4-Phenylcoumarin (4-PC) Glucoside from Exostema caribaeum as Corrosion Inhibitor in 3% NaCl Saturated with CO2 in AISI 1018 Steel: Experimental and Theoretical Study.

The corrosion inhibition of 5-O-ß-D-glucopyranosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (4-PC) in AISI 1018 steel immersed in 3% NaCl + CO2 was studied by electrochemical impedance spectroscopy (EIS). The results showed that, at just 10 ppm, 4-PC exerted protection against corrosion with Õ² = 90% and 97% at 100 rpm. At static conditions, the polarization curves indicated that, at 5 ppm, the inhibitor presented anodic behavior, while at 10 and 50 ppm, there was a cathodic-type inhibitor. The inhibitor adsorption was demonstrated to be chemisorption, according to the Langmuir isotherm for 100 and 500 rpm. By means of SEM-EDS, the corrosion inhibition was demonstrated, as well as the fact that the organic compound was effective for up to 72 h of immersion. At static conditions, dispersion-corrected density functional theory results reveal that the chemical bonds established by the phenyl group of 4-PC are responsible of the chemisorption on the steel surface. According with Fukui reactivity indices, the molecules adsorbed on the metal surface provide a protective cover against nucleophilic and electrophilic attacks, pointing to the corrosion inhibition properties of 4-PC.

Clinical spectrum and prognosis of neurological complications of reactivated varicella-zoster infection: the role of immunosuppression.

Immunosuppressed patients are at higher risk for developing herpes zoster (HZ), and neurological complications are frequent in them. However, the influence of immunosuppression (IS) on the severity and prognosis of neurological complications of varicella-zoster virus (VZV) reactivation is unknown. We studied retrospectively patients with neurological complications due to VZV reactivation who attended our hospital between 2004 and 2019. We aimed to assess the clinical spectrum, potential prognostic factors, and the influence of the immune status on the severity of neurological symptoms. A total of 98 patients were included (40% had IS). Fifty-five patients (56%) had cranial neuropathies which included Ramsay-Hunt syndrome (36 patients) and cranial multineuritis (23 patients). Twenty-one patients developed encephalitis (21%). Other diagnosis included radiculopathies, meningitis, vasculitis, or myelitis (15, 10, 6, and 4 patients, respectively). Mortality was low (3%). At follow-up, 24% of patients had persistent symptoms although these were usually mild. IS was associated with severity (defined as a modified Rankin scale greater than 2) (odds ratio, 4.23; 95% confidence interval, 1.74-10.27), but not with prognosis. Shorter latency between HZ and neurologic symptoms was the only factor associated with an unfavorable course (death or sequelae) (odds ratio, 0.82; 95% confidence interval, 0.71-0.95). In conclusion, the clinical spectrum of neurological complications in VZV reactivation is wide. Mortality was low and sequelae were mild. The presence of IS may play a role on the severity of neurological symptoms, and a shorter time between HZ and the onset of neurological symptoms appears to be a negative prognostic factor.

Morphological Characterization of Root System Architecture in Diverse Tomato Genotypes during Early Growth.

Plant roots exploit morphological plasticity to adapt and respond to different soil environments. We characterized the root system architecture of nine wild tomato species and four cultivated tomato (Solanum lycopersicum L.) varieties during early growth in a controlled environment. Additionally, the root system architecture of six near-isogenic lines from the tomato 'Micro-Tom' mutant collection was also studied. These lines were affected in key genes of ethylene, abscisic acid, and anthocyanin pathways. We found extensive differences between the studied lines for a number of meaningful morphological traits, such as lateral root distribution, lateral root length or adventitious root development, which might represent adaptations to local soil conditions during speciation and subsequent domestication. Taken together, our results provide a general quantitative framework for comparing root system architecture in tomato seedlings and other related species.

Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel.

An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which the aldehyde-1,2,3-triazoles reacted with ethyl acetoacetate and urea in the presence of Ce(OTf)3 as the catalyst. The corrosion inhibition of steel grade API 5 L X52 in 1 M HCl by the synthesized compounds was investigated using the electrochemical impedance spectroscopy technique. The measurements revealed that these heterocycles are promising candidates to inhibit acidic corrosion of steel.

The level of acceptance of spanish medical students of the transplantation of solid organs from animals: a stratified and multicentre study.

