[Risk factors of retinopathy of prematurity in extremely low birth weight infants by strictly controlling oxygen inhalation after birth].

Objective: To observe the incidence and severity of retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) infants by strictly controlling the risk factors of ROP, such as oxygen inhalation after birth, to explore the related factors of ROP in ELBW infants. Methods: This was a cross-sectional study. 166 ELBW infants underwent neonatal screening were enrolled in this study, whose birth weight was less than 1 000 g. There were 79 males and 87 females infants, whose average gestational age was (27.99±1.73)weeks, and average birth weight was (904.45±80.23)g. According to the final screening results, the ELBW infants were grouped as follows: (1)ROP group and non-ROP group; (2)severe ROP group and mild or no ROP group. Risk factors included gestational age, birth weight, test-tube infants, fetuses number, complications during pregnancy, delivery mode and Apgar scores in 1 to 10 minutes, weight and weight gain proportion at 1-6 weeks after birth, postnatal feeding mode, history of oxygen inhalation, anemia and blood transfusion, and other systemic diseases were recorded. And their correlation with severe ROP was analyzed by SPSS 20.0 statistical software. Results: Ninty-four (56.63%) ELBW infants developed ROP, 16 (9.64%) were severe ROP and 14(8.43%) received treatment. Average birth weight between ROP group (911.95±72.80)g and non-ROP group (894.67±88.58)g had no difference(t=1.379, P=0.170). Average gestational age between ROP group (27.49±1.53) weeks and non-ROP group (28.64±1.76) weeks had significant difference(t=-4.491,P<0.001).And pregnancy-induced hypertension during pregnancy (χ(2)=4.479, P=0.034), Apgar score in 5 minutes (t=-2.760, P=0.006) and 10 minutes (t=-2.099, P=0.043), pneumonia (χ(2)=6.233, P=0.013), neonatal pneumonia (χ(2)=18.026, P<0.001) had significant difference between ROP group and non-ROP group. There was no effect on weight (F=0.009,P=0.753) or weight gain proportion (F=2.394,P=0.124) at 1-6 weeks after birth in ELBW infants with or without ROP. Average birth weight between severe ROP group(875.63±74.85)g and mild or no ROP group(907.53±80.41)g had no difference(t=-1.518, P=0.131).Average gestational age between severe ROP group(26.88±1.31)weeks and mild or no ROP group (28.11±1.73)weeks had significant difference(t=-2.766,P=0.006).And only fundus hemorrhage (χ(2)=4.507,P=0.034) had significant difference between severe ROP group and mild or no ROP group. There was no effect on weight (F=2.683,P=0.103) or weight gain proportion (F=0.431,P=0.513) at 1-6 weeks after birth in ELBW infants with or without ROP. Logistic regression analysis revealed that only gestational age was correlated to the incidence (ß=-0.437,P<0.001) and severity (ß=-0.616,P=0.007) of ROP significantly. Conclusion: By strictly controlling the risk factors of ROP, such as oxygen inhalation after birth, the severe rate of ROP in ELBW infants is low. However, gestational age is still the inevitable independent high risk factor for the incidence of ROP in ELBW infants. (Chin J Ophthalmol, 2019, 55:280-288).

[Correlation of capillary plexus with visual acuity in idiopathic macular epiretinal membrane eyes using optical coherence tomography angiography].

