Early neonatal morbidity and mortality in growth-discordant twins

Objective. To evaluate early neonatal morbidity and mortality in twin pregnancies with growth discordance. Design. Retrospective study. Setting. Tertiary teaching hospital, Sao Paulo, Brazil. Population. A total of 151 twin pregnancies managed and delivered at the Multiple Pregnancy Unit at Sao Paulo University Hospital between 1998 and 2004. Methods. Comparison between twin pregnancies with weight discordance 20% and pregnancies concordant for fetal weight. Cases with fetal death, abnormalities, twin-to-twin transfusion and delivery before 26 weeks or in another hospital were excluded. Outcome measures. Early neonatal morbidity (Apgar at 5 minutes 7, respiratory or neurological complications, infection, necrotizing enterocolitis, length of hospital stay) and mortality. Results. Forty (26.5%) pregnancies presented discordance 20% and 111 (73.5%) were concordant. In the discordant group, 75% of pregnancies had at least one growth restricted fetus (10th centile). In concordant twin pregnancies, monochorionic cases (22.5%) presented with lower gestational age (34.3 vs. 36.2 weeks), lower birthweight (2,067 vs. 2,334 g) and a longer period of hospital stay (5.5 vs. 3.0) compared to dichorionic concordant twins. No differences between monochorionic and dichorionic subgroups were observed in discordant twins. Pregnancies in which at least one baby was born with a birthweight below the 10th centile showed that discordant pregnancies had a lower gestational age at delivery (35.2 vs. 36.8 weeks) and a longer period of hospital stay (9 vs. 4 weeks) compared to concordant cases. Neonatal mortality was similar in discordant (3.7%) and concordant (4.5%) twins. Conclusion. Early perinatal morbidity is increased in twin pregnancies with birthweight discordance 20% only when associated with fetal growth restriction and low birthweight.

Sepsis and Neutropenia in Very Low Birth Weight Infants Delivered of Mothers with Preeclampsia

Objective To study the association between maternal preeclampsia and neonatal sepsis in very low birth weight newborns. Study design We studied all infants with birth weights between 500 g and 1500 g who were admitted to 6 neonatal intensive care units of the Brazilian Network on Neonatal Research for 2 years. Exclusion criteria were major malformations, death in the delivery room, and maternal chronic hypertension. Absolute neutrophil count was performed in the first 72 hours of life. Results A total of 911 very low birth weight infants (preeclampsia, 308; non-preeclampsia, 603) were included. The preeclampsia group had significantly higher gestational age, more cesarean deliveries, antenatal steroid, central catheters, total parenteral nutrition, and neutropenia, and less rupture of membranes >18 hours and mechanical ventilation. Both groups had similar incidences of early sepsis (4.6% and 4.2% in preeclampsia and non-preeclampsia groups, respectively) and late sepsis (24% and 22.1% in preeclampsia and non-preeclampsia groups, respectively). Vaginal delivery and neutropenia were associated with multiple logistic regressions with early sepsis, and mechanical ventilation, central catheter, and total parenteral nutrition were associated with late sepsis. Death was associated with neutropenia in very preterm infants. Conclusions Preeclampsia did not increase neonatal sepsis in very low birth weight infants, and death was associated with neutropenia in very preterm infants. (J Pediatr 2010; 157: 434-8).

Hantavirus infection associated to a staphylococcal sepsis. Report of one case

We report a previously healthy 36-year-old male who developed a pulmonary syndrome caused by Hantavirus infection He was admitted to an intensive care unit in shock awl respiratory failure and died four hours after admission. Blood cultures were positive for Staphylococcus aureus This patient could be an index case that shows, for the first time, an association of Hantavirus Pulmonary Syndrome with Staphylococcus nitwits infection similar to what happens with other viruses (Rev Med Chile 2010, 138: 338-340).

