Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome.

INTRODUCTION: Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a ß3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy. MATERIALS AND METHODS: Urinary NGF and BDNF levels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50 mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3 months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire. RESULTS: Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05). CONCLUSION: Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study.

Neutrophil gelatinase-associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) are present in a variety of human tissues and extracellular fluids. The aim of this pilot prospective case-control study was to detect NGAL and MMP-9/NGAL complex in human breast milk postpartum in women with normal and pregnancies that developed insulin-depended gestational diabetes mellitus (iGDM). We detected both biomarkers in human breast milk and concentrations were determined at the first day of colostrum secretion and two days after, in 22 normal pregnancies and 13 pregnancies with iGDM. Mean NGAL concentration decreased significantly from the first to the second sample, in both groups. Mean MMP-9/NGAL complex concentration decreased also significantly from the first to the second sample in normal pregnancies. Mean complex concentration was significantly higher in diabetic pregnancies compared to normal ones in the second sample.IMPACT STATEMENTWhat is already known on this subject? There is limited information on the presence of Neutrophil gelatinase-associated lipocalin (NGAL) in human milk and its physiological role.What the results of this study add? It is the first time that MMP-9/NGAL complex is detected in human milk in both normal and pregnancies complicated with insulin-depended gestational diabetes mellitus (iGDM). We confirm the presence of NGAL in colostrum of normal pregnancies and for the first time we detected NGAL in milk of pregnancies with iGDM. Concentrations of NGAL and MMP-9/NGAL complex tend to lessen postpartum in both groups. Pregnancies with iGDM compared to normal ones showed significantly higher concentration of MMP-9/NGAL complex two days after the beginning of lactation.What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to determine the levels of NGAL and MMP-9/NGAL complex in human milk postpartum in normal and pathological pregnancies. Taking into consideration the well-established NGAL's ability to act as a bacteriostatic agent and its mucosal healing activity in gastrointestinal track, early breastfeeding of neonates is a logical recommendation. Finally, new studies on the actual physiological role of milk NGAL in neonates are necessary.

The European Federation of Clinical Chemistry and Laboratory Medicine syllabus for postgraduate education and training for Specialists in Laboratory Medicine: version 5 - 2018.

Although laboratory medicine practise varies across the European Union's (EU) member states, the extent of overlap in scope is such that a common syllabus describing the education and training associated with high-quality, specialist practise can be identified. In turn, such a syllabus can help define the common set of skills, knowledge and competence in a Common Training Framework (CTF) for non-medical Specialists in Laboratory Medicine under EU Directive 2013/55/EU (The recognition of Professional Qualifications). In meeting the requirements of the directive's CTF patient safety is particularly enhanced when specialists seek to capitalise on opportunities for free professional migration across EU borders. In updating the fourth syllabus, the fifth expands on individual discipline requirements, new analytical techniques and use of statistics. An outline structure for a training programme is proposed together with expected responsibilities of trainees and trainers; reference is provided to a trainee's log book. In updating the syllabus, it continues to support national programmes and the aims of EU Directive 2013/55/EU in providing safeguards to professional mobility across European borders at a time when the demand for highly qualified professionals is increasing in the face of a disparity in their distribution across Europe. In support of achieving a CTF, the syllabus represents EFLM's position statement for the education and training that underpins the framework.

Endogenous sex hormones and memory performance in middle-aged Greek women with subjective memory complaints.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R 2 = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.

Ovarian volume is associated with adiposity measures and bone mineral density in postmenopausal women.