Objective: To observe changes in foveal avascular zone(FAZ) and capillary plexus in idiopathic macular epiretinal membrane (IMEM) in optical coherence tomography angiography (OCTA) and analyze their correlation with the visual acuity. Methods: Cross-sectional study. 42 patients (15 Males and 27 females, age 64.8) from the Eye Hospital of Wenzhou Medical University were included with 51 eyes diagnosed as IMEM (IMEM group), and 23 normal eyes (9 Males and 14 females, control group). All patients received the examination of fissure lamp combined with fundus pre-set lens, best corrected visual acuity (BCVA), OCT angiography (OCTA) and fundus photo. OCTA was performed on 3 mm× 3 mm sections centred on the fovea. The software automatically measured the superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density(VD) and retinal thickness(RT) and FAZ area. The IMEM eyes were compared with the normal eyes and correlation between the parameters of OCTA and BCVA was analyzed in IMEM. Independent-sample t test and MannWhitney test were used for comparison between groups, and Spearman test was used for correlation analysis. Results: LogMAR BCVA in the IMEM group was 0.40(0.15, 0.70), in the control group was 0.10(0.05, 0.22). FAZ area of IMEM group was (0.09±0.05) mm(2), while that of control group was (0.34±0.13)mm(2).Compared with the control group, in IMEM group, the BCVA was worse (Z=-4.443, P<0.001), FAZ area was smaller (t=-9.198, P<0.001), RT was increased (P<0.001), The foveal DCP and SCP vessel density was increased (t=4.280, 9.079, P<0.01), The parafoveal DCP vessel density was decreased (P<0.05), The parafoveal SCP vessel density was decreased in superior, inferior and nasal side (t=-2.759, Z=-3.998, Z=-2.108; P<0.05). The BCVA was negatively correlated with FAZ area (r=-0.337, P=0.017), positively correlated with center macular thickness (r=0.324, P=0.020). The BCVA was no correlated with foveal VD and parafoveal DCP vessel density (P>0.05), but correlated with SCP vessel density(P<0.05). Conclusions: In the IMEM eyes the BCVA was worse, FAZ area was smaller, foveal vessel density was increased and the parafoveal vessel density was decreased compared with the normal eyes. The smaller the FAZ area, the smaller foveal SCP vessel density, the poorer BCVA. There was no correlation between BCVA and DCP vessel density. Changes in VD in IMEM eyes may lead to changes in vision. (Chin J Ophthalmol, 2019, 55:757-762).

A retrospective research of HIV-negative cryptococcal meningoencephalitis patients with acute/subacute onset.

Cryptococcal meningoencephalitis (CM) may present as an acute, subacute, or chronic infection. It manifests as a chronic process in over 75 % of cases, but, sometimes, it presents with a more acute onset, mostly in HIV-associated patients. Until now, there has been no study performed on the clinical features of HIV-negative CM patients with acute/subacute onset. We collected 106 HIV-negative patients diagnosed with CM in our hospital during a 15-year period, analyzed their epidemiological and clinical features, as well as the outcomes, and explored the independent prognosis factors and the factors related to the survival time among them. We found that impaired consciousness (23.4 % vs. 3.4 %, p = 0.017) was more common in CM patients with acute/subacute onset, while decreased cerebrospinal fluid (CSF) glucose (51.9 % vs. 75.9 %, p = 0.026) was less common. The ratio of CSF glucose/blood glucose [odds ratio (OR) 0.04, 95 % confidence interval (CI) 0.004-0.262, p = 0.02], impaired consciousness (OR 5.09, 95 % CI 1.477-17.522, p = 0.01), and hospitalization length (OR 0.98, 95 % CI 0.977-0.999, p = 0.04) were indicated to be not only independent prognosis factors in HIV-negative CM patients with acute/subacute onset, but also factors significantly related to the survival time. The results of our study demonstrated that the contact history and potential history risk factors would not affect the onset process of HIV-negative CM patients, and the mortality, hospitalization length, and survival time has not been related to the onset process. However, the ratio of CSF glucose/blood glucose, consciousness level, and hospitalization length of the HIV-negative CM patients with acute/subacute onset should be of greater focus in the clinical work.

Rapid sedation induced by fentanyl combined with propofol via an intrathecal chemotherapy injection for leukemia in children.

This study explored the sedative and analgesic effects of fentanyl combined with propofol via an intrathecal chemotherapy injection for acute leukemia (acute lymphocytic leukemia or acute myelocytic leukemia) among children, to relieve pain and difficulty during intrathecal injection, improve treatment compliance, increase the success rate of single puncture, and reduce procedure failure, with the aim of developing a painless procedure for children with acute leukemia. Fifty person-times received fentanyl combined with propofol via an intrathecal chemotherapy injection among the hospitalized children with leukemia. The patients' cooperation with the procedure, response to the medication, dosages of fentanyl and propofol, reaction to the procedures, wake-up time, and changes in oxygen saturation (SpO2), heart rate (HR), respiration, and blood pressure (BP) before, during, and after the procedures were observed. The doctors who performed the procedures assessed the quality of sedation and analgesia. In the treatment group, the patients were quiet during the lumbar puncture and intrathecal injection, showing good sedation and analgesia. HR and respiration decreased slightly. There were no changes in SpO2 and BP. No obvious respiratory depression occurred with proper dosages. Only a few patients showed stertorous respiration, which stopped soon after the procedures. In the control group, the patients were agitated, crying, and not cooperative before and during the procedures, which made the procedures very difficult. During intrathecal injection, pain obviously reduced and the success rate of single lumbar puncture increased. It is safe and effective to apply fentanyl combined with propofol for sedation and analgesia.