INTRODUCTION: Research into the transplantation of solid organs from animals (xenotransplantation) is generating interest and curiosity given that this could be a way of resolving the shortage in transplant organs. However, the fact is that currently xenotransplantation is far from becoming a clinical practice. OBJECTIVE: To analyse the attitude of medical students from Spanish universities towards the donation of organs from animals and to determine the factors affecting their attitudes. TYPE OF STUDY: A sociological, interdisciplinary, observational and multicentre study in Spain. STUDY POPULATION: Students enrolled on the medical degree in Spain (n = 34 000). SAMPLE SIZE: A sample of 9598 students (a confidence level of 99% and precision of ± 1%) stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ xenotransplantation (PCID-XenoTx RIOS) which was self-administered and completed anonymously. RESULTS: A completion rate of 95.7% (n = 9275) was obtained. If the results of xenotransplantation were as good as in human donation, 81% (n = 7491) would be in favour, 3% (n = 308) against and 16% (n = 1476) undecided. The following variables affected this attitude: sex (P < 0.001); academic year (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); the opinion of one's partner (P < 0.001); the respondent's attitude towards organ donation (P < 0.001); religion (P < 0.001); and participation in altruistic activities (P < 0.001). The following variables persisted in the multivariate analysis: (1) being a female (OR = 1.794; P < 0.001); (2) academic year (OR = 2.487; P < 0.001); (3) having spoken about the issue with one's family (OR = 1.200; P = 0.019); (4) the favourable opinion of one's partner (OR = 1.526; P = 0.028); (5) an attitude in favour of donation (OR = 2.087; P < 0.001); (6) being an atheist/agnostic, (OR = 2.5; P < 0.001); and (7) a belief that one's religion is in favour of transplantation (OR = 1.317; P = 0.005). CONCLUSIONS: Spanish medical students have a favourable attitude towards xenotransplantation. This willingness and interest could be a decisive platform for the development and strengthening of research, both for centres with a pre-clinical xenotransplantation programme and new healthcare centres.

[Aortic valve calcification evaluated by echocardiography associated with baseline conduction abnormalities as a predictor for pacemaker placement after aortic valve replacement]. / La extension de la calcificación aórtica evaluada mediante ecocardiografia asociada a trastornos de la conducción como predictors de marcapasos dedinitivos en el postoperatorio de cambio valvular aórtico.

INTRODUCTION: Aortic valve replacement in patients with severe aortic stenosis may be complicated by complete atrioventricular block (CAVB), requiring a permanent pacemaker (PPM) implantation. Predicting this complication could help to plan the surgical. OBJECTIVE: Determine whether electrocardiography and echocardiography are useful methods for predicting the need for PPM. MATERIAL AND METHODS: A retrospective, observational and transversal study was performed. An echocardiography based semi-quantitative classification was implemented to graduate the extent of calcification of the aortic valve. RESULTS: We included 95 patients; 10 of them required PPM implantation (10.52%). In the pre-surgical basal electrocardiogram we observed that 90% of patients that required PPM had conduction abnormalities as opposed to only 24.7% in the other group, p = 0.001. A 1st and 2nd degree AV block (AVB 1 and 2) was identified in 8 patients that subsequently needed PPM (80%) vs. 5 patients (5.9%), in the group that did not required it, p = 0.001.OR 41.7, IC 95% 6.5-68. We found a grade 3 calcification extent in 80% of patients who required PPM implant compared with only 17.6% of patients in the other group, p = 0.04, OR 4.8, IC 95% 0.76-29. The AVB 1 and 2 were the single predictor in multivariate analysis but the calcification 3 + AVB 1 and 2, increased sensibility. CONCLUISON: In patients with aortic stenosis in whom aortic valve replacement was performed, identifying AVB 1 and 2 on the basal electrocardiogram is a useful tool in order to identify requirement of PPM. The grade 3 of calcification extent increased the sensibility of this prediction.

[Patient with late-start hypogonadism and sexual dysfunction]. / Paciente con hipogonadismo de origen tardío y disfunción sexual.

OBJECTIVES: Testosterone deficit syndrome (TDS)is a clinical and biochemical entity characterized by low testosterone levels and androgenic deprivation clinic, which can cause a decrease in the quality of life. However, today there are doubts about its diagnosis and therapeutic management. METHODS: Bibliographic review using the MedLine database and detailed presentation of one clinical case. RESULTS: Testosterone deficit syndrome is associated with metabolic syndrome (visceral obesity, arterial hypertension, diabetes mellitus and dyslipemia). Currently, the performance of TDS screening in all males over the age of 45 years is under discussion. We propose a diagnostic-therapeutic algorithm for the management of TDS and erectile dysfunction. CONCLUSIONS: The treatment of erectile dysfunction associated with late start hypogonadism follows the same steps tha other generic cases of erectile dysfunction.

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry.

