TDF were calculated to be 25.25 and 42.87 g/kg DMI, respectively. The SID of TDF in diets containing RS 60, SCF, and pullulan were greater (P < 0.01) than the SID of TDF in the cellulose diet, but the STTD of the SCF diet was greater (P < 0.05) than for the cellulose and pullulan diets. Results of this experiment indicate that the presence of TDF reduces small intestinal disappearance of total carbohydrates and energy which may reduce the DE and ME of diets and ingredients. Therefore, the objective of Exp. 3 was to determine the DE and ME in yellow dent corn, Nutridense corn, dehulled barley, dehulled oats, polished rice, rye, sorghum, and wheat fed to growing pigs and to determine the AID and ATTD of GE, OM, CP, AEE, starch, total carbohydrates, and TDF in these cereal grains fed to pigs. Results indicated that the AID of GE, OM, and total carbohydrates was greater (P < 0.001) in rice than in all other cereal grains. The AID of starch was also greater (P < 0.001) in rice than in yellow dent corn, dehulled barley, rye, and wheat. The ATTD of GE was greater (P < 0.001) in rice than in yellow dent corn, rye, sorghum, and wheat. With a few exceptions, the AID and ATTD of GE and nutrients in Nutridense corn was not different from the values for dehulled oats. Likewise, with a few exceptions, the AID, ATTD, and HGD of GE, OM, total carbohydrates, and TDF in yellow corn, sorghum, and wheat were not different from each other. The AID of GE and AEE in dehulled barley was greater (P < 0.001) than in rye. The ATTD of GE and most nutrients was greater (P < 0.001) in dehulled barley than in rye. Dehulled oats had the greatest (P < 0.001) ME (kcal/kg DM) whereas rye had the least ME (kcal/kg DM) among the cereal grains. Results of the experiment indicate that the presence of TDF and RS may reduce small intestinal digestibility of starch in cereal grains resulting in reduced DE and ME in these grains. Digestibility experiments involving animals are time consuming and expensive. Therefore, the objective of Exp. 4 was to correlate DM and OM digestibility obtained from 3 in vitro procedures with ATTD of GE and with the concentration of DE in 50 corn samples that were fed to growing pigs. The second objective was to develop a regression model that can predict the ATTD of GE or the concentration of DE in corn. The third objective was to evaluate the suitability of using the DaisyII incubator as an alternative to the traditional water bath when determining in vitro DM and OM digestibility. Results indicated that corn samples incubated with Viscozyme for 48 h in the DaisyII incubator improved (P < 0.001) the ability of the procedure to detect small differences in the ATTD of GE or to detect small differences in the concentration of DE in corn. Likewise, compared with using cellulase or fecal inoculum, the variability in the ATTD of GE and the variability in the DE in corn was better (R2 = 0.56; P < 0.05 and R2 = 0.53; P < 0.06, respectively) explained if Viscozyme was used than if cellulase or fecal inoculum was used. A validated regression model that predicted the DE in corn was developed using Viscozyme and with the corn samples incubated in the DaisyII incubator for a 48 h. In conclusion, this present work used the pig as a model for human gastrointestinal function and evaluates carbohydrates from 2 different nutritional perspectives – humans and animals. The addition of novel carbohydrates reduced the digestibility of energy in the diets without necessarily reducing the digestibility of other nutrients. Thus, supplementation of novel carbohydrates in the diets may be beneficial for the management of diabetes. Aside from diabetic management, cereal grains such as rye and sorghum, may also help in BW management because of there low caloric value, but for undernourished individuals, dehulled oats, dehulled barley, and rice are the ideal grains. From an animal nutrition standpoint, high concentration of dietary fiber is undesirable because it reduces feed efficiency. Therefore, the inclusion of feed ingredients that have a high concentration of dietary fiber is often limited in animal diets. Although in vivo determination is ideal, in vitro procedures are useful tools to determine caloric value of food and feed ingredients.