The incidence of acute kidney injury in hospitalized patients receiving aminoglycoside antibiotics: a retrospective study.

OBJECTIVE: Our aim is to investigate the incidence and risk factors of acute kidney injury (AKI) in hospitalized patients who received aminoglycoside antibiotics. MATERIALS AND METHODS: A retrospective analysis was performed on the electronic medical record information of inpatients who received aminoglycoside (AG) antibiotics in our center from January 2018 to December 2020. The diagnosis of AKI was based on serum creatinine changes. Several statistical methods, including chi square test and two sample Wilcoxon rank sum test, were used to evaluate the epidemiological characteristics of aminoglycosides associated AKI. The multivariate logistic regression analysis was used to screen the risk factors. RESULTS: Finally, 8,040 patients who received AGs were included in the study. Among them, 494 patients (6.14%) were judged as incidence with AKI, while only 29 patients were diagnosed with AKI in the medical record. The multiple logistic regression analysis suggested that admission to ICU, complicated with diabetes mellitus, heart failure, anemia, shock, combined use of diuretics, ß-lactam antibiotics, proton pump inhibitors were independent risk factors for AKI related to aminoglycosides. CONCLUSIONS: It is urgent to improve the understanding and attention of AKI for medical workers, and the assessment of risk factors before the use of aminoglycosides should be contributed to the early prevention, diagnosis, and treatment of AKI.

Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial. PATIENTS AND METHODS: patients were treated with LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21days associated with standard trastuzumab dose and pegfilgrastim support. RESULTS: fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed. CONCLUSIONS: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.

Effects of strontium-doped bioactive glass on the differentiation of cultured osteogenic cells.

There is accumulating evidence that strontium-containing biomaterials have positive effects on bone tissue repair. We investigated the in vitro effect of a new Sr-doped bioactive glass manufactured by the sol-gel method on osteoblast viability and differentiation. Osteoblasts isolated from foetal mouse calvaria were cultured in the presence of bioactive glass particles; particles were undoped (B75) or Sr-doped with 1 wt.% (B75-Sr1) and 5 wt.% (B75-Sr5). Morphological analysis was carried out by contrast-phase microscopy and scanning electron microscopy (SEM). Cell viability was evaluated by the MTS assay at 24 h, 48 h and 72 h. At 24 h, day 6 and day 12, osteoblast differentiation was evaluated by assaying alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion and gene expression of various bone markers, using Real-Time-PCR. Alizarin Red staining and ALP histoenzymatic localisation were performed on day 12. Microscopic observations and MTS showed an absence of cytotoxicity in the three investigated bioactive glasses. B75-Sr5 particles in cell cultures, in comparison with those of B75 and B75-Sr1, resulted in a significant up-regulation of Runx2, Osterix, Dlx5, collagen I, ALP, bone sialoprotein (BSP) and OC mRNA levels on day 12, which was associated with an increase of ALP activity on day 6 and OC secretion on day 12. In conclusion, osteoblast differentiation of foetal mouse calvarial cells was enhanced in the presence of bioactive glass particles containing 5 wt.% strontium. Thus, B75-Sr5 may represent a promising bone-grafting material for bone regeneration procedures.

Can we predict top-level sports performance in power vs endurance events? A genetic approach.

The goal of our study was to discriminate potential genetic differences between humans who are in both endpoints of the sports performance continuum (i.e. world-class endurance vs power athletes). We used DNA-microarray technology that included 36 genetic variants (within 20 different genes) to compare the genetic profile obtained in two cohorts of world-class endurance (N=100) and power male athletes (N=53) of the same ethnic origin. Stepwise multivariate logistic regression showed that the rs1800795 (IL6-174 G/C), rs1208 (NAT2 K268R) and rs2070744 (NOS3-786 T/C) polymorphisms significantly predicted sport performance (model χ(2) =25.3, df=3, P-value <0.001). Receiver-operating characteristic (ROC) curve analysis showed a significant discriminating accuracy of the model, with an area under the ROC curve of 0.72 (95% confidence interval: 0.66-0.81). The contribution of the studied genetic factors to sports performance was 21.4%. In summary, although an individual's potential for excelling in endurance or power sports can be partly predicted based on specific genetic variants (many of which remain to be identified), the contribution of complex gene-gene interactions, environmental factors and epigenetic mechanisms are also important contributors to the "complex trait" of being an athletic champion. Such trait is likely not reducible to defined genetic polymorphisms.