Acute hyperglycemia rapidly stimulates VEGF mRNA translation in the kidney. Role of angiotensin type 2 receptor (AT2)

Angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) are important mediators of kidney injury in diabetes. Acute hyperglycemia increased synthesis of intrarenal Ang I and Ang II and resulted in activation of both Ang II receptors, AT1 and AT2, in the kidney. Losartan (specific AT1 antagonist) or PD123319 (specific AT2 antagonist) did not affect hyperglycemia but prevented activation of renal AT1 and AT2, respectively. In murine renal cortex, acute hyperglycemia increased VEGF protein but not mRNA content after 24 h, which suggested translational regulation. Blockade of AT2, but not AT1, prevented increase in VEGF synthesis by inhibiting translation of VEGF mRNA in renal cortex. Acute hyperglycemia increased VEGF expression in wild type but not in AT2 knockout mice. Binding of heterogeneous nuclear ribonucleoprotein K to VEGF mRNA, which stimulates its translation, was prevented by blockade of AT2, but not AT1. The Akt-mTOR-p70(S6K) signaling pathway, involved in the activation of mRNA translation, was activated in hyperglycemic kidneys and was blocked by the AT2 antagonist. Elongation phase is an important step of mRNA translation that is controlled by elongation factor 1A (eEF1A) and 2 (eEF2). Expression of eEF1A and activity of eEF2 was higher in kidney cortex from hyperglycemic mice and only the AT2 antagonist prevented these changes. To assess selectivity of translational control of VEGF expression, we measured expression of fibronectin (FN) and laminin beta 1 (lam beta 1): acute hyperglycemia increased FN expression at both protein and mRNA levels, indicating transcriptional control, and did not affect the expression of lam beta 1. To confirm results obtained with PD123319, we induced hyperglycemia in AT2 knockout mice and found that in the absence of AT2, translational control of VEGF expression by hyperglycemia was abolished. Our data show that acute hyperglycemia stimulates Ang II synthesis in murine kidney cortex, this leads to AT2 activation and stimulation of VEGF mRNA translation, via the Akt-mTOR-p70(S6K) signaling pathway. Our data show that exclusive translational control of protein expression in the kidney by acute hyperglycemia is not a general phenomenon, but do not prove that it is restricted to VEGF. (C) 2010 Elsevier Inc. All rights reserved.

LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

Background: The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of LIthium and CArbamazepine compared to lithium and VALproic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs. Methods: LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study. Results: LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012. Conclusions: Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.

Latent class analysis of manic and depressive symptoms in a population-based sample in Sao Paulo, Brazil

Background: Current diagnostic criteria cannot capture the full range of bipolar spectrum. This study aims to clarify the natural co-segregation of manic-depressive symptoms occurring in the general population. Methods: Using data from the Sao Paulo Catchment Area Study, latent class analysis (LCA) was applied to eleven manic and fourteen depressive symptoms assessed through CIDI 1.1 in 1464 subjects from a community-based study in Sao Paulo, Brazil. All manic symptoms were assessed, regardless of presence of euphoria or irritability, and demographics, services used, suicidality and CIDI/DSM-IIIR mood disorders used to external validate the classes. Results: The four obtained classes were labeled Euthymics (EU; 49.1%), Mild Affectives (MA; 31.1%), Bipolars (BIP; 10.7%), and Depressives (DEP; 9%). BIP and DEP classes represented bipolar and depressive spectra, respectively. Compared to DEP class, BIP exhibited more atypical depressive characteristics (hypersomnia and increase in appetite and/or weight gain), risk of suicide, and use of services. Depressives had rates of atypical symptoms and suicidality comparable to oligosymptomatic MA class subjects. Limitations: The use of lay interviewers and DSM-IIIR diagnostic criteria, which are more restrictive than the currently used DSM-IV TR. Conclusions: Findings of high prevalence of bipolar spectrum and of atypical symptoms and suicidality as indicators of bipolarity are of great clinical importance, due to different treatment needs, and higher severity. Lifetime sub-affective and syndromic manic symptoms are clinically significant, arguing for the need Of revising DSM bipolar spectrum categories. (C) 2009 Elsevier B.V. All rights reserved.

Hypomania: a transcultural perspective

This study examined the transcultural robustness of a screening instrument for hypomania, the Hypomania Checklist-32. first revised version(HCL-32 R1) It was carried out in 2606 patients from twelve countries in five geographic regions (Northern, Southern and Eastern Europe, South America and East Asia) In addition, GAMIAN Europe contributed data from its members Exploratory and confirmatory factor analyses were used to examine the transregional stability of the measurement properties of the HCL-32 R 1, including the influence of sex and age as covariates A cross cultures, a two-factor structure was confirmed the first factor (F 1) reflected the more positive aspects of hypomania (being more active, elated, self-confident, and cognitively, enhanced), the second factor (F2) reflected the more negative aspects (being irritable, impulsive, careless. more substance use). The measurement properties of the HCL-32 R1 were largely invariant across cultures Only few items showed transcultural differences in their relation to hypomania as measured by the test F2 was higher among men and in more severe manic syndromes, F1 was highest in North and East Europe and lowest in South America Vie scores decreased slightly with age The frequency of the 32 items showed remarkable similarities across geographic areas, with two exceptions. South Europeans had lower symptom frequencies in general and East Europeans higher rates of substance use These findings support the international applicability of the HCL-32 R1 as a screening instrument for hypomania

Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries

Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved.