From genes to radioresistance in head and neck squamous cell carcinoma

Head and Neck Cancers (HNC) are a group of tumours located in the upper aero-digestive tract. Head and Neck Squamous Cell Carcinoma (HNSCC) represent about 90% of all HNC cases. It has been considered the sixth most malignant tumour worldwide and, despite clinical and technological advances, the five-year survival rate has not improved much in the last years. Nowadays, HNSCC is well established as a heterogeneous disease and that its development is due to accumulation of genetic events. Apart from the majority of the patients being diagnosed in an advanced stage, HNSCC is also a disease with poor therapeutic outcome. One of the therapeutic approaches is radiotherapy. However, this approach has different drawbacks like the radioresistance acquired by some tumour cells, leading to a worse prognosis. A major knowledge in radiation biology is imperative to improve this type of treatment and avoid late toxicities, maintaining patient quality of life in the subsequent years after treatment. Then, identification of genetic markers associated to radiotherapy response in patients and possible alterations in cells after radiotherapy are essential steps towards an improved diagnosis, higher survival rate and a better life quality. Not much is known about the radiation effects on cells, so, the principal aim of this study was to contribute to a more extensive knowledge about radiation treatment in HNSCC. For this, two commercial cell lines, HSC-3 and BICR-10, were used and characterized resorting to karyotyping, aCGH and MS-MLPA. These cell lines were submitted to different doses of irradiation and the resulting genetic and methylation alterations were evaluated. Our results showed a great difference in radiation response between the two cell lines, allowing the conclusion that HSC-3 was much more radiosensitive than BICR-10. Bearing this in mind, analysis of cell death, cell cycle and DNA damages was performed to try to elucidate the motifs behind this difference. The characterization of both cell lines allowed the confirmation that HSC-3 was derived from a metastatic tumour and the hypothesis that BICR-10 was derived from a dysplasia. Furthermore, this pilot study enabled the suggestion of some genetic and epigenetic alterations that cells suffer after radiation treatment. Additionally, it also allowed the association of some genetic characteristics that could be related to the differences in radiation response observable in this two cell lines. Taken together all of our results contribute to a better understanding of radiation effects on HNSCC allowing one further step towards the prediction of patients’ outcome, better choice of treatment approaches and ultimately a better quality of life.

Muscle fatigue resistance: comparison of Martin vigorimeter and Jamar dynamometer in community-dwelling people

Background: For the diagnosis of frailty exhaustion is a criteria currently measured by self-reported questionnaires, which are subjective and dependent on individual perception. The FR test has been developed as a bed side objective evaluation of muscle fatigue. The test was validated for the VM. However, the JD is frequently used to measure the grip strength. So the comparison of these devices is required to understand if FR is similar when measured with both devices. Methods: Fifty-four (29 female and 25 male; mean age: 39.98 ± 18.09) community-dwelling people were tested for muscle function. The Fatigue resistance (FR), which is the time during that grip strength drops to 50% of its maximum, was recorded with each device and simultaneous sEMG of the forearm muscles was obtained. The (co-)activation of agonist and antagonist muscles was calculated and compared with the differences between the performances with each device (controlling for gender and age). Results: FR was significantly better when measured with VM compared to JD. At all phases of the FR-test the antagonist muscle co-activation was significantly higher for VM compared to JD. In contrast, the agonist muscle activation level was significantly higher in JD compared to VM. When performing the FR-test with VM, both the agonist muscle activation and antagonist muscle co-activation decreased significantly (p<0.05). Whereas when using the JD, only a significant decrease in the antagonist muscle co-activation was observed. The difference in antagonist muscle activation between VM and JD was significantly related to the difference in FR between both devices. Conclusion: The results suggest that the FR-test when using the VM induces a more prominent muscle exhaustion than when using the JD, which makes the VM more suitable for measuring muscle fatigue resistance. However, these findings must be confirmed in a larger study population.

Characterization of the effect of nitrogen deficiency on above-ground plant phenotypes in relation to root complexity in maize

Nitrogen (N) is an essential plant nutrient in maize production, and if considering only natural sources, is often the limiting factor world-wide in terms of a plant’s grain yield. For this reason, many farmers around the world supplement available soil N with synthetic man-made forms. Years of over-application of N fertilizer have led to increased N in groundwater and streams due to leaching and run-off from agricultural sites. In the Midwest Corn Belt much of this excess N eventually makes its way to the Gulf of Mexico leading to eutrophication (increase of phytoplankton) and a hypoxic (reduced oxygen) dead zone. Growing concerns about these types of problems and desire for greater input use efficiency have led to demand for crops with improved N use efficiency (NUE) to allow reduced N fertilizer application rates and subsequently lower N pollution. It is well known that roots are responsible for N uptake by plants, but it is relatively unknown how root architecture affects this ability. This research was conducted to better understand the influence of root complexity (RC) in maize on a plant’s response to N stress as well as the influence of RC on other above-ground plant traits. Thirty-one above-ground plant traits were measured for 64 recombinant inbred lines (RILs) from the intermated B73 & Mo17 (IBM) population and their backcrosses (BCs) to either parent, B73 and Mo17, under normal (182 kg N ha-1) and N deficient (0 kg N ha-1) conditions. The RILs were selected based on results from an earlier experiment by Novais et al. (2011) which screened 232 RILs from the IBM to obtain their root complexity measurements. The 64 selected RILs were comprised of 31 of the lowest complexity RILs (RC1) and 33 of the highest complexity RILs (RC2) in terms of root architecture (characterized as fractal dimensions). The use of the parental BCs classifies the experiment as Design III, an experimental design developed by Comstock and Robinson (1952) which allows for estimation of dominance significance and level. Of the 31 traits measured, 12 were whole plant traits chosen due to their documented response to N stress. The other 19 traits were ear traits commonly measured for their influence on yield. Results showed that genotypes from RC1 and RC2 significantly differ for several above-ground phenotypes. We also observed a difference in the number and magnitude of N treatment responses between the two RC classes. Differences in phenotypic trait correlations and their change in response to N were also observed between the RC classes. RC did not seem to have a strong correlation with calculated NUE (ΔYield/ΔN). Quantitative genetic analysis utilizing the Design III experimental design revealed significant dominance effects acting on several traits as well as changes in significance and dominance level between N treatments. Several QTL were mapped for 26 of the 31 traits and significant N effects were observed across the majority of the genome for some N stress indicative traits (e.g. stay-green). This research and related projects are essential to a better understanding of plant N uptake and metabolism. Understanding these processes is a necessary step in the progress towards the goal of breeding for better NUE crops.

