Assessment of seasonal and annual patterns in phosphorus content in a monitored catchment through a partitioning approach based on hydrometeorological data.

High amounts of phosphorus (P) in rivers come mainly from two sources: fertilizers washed off from agricultural and urban areas by runoff water (non-point sources) and urban and industrial development which are translated in P discharges from wastewater treatment plants (WWTP). This work analyses the content of P in water for nearly 40 years inquiring into the origin of the sources, based on the hypothesis of runoff generation from the detection of river streamflow increases during the P contribution episode and the previous precipitation. For this purpose, the Guadaira River, which is located in the South of Spain and has a drainage surface of 1524 km2, was selected. In this watershed agricultural land use converges with numerous human activities resulting in high pressures on water quality. We found 40% of the P contribution episodes found seem to come from the runoff generated after the heaviest rainfall events, which normally occur between November and May. The remaining 60% of the P contribution episodes were found to be linked to point sources, which become more relevant from June to September, reaching the highest concentration values (6-17 mg/L). The results highlight that the target phosphate concentration value of 0.34 mg PO4/L imposed by the national legislation for a good state following the Water Framework Directive 2000/60/EC is exceeded by 96% of the measurements during the period from 1981 to 2022. On a monthly basis, PO4 loads showed a linear relationship with river streamflow (R2 = 0.94). However, on field measurements scale, a potential relationship between both variables was found, which changed according to the improvement in the wastewater treatment and facilities for 1982-1994, 1995-2017 and 2018-2022. In these three periods, different significant decreasing trends of the P content were found, mainly marked by the setup of each individual WWTP.

Resistance Exercise Program in Cognitively Normal Older Adults: CERT-Based Exercise Protocol of the AGUEDA Randomized Controlled Trial.

OBJECTIVES: To provide a comprehensive CERT (Consensus on Exercise Reporting Template)-based description of the resistance exercise program implemented in the AGUEDA (Active Gains in brain Using Exercise During Aging) study, a randomized controlled trial investigating the effects of a 24-week supervised resistance exercise program on executive function and related brain structure and function in cognitively normal older adults. DESIGN AND PARTICIPANTS: 90 cognitively normal older adults aged 65 to 80 were randomized (1:1) to a: 1) resistance exercise group; or a 2) wait-list control group. Participants in the exercise group (n = 46) performed 180 min/week of resistance exercise (3 supervised sessions per week, 60 min/session) for 24 weeks. INTERVENTION: The exercise program consisted of a combination of upper and lower limb exercises using elastic bands and the participant's own body weight as the main resistance. The load and intensity were based on the resistance of the elastic bands (7 resistances), number of repetitions (individualized), motor complexity of exercises (3 levels), sets and rest (3 sets/60 sec rest), execution time (40-60 sec) and velocity (as fast as possible). SETTINGS: The maximum prescribed-target intensity was 70-80% of the participants' maximum rate of perceived exertion (7-8 RPE). Heart rate, sleep quality and feeling scale were recorded during all exercise sessions. Those in the wait-list control group (n = 44) were asked to maintain their usual lifestyle. The feasibility of AGUEDA project was evaluated by retention, adherence, adverse events and cost estimation on the exercise program. RESULTS AND CONCLUSIONS: This study details the exercise program of the AGUEDA trial, including well-described multi-language manuals and videos, which can be used by public health professionals, or general public who wish to implement a feasible and low-cost resistance exercise program. The AGUEDA exercise program seems to be feasible by the high retention (95.6%) and attendance rate (85.7%), very low serious adverse event (1%) and low economic cost (144.23 € /participant/24 weeks). We predict that a 24-week resistance exercise program will have positive effects on brain health in cognitively normal older adults.

Use of the flavonoid taxifolin for sperm cryopreservation from the threatened Bermeya goat breed.