Apolipoprotein E genotype and Cognition in Bipolar Disorder

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer`s Disease (AD). APOE allele *3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the *4 allele is a well-established risk factor for CD, while the *2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD-type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18-35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele *2 presented better cognitive performance. The presence of allele *4 was associated with worse performance in a few executive tasks. APOE *3*3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD-type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.

Violence against women is strongly associated with suicide attempts: Evidence from the WHO multi-country study on women`s health and domestic violence against women

Suicidal behaviours are one of the most important contributors to the global burden of disease among women, but little is known about prevalence and modifiable risk factors in low and middle income countries. We use data from the WHO multi-country study on women`s health and domestic violence against women to examine the prevalence of suicidal thoughts and attempts, and relationships between suicide attempts and mental health status, child sexual abuse, partner violence and other variables. Population representative cross-sectional household surveys were conducted from 2000-2003 in 13 provincial (more rural) and city (urban) sites in Brazil, Ethiopia, japan, Namibia, Peru, Samoa, Serbia, Thailand and Tanzania. 20967 women aged 15-49 years participated. Prevalence of lifetime suicide attempts, lifetime suicidal thoughts, and suicidal thoughts in the past four weeks were calculated, and multivariate logistic regression models were fit to examine factors associated with suicide attempts in each site. Prevalence of lifetime suicide attempts ranged from 0.8% (Tanzania) to 12.0% (Peru city): lifetime thoughts of suicide from 7.2% (Tanzania province) to 29.0% (Peru province), and thoughts in the past four weeks from 1.9% (Serbia) to 13.6% (Peru province). 25-50% of women with suicidal thoughts in the past four weeks had also visited a health worker in that time. The most consistent risk factors for suicide attempts after adjusting for probable common mental health disorders were: intimate partner violence, non-partner physical violence, ever being divorced, separated or widowed, childhood sexual abuse and having a mother who had experienced intimate partner violence. Mental health policies and services must recognise the consistent relationship between violence and suicidality in women in low and middle income countries. Training health sector workers to recognize and respond to the consequences of violence may substantially reduce the health burden associated with suicidal behaviour. (C) 2011 Elsevier Ltd. All rights reserved.

Performance of Brazilian long and short IQCODE on the screening of dementia in elderly people with low education

Background: Dementia screening in elderly people with low education can be difficult to implement. For these subjects, informant reports using the long (L) (26 items) and short (C) (16 items) versions of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) can be useful. The objective of the present study was to investigate the performance of Brazilian versions of the IQCODE L, S and a new short version (SBr) (15 items) in comparison with the Mini-mental State Examination (MMSE) for dementia screening in elderly people with low education. Methods: Thirty-four patients with mild to moderate dementia, diagnosed according to ICD-10 criteria, and 57 controls were evaluated and divided into three groups based on their socioeconomic status and level of education. Patients were evaluated using the MMSE and the informants were interviewed using the IQCODE by interviewers blind to the clinical diagnosis. Results: Education was correlated with MMSE results (r = 0.280, p = 0.031), but not with the versions of the IQCODE. The performance of the instruments, evaluated by the ROC curves, was very similar, with good internal consistency (Cronbach`s alpha = 0.97). MMSE correctly classified 85.7% of the subjects while the three IQCODE versions (L, S and SBr) correctly classified 91.2% of the subjects. Conclusions: The long, short and the new short Brazilian IQCODE versions can be useful as a screening tool for mild and moderate patients with dementia in Brazil. The IQCODE is not biased by schooling, and it seems to be an adequate instrument for samples with low levels of education.