Medizinischer und gesundheitsökonomischer Nutzen der Untersuchung auf Helicobacter pylori-Besiedlung mittels 13C-Harnstoff-Atemtest in der Primärdiagnostik im Vergleich zu invasiven und nichtinvasiven diagnostischen Verfahren

Hintergrund: Helicobacter pylori (H. pylori) zählt trotz abnehmender Inzidenz zu den häufigsten bakteriellen Infektionskrankheiten des Menschen. Die Infektion mit H. pylori ist ein Risikofaktor für Krankheiten wie gastroduodenale Geschwüre, Magenkarzinomen und MALT (Mucosa Associated Lymphoid Tissue)-Lymphomen. Zur Diagnostik von H. pylori stehen verschiedene invasive und nichtinvasive Verfahren zur Verfügung. Der 13C-Harnstoff-Atemtest wird zur Kontrolle einer Eradikationstherapie empfohlen, kommt in der Primärdiagnostik von H. pylori derzeit jedoch nicht standardmäßig in Deutschland zum Einsatz. Fragestellung: Welchen medizinischen und gesundheitsökonomischen Nutzen hat die Untersuchung auf H. pylori-Besiedlung mittels 13C-Harnstoff-Atemtest in der Primärdiagnostik im Vergleich zu invasiven und nichtinvasiven diagnostischen Verfahren? Methodik: Basierend auf einer systematischen Literaturrecherche in Verbindung mit einer Handsuche werden Studien zur Testgüte und Kosten-Effektivität des 13C-Harnstoff-Atemtests im Vergleich zu anderen diagnostischen Verfahren zum primären Nachweis von H. pylori identifiziert. Es werden nur medizinische Studien eingeschlossen, die den 13C-Harnstoff-Atemtest direkt mit anderen H. pylori-Testverfahren vergleichen. Goldstandard ist eines oder eine Kombination der biopsiebasierten Testverfahren. Für die gesundheitsökonomische Beurteilung werden nur vollständige gesundheitsökonomische Evaluationsstudien einbezogen, bei denen die Kosten-Effektivität des 13C Harnstoff-Atemtests direkt mit anderen H. pylori-Testverfahren verglichen wird. Ergebnisse: Es werden 30 medizinische Studien für den vorliegenden Bericht eingeschlossen. Im Vergleich zum Immunglobulin G (IgG)-Test ist die Sensitivität des 13C-Harnstoff-Atemtests zwölfmal höher, sechsmal niedriger und einmal gleich, und die Spezifität 13-mal höher, dreimal niedriger und zweimal gleich. Im Vergleich zum Stuhl-Antigen-Test ist die Sensitivität des 13C-Harnstoff-Atemtests neunmal höher, dreimal niedriger und einmal gleich, und die Spezifität neunmal höher, zweimal niedriger und zweimal gleich. Im Vergleich zum Urease-Schnelltest sind die Sensitivität des 13C-Harnstoff-Atemtests viermal höher, dreimal niedriger und viermal gleich und die Spezifität fünfmal höher, fünfmal niedriger und einmal gleich. Im Vergleich mit der Histologie ist die Sensitivität des 13C-Harnstoff-Atemtests einmal höher und zweimal niedriger und die Spezifität zweimal höher und einmal niedriger. In je einem Vergleich zeigt sich kein Unterschied zwischen 13C-Harnstoff-Atemtest und 14C-Harnstoff-Atemtest, sowie eine niedrigere Sensitivität und höhere Spezifität im Vergleich zur Polymerase-Kettenreaktion (PCR). Inwieweit die beschriebenen Unterschiede statistisch signifikant sind, wird in sechs der 30 Studien angegeben. Es werden neun gesundheitsökonomische Evaluationen in dem vorliegenden Bericht berücksichtigt. Die Test-and-Treat-Strategie mittels 13C-Harnstoff-Atemtest wird in sechs Studien mit einem