Taxifolin is a plant flavonoid effective as an antioxidant. This study aimed to assess the effect of adding taxifolin to the semen extender during the cooling period before freezing on the overall post-thawing sperm variables of Bermeya goats. In the first experiment, a dose-response experiment was performed with four experimental groups: Control, 10, 50, and 100 µg/ml of taxifolin using semen from 8 Bermeya males. In the second experiment, semen from 7 Bermeya bucks was collected and extended at 20 °C using a Tris-citric acid-glucose medium supplemented with different concentrations of taxifolin and glutathione (GSH): control, 5 µM taxifolin, 1 mM GSH, and both antioxidants. In both experiments, two straws per buck were thawed in a water bath (37 °C, 30 s), pooled, and incubated at 38 °C. Motility (CASA) was assessed at 0, 2, and 5 h, and sperm physiology was assessed at 0 and 5 h by flow cytometry (viability, intact acrosome membrane, mitochondria membrane potential, capacitation, intracellular reactive oxygen species -ROS-, mitochondrial superoxide, and chromatin status). In experiment 2, an artificial insemination trial (AI) was included with 29 goats for testing the taxifolin 5-µM treatment on fertility. Data were analyzed with the R statistical environment using linear mixed-effects models. In experiment 1 and compared to the control, T10 increased progressive motility (P < 0.001) but taxifolin decreased total and progressive motility at higher concentrations (P < 0.001), both post-thawing and after the incubation. Viability decreased post-thawing in the three concentrations (P < 0.001). Cytoplasmic ROS decreased at 0 and 5 h at T10 (P = 0.049), and all doses decreased mitochondrial superoxide post-thawing (P = 0.024). In experiment 2, 5 µM taxifolin or 1 mM GSH (alone or combined) increased total and progressive motility vs. the control (P < 0.01), and taxifolin increased kinematic parameters such as VCL, ALH, and DNC (P < 0.05). Viability was not affected by taxifolin in this experiment. Both antioxidants did not significantly affect other sperm physiology parameters. The incubation significantly affected all the parameters (P < 0.004), overall decreasing sperm quality. Fertility after artificial insemination with doses supplemented with 5 µM taxifolin was 76.9% (10/13), not significantly different from the control group (69.2%, 9/13). In conclusion, taxifolin showed a lack of toxicity in the low micromolar range and could benefit goat semen cryopreservation.

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Control of trace metal distribution and variability in an interdunal wetland.

Trace elements are serious pollutants in the natural environment and are of increasing concern due to the adverse effects at global scale. To refine the current understanding of trace metal distribution and variability in natural environments, concentrations of dissolved trace metals (Ag, Al, As, B, Ba, Be, Co, Cr, Cd, Cu, Fe, Hg, Mo, Ni, Pb, Sb, Se, Th,Tl, U, V, Mn, Zn), major ions, inorganic nutrients (NO3, PO4), TOC and stable isotopes of water were determined in water samples from rainwater, seven piezometers and a pond in the coastal Doñana wetland during four sampling campaigns between 2017 and 2019. Results show clear evaporation signatures of stable isotopes in the pond but not in the groundwater. Hydrochemical analyses yield significant, systematic changes in groundwater trace metal and nutrient composition along the flowpath from the dune belt to the pond, controlled by organic matter in the sediments. Whereas major ions reached maximum concentrations in the pond due to evapoconcentration, most trace metals showed highest concentrations at sites with lower redox levels, except for B, As and U, which showed very high concentrations in the pond. Cu, Zn, Ni, Sb and Tl yielded higher median concentrations in rainwater than in most of the groundwater points and in case of Cu and Zn higher even than in surface water which points to an atmospheric input source of these elements. Temporal variability of trace metals was related to lower hydraulic heads after an elongated dry period which led to lower redox levels and higher concentrations of most of the trace elements whereas major ions showed more constant concentration levels. This is of special concern regarding climate change and the predicted higher frequency of prolonged dry periods, which could modify the natural hydrochemical patterns in undisturbed wetlands systems.

Targeted and untargeted metabolomic analysis of Procambarus clarkii exposed to a "chemical cocktail" of heavy metals and diclofenac.