[Swertiamarin alleviates diabetic peripheral neuropathy in rats by suppressing NOXS/ ROS/NLRP3 signal pathway].

OBJECTIVE: To observe the therapeutic effect of swertiamarin on diabetic peripheral neuropathy (DPN) in rats and explore the molecular mechanism in light of the NOXS/ROS/NLRP3 signal pathway. OBJECTIVE: Thirty-two SD rats were randomly divided into control group, DPN model group (treated with saline), swertiamarin (5 mg/kg) treatment group and NOXS inhibitor (10 mL/kg DPI) treatment group. Rat models of DPN were established in the latter 3 groups by intraperitoneal injections of STZ, and the treatments were administered on days 1, 7 and 14 after modeling. Tactile hypersensitivity of the rats was evaluated 30 min after the treatment. The expressions of NOXS, ROS, NLRP3 and inflammatory factors in the spinal cord tissue were detected using ELISA, and the protein expressions of NOXS, ROS, and NLRP3 were also detected with Western blotting. OBJECTIVE: Compared with those in the control group, the rats in DPN group showed significant hyperalgesia (P < 0.001), increased expressions of TNF-α (P < 0.001) and IL-6 (P < 0.001), decreased expressions of TGF-ß (P < 0.001), and increased expressions of NOXS/ROS/NLRP3 signal pathway (P < 0.001). Compared with those in DPN model group, the rats with swertiamarin treatment showed improved hyperalgesia (P < 0.001), decreased expressions of TNF-α (P=0.03) and IL-6 (P=0.002), increased expressions of TGF-ß (P=0.04), and decreased expressions of NOXS (P < 0.001), ROS (P < 0.001) and NLRP3 (P=0.002). Treatment with swertiamarin and the NOXS inhibitor produced similar effects on the expressions of the inflammatory factors in the rat models (P>0.05). OBJECTIVE: DPN effectively relieves hyperalgesia in rat models of DPN by restoring the balance in the expressions of the inflammatory factors by suppressing NOXs/ROS/NLRP3 signaling pathway.

Watchers do not follow the eye movements of Walkers.

Eye movements are a functional signature of how the visual system effectively decodes and adapts to the environment. However, scientific knowledge in eye movements mostly arises from studies conducted in laboratories, with well-controlled stimuli presented in constrained unnatural settings. Only a few studies have attempted to directly compare and assess whether eye movement data acquired in the real world generalize with those in laboratory settings, with same visual inputs. However, none of these studies controlled for both the auditory signals typical of real-world settings and the top-down task effects across conditions, leaving this question unresolved. To minimize this inherent gap across conditions, we compared the eye movements recorded from observers during ecological spatial navigation in the wild (the Walkers) with those recorded in laboratory (the Watchers) on the same visual and auditory inputs, with both groups performing the very same active cognitive task. We derived robust data-driven statistical saliency and motion maps. The Walkers and Watchers differed in terms of eye movement characteristics: fixation number and duration, saccade amplitude. The Watchers relied significantly more on saliency and motion than the Walkers. Interestingly, both groups exhibited similar fixation patterns towards social agents and objects. Altogether, our data show that eye movements patterns obtained in laboratory do not fully generalize to real world, even when task and auditory information is controlled. These observations invite to caution when generalizing the eye movements obtained in laboratory with those of ecological spatial navigation.

Phase I clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neo-adjuvant treatment in stages II and IIIA, HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: We carried out a phase I clinical trial to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination of liposome-encapsulated doxorubicin citrate (LD) and docetaxel in breast cancer patients. PATIENTS AND METHODS: Patients with HER-2-overexpressing stages II and IIIA breast cancers were treated in different dose cohorts of three patients. The MTD cohort was expanded up to six patients. The patients received LD and docetaxel every 21 days, plus weekly trastuzumab, with pegfilgrastim support. RESULTS: A total of 20 patients were enrolled, 18 of them being assessable for toxicity and response. DLTs observed for this combination were diarrhea, fatigue, febrile neutropenia, stomatitis, myalgia, and nonneutropenic infection (pneumonia). LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21 days have been the MTD, with no episode of DLT observed. Seven patients developed left ventricular ejection fraction decline (six grade 1 and one grade 2). No interruptions of the treatment were needed as a consequence of cardiac toxicity. Pathologic complete response was achieved in eight patients (44%). CONCLUSIONS: The MTD and recommended dose for phase II trials of LD and docetaxel are 50 and 60 mg/m(2), respectively. The achieved results on cardiotoxicity are promising.