Test-and-Treat-Verfahren auf Basis der Serologie sowie in drei Studien mit einem Test-and-Treat-Verfahren auf Basis des Stuhl-Antigen-Tests verglichen. Dabei ist das Atemtestverfahren dreimal kosteneffektiv gegenüber der serologischen Methode und wird von der Stuhl-Antigen-Test-Strategie einmal dominiert. Vier Studien beinhalten einen Vergleich der Test-and -Treat-Strategie auf Basis des 13C-Harnstoff-Atemtests mit einer empirischen antisekretorischen Therapie, wobei sich das Atemtesverfahren zweimal als kosteneffektive Prozedur erweist und zwei Studien einen Vergleich mit einer empirischen Eradikationstherapie. In fünf Studien wird das Test-and-Treat-Verfahren mittels 13C-Harnstoff-Atemtest einer endoskopiebasierten Strategie gegenübergestellt. Zweimal dominiert die Atemteststrategie die endoskopische Prozedur und einmal wird sie von dieser Strategie dominiert. Diskussion:Sowohl die medizinischen als auch die ökonomischen Studien weisen mehr oder minder gravierende Mängel auf und liefern heterogene Ergebnisse. So werden in der Mehrzahl der medizinischen Studien keine Angaben zur statistischen Signifikanz der berichteten Unterschiede zwischen den jeweiligen Testverfahren gemacht. Im direkten Vergleich weist der 13C-Harnstoff-Atemtest überwiegend eine höhere Testgüte als der IgG und der Stuhl-Antigen-Test auf. Aus den Vergleichen mit dem Urease-Schnelltest lassen sich keine Tendenzen bezüglich der Sensitivität ableiten, wohingegen die Spezifität des 13C-Harnstoff-Atemtests höher einzuschätzen ist. Für die Vergleiche des 13C-Harnstoff-Atemtest mit der Histologie, dem 14C-Harnstoff-Atemtest und der PCR liegen zu wenige Ergebnisse vor. In der eingeschlossenen ökonomischen Literatur deuten einige Studienergebnisse auf eine Kosten-Effektivität der Test-and-Treat-Strategie mittels 13C-Harnstoff-Atemtest gegenüber dem Test-and-Treat-Verfahren auf Basis der Serologie und der empirischen antiskretorischen Therapie hin. Um Tendenzen bezüglich der Kosten-Effektivität der Atemteststrategie gegenüber der Test-and-Treat-Strategie mittels Stuhl-Antigen-Test sowie der empirischen Eradikationstherapie abzuleiten, mangelt es an validen Ergebnissen bzw. ökonomischer Evidenz. Die Untersuchungsresultate hinsichtlich eines Vergleichs mit endoskopiebasierten Verfahren fallen diesbezüglich zu heterogen aus. Insgesamt kann keines der ökonomischen Modelle der Komplexität des Managements von Patienten mit dyspeptischen Beschwerden gänzlich gerecht werden. Schlussfolgerungen/Empfehlungen: Zusammenfassend ist festzuhalten, dass die Studienlage zur medizinischen und ökonomischen Beurteilung des 13C-Harnstoff-Atemtests im Vergleich zu anderen diagnostischen Methoden nicht ausreichend ist, um den Atemtest als primärdiagnostisches Standardverfahren im Rahmen einer Test-and-Treat-Strategie beim Management von Patienten mit dyspeptischen Beschwerden für die deutsche Versorgungslandschaft insbesondere vor dem Hintergrund der Leitlinien der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS) anstelle einer endoskopiebasierten Methode zu empfehlen.

A comparison of the physiological demands of rugby union match-play when determined by absolute (ABS) or individual (IND) velocity bands in Global Positioning System (GPS) analysis