Water pollution poses an important problem, but limited information is available about the joined effects of xenobiotics of different chemical groups to evaluate the real biological response. Procambarus clarkii (P. clarkii) has been demonstrated to be a good bioindicator for assessing the quality of aquatic ecosystems. In this work, we studied the bioaccumulation of cadmium (Cd), arsenic (As) and diclofenac (DCF) in different tissues of P. clarkii during 21 days after the exposure to a "chemical cocktail" of As, Cd and DCF, and until 28 days considering a depuration period. In addition, a combined untargeted and targeted metabolomic analysis was carried out to delve the metabolic impairments caused as well as the metabolization of DCF. Our results indicate that As and Cd were mainly accumulated in the hepatopancreas followed by gills and finally abdominal muscle. As and Cd show a general trend to increase the concentration throughout the exposure experience, while a decrease in the concentration of these elements is observed after 7 days of the depuration process. This is also the case in the abdominal muscle for Cd, but not for As and DCF, which increased the concentration in this tissue in the depuration phase. The hepatopancreas showed the greatest number of metabolic pathways affected. Thus, we observed a crucial bioaccumulation of xenobiotics and impairments of metabolites in different tissues. This is the first study combining the exposure to metals and pharmaceutically active compounds in P. clarkii by untargeted metabolomics including the biotransformation of DCF.

Efectos de la rehabilitación pulmonar sobre los síntomas asociadosa las exacerbaciones en pacientes / Effects of pulmonary rehabilitation on symptoms associated with exacerbations in patients with COPD

Las exacerbaciones de enfermedad pulmonar obstructiva crónica (EPOC) son responsables del deterioro físico de los pacientes, del ingreso y reingreso hospitalario, así como de su muerte. Esta revisión evidencia los beneficios de la rehabilitación pulmonar en la reducción de episodios de exacerbaciones en la EPOC. La metodología de búsqueda abarcó un total de 2.473 artículos, de los cuales fueron usados 14 para esta revisión según el cumplimiento de criterios establecidos. Los resultados obtenidos fueron significativos en las siguientes variables vinculadas directamente con la frecuencia de los episodios de exacerbación: disnea, saturación de oxígeno, volumen espiratorio forzado en el primer segundo, días de hospitalización, número de reingresos hospitalarios, capacidad de ejercicio, depresión y calidad de vida. La rehabilitación pulmonar mostró efectos positivos en las variables mencionadas, disminuyendo los episodios de exacerbaciones de la EPOC como las limitaciones en las actividades de los pacientes (AU)

Exacerbations of chronic obstructive pulmonary disease (COPD) are responsible for the physical deterioration of patients, hospital admission and readmission, as well as their death. This review demonstrates the benefits of pulmonary rehabilitation in reducing exacerbation episodes in COPD. A search was carried obtained a total of 2473 articles, of which 14 were used for this review according to the fulfillment of established criteria. The results obtained were significant in relation to the variables directly related to the frequency of exacerbation episodes: dyspnea, oxygen saturation, forced expiratory volume in the first second, days of hospitalization, number of hospital readmissions, exercise capacity, depression and quality of life. Pulmonary rehabilitation causes positive effects on the aforementioned variables, reducing episodes of COPD exacerbations as well as limitations in patients’ activities (AU)

Selective, rapid and simultaneous determination of ergosterol and ergocalciferol in mushrooms by UPLC-Q-TOF-MS.

An ultra-performance liquid chromatography coupled to atmospheric pressure chemical ionization-quadrupole time-of-flight mass spectrometry method has been optimized and validated for the determination of ergosterol and ergocalciferol in mushroom samples, using cholecalciferol as surrogate standard. The separation was carried out with a Synergi Hydro-RP column (100 mm x 3.00 mm i.d, 2.5 µm particle size), (Phenomenex, CA, USA) column, thermostated at 35 °C. The mobile phase was 0.1 % formic acid aqueous solution and methanol in gradient elution mode and it was achieved in 5 min approximately. Detection was achieved by atmospheric pressure chemical ionization in positive mode and quadrupole time-of-flight mass spectrometry. Desolvation and interface temperatures were set at 500 °C and 150 °C, respectively. The recoveries obtained were within 92-105 % for ergosterol, 77-81 % for ergocalciferol and 83-87 % for cholecalciferol. Method limits of detection were 0.4 and 0.5 µg g-1 for ergosterol and ergocalciferol, respectively, and method limits of quantitation were 1.2 and 1.3 µg g-1 for ergosterol and ergocalciferol, respectively. A rapid and simple extraction procedure using small amount of sample (100 mg) with hexane was optimized and the method was applied to the determination of ergosterol and ergocalciferol in white button mushrooms (Agaricus bisporus var. bisporus) exposed to UV irradiation. Results were compared to the corresponding non-irradiated mushrooms.