INTRODUCTION: The present study aimed to assess the association between ovarian volume and demographic and anthropometric parameters, as well as sex hormones and bone mineral density (BMD) in postmenopausal women. METHODS: 161 healthy postmenopausal women participated in this cross-sectional study. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Anthropometric parameters included body mass index (BMI) and waist-to-hip ratio (WHR). Ultrasonography was used to estimate the average ovarian volume for each participant. BMD was measured in the femoral neck (FN) and the lumbar spine (LS) using DXA. RESULTS: Mean ovarian volume increased linearly with increasing quartiles of BMI (Q1:0.985±0.25, Q2: 1.11±0.29, Q3: 1.07±0.28, Q4: 1.19±0.38, p-value for linear trend 0.013). Ovarian volume correlated positively with BMI (r=0.128, p-value=0.038), FN BMD (r=0.233, p-value=0.003), FN T-score (r=0.223, p-value=0.004) and FN Z-score (r=0.171, p-value=0.027). Multivariate analysis showed that ovarian volume was predicted by WHR (b-coefficient=0.157, p-value=0.047) and SHBG (b-coefficient= -0.160, p-value=0.042), independently of age and BMI. Finally, FN BMD was predicted by ovarian volume, independently of age, menopausal age and BMI. CONCLUSION: Ovarian volume was positively and independently associated with adiposity indexes and femoral BMD in postmenopausal women. Lower SHBG levels were associated with higher ovarian volume. Insulin resistance may mediate these results. The significance of these findings should be assessed in larger prospective studies.

The metabolic syndrome is associated with carotid atherosclerosis and arterial stiffness in asymptomatic, nondiabetic postmenopausal women.

The menopause transition is associated with adverse changes in cardiometabolic risk factors. We aimed to examine the association of the metabolic syndrome (MS) and its features with indices of vascular structure and function in a population of asymptomatic postmenopausal women. A total of 473 informed-consenting, nondiabetic postmenopausal women were included in the study. The MS was defined according to the Joint Definition. We evaluated the association between the presence of MS and indices of vascular structure (carotid artery intima-media thickness (IMT); atherosclerotic plaques) and function (flow-mediated dilatation (FMD); pulse wave velocity (PWV)). The mean age of women was 56.4 ± 6.7 and the mean menopausal age was 7.91 ± 6.31. The MS was present in 17.3% of our population. Mean values of PWV increased linearly with the accumulation of features of the MS. IMT was higher in women with the MS compared to women without the MS (0.78 ± 0.12 mm vs. 0.74 ± 0.11, p = .003). Multivariate analysis showed that the presence of the MS was independently associated with common carotid artery IMT (b = 0.149, p = .001), PWV (b = 0.114, p = .012) as well as central systolic and diastolic blood pressure (b = 0.293, p < .001 and b = 0.163, p < .001 respectively). The presence of the MS is associated with subclinical atherosclerosis already in the first postmenopausal decade of this sample of asymptomatic, nondiabetic women. Additional evidence is required to support the causative effect of these associations.

The TyG Index as a Marker of Subclinical Atherosclerosis and Arterial Stiffness in Lean and Overweight Postmenopausal Women.

BACKGROUND: The present study aims to examine the association of the metabolic syndrome (MS) as well as of the triglyceride-glucose index (TyG-Index), a novel marker of insulin resistance, with subclinical atherosclerosis in a cohort of postmenopausal women, stratified according to their body mass index. METHODS: A total of 473 informed-consenting, non-diabetic postmenopausal women, without overt cardiovascular disease, were included in this study. We aimed to compare the association between structural and functional indices of subclinical atherosclerosis (i.e. carotid artery intima-media thickness (IMT), flow-mediated dilation of the brachial artery, pulse wave velocity (PWV)) with the TyG-index or MS, separately for lean and overweight/obese women. RESULTS: The TyG-Index correlated significantly with carotid IMT (r=0.155, p=0.012) and PWV (r=0.157, p=0.013) only in the group of lean women. Multivariate analysis showed that subclinical atherosclerosis was predicted by MS, in the overweight/obese group (OR=2.517, 95% CI: 1.078-5.878, p=0.033), and by the TyG-Index the lean group (OR=3.119, 95% CI: 1.187-8.194, p<0.001). Using a TyG-Index cut-off value of 8.0 in the lean subpopulation, women above the cut-off had 44.1% prevalence of subclinical atherosclerosis compared to 29.4% in women below the cut-off (p=0.043). CONCLUSIONS: The TyG-Index is associated with carotid atherosclerosis and arterial stiffness mainly in lean postmenopausal women, while the MS serves as a better predictor of subclinical atherosclerosis in overweight/obese women. The TyG-Index may prove a useful marker for identifying high-risk women in the normal-weight postmenopausal population.