Since turning professional in 1995 there have been considerable advances in the research on the demands of rugby union, largely using Global Positioning System (GPS) analysis over the last 10 years. A systematic review on the use of GPS, particularly the setting of absolute (ABS) and individual (IND) velocity bands in field based, intermittent, high-intensity (HI) team sports was undertaken. From 3669 records identified, 38 studies were included for qualitative analysis. Little agreement on the definition of movement intensities within team sports was found, only three papers, all on rugby union, had used IND bands, with only one comparing ABS and IND methods. Thus, the aim of this study was to determine if there is a difference in the demands within positions when comparing ABS and IND methods for GPS analysis and if these differences are significantly different between the forward and back positional groups. A total of 214 data files were recorded from 26 players in 17 matches of the 2015/2016 Scottish BT Premiership. ABS velocity zones 1-7 were set at 1) 0-6, 2) 6.1-11, 3) 11.1-15, 4) 15.1-18, 5) 18.1-21, 6) 21.1-15 and 7) 25.1-40km.h-1 while IND zones 1-7 were 1) <20, 2) 20-40, 3) 40-50, 4) 50-70, 5) 70-80, 6) 80-95 and 7) 95-100% of player’s individually determined maximum velocity (Vmax). A 40m sprint test measured Vmax using OptaPro S4 10 Hz (catapult, Australia) GPS units to derive IND bands. The same GPS units were worn during matches. GPS outputs analysed were % distance, % time, high intensity efforts (HIEs) over 18.1 km.h-1 / 70% max velocity and repeated high intensity efforts (RHIEs) which consists of three HIEs in 21secs. General linear model (GLM) analysis identified a significant difference in the measurement of % total distance covered, between the ABS and IND methods in all zones for forwards (p<0.05) and backs (p<0.05). This difference was also significant between forwards and backs in zones 1, shown as mean difference ± standard deviation (3.7±0.7%), 6 (1.2±0.4%) and 7 (1.0±0.0%) respectively (p<0.05). Percentage time estimations were significantly different between ABS and IND analysis within forwards in zones 1 (1.7±1.7%), 2 (-2.9±1.3%), 3 (1.9±0.8%), 4 (-1.4±0.8%) and 5 (0.2±0.4%), and within backs in zones 1 (-10±1.5%), 2 (-1.2±1.1%), 3 (1.8±0.9%) and 5 (0.6±0.5%) (p<0.05). The difference between groups was significant in zones 1, 2, 4 and 5 (p<0.05). The number of HIEs was significantly different between forwards and backs in zones 6 (6±2) and 7 (3±2). RHIEs were significantly different between ABS and IND for forwards (1±2, p<0.05) although not between groups. Until more research on the differences in ABS and IND methods is carried out, then neither can be deemed a criterion method. In conclusion, there are significant differences between the ABS and IND methods of GPS analysis of the physical demands of rugby union, which must be considered when used to inform training load and recovery to improve performance and reduce injuries.