Inhibiting diacylglycerol acyltransferase-1 reduces lipid biosynthesis in bovine blastocysts produced in vitro.

Diacylglycerol acyltransferase-1 (DGAT1) is one of the DGAT enzymes that catalyzes the final step in the synthesis of triacylglycerol, which is a major component of the lipid droplets in embryos. Intracellular lipids accumulated in embryos produced in vitro have been associated with reduced cryotolerance and quality. The objective of the present study was to investigate the influence of DGAT1 inhibition on embryo development, quality, and post-vitrification survival, in addition to expression profiles of selected lipid metabolism-regulating and oxidative stress genes. Bovine cumulus-oocyte complexes were matured and fertilized in vitro and were cultured in synthetic oviduct fluid (SOF) supplemented with 5% fetal calf serum (FCS) alone (Control) or with 1, 5, 10 or 50 µM DGAT1 inhibitor (A922500®; D1, D5, D10, and D50, respectively) or 0.1% dimethyl sulfoxide (CDMSO: vehicle for DGAT1 inhibitor dilution) from 54 h post-insemination until Day 8 post insemination. No differences were found in blastocyst yield on days 7 and 8 in Control, CDMSO, D10, and D50 groups. Embryos cultured with 10 or 50 µM DGAT1 inhibitor had greater mitochondrial activity (P < 0.01), and increased number of cells (P < 0.05), while the cytoplasmic lipid content was reduced (P < 0.01), the latter associated with altered expression profiles of selected genes regulating lipid metabolism or genes related with oxidative stress (transcript abundance increased for SLC2A1 and SLC2A5 and decreased for DGAT1 and GPX1). Importantly, the survival rate of blastocysts produced with 10 µM DGAT1 was higher than that of Control, CDMSO and D50 groups at 72 h after vitrification and warming (73.8 vs 57.1, 55.9 and 56.1%, respectively, P < 0.001). In conclusion, inhibition of DGAT1 synthesis in bovine embryos produced in vitro abrogates the negative effect of FCS by decreasing their lipid content, increasing mitochondria activity and improving embryo cryotolerance, as well as favoring the expression of lipid metabolism regulating and oxidative stress-related transcripts.

[Factors that influence compliance with hand hygiene in healthcare professionals: A concept mapping study]. / Factores que influyen en el cumplimiento de la higiene de manos en profesionales sanitarios: un estudio de mapeo de conceptos.

OBJECTIVE: To identify factors that may influence hand hygiene compliance by professional category and clinical department. MATERIALS AND METHODS: Use was made of concept mapping methodology, a tool that combines a qualitative analysis with a quantitative statistical analysis, in order to identify the most influential and important factors for the fulfilment of hand hygiene in 2 clinical departments (Infectious and General Surgery) of the Hospital del Mar. RESULTS: The study included a total of 42 volunteer professionals from General Surgery (6 doctors and 10 nurses) and from Infectious Diseases (11 doctors and 10 nurses) clinical departments, as well as 5 hospital porters. High correlations of influential and important factors for hand hygiene compliance were observed between nurses and doctors in the Infectious Diseases Department (r=0.93 vs. r=0.69, respectively). In contrast, the correlation was lower among surgical professionals (r=-0.17 for influence and r=0.51 for importance). Professionals identified the most influential factors in compliance as training and adequate resources, taking into account professional category and clinical department. CONCLUSION: The design of interventions to improve compliance with hand hygiene should take into account the perceptions of different professionals in order to adapt actions to each professional group.