Thyroid function and autoimmunity are associated with the risk of vertebral fractures in postmenopausal women.

Overt or subclinical thyroid dysfunction may affect the risk of fragility fractures. The aim of the present study was to assess the association of thyroid function and autoimmunity with vertebral fractures (VF) in a large sample of Greek postmenopausal women. This cross-sectional study recruited 335 euthyroid postmenopausal women, aged 35-79 years. Euthyroidism was verified by serum thyroid-stimulating hormone (TSH) within the laboratory reference range (0.4-4.5 µIU/mL). VFs were diagnosed by lumbar spine lateral radiographs, according to quantitative procedures. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, as well as levels of anti-thyroglobulin (anti-TG) and thyroid peroxidase antibodies (anti-TPO) were compared according to the presence of VFs. Multivariate logistic regression showed that the presence of VFs was predicted independently by ln-TSH levels (OR = 0.290, p = 0.037) and positive anti-TG antibodies (OR = 3.308, p = 0.026) in models adjusted for age, menopausal age, and ln-HOMA-IR. Stepwise logistic regression analysis showed that the presence of VFs was predicted by menopausal age (OR = 1.120, p = 0.001), ln-TSH (OR = 0.312, p = 0.052), and thyroid autoimmunity (anti-TG and anti-TPO positive: OR = 6.637, p = 0.007) in a model that also included age and ln-HOMA-IR. Women with lower circulating TSH had higher risk of having a VF, independently of age, menopausal age, and insulin resistance. The presence of positive anti-TG/anti-TPO antibodies also indicated an elevated risk of fracture. Levels of thyroid hormones had no apparent effect on the risk of fracture. Further studies are necessary to establish the significance of our findings.

Stress urinary incontinence and endogenous sex steroids in postmenopausal women.

AIMS: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). METHODS: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. RESULTS: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. CONCLUSIONS: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121-125, 2017. © 2015 Wiley Periodicals, Inc.

Greek-origin royal jelly improves the lipid profile of postmenopausal women.

AIM: Menopause transition is associated with chronic conditions such as osteoporosis and cardiovascular disease. Concerns about the long-term safety of menopausal hormone therapy make alternative natural methods an appealing approach to management. The aim of this study was to examine the effect of royal jelly (RJ) on cardiovascular and bone turnover markers in clinically healthy postmenopausal women. METHODS: A total of 36 postmenopausal healthy women were studied in a prospective follow-up study. Participants received 150 mg of RJ daily for three months. Circulating cardiovascular risk markers [lipid profile, antithrombin-III (ATIII), Protein C, Protein S, Plasminogen Activator Inhibitor-1 (PAI-1)] and bone turnover parameters [Total calcium, phosphate (P), parathormone (PTH), total type-1 Procollagen N-terminal (P1NP), Osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX)] were compared between the baseline and the three-month visit. RESULTS: The RJ used in this study was particularly rich in medium chain fatty acids, compounds with hypolipidemic properties, which comprised 63% of the dry weight fatty content. RJ treatment resulted in a significant increase in high density lipoprotein - cholesterol (HDL-C 60.2 mg/dL ± 12.3 versus 64.7 mg/dL ± 13.9, 7.7% increase, p = 0.0003), as well as in a significant decrease in low density lipoprotein - cholesterol (LDL-C, 143.9 ± 37.5 versus 136.2 ± 32, 4.1% decrease, p = 0.011) and in total cholesterol (224.4 ± 38.6 to 216.1 ± 36.5, 3.09% decrease, p = 0.018). No statistical significant changes were found in the remaining cardiovascular or the bone turnover parameters. CONCLUSIONS: The intake of RJ 150 mg for three months is associated with significant improvements of the lipid profile of postmenopausal women. RJ supplementation may offer an alternative method of controlling the menopause - associated dyslipidemia.

Association of sex hormones and glucose metabolism with the severity of multiple sclerosis.