Oxidative stress and its haemodynamic consequences in chronic kidney disease

Chronic kidney disease (CKD) is associated with increased cardiovascular risk in comparison with the general population. This can be observed even in the early stages of CKD, and rises in proportion to the degree of renal impairment. Not only is cardiovascular disease (CVD) more prevalent in CKD, but its nature differs too, with an excess of morbidity and mortality associated with congestive cardiac failure, arrhythmia and sudden death, as well as the accelerated atherosclerosis which is also observed. Conventional cardiovascular risk factors such as hypertension, dyslipidaemia, obesity, glycaemia and smoking, are highly prevalent amongst patients with CKD, although in many of these examples the interaction between risk factor and disease differs from that which exists in normal renal function. Nevertheless, the extent of CVD cannot be fully explained by these conventional risk factors, and non-conventional factors specific to CKD are now recognised to contribute to the burden of CVD. Oxidative stress is a state characterised by excessive production of reactive oxygen species (ROS) and other radical species, a reduction in the capacity of antioxidant systems, and disturbance in normal redox homeostasis with depletion of protective vascular signalling molecules such as nitric oxide (NO). This results in oxidative damage to macromolecules such as lipids, proteins and DNA which can alter their functionality. Moreover, many enzymes are sensitive to redox regulation such that oxidative modification to cysteine thiol groups results in activation of signalling cascades which result in adverse cardiovascular effects such as vascular and endothelial dysfunction. Endothelial dysfunction and oxidative stress are present in association with many conventional cardiovascular risk factors, and can be observed even prior to the development of overt, clinical, vascular pathology, suggesting that these phenomena represent the earliest stages of CVD. In the presence of CKD, there is increased ROS production due to upregulated NADPH oxidase (NOX), increase in a circulating asymmetric dimethylarginine (ADMA), uncoupling of endothelial nitric oxide synthase (eNOS) as well as other mechanisms. There is also depletion in exogenous antioxidants such as ascorbic acid and tocopherol, and a reduction in activity of endogenous antioxidant systems regulated by the master gene regulator Nrf-2. In previous studies, circulating markers of oxidative stress have been shown to be increased in CKD, together with a reduction in endothelial function in a stepwise fashion relating to the severity of renal impairment. Not only is CVD linked to oxidative stress, but the progression of CKD itself is also in part dependent on redox sensitive mechanisms. For example, administration of the ROS scavenger tempol attenuates renal injury and reduces renal fibrosis seen on biopsy in a mouse model of CKD, whilst conversely, supplementation with the NOS inhibitor L-NAME causes proteinuria and renal impairment. Previous human studies examining the effect of antioxidant administration on vascular and renal function have been conflicting however. The work contained in this thesis therefore examines the effect of antioxidant administration on vascular and endothelial function in CKD. Firstly, 30 patients with CKD stages 3 – 5, and 20 matched hypertensive controls were recruited. Participants with CKD had lower ascorbic acid, higher TAP and ADMA, together with higher augmentation index and pulse wave velocity. There was no difference in baseline flow mediated dilatation (FMD) between groups. Intravenous ascorbic acid increased TAP and O2-, and reduced central BP and augmentation index in both groups, and lowered ADMA in the CKD group only. No effect on FMD was observed. The effects of ascorbic acid on kidney function was then investigated, however this was hindered by the inherent drawbacks of existing methods of non-invasively measuring kidney function. Arterial spin labelling MRI is an emerging imaging technique which allows measurement of renal perfusion without administration of an exogenous contrast agent. The technique relies upon application of an inversion pulse to blood within the vasculature proximal to the kidneys, which magnetically labels protons allowing measurement upon transit to the kidney. At the outset of this project local experience using ASL MRI was limited and there ensued a prolonged pre-clinical phase of testing with the aim of optimising imaging strategy. A study was then designed to investigate the repeatability of ASL MRI in a group of 12 healthy volunteers with normal renal function. The measured T1 longitudinal relaxation times and ASL MRI perfusion values were in keeping with those found in the literature; T1 time was 1376 ms in the cortex and 1491 ms in the whole kidney ROI, whilst perfusion was 321 mL/min/100g in the cortex, and 228 mL/min/100g in the whole kidney ROI. There was good reproducibility demonstrated on Bland Altman analysis, with a CVws was 9.2% for cortical perfusion and 7.1% for whole kidney perfusion. Subsequently, in a study of 17 patients with CKD and 24 healthy volunteers, the effects of ascorbic acid on renal perfusion was investigated. Although no change in renal perfusion was found following ascorbic acid, it was found that ASL MRI demonstrated significant differences between those with normal renal function and participants with CKD stages 3 – 5, with increased cortical and whole kidney T1, and reduced cortical and whole kidney perfusion. Interestingly, absolute perfusion showed a weak but significant correlation with progression of kidney disease over the preceding year. Ascorbic acid was therefore shown to have a significant effect on vascular biology both in CKD and in those with normal renal function, and to reduce ADMA only in patients with CKD. ASL MRI has shown promise as a non-invasive investigation of renal function and as a biomarker to identify individuals at high risk of progressive renal impairment.

Effect of remote ischaemic preconditioning in cardiac dysfunction and end-organ injury following cardiac surgery with cardiopulmonary bypass in children: A translational approach investigating clinical outcome and myocardial molecular biology

