End Of Recovery Period Research Articles

Effects of Complete Submergence on Growth, Survival and Recovery Growth of Alisma orientale (Samuel.) Juz.

Intense precipitations caused by global climate change will result in the occurrence of greater frequencies and longer durations of flooding, influencing the survival and yields of wetland plants. Alisma orientale (Samuel.) Juz., an important traditional medicine with edible scape and inflorescence, naturally grows in wetlands and artificially cultivates in paddy fields prone to flood in China. However, we lack understanding of the effect of complete submergence on A. orientale. Here, experiments with four durations of complete submergence including 5 days (ds), 10 ds, 15 ds and 20 ds followed by 20 ds recovery were performed. In the submergence experiments, the number of, length of and biomass of surviving leaves and the total biomass and new blade biomass were measured; in recovery experiments, number and length of surviving leaves were measured. A. orientale grew out longer new leaves during complete submergence, with a dramatic decline in the biomass of both the leaves and tubers as well as the total biomass at the ends of the submergence experiments. The A. orientale plants had a high survival rate after submergence. The duration of submergence did not influence the time for A. orientale needed to start regrowing. At the end of recovery period, the submerged A. orientale plants generated more leaves, had more surviving leaves, had shorter new leaves and a shorter total length of surviving leaves than the control plants. This study highlights that A. orientale plants can resist at least 20 ds of complete submergence caused by flooding and regrow rapidly after submergence and improves our understanding of the flooding tolerance mechanisms of A. orientale plants.

Nonclinical safety and immunogenicity assessment of a combined DTacP vaccine in animal models.

The (diphtheria, tetanus, and pertussis [acellular, component] [DTacP]) vaccine is a combined vaccine designed to prevent three potentially fatal diseases including pertussis, tetanus, and diphtheria in both children and adults. We utilized advanced technology to develop a novel DTacP vaccine that was previously unavailable in China. The nonclinical studies were performed to evaluate the immunogenicity, potential toxicity, and local tolerance of the vaccine in animal models. In the immunogenicity study, three batches of the vaccine were intraperitoneally administered to National Institutes of Health (NIH)mice, resulting in 100% seropositivity for all three batches. Additionally, antibody levels notably increased as the immunization dosage increased. In acute toxicity study, no mortality was observed among the animals during the 14-day observation period, and no abnormalities in clinical signs were reported. Active systemic anaphylaxis assessment in guinea pigs showed no evidence of serious allergic reactions in the vaccine groups. In the repeat-dose toxicity study, where five intramuscular doses were administered every 2weeks, gross autopsy and histopathological examination revealed no vaccine-related systemic pathological changes in rats, with dose site irritant reactions mostly recovered at the end of recovery period. In conclusion, the vaccine demonstrated good local and systemic tolerance, supporting its clinical development.

Ecological model of health behaviour of hypertensive stroke patients at the end of recovery period.

This study aimed to construct a structural equation model guided by the ecological model to explore the factors influencing health behaviour among hypertensive stroke patients 6 months post-stroke. Health behaviour is important for recurrence prevention in hypertensive stroke patients. Moreover, previous studies have indicated that health behaviour at the end of the recovery period is of particular concern. The ecological model provides an integrated perspective for explaining the factors influencing health behaviour. A cross-sectional study guided by the STROBE. A total of 121 hypertensive stroke patients were included to assess stroke knowledge, health belief, depression, family function, chronic illness resource and health behaviour. A structural equation model was used to explore the health behaviour's factors and pathways. In the final ecological model, sex, education level, depression and chronic illness resource directly affected health behaviour. Stroke knowledge directly affected health behaviour and indirectly affected health behaviour through health belief and chronic illness resource. Family function indirectly affected health behaviour through health belief, depression and chronic illness resource. Health belief affected health behaviour indirectly through depression and chronic illness resource. Hypertensive stroke patients' health behaviour is jointly and interactively influenced by stroke knowledge, health belief, depression, family function and chronic illness resource. In particular, chronic illness resource is an important mediator of health behaviour. For clinical practitioners, health behaviour of men and patients with low educational levels should be specifically focused on. Additionally, it is necessary to provide stroke knowledge, establish health beliefs, control depression emotion and improve family function. Furthermore, chronic illness resources should be improved particularly due to its important mediating role. Participants completed demographic and disease-related questionnaires during hospitalisation and completed other questionnaires when returning to hospital at 6 months follow-up.