PURPOSE/AIM OF THE STUDY: We evaluated possible associations between the severity of multiple sclerosis (MS) and levels of sex hormones as well as biochemical parameters in a sample of ambulatory patients. MATERIAL AND METHODS: This cross-sectional study recruited 133 adults (52 men, 66 premenopausal and 15 postmenopausal women), with relapsing-remitting MS. Fasting venous blood samples were drawn for biochemical and hormonal evaluation. These parameters were tested for possible associations with MS severity, assessed using the Expanded Disability Status Scale (EDSS)-scores. RESULTS: Follicle-stimulating hormone correlated with mean EDSS scores (r = -0.369, p = 0.038) in the premenopausal subgroup. However, this association became non-significant in the age-adjusted multivariate analysis (p = 0.141; power = 67%, type α error 0.10). Free androgen exhibited a borderline negative effect on EDSS-scores in the subgroup of men (r = -0.367, p = 0.093), which was lost after adjusting for age and duration of disease (p = 0.192; statistical power = 93%, type α error 0.05). Levels of estradiol tended to affect disability status of postmenopausal women (normal-mild vs. severe impairment: 23.33 ± 11.73pg/mL vs. 14.74 ± 6.30pg/mL, p = 0.095). Levels of sex hormones or indices of glycemic metabolism did not differ between patients presenting with EDSS scores higher or lower than the median value. CONCLUSION: Sex hormones and indices of glucose metabolism exhibited only a middle effect on EDSS scoring, which was not independent from the presence of confounders like age and duration of MS. The present study highlights the need for additional research, in order to elucidate the role of sex hormones and insulin resistance in the course of MS.

Maternal serum levels of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study.

BACKGROUND: The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and MMP-9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA). METHODS: Neutrophil gelatinase-associated lipocalin, MMP-9, and MMP-9/NGAL were determined in the first, second, and third trimesters in 33 normal pregnancies, 12 pregnancies complicated by preeclampsia, and 14 pregnancies that delivered a SGA neonate. RESULTS: Median NGAL concentration (ng/mL) in normal pregnancies increased significantly from 12.8 in the first trimester to 25.9 in the second trimester (p = 0,002) and 48.0 (p < 0.0001) in the third trimester. In preeclamptic pregnancies, NGAL was significantly higher, compared with normal pregnancies, in the first (30.9; p = 0.006) and second (44.6; p = 0.015) trimesters. MMP-9 and MMP-9/NGAL complex concentrations in preeclamptic pregnancies did not differ significantly from normal pregnancies in either trimester. Pregnancies with an SGA infant did not have different marker concentrations in either trimester, compared with normal pregnancies. CONCLUSION: Maternal serum NGAL, MMP-9, and MMP-9/NGAL complex concentrations tend to increase during pregnancy in normal and preeclamptic pregnancies. NGAL was significantly elevated in the first and second trimesters, in pregnancies that later developed preeclampsia.

The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype.

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2 mg 17ß-estradiol/1 mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4 mg/dl versus 40.1 mg/dl, p = 0.019) while lowering TG (166 mg/dl versus 109 mg/dl, p = 0.026) and AIP (0.24 versus 0.04, p = 0.007). No changes were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus 76.35 mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05 ng/ml versus 2.20 ng/ml, p = 0.002) and E-selectin (73.98 ng/ml versus 56.73 ng/ml, p = 0.004). No change was observed in Thrombomodulin and vWf (11.76 ng/ml versus 13.90 ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p = 0.003), while only carotid bulb IMT decreased significantly (0.65 mm versus 0.60 mm, p = 0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.

Vitamin D receptor Bsm1 polymorphism, calcium metabolism and bone mineral density in patients with multiple sclerosis: a pilot study.

