Objective Supervised Machine Learning-Based Classification and Inference of Biological Neuronal Networks.

The classification of biological neuron types and networks poses challenges to the full understanding of the human brain's organisation and functioning. In this paper, we develop a novel objective classification model of biological neuronal morphology and electrical types and their networks, based on the attributes of neuronal communication using supervised machine learning solutions. This presents advantages compared to the existing approaches in neuroinformatics since the data related to mutual information or delay between neurons obtained from spike trains are more abundant than conventional morphological data. We constructed two open-access computational platforms of various neuronal circuits from the Blue Brain Project realistic models, named Neurpy and Neurgen. Then, we investigated how we could perform network tomography with cortical neuronal circuits for the morphological, topological and electrical classification of neurons. We extracted the simulated data of 10,000 network topology combinations with five layers, 25 morphological type (m-type) cells, and 14 electrical type (e-type) cells. We applied the data to several different classifiers (including Support Vector Machine (SVM), Decision Trees, Random Forest, and Artificial Neural Networks). We achieved accuracies of up to 70%, and the inference of biological network structures using network tomography reached up to 65% of accuracy. Objective classification of biological networks can be achieved with cascaded machine learning methods using neuron communication data. SVM methods seem to perform better amongst used techniques. Our research not only contributes to existing classification efforts but sets the road-map for future usage of brain-machine interfaces towards an in vivo objective classification of neurons as a sensing mechanism of the brain's structure.

Circulating chemoattractants RANTES, negatively related to endogenous androgens, and MCP-1 are differentially suppressed by hormone therapy and raloxifene.

BACKGROUND: The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system. OBJECTIVE: The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women. METHODS: Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months. RESULTS: Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011). CONCLUSION: Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.

On the blind recovery of cardiac and respiratory sounds.

We present a method for smart auscultation by proposing a novel blind recovery of the original cardiac and respiratory sounds from a single observation mixture, in the framework of nonnegative matrix factorization (NMF). The method learns the basis spectra of the mixing sources in unsupervised or semisupervised fashion depending upon the applications. A modified NMF technique is proposed, which enforces the spectral structure of the target sources in mixture factorization, resulting in good separation of target sources, even in the presence of nonstationary noise. Moreover, data is processed in small batches which 1) enables dynamic bases spectra update technique to mitigate the spectral variations of the mixing sources, and 2) reduces computational complexity. The analytical work is verified through simulations using synthetic as well as actual clinical data collected from different subjects in different clinical sittings. The proposed smart auscultation method demonstrates excellent results even in noisy clinical environments.

Effect of hormone therapy and raloxifene on serum VE-cadherin in postmenopausal women.

OBJECTIVE: To investigate the effect of continuous combined hormone therapy and raloxifene on serum VE-cadherin. DESIGN: The study was double blinded, with a placebo run-in period of 28-50 days. SETTING: University menopause clinic. PATIENT(S): Twenty-eight healthy postmenopausal women devoid of climacteric complaints. INTERVENTION(S): Subjects were randomized to 17beta-estradiol (2 mg) + norethisterone acetate (1 mg; E(2)-NETA) or raloxifene hCL (60 mg) for a period of 6 months. MAIN OUTCOME MEASURE(S): Serum VE-cadherin, which was estimated at baseline and at month 6. RESULT(S): Serum VE-cadherin decreased significantly in both E(2)-NETA and raloxifene groups (raloxifene baseline +/- SD: 1.17 +/- 0.44 ng/mL, 6 months: 0.82 +/- 0.29 ng/mL; E(2)-NETA baseline: 1.19 +/- 0.47 ng/mL, 6 months: 0.92 +/- 0.49 ng/mL). Percentage changes from baseline were -21.7 +/- 24.3 for E(2)-NETA and -26.0 +/- 20.6 for raloxifene. CONCLUSION(S): The effect of E(2)-NETA and raloxifene suggests that these drugs may preserve interendothelial junction integrity and control vascular permeability. Although this effect may influence the progress of the atheromatous lesion, its clinical impact on coronary artery disease (CAD) remains uncertain.

Thyroid function and postpartum mood disturbances in Greek women.

BACKGROUND: Postpartum mood disturbances are very common with postpartum blues being as high as 44.5% among Greek women. This study aimed to investigate whether thyroid function within the normal range affects the incidence of postpartum mood disturbances. METHODS: In a cross-sectional study in the maternity ward of Aretaieion Hospital, 57 Greek women were evaluated for postpartum mood swings by the Maternity Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the first and sixth week postpartum. Serum Free T4, Free T3 and TSH concentrations as well as thyroglobulin and thyroid peroxidase antibodies were measured on admission for delivery and daily until the fourth postpartum day. We examined the association between hormone and antibody levels, and scores in the two scales evaluating postpartum mood disturbances. RESULTS: Prepartum serum FT3 and FT4 correlated negatively with blues scores in the first week postpartum (blues on day 4: with FT3, rho=-0.44, p < or = 0.01; with FT4 rho=-0.36, p < or = 0.01). Women with lower FT3 and FT4 levels belonged to the high scoring group (high scoring group: FT3=1.22 pg/ml, FT4=0.66 ng/dl; low scoring group: FT3=1.64 pg/ml, FT4=0.73 ng/dl). Serum FT3 showed a negative independent correlation with postpartum blues scores in the first postpartum days. No association was found between thyroid antibody levels and mood scores. CONCLUSION: Our findings indicate an association between the occurrence of postpartum mood disorders and antenatal thyroid function. Within normal limits, lower levels of serum FT3 and FT4 are associated with increased incidence of mood disturbances in the first postpartum week.