Stochastic processes and ecological connectivity drive stream invertebrate community responses to short-term drought.

Community responses to and recovery from disturbances depend on local (e.g. presence of refuges) and regional (connectivity to recolonization sources) factors. Droughts are becoming more frequent in boreal regions, and are likely to constitute a severe disturbance for boreal stream communities where organisms largely lack adaptations to such hydrological extremes. We conducted an experiment in 24 semi-natural stream flumes to assess the effects of local and regional factors on the responses of benthic invertebrate communities to a short-term drought. We manipulated flow (drought vs. constant-flow), spatial arrangement of leaf litter patches (aggregated vs. evenly distributed) and colonization from regional species pool (enhanced vs. ambient connectivity) to test the combined effects of disturbance, resource arrangement and connectivity on the structural and functional responses of benthic invertebrate communities. We found that a drought as short as 1week reduced invertebrate taxonomic richness and abundance, mainly through stochastic extinctions. Such changes in richness were not reflected in functional diversity. This suggests that communities were characterized by a high degree of functional redundancy, which allowed maintenance of functional diversity despite species losses. Feeding groups responded differently to drought, with organic matter decomposers responding more than scrapers and predators. Three weeks were insufficient for complete invertebrate community recovery from drought. However, recovery was greater in channels subjected to enhanced connectivity, which increased taxonomic diversity and abundance of certain taxa. Spatial configuration of resources explained the least variation in our response variables, having a significant effect only on invertebrate abundance and evenness (both sampling occasions) and taxonomic richness (end of recovery period). Even a short drought, if occurring late in the season, may not allow communities to recover before the onset of winter, thus having a potentially long-lasting effect on stream communities. For boreal headwaters, extreme dewatering poses a novel disturbance regime that may trigger substantial and potentially irreversible changes. An improved understanding of such changes is needed to underpin adaptive management strategies in these increasingly fragmented and disturbed ecosystems.

Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps

Accumulation, contents of protein, non-enzymatic antioxidant glutathione (GSH and GSSG), lipid peroxidation product (melondialdehyde-MDA) and organic acids (fumarate, succinate, malate and citrate), and activities of neurological (acetylcholinesterase-AChE), detoxification (glutathione S-transferase-GST) and metabolic (lactate dehydrogenase-LDH, aspartate transaminase-AST and alanine transaminase-ALT) enzymes were recorded in the hatchlings of Cyprinus carpio, Ctenopharyngodon idella, Labeo rohita and Cirrhinus mrigala after 7 and 14 days exposure and 10 days post exposure (recovery period) to sublethal concentrations (0.005, 0.01, 0.02 and 0.05 mg/L) of triclosan, a highly toxic and persistent biocide used in personal care products. Accumulation was maximum between 7–14 days at 0.01 mg/L for C. carpio and L. rohita but at 0.005 mg/L for C. idella and C. mrigala. No triclosan was observed at 0.005 mg/L in C. carpio and C. mrigala after recovery. Significant decline in protein, glutathione and acetylcholinesterase but increase in glutathione S-transferase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, melondialdehyde and organic acids over control during exposure continued till the end of recovery period. Integrated biomarker response (IBR) analysis depicted higher star plot area for glutathione and glutathione S-transferase during initial 7 days of exposure, thereafter, during 7–14 days of exposure and the recovery period, higher star plot area was observed for acetylcholinesterase, aspartate transaminase, alanine transaminase and organic acids. Higher star plot area was observed for protein in all the species throughout the study. The study shows that L. rohita is most sensitive and glutathione, acetylcholinesterase, aspartate transaminase and alanine transaminase are the biomarkers for the toxicity of sublethal concentrations of TCS.