BACKGROUND: The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE. RESULTS: A total of 32 administrations of [177Lu]Lu-DOTA-TATE (7.4 GBq/session) carried out by a physician and a nurse, were studied. In total, two physicians and four nurses were independently monitored with cumulative (passive) and/or real-time (active) dosemeters. Extremity, eye lens and whole-body doses were evaluated in terms of the dosimetric quantities Hp(0.07), Hp(3) and Hp(10), respectively. It was obtained that lead aprons reduced dose rates and whole-body doses by 71% and 69% for the physicians, respectively, and by 56% and 68% for the nurses. On average, normalised Hp(10) values of 0.65 ± 0.18 µSv/GBq were obtained with active dosimetry, which is generally consistent with passive dosemeters. For physicians, the median of the maximum normalised Hp(0.07) values was 41.5 µSv/GBq on the non-dominant hand and 45.2 µSv/GBq on the dominant hand. For nurses 15.4 µSv/GBq on the non-dominant and 13.9 µSv/GBq on the dominant hand. The ratio or correction factor between the maximum dose measured on the hand and the dose measured on the base of the middle/ring finger of the non-dominant hand resulted in a factor of 5/6 for the physicians and 3/4 for the nurses. Finally, maximum normalised Hp(3) doses resulted in 2.02 µSv/GBq for physicians and 1.76 µSv/GBq for nurses. CONCLUSIONS: If appropriate safety measures are taken, the administration of [177Lu]Lu-DOTA-TATE is a safe procedure for workers. However, regular monitoring is recommended to ensure that the annual dose limits are not exceeded.

Identification of High Platelet Reactivity Despite ADP P2Y 12 Inhibitor Treatment: Two Populations in the Vasodilator-Stimulated Phosphoprotein Assay and Variable PFA-P2Y Shapes of Curve.

Introduction Response to ADP P2Y 12 receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y 12 assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time <106 seconds or VASP/P2Y 12 platelet reactivity index (PRI) >50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y 12 assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (<106 seconds, 106 to 300 seconds, >300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y 12 assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y 12 assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y 12 and PFA-P2Y is necessary for optimal detection of HPR.

Effect of the historic Spanish heatwave over glycemic control in adult patients with type 1 diabetes.

AIM: To evaluate the effect of the historic Spanish heatwave (9th-26th July 2022) over glycemic control in adults with type 1 diabetes (T1D). METHODS: Cross-sectional retrospective analysis of adult patients with T1D in Castilla-La Mancha (south-central Spanish region) using intermittently scanned continuous glucose monitoring (isCGM) during and after the heatwave. Primary outcome was change in time in range (TIR) 3.0-10 mmol/L (70-180 mg/dL) of interstitial glucose in the two weeks following the heatwave. RESULTS: A total of 2701 T1D patients were analyzed. We detected a TIR reduction of 4.0 % (95 % CI -3.4, -4.6; P < 0.001) in the two weeks following the heatwave. Patients in the highest daily scan frequency quartile (>13 scans/day) during the heatwave showed the greatest deterioration in TIR after it concluded (-5.4 % [95 % CI -6.5, -4.3; P < 0.001]). The percentage of patients meeting all the recommendations of the International Consensus of Time in Range was greater during the heatwave than after it ended (10.6 % vs. 8.4 %, P < 0.001). CONCLUSIONS: Adults with T1D had better glycemic control during the historic Spanish heatwave compared to the following period.

MSIMEP: Predicting microsatellite instability from microarray DNA methylation tumor profiles.

Deficiency in DNA MMR activity results in tumors with a hypermutator phenotype, termed microsatellite instability (MSI). Beyond its utility in Lynch syndrome screening algorithms, today MSI has gained importance as predictive biomarker for various anti-PD-1 therapies across many different tumor types. Over the past years, many computational methods have emerged to infer MSI using either DNA- or RNA-based approaches. Considering this together with the fact that MSI-high tumors frequently exhibit a hypermethylated phenotype, herein we developed and validated MSIMEP, a computational tool for predicting MSI status from microarray DNA methylation tumor profiles of colorectal cancer samples. We demonstrated that MSIMEP optimized and reduced models have high performance in predicting MSI in different colorectal cancer cohorts. Moreover, we tested its consistency in other tumor types with high prevalence of MSI such as gastric and endometrial cancers. Finally, we demonstrated better performance of both MSIMEP models vis-à-vis a MLH1 promoter methylation-based one in colorectal cancer.

[Inhibiting contractility without necrosis: would it be helpful for hypertrophic cardiomyopathy? Experimental model of intramyocardial botulinum toxin and wortmannin]. / Inhibir la contractilidad sin provocar necrosis: ¿sería útil en miocardiopatía hipertrófica? Modelo experimental de administración intramiocárdica de toxina botulínica y de wortmanina.

The purpose of this paper is to introduce a new idea: local inhibition of contractility without necrosis. It's potential usefulness in hypertrophic cardiomyopathy treatment is discussed and 2 pharmacological models, administrating botulinum toxin and wortmannin directly in the myocardium are disclosed.