Unique among unique. Is it genetically determined?

The cross-country world championship is one of the best models to study characteristics needed to achieve top-level endurance athletic capacity. We report the genotype combination of a recent cross-country champion (12 km race) in polymorphisms of seven genes that are candidates to influence endurance phenotype traits (ACTN3, ACE, PPARGC1A, AMPD1, CKMM, GDF8 (myostatin) and HFE). His data were compared with those of eight other runners (world-class but not world champions). The only athlete with the genotype theoretically more suited to attaining world-class endurance running performance was the case study subject. A favourable genetic endowment, together with exceptional environmental factors (years of altitude living and training in this case), seems to be necessary to attain the highest possible level of running endurance performance.

[Lag effect and influencing factors of temperature on other infectious diarrhea in Zhejiang province].

Objective: To study the lag effect of temperature and the source of heterogeneity on other infectious diarrhea (OID) in Zhejiang province, so as to identify related vulnerable populations at risk. Methods: Data on OID and meteorology in Zhejiang province from 2014 to 2016 were collected. A two-stage model was conducted, including: 1) using the distributed lag non-linear model to estimate the city-specific lag effect of temperature on OID, 2) applying the multivariate Meta- analysis to pool the estimated city-specific effect, 3) using the multivariate Meta-regression to explore the sources of heterogeneity. Results: There were 301 593 cases of OID in Zhejiang province during the study period. At the provincial level, temperature that corresponding to the lowest risk of OID was 16.7 ℃, and the temperature corresponding to the highest risk was 6.2℃ (RR=2.298, 95%CI: 1.527- 3.459). 16.7 ℃ was recognized as the reference temperature. P(5) and P(95) of the average daily temperature represented low and high temperature respectively. When the temperature was cold, the risk was delayed by 2 days, with the highest risk found on the 5(th) day (RR=1.057, 95%CI: 1.030-1.084) before decreasing to the 23(rd) day. When the temperature got hot, the risk of OID occurred on the first day (RR=1.081, 95%CI: 1.045-1.118) and gradually decreasing to the 8(th) day. Differences on heterogeneous sources related to the risks of OID in different regions, presented on urban latitude and the rate of ageing in the population. Conclusions: Both high or low temperature could increase the risk of OID, with a lag effect noticed. Prevention program on OID should be focusing on populations living in the high latitude and the elderly population at the low temperature areas.

[Influence of diurnal temperature range on influenza incidence in the elderly].

Objective: To understand the influence of diurnal temperature range (DTR) on influenza incidence in the elderly in Beijing and to conduct a subgroup analysis. Methods: The incidence data of daily influenza cases in the elderly and daily meteorological data from 2014 to 2016 in Beijing were collected for this study. A generalized additive model (GAM) was used to explore whether the relationship between daily influenza cases and DTR is a linear one. A distributed lag non-linear model (DLNM) was established to quantify the lagged effect of DTR on daily influenza incidence in the elderly. The model was also used to estimate the effects of DTR on daily influenza incidence among various subgroups. Results: A total of 4 097 influenza cases in the elderly were notified during study period. The mean DTR was 10.153 ℃. A linear relationship between daily influenza incidence and DTR was detected by using GAM. DTR was significantly associated with daily influenza incidence between lag0 and lag5 with a maximal effect at lag0. An 1 ℃ increase of DTR was associated with a 2.0% increase in daily influenza incidence in the elderly (95%CI: 0.9%-3.0%). The RR values of males, females, people aged 60-69 years, people aged ≥70 years were 1.018 (95%CI: 1.005-1.032), 1.021(95%CI: 1.007-1.035), 1.012 (95%CI: 1.002-1.022), 1.025 (95%CI: 1.012-1.039), respectively. The influencing time of DTR on females (lag6) was longer than males (lag2). Conclusions: DTR was associated with increased risk of influenza in the elderly in Beijing. It is necessary to take targeted measures in the elderly to control the incidence of influenza when DTR becomes greater.

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. MATERIALS AND METHODS: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Correction to: Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

A sentence under 'Results' heading in the Abstract section was published incorrectly. The correct sentence should read as follows.

[Insulin glargine in intensively-treated type 1 diabetes mellitus]. / Insulina glargina en diabetes mellitus tipo 1 en tratamiento intensivo.