Effect of temperature and filler volume fraction on the creep and recovery behaviour of MWCNT–COOH–reinforced polypropylene films

Nonlinear viscoelastic behaviour of –COOH functionalized multi-walled carbon nanotubes reinforced polypropylene nanocomposites is examined up to 2% MWCNT concentration. Isochronal creep and strain recovery experiments are conducted in dynamic mechanical analyser with oscillatory inputs. Creep stress level of 5 MPa is selected and successive creep and recovery experiments are performed at $$-\,20\,^\circ $$ C, $$25\,^\circ $$ C and $$50\,^\circ $$ C to analyse the effect of temperature and MWCNT concentration on strain developed during creep loading and strain recovery stages. A well-known Schapery nonlinear viscoelastic solid model with Zapas–Crissman viscoplastic term is fitted to the experimental observations. Stress-dependent nonlinear model parameters are obtained under temperature and MWCNT loading. Viscoelastic and viscoplastic strains are predicted at the end of recovery period. High temperatures and low concentrations of MWCNT are observed to cause higher viscoplastic strain. Strengthening MWCNT up to 1% improves the thermomechanical behaviour and viscoelastic recovery and decreases the viscoplastic strain in nanocomposites. Temperature-dependent compliance behaviour of nanocomposites is investigated with Williams–Landel–Ferry model and Arrhenius model using time–temperature superposition principle.

Abstract 1: Transdermal Deferoxamine Alleviates Radiation-Induced Damage In Porcine Skin

Purpose: Adjuvant radiation therapy is an effective treatment for oncologic malignancies; however, it can cause adverse collateral effects to surrounding soft tissue such as dermal thickening, destruction of vessels, and loss of skin elasticity making reconstruction a burden. To alleviate these detrimental effects, we tested the efficacy of a novel transdermal drug delivery system (TDDS) to provide cutaneous delivery of deferoxamine (DFO) to irradiated porcine skin. DFO is an FDA approved drug which stabilizes hypoxia-inducible factor-1 alpha to increase tissue vascularization. Direct inject of DFO has previously been shown to improve irradiated mouse skin. We hypothesize that application of the DFO TDDS to irradiated soft tissue will also improve radiation-induced fibrosis in our pig model. Methods: Three, red Duroc pigs (three months old) were irradiated with a single fraction of 30 Gray delivered to 5 equal localized regions on either side. The pigs were allowed to recover for eight weeks allowing for chronic radiation damage to develop. At the end of recovery period, the pigs were divided into 3 treatment conditions: 1% DFO TDDS patch, control TDDS patch with not medication, and no treatment. Biopsies from each group, with their respective adjacent non-irradiated skin, were acquired at 1, 2, 3, 4, and 8 week time points. Histological sections were stained with hematoxylin and eosin and Picrosirius Red to evaluate dermal thickness and collagen deposition. Vascularity was determined by CD31 immunofluorescence staining. Mechanical testing was performed to determine skin stiffness, and cutometer readings for each condition were performed to test for skin deformation. Results: Skin histology revealed that DFO TDDS treated irradiated skin demonstrated significant reduction in dermal thickness (hematoxylin and eosin), lower collagen content (Picrosirius Red), and higher vascularity (CD31 immunofluorescence) compared to no patch (***p<0.001, **p<0.01, *p<0.05, respectively) and control patch treated skin (*p<0.05, ****p<0.0001, **p<0.01, respectively). Furthermore, mechanical testing of DFO treated skin exhibited decreased stiffness starting from week 2 onwards after patch placement. Finally, overall skin deformation, from cutometer data, was higher for DFO treated skin compared to the control and no patch treatment groups. Conclusions: Currently, there are limited effective treatments for radiation-induced skin damage. The DFO TDDS patch provides a method to mitigate the chronic effects of radiation-induced skin damage for oncological patients who are in need of reconstructive surgery. The histological and immunofluorescent data indicate the morphological characteristics of the irradiated skin after DFO TDDS patches are similar to normal skin. Furthermore, the mechanical properties of the irradiated skin after DFO TDDS patches mirror normal skin. As porcine skin closely resembles human skin, our findings establish incredible potential to treat patients with radiation induced soft tissue fibrosis.