The influence of Flutter (R) VRP1 components on mucus transport of patients with bronchiectasis

Background: The Flutter (R) VRP1 combines high frequency oscillation and positive expiratory pressure (PEP). Objective: To separately evaluate the effect of the Flutter (R) VRP1 components (high frequency oscillation and PEP) on mucus transportability in patients with bronchiectasis. Methods: Eighteen patients with bronchiectasis received sessions with the Flutter (R) VRP1 or PEP for 30 min daily in a randomized, crossover study. The treatment duration was four weeks with one of the therapies, one week of a ""wash-out"" period and followed by four more weeks with the other treatment. Weekly secretion samples were collected and evaluated for mucociliary relative transport velocity (RTV), displacement in a simulated cough machine (SCM) and contact angle measurement (CAM). For the proposed comparisons, a linear regression model was used with mixed effects with a significance level of 5%. Results: The Flutter (R) VRP1 treatment resulted in greater displacement in SCM and lower CAM when comparing results from the first (9.6 +/- 3.4 cm and 29.4 +/- 5.7 degrees, respectively) and fourth weeks of treatment (12.44 +/- 10.5 cm and 23.28 +/- 6.2, respectively; p < 0.05). There was no significant difference in the RTV between the treatment weeks for either the Flutter (R) VRP1 or PEP. Conclusion: The use of the Flutter (R) VRP1 for four weeks is capable of altering the respiratory secretion transport properties, and this alteration is related to the high frequency oscillation component. (C) 2011 Elsevier Ltd. All rights reserved.

Synaptic transmission block by presynaptic injection of oligomeric amyloid beta

Early Alzheimer`s disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)A beta 42, but not oA beta 40 or extracellular oA beta 42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oA beta 42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD.

Abnormal Methylation of Histone Deacetylase Genes: Implications on Etiology and Epigenetic Therapy of Astrocytomas

Background: A growing body of evidence has revealed, the involvement of epigenetic alterations in the etiology of astrocytomas. In the present study, we aimed to evaluate the association of DNA methylation of histone deacetylase genes (HDAC) with the etiology of astrocytoma, and the implications for epigenetic therapy. Materials and Methods: Methylation of the HDAC4, HDAC5 and HDAC6 genes was assessed in 29 tumor samples (astrocytomas grades I, III, and IV) and in the glioblastoma cell lines U87, U251, U343, SF188, and T98G by methylation-specific quantitative PCR (MSED-qPCR). Results: Significantly increased methylation of the HDAC5 gene was observed in astrocytomas when compared to non-neoplastic brain samples (p=0.0007) and to glioblastomas cell lines (p=0.001). A heterogenic methylation pattern was evidenced when compared to the glioblastoma cell lines. Distinct effects on methylation and gene expression were observed after in vitro treatment of the different cell lines with decitabine. Conclusion: Our results suggest that abnormal methylation of HDAC genes is involved in the etiology of astrocytomas and indicate that loci-specific epigenetic interindividualities might be associated to the differential responses to treatment with decitabine.

Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects

Folic acid (FA) supplementation during carcinogenesis is controversial. Considering the impact of liver cancer as a public health problem and mandatory FA fortification in several countries, the role of FA supplementation in hepatocarcinogenesis should be elucidated. We evaluated FA supplementation during early hepatocarcinogenesis. Rats received daily 0.08 mg (FA8 group) or 0.16 mg (FA16 group) of FA/100 g body weight or water (CO group, controls). After a 2-week treatment, animals were subjected to the ""resistant hepatocyte"" model of hepatocarcinogenesis (initiation with diethylnitrosamine, selection/promotion with 2-acetylaminofluorene and partial hepatectomy) and euthanized after 8 weeks of treatment. Compared to the CO group, the FA16 group presented: reduced (p < 0.05) number of persistent and increased (p < 0.05) number of remodeling glutathione S-transferase (GST-P) positive preneoplastic lesions (PNL); reduced (p < 0.05) cell proliferation in persistent GST-P positive PNL; decreased (p < 0.05) hepatic DNA damage; and a tendency (p < 0.10) for decreased c-myc expression in microdissected PNL. Regarding all these parameters, no differences (p > 0.05) were observed between CO and FA8 groups. FA-treated groups presented increased hepatic levels of S-adenosylmethionine but only FA16 group presented increased S-adenosylmethionine/S-adenosylhomocysteine ratio. No differences (p > 0.05) were observed between experimental groups regarding apoptosis in persistent and remodeling GST-P positive PNL, and global DNA methylation pattern in microdissected PNL. Altogether, the FA16 group, but not the FA8 group, presented chemopreventive activity. Reversion of PNL phenotype and inhibition of DNA damage and of c-myc expression represent relevant FA cellular and molecular effects.