Effects of a functional food supplemented with probiotics on biological factors related to dental caries in children: a pilot study.

PURPOSE: The aim of this study was to evaluate the effects of a functional food supplemented with probiotics on biological factors related to dental caries in children aged 3-5 years. METHODS: A repeated measures pilot study was conducted with children who have consumed a commercial milk containing two lactic acid bacteria as probiotics (WP milk) for a period of 3 months and another period of 3 months consuming a milk without probiotics (NP milk). Salivary pH, plaque index, pH variation before and after a sugar rinse, quantification of Streptococcus mutans in saliva and demineralisation of the carious lesions were determined at the beginning and at the end of both milk ingestion periods. RESULTS: Regarding WP milk, a non-significant decrease in terms of the concentration of S. mutans and pH variation (p > 0.05), a significant decrease (i.e. acidification) in salivary pH (p < 0.01) and a remineralisation of 39.4% of the caries were found. On the other hand, for NP milk, a non-significant increase in terms of the concentration of S. mutans, pH variation, salivary pH (p > 0.05) and a remineralisation of 64.2% were found. CONCLUSIONS: Lactic acid probiotics can contribute to the decrease in the number of cariogenic microorganisms. However, the appropriate selection of the bacteria type with regard to its acidogenicity is fundamental to avoid the generation of an effect contrary to that expected, e.g. a significant decrease in salivary pH.

[Prevalence among males from the general population of agents responsible of not ulcerative genital tract infections, assisted in specialized care]. / Prevalencia en varones de la población general de agentes productores de infecciones no ulcerativas del aparato genital, asistidos en atención especializada.

OBJECTIVE: Male genital infections are a major problem due to their high frequency and morbidity and their role in cases of male infertility. We studied the presence, in males assisted in specialized care, of non-ulcerative genital tract infections-producing agents. METHODS: We studied descriptively and retrospective microbiological results of 3,066 samples of male patients, with diagnosis of genital tract infection episode, received between January 1, 2016 and December 31, 2017. Detection of microorganisms in the sample was performed using techniques of artificial culture and PCR (BD-MAX). RESULTS: Positive results were obtained in 451 samples (14.71%). By culture, the most frequent pathogens were Enterobacterales (18.40%), Enterococcus (13.75%), Haemophilus (8.65%), Neisseria gonorrhoeae (8.43%), Ureaplasma (5.10%), and Candida (3.77%). By polymerase chain reaction (PCR), the most frequent were N. gonorrhoeae (28.37%), Chlamydia trachomatis (26.95%), Ureaplasma urealyticum (17.73%), Mycoplasma hominis/Ureaplasma parvum (10.64%), and Mycoplasma genitalium (7.10%). The age was older in patients infected with Enterobacterales, Candida, or Enterococcus and younger in those infected with N. gonorrhoeae. CONCLUSIONS: N. gonorrhoeae and C. trachomatis are still more common in male genital infection pathogens, although other culturable microorganisms have an important role. These findings demonstrate the importance of systematically applying both conventional culture and PCR techniques for pathogen detection.

18FDG PET/CT & arterial inflammation: predicting cardiovascular events in lung cancer.