Safety of aerosol inhalation of recombinant human interferon alpha 2b injection(P.putida)and excipient hydroxyethyl starch 40 to healthy SD rats

Objective To investigate the effects of recombinant human interferon alpha 2b injection(P.putida)and hydroxyethyl starch inhalation on physiological indexes and tissues and organs of SD rats, such as lungs, trachea and bronchus, and thus to explore the safety of the drug and excipients for inhalation. Methods Rats were randomly divided into two groups(hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group).5 million IU/ml recombinant human interferon alpha 2b injection or 6% hydroxyethyl starch 40 injection were given respectively, which were diluted with 0.9% sodium chloride injection in a radio of 1: 2.Both groups were given aerosol inhalation for 30 minutes once a day for 14 days.Within 14 days after administration, the behavior of rats and the degree of toxicity were continuously observed.During the drug administration and recovery period, the clinical signs of the rats in each group were observed daily, and the body weight and food consumption were measured once a week.At the end of drug administration and the end of recovery period, hematology test, blood biochemical test, gross anatomical observation, organ weight determination, and histopathological examination were performed. Results The mass median aerodynamic diameter(MMAD)of the drug mist was 3.56 μm, and the geometric standard deviation(GSD)was 1.84 μm, which met the particle size requirements of arrival and deposition in the lower respiratory tract via atomization inhalation.No abnormality in clinical signs, body weight and food consumption, hematology and blood biochemical indexes were found in hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group.No abnormal histopathological changes were observed in oral mucosa, tongue, nasal cavity(paranasal sinus), larynx, trachea, main bronchial tube, lung, heart, liver, spleen, kidney, reproductive system and other organs or tissues examined. Conclusion Results suggest the drug particle size of recombinant human interferon alpha 2b injection(pseudomonas)can reach the lower respiratory tract and deposit in the lower respiratory tract.Continuous atomization inhalation for 14 days has a good safety, and the excipient hydroxyethyl starch 40 has a high safety. Key words: Recombinant human interferon alpha 2b; Injection; Aerosol inhalation; Hydroxyethyl starch 40; Safety

Effects of interval training on risk markers for arrhythmic death: a randomized controlled trial

Objective: To compare the effects of high-intensity interval training versus moderate-intensity continuous training on risk markers of arrhythmic death in patients who recently suffered from an acute coronary syndrome. Design: Double-blind (patient and evaluator) randomized controlled trial. Setting: Cardiovascular Prevention and Rehabilitation Centre (EPIC Centre) of the Montreal Heart Institute, Montreal, Canada. Subjects: A total of 43 patients were randomized following an acute coronary syndrome. Interventions: Patients were assigned to either high-intensity interval training (n = 18) or isocaloric moderate-intensity continuous training (n = 19), three times a week for a total of 36 sessions. Main measures: Heart rate recovery for 5 minutes, heart rate variability for 24 hours, occurrence of ventricular arrhythmias, and QT dispersion were measured before and after the 36 sessions of training. Results: Among the 43 patients randomized, 6 participants in the high-intensity interval training group stopped training for reasons unrelated to exercise training and were excluded from the analyses. Heart rate recovery improved solely in the high-intensity interval training group, particularly at the end of recovery period (p < 0.05). There were no differences in heart rate variability, occurrence of ventricular arrhythmias, or QT dispersion parameters between the groups at study end. Conclusion: Despite the lack of power to detect any large difference between the two interventions with respect to risk markers of arrhythmic death, high-intensity interval training appears safe and may be more effective at improving heart rate recovery relative to moderate-intensity continuous training in our patients following acute coronary syndrome.