Endometriosis and other benign and malignant müllerian lesions in pelvic and extrapelvic organs.

OBJECTIVE: To conduct a retrospective study on case reports found in literature across the world on benign müllerian lesions of the urogenital tract and on cases of malignant transformation from müllerian duct remnants in order to better understand these rare anatomopathologic entities and to avoid overdiagnosis and overtreatment. STUDY DESIGN: We reviewed a number of case reports on benign and malignant müllerian lesions and compared the developments associated with endometriosis, endosalpingiosis and endocervicosis. RESULTS: Our sampling of case reports confirm the suggestion that both malignant neoplasms and benign müllerian lesions can arise in foci of endometriosis in both pelvic and extrapelvic sites. CONCLUSION: The development of malignant tumors is a well-known complication of endometriosis and endosalpingiosis, but data about endocervicosis are unclear.

Measurable serum markers of oxidative stress response in women with endometriosis.

OBJECTIVE: To evaluate the hypothesis of increased systemic oxidative stress in patients with endometriosis. SETTING: Tertiary care university hospital. DESIGN: Cross-sectional study. PATIENT(S): Sixty-six women of reproductive age undergoing laparoscopy. INTERVENTION(S): All women were investigated for endometriotic foci during laparoscopy. Forty-five women had laparoscopically and histologically confirmed endometriosis, and 21 women did not have endometriosis. MAIN OUTCOME MEASURE(S): Four markers of oxidative stress were assessed in the serum of each patient: heat shock protein 70 (HSP70), HSP70b', thioredoxin (TRX), and ischemia-modified albumin (IMA). RESULT(S): Mean serum HSP 70b' level was higher in patients with endometriosis compared with controls (0.178 ng/mL, SD 0.103, and 0.135 ng/mL, SD 0.014, respectively). The disease stage did not affect HSP70b' levels. Heat shock protein 70, IMA, and TRX levels did not differ between patients with endometriosis and controls. Women with a history of arterial hypertension had higher mean IMA levels compared with women with normal blood pressure independently of the presence of endometriosis (106.7 [SD 25.4] U/mL and 85.0 [SD 11.5] U/mL, respectively). CONCLUSION(S): Endometriosis is associated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies.

Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome.

The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1beta and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1beta, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

Differential effect of hormone therapy and tibolone on lipids, lipoproteins, and the atherogenic index of plasma.

The aim of our study was to assess the effect of various regimens and doses of hormone therapy and tibolone on the Atherogenic Index of Plasma (AIP). A total of 519 postmenopausal women attending our menopause clinic were studied in a prospective design. Women with climacteric symptoms were randomly assigned to receive 1 of the following regimens: tibolone 2.5 mg, conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA), or 17beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2/NETA). Serum parameters were assessed at baseline and after 6 months and included total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoprotein A1 and apolipoprotein B. The AIP was assessed as the log (triglycerides [mmol/L]/HDL-C [mmol/L]). CEE/MPA treatment associated with lower mean LDL-C but higher mean triglyceride levels (-15.5 mg/dL +/- 3.6, P = 0.0001; 12.6 mg/dL +/- 4.8, P = 0.01). Furthermore, CEE/MPA treatment resulted in higher AIP levels (0.073 +/- 0.021, P = 0.001). On the contrary, both E2/NETA regimens and tibolone associated with lower mean triglyceride and HDL-C levels (E2/NETA, triglycerides: -9.8 mg/dL +/- 5.0, P = 0.049; HDL-C: -4.9 mg/dL +/- 1.8, P = 0.01, low E2/NETA triglycerides: -12.5 mg/dL +/- 4.1, P = 0.003; HDL-C: -4.7 mg/dL +/- 1.3, P = 0.001; tibolone, triglycerides: -21.9 mg/dL +/- 2.7, P = 0.0001; HDL-C: -12.7 mg/dL +/- 1.1, P = 0.0001). None of the 3 regimens had any effect on AIP. The effect of a particular regimen of hormone therapy on the lipid-lipoprotein profile differs depending on the parameter assessed. The use of unified markers such as AIP will be helpful in evaluating the overall effect of lipid-lipoprotein modulation on the cardiovascular system. In fact, the concurrent assessment of the therapy effect on both LDL-C and AIP may be more dependable in evaluating the cardiovascular impact of a given regimen.