Vitamin D receptor's (VDR) genotypes have been associated both with the development of bone disease and the pathogenesis of multiple sclerosis (MS). We aimed to evaluate the association between the presence of Bsm1 restriction fragment length polymorphism of VDR and bone loss in ambulatory patients with MS. This cross-sectional study included 82 adult patients with relapsing-remitting MS. Fasting blood samples were obtained for biochemical-hormonal assessment and genotyping. Bone mineral density (BMD) was assessed at the lumbar spine (LS) and the femoral neck (FN), using dual energy X-ray absorptiometry. Possible associations between VDR's genotypes and BMD levels as well as biochemical and hormonal indices were evaluated. Among premenopausal women and men, carriers of the B allele exhibited higher BMD and Z score at the FN and a trend toward higher BMD at the LS, compared to patients with the bb genotype, after adjusting for age, BMI, sex, EDSS scoring, interferon administration, duration of MS and total steroids intake. Among postmenopausal women, the presence of the B allele was not associated with BMD or T score at any site, whereas carriers of the B allele exhibited higher levels of calcium (p value 0.008, univariate). No other significant differences were exhibited between levels of electrolytes, parathormone, 25-hydroxyvitamin D3 and the genotype of VDR, in any of the groups. VDR's Bsm1 polymorphism is associated with a mild effect on BMD in younger patients with MS. Larger studies are necessary to corroborate these findings.

Prevalence of vasomotor, psychological, psychosomatic and sexual symptoms in perimenopausal and recently postmenopausal Greek women: association with demographic, life-style and hormonal factors.

AIM: To assess the prevalence of climacteric symptoms and their association with demographic, life-style and hormonal parameters in Greek peri- and recently postmenopausal women. METHODS: 1025 Greek women who were either perimenopausal or within their first 5 postmenopausal years participated in this cross-sectional observational study. Menopausal symptoms were assessed by the Greene Climacteric Scale and were tested for associations with demographic, anthropometric, life-style and hormonal parameters. RESULTS: 29.8% Of the women reported moderate to severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3% psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r = -0.157; p < 0.01) correlated with the intensity of menopausal symptoms. In the multivariate analysis years since menopause and serum estradiol were the only significant predictors of menopausal symptoms (b = -0.158 and b = -0.198, p < 0.001, respectively), explaining though only 4.8% of the variance. CONCLUSION: One out of three Greek women has moderate to severe climacteric symptoms during the menopause transition or the first postmenopausal years. This frequency is comparable to other White populations. Menopausal age and endogenous estrogens are significant predictors of climacteric symptoms.

The severity of menopausal symptoms is associated with diabetes, and cardiometabolic risk factors in middle-aged women.

BACKGROUND: Ovarian senescence is associated with increased cardiovascular risk. We aimed to evaluate the association between menopausal symptoms and cardiometabolic risk factors in a cohort of apparently healthy middle-aged women. METHODS: The cohort included 2793 peri- and postmenopausal women not on menopausal hormone therapy. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric Scale (GCS). RESULTS: GCS-Total Score was associated with BMI (b=0.12, 95% CI: 0.04 to 0.20), T2DM (b=2.10, 95% CI: 0.06 to 4.15), and late-postmenopause (b=-1.24, 95% CI: -2.17 to -0.33). GCS-psychological score was associated with BMI (b=0.06, 95% CI: 0.00 to 0.11). GCS-Physical Score was associated with BMI (b=0.06, 95% CI: 0.03 to 0.09), central obesity (b=0.18, 95% CI: 0.02 to 0.34), and postmenopause (early-/late-postmenopause vs. perimenopause, b=-0.36, 95% CI: -0.59 to -0.13 and b=-0.65, 95% CI: -0.97 to -0.34, respectively). All GCS-scores were negatively associated with age. GCS-Sexual Score was associated with early-postmenopause (incidence rate ratio (IRR)=1.53, 95% CI: 1.21 to 1.94), central obesity (IRR=1.18, 95% CI: 1.00 to 1.39), smoking, diastolic blood pressure, age. Cox-regression analysis showed that incident T2DM was positively associated with increasing age, BMI, daily alcohol consumption, moderate-to-severe vasomotor symptoms (VMS, OR=1.045, 95% CI: 1.011 to 1.079), and negatively with moderate-to-strenuous physical activity. These associations persisted in lean but not in obese women. CONCLUSIONS: The severity of menopausal symptoms is associated with T2DM, obesity, and smoking in a cohort of peri-/postmenopausal women. VMS were associated with incident T2DM, especially in lean women. These associations must be considered in implementing primary and secondary prevention strategies.

Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein of the lipocalin superfamily. This protein is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL has recently generated great interest as an early biomarker of renal injury. However, like many other endogenous biomarkers it is not produced by just one cell type and it exists in more than one molecular form. As recent research has shown different pathological conditions may involved in the production of this molecule. This review summarizes the current knowledge about the biology of NGAL and examines the role of this molecule of acute renal injury as well as in other pathologic conditions like neoplasia, anemia, pregnancy, cardiovascular disease chronic kidney disease and in cardiorenal syndrome. Commercial and research immunoassays are used to measure NGAL in both plasma and urine but these assays are not standardized. The existence of different molecular forms of NGAL and their expression at various disease states further complicates the interpretation of the results. Pre analytical issues and biological variation are also not fully elucidated.

The EC4 European syllabus for post-graduate training in clinical chemistry and laboratory medicine: version 4--2012.

Laboratory medicine's practitioners across the European community include medical, scientific and pharmacy trained specialists whose contributions to health and healthcare is in the application of diagnostic tests for screening and early detection of disease, differential diagnosis, monitoring, management and treatment of patients, and their prognostic assessment. In submitting a revised common syllabus for post-graduate education and training across the 27 member states an expectation is set for harmonised, high quality, safe practice. In this regard an extended 'Core knowledge, skills and competencies' division embracing all laboratory medicine disciplines is described. For the first time the syllabus identifies the competencies required to meet clinical leadership demands for defining, directing and assuring the efficiency and effectiveness of laboratory services as well as expectations in translating knowledge and skills into ability to practice. In a 'Specialist knowledge' division, the expectations from the individual disciplines of Clinical Chemistry/Immunology, Haematology/Blood Transfusion, Microbiology/ Virology, Genetics and In Vitro Fertilisation are described. Beyond providing a common platform of knowledge, skills and competency, the syllabus supports the aims of the European Commission in providing safeguards to increasing professional mobility across European borders at a time when demand for highly qualified professionals is increasing and the labour force is declining. It continues to act as a guide for the formulation of national programmes supplemented by the needs of individual country priorities.

Serum glial fibrillary acidic protein as a biomarker of brain injury in premature neonates.

Neonatal brain injury is a serious adverse outcome of prematurity. Early detection of high risk premature neonates to develop neonatal brain injury is not currently feasible. The predictive value of many biomarkers has been tested, but none is used currently in clinical practice. The purpose of this study was to determine the levels and predictive value of serum glial fibrillary acidic protein (GFAP) in a prospective longitudinal case-control study during the first three days of life in premature neonates (<34 weeks of gestation) that later developed either intraventricular hemorrhage or periventricular leukomalacia. Each case (n=29) was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. No significant difference on GFAP levels was observed between the groups. Nevertheless, neonates with brain injury presented more frequently GFAP levels above the lowest detection limit (0.056 ng/ml) and this trend was significantly different during all days. The effectiveness of GFAP as an early biomarker of neonatal brain injury in premature neonates seems to be limited.

An evidence based strategy for follow up after breast conserving treatment for breast cancer.

BACKGROUND AND OBJECTIVES: Follow up for breast cancer patients aims at the timely detection of loco-regional recurrences and contralateral breast cancers (LRR). This study investigates the annual risk of LRR after breast conserving treatment (BCT) and the potential value of mammographic surveillance and/or routine clinical examination. METHODS: Data on 650 women who underwent BCT were obtained and LRR was divided into parenchymal and non-parenchymal. LRR-free and cumulative LRR-free rates were calculated. In patients where recurrence was diagnosed at a routine clinic visit and had negative mammography ("clinical detection only" group) were also separately examined. RESULTS: Median follow up was 115 months, range 9-196. Seventy-three patients had parenchymal and 16 nodal recurrence. The median probability of LRR was 1.4% and of parenchymal LRR was 1.32% per year, remaining constant for up to 168 months. The 16 patients in the "clinical detection only" group relapsed mainly during the first 2 years (annual risk 0.77% and 0.80%, respectively). CONCLUSIONS: This study shows that the risk of parenchymal LRR remains constant for at least 14 years and is significant enough to warrant routine long-term follow up mammography. Routine clinical examination contributes significantly to the detection of LRR only for the first 2 years.