Response of Different Citrus Genotypes to Continuous Flooding Conditions

Hypoxia is a potential threat to various horticultural cropsin lands prone to flooding. Citrus is mostly known as a sub-tropical crop that is often exposed to environmental stresses. In order to evaluate response of six different citrus genotypes, including sour orange, rough lemon, Trifoliate orange, Troyer citrange and two local genotypes labeled; CRC1 and CRC2 to flooding conditions, an experiment was carried out in factorial experiment based on a completely randomized design with two treatments including flooded and control plants and three replications. Flooding stress significantly decreased leaf chlorophyll content, and plant total fresh and dry weights (P≤ 0.05). Flooding caused a significant increase in foliar concentration of proline in CRC1 and CRC2 (P≤ 0.05). Guaiacol peroxidase activity was significantly increased in Trifoliate orange. CRC2 and sour orange showed a significant increase in superoxide dismutase activity (P≤ 0.05). The longest survival period in continuous flooding condition was observed in Troyer citrange and Trifoliate orange (more than 60 days); while sour orange was the most sensitive genotype (less than 30 days). The best thriving genotype at the end of recovery period was Troyer citrange, while sour orange showed the least ability to re-establish. The results suggest that among the studied genotypes, Troyer citrange and Trifoliate orange are able to resist for longer periods of flooding exposure. Troyer citrange had the highest capacity to re-establish after being flooded to their critical surviving point. Furthermore, CRC2 tolerated anoxic condition and recovered more successfully than the other sensitive genotypes.

Differential expression of Sub1A loci in rice under submergence

Two rice land races (Meghi and Bhashakalmi) earlier reported to be submergence tolerant were experimented for differential expression of Sub1A loci under induced submergence with reference to FR13A and IR42 as tolerant and susceptible genotypes, respectively. Two weeks old seedlings were subjected to complete submergence for another 2 weeks and total transcripts were collected at the end of each week for expression study. Relative expression of the said loci was studied with respect to constitutive expression of Ubiquitin 5 for the studied lines. Up regulation of Sub1A loci relative to control was recorded for all the studied lines except IR42. Both the land races showed enhanced expression of Sub1A under induced submergence than IR42 but less than FR13A. After 7 days of complete submergence Meghi showed its higher expression than both FR13A and Bhashakalmi, which was not continued after 14 days as the expression of Sub1A in FR13A exceeded both the Meghi and Bhashakalmi. At the end of recovery period of 7 days, the expression of Sub1A were gradually decreased for all the genotypes. The expression profile of the tested landraces documented in this investigation support their superior submergence tolerance as recorded in our earlier report for physiological and biochemical screening under induced submergence.

EFFECTS OF TRAINING MASK ON HEART RATE AND ANXIETY DURING THE GRADED EXERCISE TEST AND RECOVERY

The aim of this study is to examine the effect of training mask on heart rate (HR) and related anxiety during Graded Exercise Exercise (GXT). Six volunteer participants (age 20,5 ± 0,5 yrs, height 181,8 ± 5,5 cm, weight 74,5 ± 7 kg, BMI 22,51 ± 0,81) have been included in the study. PARQ and ACSM (American College of Sports Medicine) risk factor analysis have been made to all of the participants before the tests. Only healthy experimental subjects have been included in the study. The participants have been randomly separated into two groups (A, B) including 3 people. On the first day of the test, Group A completed the test with the training mask (TM) while the Group B completed it without training mask (NTM). Two days later, the groups were changed and they repeated the tests (Crossover Design). GXT have been applied to the participants on the treadmill until they got exhausted. During the 5-minute recovery time given after the end of GXT, HR variables have been measured. At the end of recovery, Becks Anxiety Inventory (BAI) has been implemented. In order to determine the differences came out at the measurements made after TM and NTM exercises, non-parametric t-test has been used and the confidence interval has been taken as p˂0,05. At the end of GXT and the following 5-minute recovery time, a significant difference has been found in HR variables between both groups (p˂, 005). The termination process of the test with TM has been 2.45% earlier (from 15.02 sec. to 14.49 sec.) than the NTM group and HR average at the end of recovery period has been found 9.12% lower than NTM group. In addition to this, there is no significant difference between anxiety total scores of the two groups (p˃, 005). As a conclusion, while low HR averages of TM group can be explained as CO 2 diaspora, it can be figured that the similarity in terms of anxiety levels between the groups has resulted from the fact that the running test has been finished up to the participation own decision. Article visualizations:

EFFECTS OF TRAINING MASK ON HEART RATE AND ANXIETY DURING THE GRADED EXERCISE TEST AND RECOVERY

The aim of this study is to examine the effect of training mask on heart rate (HR) and related anxiety during Graded Exercise Exercise (GXT). Six volunteer participants (age 20,5 ± 0,5 yrs, height 181,8 ± 5,5 cm, weight 74,5 ± 7 kg, BMI 22,51 ± 0,81) have been included in the study. PARQ and ACSM (American College of Sports Medicine) risk factor analysis have been made to all of the participants before the tests. Only healthy experimental subjects have been included in the study. The participants have been randomly separated into two groups (A, B) including 3 people. On the first day of the test, Group A completed the test with the training mask (TM) while the Group B completed it without training mask (NTM). Two days later, the groups were changed and they repeated the tests (Crossover Design). GXT have been applied to the participants on the treadmill until they got exhausted. During the 5-minute recovery time given after the end of GXT, HR variables have been measured. At the end of recovery, Becks Anxiety Inventory (BAI) has been implemented. In order to determine the differences came out at the measurements made after TM and NTM exercises, non-parametric t-test has been used and the confidence interval has been taken as p˂0,05. At the end of GXT and the following 5-minute recovery time, a significant difference has been found in HR variables between both groups (p˂, 005). The termination process of the test with TM has been 2.45% earlier (from 15.02 sec. to 14.49 sec.) than the NTM group and HR average at the end of recovery period has been found 9.12% lower than NTM group. In addition to this, there is no significant difference between anxiety total scores of the two groups (p˃, 005). As a conclusion, while low HR averages of TM group can be explained as CO 2 diaspora, it can be figured that the similarity in terms of anxiety levels between the groups has resulted from the fact that the running test has been finished up to the participation own decision. Article visualizations:

Effect of carbohydrate and protein solutions consumed during a moderate-intensity exercise on post-exercise appetite

This study aimed to investigate whether co-ingestion of carbohydrate and protein during exercise affect the post-exercise ad libitum food intake. Twelve healthy active male participants (mean±SD, age: 20±1; height: 176±6cm; weight: 63.6±5.3kg; VO2peak: 51.2±7.1ml/kg/min) completed three main experimental trials in a randomized cross-over design. In each trial, the participants completed 1h of ergometer cycling at 60% VO2peak, followed by 2h recovery. The participants were required to consume one of three solutions every 15min during exercise: distilled water (DW), carbohydrate-electrolyte solution (CE), and carbohydrate-electrolyte-protein solution (CEP). The energy was matched between the two latter solutions. The CHO-to-protein ratio in CEP was 2:1. At the end of recovery period, participants were provided with pizza lunch ad libitum, and the amount consumed was recorded. Several subjective feelings, appetite scores and blood glucose were determined during the experimental trials. No differences were found in either the amount of consumed pizza (DW vs. CE vs. CEP: 607±128 vs. 592±119 vs. 599±125g, P=0.845) or the appetite score before pizza was consumed (DW vs. CE vs. CEP: 14±9 vs. 12±14 vs. 14±10, P=0.357) among the three trials. The blood glucose concentrations during exercise were higher in the CE and CEP trials than in the DW trial. In conclusion, different solutions consumed during a 1h moderate-intensity exercise in the present study did not affect post-exercise appetite.

The physiological responses of various pomegranate cultivars to drought stress and recovery in order to screen for drought tolerance

In order to screen pomegranate cultivars for drought tolerance, few rapid, less expensive and reliable methods were used. Two-year-old pomegranate (Punica granatum L.) plants of various commercial cultivars namely ‘Rabab-e-Neyriz’ (‘Rabab’), ‘Shishe-cap-e-Ferdows’ (‘Shishecap’), ‘Malas-e-Saveh’ (‘M-Saveh’), ‘Malas-e-Yazdi’ (‘M-Yazdi’), and ‘Ghojagh-e-Qom’ (‘Ghojagh’) were grown in large containers filled with a mixture of leaf mould, sand, and soil (1:1:1, by volume) in greenhouse. The plants were subjected to 14-day drought stress by withholding irrigation, followed by re-watering for 7 days. Midday stem water potential (Ψstem), leaf relative water content (RWC), membrane stability index (MSI), leaf dry mass per area (LMA), rapid test for drought tolerance (DTI), gas exchange parameters including net photosynthesis (An), leaf scale transpiration (Tr), and stomatal conductance (gs), and intrinsic water use efficiency (IWUE) were determined in well-watered and drought-stressed plants. All cultivars showed an ability to tolerate drought stress, but ‘Ghojagh’ exhibited more tolerance, with a higher RWC and Ψstem and a greater osmotic adjustment. ‘Ghojagh’ also revealed higher cell membrane stability and IWUE and a lower reduction in net CO2 assimilation rate. This study found that ‘M-Yazdi’ was more vulnerable to severe water stress, and displayed the lowest degree of cell membrane stability as compared to the other examined cultivars and showed no recovery for RWC at the end of recovery period.