OBJECTIVES: To evaluate the use of insulin glargine in intensively-treated children and adolescents. To assess the degree of patient and parent satisfaction with this treatment. PATIENTS AND METHODS: We studied 42 patients with type 1 diabetes. There were 27 girls and 15 boys. The mean age at diagnosis was 6.8 years (range 1.2-13.2), the mean age at initiation of glargine therapy was 12.8 years (range 7.0-17.7), and the mean duration of diabetes was 6.1 years (range 2.0-11.9). Glargine indications were poor metabolic control or frequent hypoglycemia with multiple daily injections of NPH insulin, which were substituted by one dose of glargine. Patient and parent satisfaction with diabetes treatment was assessed with the scale published by Boot. ANOVA, Student's t test, Mann-Whitney and Fisher tests were applied. RESULTS: Variables are reported as mean 6 standard deviation. After 18 months, glargine reduced hemoglobin A1c levels (7.65 % +/- 0.74 vs. 8.03 % +/- 0.69; p = 0.001), with no significant changes in insulin dose (1.03 +/- 0.19 U/kg/day vs. 1.08 +/- 0.21; p = 0.052) or body mass index SDS (standard deviation score) (+0.51 +/- 0.96 vs. 10.61 +/- 1.02; p = 0.11). Glargine also increased patient satisfaction (+44.5 +/- 18.8 points vs. -9.9 +/- 26.8; p < 0.001) and parent satisfaction (+42.0 +/- 17.9 points vs. -20.8 +/- 29.1; p < 0.001) with diabetes treatment. CONCLUSIONS: 1. Glargine insulin improves metabolic control in intensively-treated children and adolescents with type 1 diabetes. 2. Glargine also improves patient and parent satisfaction with diabetes treatment.

Genetic contribution to aging: deleterious and helpful genes define life expectancy.

For the best understanding of aging, we must consider a genetic pool in which genes with negative effects (deleterious genes that shorten the life span) interact with genes with positive effects (helpful genes that promote longevity) in a constant epistatic relationship that results in a modulation of the final expression under particular environmental influences. Examples of deleterious genes affecting aging (predisposition to early-life pathology and disease) are those that confer risk for developing vascular disease in the heart, brain, or peripheral vessels (APOE, ACE, MTFHR, and mutation at factor II and factor V genes), a gene associated with sporadic late-onset Alzheimer's disease (APOE E4), a polymorphism (COLIA1 Sp1) associated with an increased fracture risk, and several genetic polymorphisms involved in hormonal metabolism that affect adverse reactions to estrogen replacement in postmenopausal women. In summary, the process of aging can be regarded as a multifactorial trait that results from an interaction between stochastic events and sets of epistatic alleles that have pleiotropic age-dependent effects. Lacking those alleles that predispose to disease and having the longevity-enabling genes (those beneficial genetic variants that confer disease resistance) are probably both important to such a remarkable survival advantage.

DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress.

The recently developed DNA microarray technology provides a powerful and efficient tool to rapidly compare the differential expression of a large number of genes. Using the DNA microarray approach, we investigated gene expression profiles in cultured human aortic endothelial cells (HAECs) in response to 24 h of laminar shear stress at 12 dyn/cm(2). This relatively long-term shearing of cultured HAECs led to the modulation of the expression of a number of genes. Several genes related to inflammation and EC proliferation were downregulated, suggesting that 24-h shearing may keep ECs in a relatively noninflammatory and nonproliferative state compared with static cells. Some genes were significantly upregulated by the 24-h shear stress; these includes genes involved in EC survival and angiogenesis (Tie2 and Flk-1) and vascular remodeling (matrix metalloproteinase 1). These results provide information on the profile of gene expression in shear-adapted ECs, which is the case for the native ECs in the straight part of the aorta in vivo.

Alzheimer's disease and the cystatin C gene polymorphism: an association study.

Cystatin C is an amyloidogenic protein that colocalizes with beta-amyloid (Abeta) within arteriolar walls in Alzheimer disease (AD) brains. Recently, a coding polymorphism in the cystatin C gene (CST3) has been claimed to confer risk for the development of late-onset AD. In the present work we have tested the frequencies of CST3-A and CST3-G alleles and used chi-square and logistic regression analyses to assess the association among the CST3 polymorphism, apolipoprotein E4 (APOE4), and AD in a series of 159 AD patients and 155 controls. The CST3-A allele was seen to be an accumulation risk factor for early-onset AD. Furthermore, a synergistic association among the CST3-A allele, APOE4 and AD was found in AD patients whose ages were between 60 and 74 years.