Congenital heart disease (CHD) is the most common birth defect, causing an important rate of morbidity and mortality. Treatment of CHD requires surgical correction in a significant percentage of cases which exposes patients to cardiac and end organ injury. Cardiac surgical procedures often require the utilisation of cardiopulmonary bypass (CPB), a system that replaces heart and lungs function by diverting circulation into an external circuit. The use of CPB can initiate potent inflammatory responses, in addition a proportion of procedures require a period of aortic cross clamp during which the heart is rendered ischaemic and is exposed to injury. High O2 concentrations are used during cardiac procedures and when circulation is re-established to the heart which had adjusted metabolically to ischaemia, further injury is caused in a process known as ischaemic reperfusion injury (IRI). Several strategies are in place in order to protect the heart during surgery, however injury is still caused, having detrimental effects in patients at short and long term. Remote ischaemic preconditioning (RIPC) is a technique proposed as a potential cardioprotective measure. It consists of exposing a remote tissue bed to brief episodes of ischaemia prior to surgery in order to activate protective pathways that would act during CPB, ischaemia and reperfusion. This study aimed to assess RIPC in paediatric patients requiring CHD surgical correction with a translational approach, integrating clinical outcome, marker analysis, cardiac function parameters and molecular mechanisms within the cardiac tissue. A prospective, single blinded, randomized, controlled trial was conducted applying a RIPC protocol to randomised patients through episodes of limb ischaemia on the day before surgery which was repeated right before the surgery started, after anaesthesia induction. Blood samples were obtained before surgery and at three post-operative time points from venous lines, additional pre and post-bypass blood samples were obtained from the right atrium. Myocardial tissue was resected during the ischaemic period of surgery. Echocardiographic images were obtained before the surgery started after anaesthetic induction and the day after surgery, images were stored for later off line analysis. PICU surveillance data was collected including ventilation parameters, inotrope use, standard laboratory analysis and six hourly blood gas analysis. Pre and post-operative quantitation of markers in blood specimens included cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP), inflammatory mediators including interleukins IL-6, IL-8, IL-10, tumour necrosis factor (TNF-α), and the adhesion molecules ICAM-1 and VCAM-1; the renal marker Cystatin C and the cardiovascular markers asymmetric dymethylarginine (ADMA) and symmetric dymethylarginine (SDMA). Nitric oxide (NO) metabolites and cyclic guanosine monophosphate (cGMP) were measured before and after bypass. Myocardial tissue was processed at baseline and after incubation at hyperoxic concentration during four hours in order to mimic surgical conditions. Expression of genes involved in IRI and RIPC pathways was analysed including heat shock proteins (HSPs), toll like receptors (TLRs), transcription factors nuclear factor κ-B (NF- κ-B) and hypoxia inducible factor 1 (HIF-1). The participation of hydrogen sulfide enzymatic genes, apelin and its receptor were explored. There was no significant difference according to group allocation in any of the echocardiographic parameters. There was a tendency for higher cTnI values and inotropic score in control patients post-operatively, however this was not statistically significant. BNP presented no significant difference according to group allocation. Inflammatory parameters tended to be higher in the control group, however only TNF- α was significantly higher. There was no difference in levels of Cystatin C, NO metabolites, cGMP, ADMA or SDMA. RIPC patients required shorter PICU stay, all other clinical and laboratory analysis presented no difference related to the intervention. Gene expression analysis revealed interesting patterns before and after incubation. HSP-60 presented a lower expression at baseline in tissue corresponding to RIPC patients, no other differences were found. This study provided with valuable descriptive information on previously known and newly explored parameters in the study population. Demographic characteristics and the presence of cyanosis before surgery influenced patterns of activity in several parameters, numerous indicators were linked to the degree of injury suffered by the myocardium. RIPC did not reduce markers of cardiac injury or improved echocardiographic parameters and it did not have an effect on end organ function; some effects were seen in inflammatory responses and gene expression analysis. Nevertheless, an important clinical outcome indicator, PICU length of stay was reduced suggesting benefit from the intervention. Larger studies with more statistical power could determine if the tendency of lower injury and inflammatory markers linked to RIPC is real. The present results mostly support findings of larger multicentre trials which have reported no cardiac benefit from RIPC in paediatric cardiac surgery.

The Effectiveness of Community-Based Nutrition Education on the Nutrition Status of Under-five Children in Developing Countries. A Systematic Review

Aim This systematic review aimed at examining the best available evidence on the effectiveness of community-based nutrition education in improving the nutrition status of under five children in developing countries. Methods A systematic search of the literature was conducted utilising the following data bases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Medline, and Web of Knowledge. 9 studies were identified for the critical appraisal process. The Joanna Briggs Institute (JBI) critical appraisal check-list for experimental studies was utilised and two reviewers conducted the appraisal process independently. 7 studies were included for this review and data was extracted using the JBI data extraction form for experimental studies. The extracted data was heterogeneous as such narrative synthesis was conducted. Results The nutritional status of children in all studies improved and this was evidenced by increases in weight, height, mid upper arm circumference and reduced morbidity. Key messages about education were age at introduction of complementary foods, nutrition value on different types of feeds found locally and frequency of feeding the children. However, there were varied Results regarding the effects of the intervention on the nutrition status of children. This was attributed by differences in implementers’ characteristics, different intervention strategy and intensity, difference in age of the children at enrolment, pre-existing children’s growth and nutritional status and follow-up periods. In addition to home visiting, conducting group meetings of care givers and community leaders, providing education twice a week and use of cooking demonstrations have shown that they produce highly significant findings. Conclusion The evidence from the identified studies suggests that community- based nutrition education improves the nutrition status of under-five children in developing countries.