Mitigating Reductions in Glucose During Exercise on Closed-Loop Insulin Delivery: The Ex-Snacks Study.

To assess whether snacking could be used with closed-loop (CL) insulin delivery to avoid exercise-induced reductions in plasma glucose (PG), as well as elevations in PG at the end of exercise. Twelve type 1 diabetes (T1D) subjects (age 13-36 years, duration 10.7 ± 8.4 years, A1c 7.4% ± 0.8% [57 ± 8.7 mmol/mol]) underwent two 105-min exercise studies while under CL control: CL alone and CL+snack. Exercise, commenced at 3 PM, consisted of four 15-min periods of brisk treadmill walking to 65%-70% HRmax (separated by three 5-min rest periods), followed by a 30-min recovery period. Fifteen to 30 g carbohydrate (Gatorade) was provided on snacking visits just before and midway through the exercise period. PG and insulin were measured every 15-20 min during the exercise studies. Baseline PG levels were similar for CL alone (164 ± 16 mg/dL) versus CL+snack (172 ± 11 mg/dL). During exercise, PG levels fell by 53 ± 10 mg/dL without snacking versus a modest 10 ± 13 mg/dL increase in PG with snacking (P = 0.0005); similar differences in the change in PG levels were observed at the end of recovery period. Hypoglycemia requiring rescue treatment (PG ≤60 mg/dL) during exercise occurred in three nonsnacking visits versus none with snacking. During the 75-min exercise period, insulin delivered was 1.8 ± 0.4 U for the CL+snack admission compared to 0.7 ± 0.1 U during CL alone (P = 0.002). These results support the use of a simple snacking strategy to avoid exercise-induced lowering of PG while on CL insulin delivery. Persistent insulin infusion during exercise with snacking also appears to be effective in limiting increases in PG at the end of exercise.

Subacute toxicity evaluation of KR-33493, FAF1 inhibitor for a new anti-parkinson's disease agent, after oral administration in rats and dogs

KR33493, a newly developed FAS-associated factor 1 (FAF1) inhibitor for Parkinson's disease, is being evaluated in a Phase I clinical trial. In the present study, the subchronic toxicity of KR33493 in Sprague-Dawley (SD) rats and beagle dogs was investigated at various oral doses for 28 and 14 days, respectively. During the study, food consumption, body weights, organ weights, gross findings, and mortality were examined; and ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, histopathology, and toxicokinetics were performed. In rats, weight gain decreased in both sexes at 500 mg/kg/day, with no significant differences. In dogs, some significant differences compared with the control were found during the trial; however, at the end of recovery periods, these were no longer observed and there was no dose correlation. Some histopathological findings were observed, but these were considered as incidental changes. Since no other significant changes were observed, doses above 500 and 1000 mg/kg KR33493 in rat and dogs, respectively, caused no observed adverse effects. Therefore, based on these results, the Phase 1 clinical trial for KR33493 was approved by the Korean Food & Drug Administration.

Effect of long-term sleep restriction and subsequent recovery sleep on the diurnal rhythms of white blood cell subpopulations.