Risk Factors for Multidrug-Resistant Gram-Negative Bacteria Carriage upon Admission to the Intensive Care Unit.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are microorganisms that have acquired resistance to extended-spectrum antibacterials and constitute an emerging threat to public health. Although carriers are an important source of transmission in healthcare settings, data about risk factors for MDR-GNB carriage are limited. Therefore, we aimed to identify risk factors for MDR-GNB carriage upon intensive care unit (ICU) admission and to optimise screening strategies. We conducted a case-control study. Admissions of adult patients to the ICU of a 1000-bed hospital during a year were included. We collected sociodemographic, clinical and microbiological data and performed a multivariate logistic regression model. A total of 1342 patients resulted in 1476 episodes of ICU admission, 91 (6.2%) of whom harboured MDR-GNB (38.5% women; median age 63.9 years). The most frequently isolated pathogens were Escherichia coli (57%) and Klebsiella pneumoniae (16%). The most frequent resistance mechanism was production of extended-spectrum beta lactamases. MDR-GNB carriage was associated to liver cirrhosis (OR 6.54, 95% CI 2.17-19.17), previous MDR-GNB carriage (OR 5.34, 1.55-16.60), digestive surgery (OR 2.83, 1.29-5.89) and length of hospital stay (OR 1.01 per day, 1.00-1.03). Several risk factors for MDR-GNB carriage upon admission to a high-risk setting were identified; the main comorbidity was liver cirrhosis.

Occupational radiation exposure assessment during the management of [68Ga]Ga-DOTA-TOC.

BACKGROUND: Since it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters. RESULTS: The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study. CONCLUSIONS: Imaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.

Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning.

The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.

Multicentre evaluation of 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, as an internal quality control in HIT functional assays: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

BACKGROUND: Functional tests for the diagnosis of heparin-induced thrombocytopenia (HIT) exhibit variable performance. OBJECTIVES: We evaluated in a multicenter study whether 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, could be used as an internal quality control. METHODS: 5B9 was sent to 11 laboratories in seven countries, and six initial concentrations ranging from 10 to 400 µg/mL were tested by heparin-induced platelet activation assay (HIPA), serotonin release assay (SRA), platelet aggregation test (PAT), flow cytometry (FC), or heparin-induced multiple-electrode aggregometry (HIMEA). Each method was evaluated in three different laboratories using experimental procedures identical to those usually applied for the diagnosis of HIT by testing platelets from 10 different healthy donors. RESULTS: The procedures used varied among the laboratories, particularly when platelet-rich plasma and whole blood were used. Nevertheless, positive results were obtained with at least 100 µg/ml of 5B9 for most donors tested by all centers (except one) performing HIPA, SRA, or HIMEA. FC and PAT results were more heterogeneous. FC results from one center that used washed platelets preincubated with PF4 were positive with all donors at 50 µg/ml 5B9, but at least 200 µg/ml of 5B9 were required to activate cells with most donors tested using PAT. CONCLUSION: This study confirms that HIT functional tests are not well standardized and exhibit variable sensitivity for the detection of platelet-activating antibodies. However, 5B9 is a potentially useful tool to standardize functional tests, to select responding platelet donors, and consequently to improve the performance of these assays and comparability between laboratories.

Long-term effects of continuous subcutaneous insulin infusion in adults with type 1 diabetes mellitus patients: Results of a public healthcare system.

AIM: To evaluate the long-term clinical effect of continuous subcutaneous insulin infusion (CSII) in adult type 1 diabetes mellitus (T1DM) patients in a regional public healthcare system real-world scenario. METHODS: All adult T1DM patients on CSII for ≥10 years subjected to follow-up in the regional Castilla-La Mancha Public Health Service were included. The primary efficacy outcome was the variation in HbA1c during follow-up. Direct patient data were compiled through the web-based Spanish national registry on CSII therapy. RESULTS: A total of 69 T1DM adult patients were treated with insulin pumps for ≥10 years in our region. The mean age was 45.0±10.5 years, with a T1DM duration of 13.9±8.5 years. The mean duration of CSII therapy was 11.4±2.1 years. The main indications for treatment were high glucose variability (39%), problematic hypoglycemia (26%), and HbA1c >53mmol/mol (7%) on multiple daily injections (20%). Sensor-augmented pump therapy was used by 31% of the patients. Glycosylated hemoglobin did not change during follow-up (58±11mmol/mol vs. 58±11mmol/mol; 7.5±1.0 vs. 7.5±1.0; p=0.66). However, the percentage of patients with at least one episode of severe hypoglycemia during the last year and unnoticed hypoglycemia decreased from 36% to 7% (p=0.006) and from 38% to 32% (p<0.001), respectively. The proportion of subjects with ≥1 episode of diabetic ketoacidosis in the last year decreased from 30% to 6% (p=0.045). CONCLUSIONS: The reduction of severe hypoglycemia without deterioration of glycemic control can be sustained over long-term CSII therapy.