Aerobic endurance in HIV-positive young adults and HIV-negative controls in Malawi

Background Aerobic endurance is an important aspect of physical fitness that enables individuals living with HIV to endure in the work place as well as in agricultural operations in order to earn a living and improve their quality of life. However, despite high HIV prevalence rates, the aerobic endurance status of young Malawians living with HIV remains unknown. The objective of this study was to determine the difference in VO2max between HIV-negative and HIV-positive individuals in Blantyre, Malawi. Methods Fifty five participants (17 males and 38 females) who have HIV and were not taking antiretroviral medication and 78 HIV-negative participants (45 males and 33 females) performed the Rockport submaximal treadmill exercise test. Measures of body weight, post-exercise heart rate and time to walk one mile were obtained and used to predict VO2max. Comparisons between groups were adjusted for age differences using analysis of covariance (ANCOVA). Results VO2max was significantly lower in HIV-positive subjects [31.1, 28.7 - 33.5mL.kg-1.min-1(mean, 95% CI)] compared with HIV-negative subjects [56.2, 54.3 - 58.1mL.kg-1.min-1]. Conclusion Aerobic endurance was markedly reduced in HIV-positive participants compared with HIV-negative participants. Findings of the current study implicate factors associated with the HIV infection as contributors to a decreased aerobic endurance in people living with HIV.

The Comparison of Under-Five-Children’s Nutrition Status Among Ethnic Groups in North of Iran, 1998 - 2013; Results of a Three Stages Cross-Sectional Study

Background: Despite improvements in child health, malnutrition still remains one of the main public health challenges in Iran. Objectives: The aim of this study was to compare under nutrition among under-five children with regard to ethnicity in rural area in north Iran. Patients and Methods: In three cross-sectional studies 7575 subjects in three time-periods including 2339 children in 1998, 2749 in 2004, and 2487 in 2013, were evaluated. All under-five-children in 20 out of 118 villages were chosen by random sampling and assessed. Under nutrition was defined as underweight, stunting and wasting lower than -2 SD (Z < -2 SD). Results: Generally, stunting was declined 17.1% and underweight and wasting were increased 0.9% and 1%, respectively during 15 years (1998 - 2013). Underweight increased 0.5% in Fars-natives and 3.2% in Turkmans and it was decreased 0.9% in Sistanis. Statistical difference in Turkman children among the three stages of the study was significant (P = 0.001). Stunting has decreased 28.7% in Fars-natives and 35.1% in Sistanis, it was increased 9.3% in Turkman group. Statistical differences among three stages in inter-ethnic groups were significant (P = 0.001 for all). Compared the group with good economic status, the odds ratio was 1.831 in poor economic group (P = 0.001). The risk of under nutrition in Sistanis was 1.754 times more than in Fars-natives (P = 0.001). Conclusions: Under nutrition remains one of the main health problems in under-five-year children in north Iran being more common in Sistani children. Stunting in Sistani children deeply decreased while in Turkman children slightly increased during the 15-year period study. Poor economic status is a risk factor for under nutrition in this area.

A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children

Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to 16 years with chronic functional abdominal pain (based on Rome III criteria) were enrolled in the study. They were randomly divided into two groups, one receiving probiotic and the other placebo. Results: Forty children received probiotic and forty others placebo. There were no significant differences in age, weight, sex, location of pain, associated symptoms, frequency and intensity of pain between the groups. The severity and frequency of abdominal pain in the first month compared to baseline was significantly less and at the end of the second month, there was no significant difference between both groups compared to the end of the first month. Conclusions: This study showed that the severity of pain was significantly reduced in both groups. There was no significant difference in pain scores between them. The effect of probiotic and placebo can probably be attributed to psychological effect of the drugs.

Clinical efficacy of paclitaxel in the treatment of mid-stage and advanced malignant gastric cancer, and effect of nursing interventions

Purpose: To investigate the clinical efficacy of paclitaxel combined with additional chemotherapy for mid-stage and advanced malignant tumors, and the benefits afforded by scientific nursing. Methods: Patients with mid-stage and advanced gastric cancer were randomly divided into test and control groups. Control group was given intravenous chemotherapy (400 mg/m2 fluorouracil and 2500 mg/m2 cisplatin) and nursed conventionally, while the test group was additionally treated with 80 mg/m2 paclitaxel and underwent special scientific nursing. Clinical effects and changes in the rates of apoptosis and cell proliferation were recorded. The effect of applying scientific nursing on therapeutic outcomes was also evaluated. Results: The overall rate of treatment effectiveness, clinical control rate, mean apoptosis and proliferation rates in the test group were 56.40, 92.30, (7.10 ± 3.17 and 28.70 ± 3.22 %, respectively, while, in the control group, the values were 38.50, 64.10, 25.40 ± 2.67 and 32.60 ± 2.93 %, respectively. The differences were all statistically significant (p < 0.05). In terms of nursing efficacy, the test group had a lower pain score and higher quality-of-life scores (Karnofsky performance status score) than control group. There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). Conclusion: Paclitaxel has a significant effect when used to treat mid-stage and advanced gastric cancer. Moreover, additional nursing not only enhances the therapeutic effect but also improves prognosis and quality-of-life.

Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax : A systematic review and meta-analysis

Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by Plasmodium vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.

Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis

Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by Plasmodium vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.