BACKGROUND: 18F-FDG PET/CT predicts cardiovascular disease. To analyze the predictive value of cardiovascular events from inflammation and arterial calcification in patients who underwent an 18F-FDG PET/CT for lung cancer. METHODS: A retrospective study of 274 patients with primary lung neoplasia. We determined: (i) TBR (target-to-background ratio), and (ii) the calcium score, at eight common arterial segments. We took as arteriosclerosis, a TBR ≥1.6 and ≥15 Calcium Score sum. We registered cardiovascular risk factors, comorbidities, histology, stage, treatment, status at the last clinical review, cause of death and cardiovascular event during the follow-up. RESULTS: The territory presenting the greatest uptake of 18F-FDG, was the thoracic aorta with an average of 1.77 (± 0.27 TBR) in the aortic arch, while the greatest degree of calcification was obtained in the abdominal aorta (52% with a Calcium Score ≥ 3). 24% of the patients presented a sum Calcium Score ≥15, and 17% a TBR ≥1.6. Patients with high TBR, (17%), had not a higher frequency of cardiovascular comorbidities beforehand, nor did they in the follow-up. However, those with a sum Calcium Score ≥15 (24%), were older, had more cardiovascular risk factors and ischemic events during follow-up. The calcium score, but not the TBR, predicted the emergence of a cardiovascular event (HR 4.9 IC95% 2.1-9.1, P < 0.05). CONCLUSION: In our cohort, a high Calcium Score was an independent predictor for developing cardiovascular events.

Isolation of Yeasts from Guajillo Pepper (Capsicum annuum L.) Fermentation and Study of Some Probiotic Characteristics.

Three yeast strains were isolated from the spontaneous fermentation of guajillo pepper: Hanseniaspora opuntiae, Pichia kudriavzevii, and Wickerhamomyces anomalus, which were identified by amplification of the ITS/5.8S ribosomal DNA. Some probiotic characteristics of these strains were evaluated and compared with one commercial probiotic yeast (Saccharomyces boulardii). The survival percentage of all the yeasts was similar to that of the commercial product. They showed different hydrophobicity characteristics with hydrocarbons, autoaggregation > 90%, and characteristics of co-aggregation with pathogenic microorganisms. The adhesion capacity to mucin of the three yeast samples was similar to the reference yeast. The antioxidant activity of the yeasts varied between 155 and 178 µM Trolox equivalents. All exhibited cholesterol reduction capacity, and W. anomalus was able to decrease up to 83% of cholesterol after 48 h of incubation. The 7.5-fold concentrated H. opuntiae supernatant had antimicrobial activity against Salmonella enterica ser. Typhimurium ATCC 14028 and Candida albicans ENCBDM2; tests suggest this activity against S. Typhimurium is due to a proteinaceous metabolite with a weight between 10 and 30 kDa. Among the yeasts, P. kudriavzevii exhibited the highest protective effect on the viability of Lactobacillus casei Shirota in gastric and intestinal conditions. These results suggest that yeasts isolated from guajillo pepper may have a probiotic potential.

Membrane Cholesterol in Skeletal Muscle: A Novel Player in Excitation-Contraction Coupling and Insulin Resistance.

Membrane cholesterol is critical for signaling processes in a variety of tissues. We will address here current evidence supporting an emerging role of cholesterol on excitation-contraction coupling and glucose transport in skeletal muscle. We have centered our review on the transverse tubule system, a complex network of narrow plasma membrane invaginations that propagate membrane depolarization into the fiber interior and allow nutrient delivery into the fibers. We will discuss current evidence showing that transverse tubule membranes have remarkably high cholesterol levels and we will address how modifications of cholesterol content influence excitation-contraction coupling. In addition, we will discuss how membrane cholesterol levels affect glucose transport by modulating the insertion into the membrane of the main insulin-sensitive glucose transporter GLUT4. Finally, we will address how the increased membrane cholesterol levels displayed by obese animals, which also present insulin resistance, affect these two particular skeletal muscle functions.

On the interplay between neoclassical tearing modes and nonlocal transport in toroidal plasmas.

This Letter presents the first observation on the interplay between nonlocal transport and neoclassical tearing modes (NTMs) during transient nonlocal heat transport events in the HL-2A tokamak. The nonlocality is triggered by edge cooling and large-scale, inward propagating avalanches. These lead to a locally enhanced pressure gradient at the q = 3/2 (or 2/1) rational surface and hence the onset of the NTM in relatively low ß plasmas (ßN < 1). The NTM, in return, regulates the nonlocal transport by truncation of avalanches by local sheared toroidal flows which develop near the magnetic island. These findings have direct implications for understanding the dynamic interaction between turbulence and large-scale mode structures in fusion plasmas.