While acute modifications of sleep duration induces a wide array of immune function alterations, less is known of how longer periods with insufficient sleep affect immune functions and how they return to normal once recovery sleep is obtained. The purpose of the present study was to investigate the effects of five days of restricted sleep and a subsequent 7-day period of sleep recovery on white blood cell (WBC) subpopulation count and diurnal rhythms. Nine healthy males participated in a sleep protocol consisting of two baseline days (8h of sleep/night), five nights with restricted sleep (4h of sleep/night) and seven days of recovery sleep (8h of sleep/night). During nine of these days, blood was drawn hourly during night-time end every third hour during daytime, and differential WBC count was analyzed. Gradual increase across the days of sleep restriction was observed for total WBC (p<.001), monocytes (p<.001), neutrophils (p<.001) and lymphocytes (p<.05). Subsequent recovery sleep resulted in a gradual decrease in monocytes (p<.001) and lymphocytes (p=.001), but not in neutrophils that remained elevated over baseline level at the end of the 7-day recovery period. These effects were associated with altered diurnal rhythms of total WBC and neutrophils, restricted sleep being associated with higher levels during the night and at awakening, resulting in a flattening of the rhythm. The diurnal alterations were reversed when recovery sleep was allowed, although the amplitude of total WBC, neutrophils and monocytes was increased at the end of the recovery period in comparison to baseline. Altogether, these data show that long-term sleep restriction leads to a gradual increase of circulating WBC subpopulations and alterations of the respective diurnal rhythms. Although some of the effects caused by five days of restricted sleep were restored within the first days of recovery, some parameters were not back to baseline even after a period of seven recovery days.

Cardiovascular fitness and haemodynamic responses to maximal cycle ergometer exercise test in children 6–8 years of age

We investigated cardiovascular fitness and haemodynamic responses to maximal cycle ergometer exercise test in children. The participants were a population sample of 425 children (204 girls, 221 boys) aged 6–8 years. Heart rate (HR) and systolic blood pressure (SBP) were measured from the beginning of pre-exercise rest to the end of recovery period. We provided reference values for peak workload and changes in HR and SBP during and after maximal exercise test in girls and boys. Girls had a lower cardiovascular fitness, indicated by peak workload per body weight [mean (2 s) 2.7 (0.9) vs. 3.1 (1.0) W · kg–1, P < 0.001] and lean mass [mean (2 s) 3.5 (0.9) vs. 3.8 (1.0) W· kg–1, P < 0.001] than boys. Plateau or decline in SBP close to the end of the test was found in about third of children and was considered a normal SBP response. Girls had a slower HR decrease within 2 min after the test than boys [mean (2 s) 53 (18) vs. 59 (22) beats · min–1, P < 0.001]. The results are useful for physicians and exercise physiologists to evaluate cardiovascular fitness and haemodynamic responses to exercise in children and to detect children with low exercise tolerance or abnormal haemodynamic responses to exercise.

Physiological mechanisms involved in the recovery of euonymus and laurustinus subjected to saline waters

The scarcity of water has frequently led to saline water being reused for the irrigation of ornamental shrubs. However, before the use of such waters can be expanded, the salt tolerance and other characteristics of the ornamentals involved, need to be considered along with their capacity to recover after salinity exposure. For this reason, Euonymus japonica (euonymus) and Viburnum tinus (laurustinus) plants were submitted for twenty weeks to three irrigation treatments applied at 100% water holding capacity: Control (EC<0.9dSm−1); NaCl solution, NaCl (EC: 4dSm−1); and wastewater, WW (EC: 4dSm−1). This was followed by a recovery period of eight weeks, when all the plants were watered in the control irrigation conditions. The results showed that biomass, leaf number and total leaf area of plants subjected to the saline treatments were lower than in the control at the end of both periods in both species. However, after recovery, only euonymus showed lower growth parameters than those observed in the saline period. The highest Na+ and Cl− concentrations were observed in saline plants at the end of saline period for both species, and were higher in shoots than in roots. The opposite was observed for the K+/Na+ and the Ca2+/Na+ ratios. In Laurustinus, the Ψstem did not diminish in the wastewater-irrigated plants with respect to the control, maintaining osmotic adjustment and a high Ψt, even after recovery, whereas in euonymus this did not occur at the end of recovery period. In both species the Pn and gs were similarly reduced during the saline exposure period. However, the recovery of gas exchange in laurustinus irrigated with wastewater might be closely related to the better water status of these plants. Although the aesthetic value and growth decreased in the plants of both species, the chemical properties of the waters applied had different effects in each case, especially as regards the capacity to recover from salinity. These results underline the importance to studying the physiological mechanisms involved in the recovery of plants.