Protein aggregation containing beta-amyloid, alpha-synuclein and hyperphosphorylated tau in cultured cells of hippocampus, substantia nigra and locus coeruleus after rotenone exposure

Background: Protein aggregates containing alpha-synuclein, beta-amyloid and hyperphosphorylated tau are commonly found during neurodegenerative processes which is often accompanied by the impairment of mitochondrial complex I respiratory chain and dysfunction of cellular systems of protein degradation. In view of this, we aimed to develop an in vitro model to study protein aggregation associated to neurodegenerative diseases using cultured cells from hippocampus, locus coeruleus and substantia nigra of newborn Lewis rats exposed to 0.5, 1, 10 and 25 nM of rotenone, which is an agricultural pesticide, for 48 hours. Results: We demonstrated that the proportion of cells in culture is approximately the same as found in the brain nuclei they were extracted from. Rotenone at 0.5 nM was able to induce alpha-synuclein and beta amyloid aggregation, as well as increased hyperphosphorylation of tau, although high concentrations of this pesticide (over 1 nM) lead cells to death before protein aggregation. We also demonstrated that the 14kDa isoform of alpha-synuclein is not present in newborn Lewis rats. Conclusion: Rotenone exposure may lead to constitutive protein aggregation in vitro, which may be of relevance to study the mechanisms involved in idiopathic neurodegeneration.

Three-dimensional visualization of human hemoglobin phenotypes with HPLC

Hemoglobinopathies were included in the Brazilian Neonatal Screening Program on June 6, 2001. Automated high-performance liquid chromatography (HPLC) was indicated as one of the diagnostic methods. The amount of information generated by these systems is immense, and the behavior of groups cannot always be observed in individual analyses. Three-dimensional (3-D) visualization techniques can be applied to extract this information, for extracting patterns, trends or relations from the results stored in databases. We applied the 3-D visualization tool to analyze patterns in the results of hemoglobinopathy based on neonatal diagnosis by HPLC. The laboratory results of 2520 newborn analyses carried out in 2001 and 2002 were used. The ""Fast"", ""F1"", ""F"" and ""A"" peaks, which were detected by the analytical system, were chosen as attributes for mapping. To establish a behavior pattern, the results were classified into groups according to hemoglobin phenotype: normal (N = 2169), variant (N = 73) and thalassemia (N = 279). 3-D visualization was made with the FastMap DB tool; there were two distribution patterns in the normal group, due to variation in the amplitude of the values obtained by HPLC for the F1 window. It allowed separation of the samples with normal Hb from those with alpha thalassemia, based on a significant difference (P < 0.05) between the mean values of the ""Fast"" and ""A"" peaks, demonstrating the need for better evaluation of chromatograms; this method could be used to help diagnose alpha thalassemia in newborns.

Analytical results on Muller's ratchet effect in growing populations

Fontanari introduced [Phys. Rev. Lett. 91, 218101 (2003)] a model for studying Muller's ratchet phenomenon in growing asexual populations. They studied two situations, either including a death probability for each newborn or not, but were able to find analytical (recursive) expressions only in the no-decay case. In this Brief Report a branching process formalism is used to find recurrence equations that generalize the analytical results of the original paper besides confirming the interesting effects their simulations revealed.

Is there a connection between long airplane flight, venous thromboembolism, and sleep-disordered breathing?

Commercial passenger flights have been increasing around the world. The effect of these flights on health is unclear. Venous thromboembolism has been noted after recent long-distance airplane flight, even in the absence of other risk factors. Hypoxia caused by the low ambient pressure during flights could contribute, and individuals with obstructive sleep apnea may be particularly vulnerable. The association between the effects of long airplane travel and sleep-disordered breathing deserves further study. (C) 2008 Elsevier B.V. All rights reserved.

Analysis of pelvic floor musculature function during pregnancy and postpartum: a cohort study

Aim. To compare the measurements of women`s pelvic floor musculature strength (PFMS) during pregnancy and postpartum period. Background. Pregnancy and childbirth can have an influence on the muscles and pelvic floor and can cause morbidities of women`s genito-urinary tract. Design. A prospective cohort study. Methods. There were included 226 primigravidae women, attended by community health services in the city of Itapecerica da Serra, Sao Paulo, Brazil. The participants were followed in four stages: (1) within 12 weeks of pregnancy; (2) between 36-40 weeks of pregnancy; (3) within 48 hours after childbirth; (4) 42-60 days after childbirth. Data were collected from February 2007-August 2008. The pelvic floor musculature strength was evaluated by perineometry and digital vaginal palpation in stages 1, 2 and 4. The final sample included 110 women who completed all four stages of the study. Results. The pelvic floor musculature strength of the women did not change significantly during pregnancy or after delivery (anova: p = 0 center dot 78). In all three examined stages, a low-intensity pelvic floor musculature strength was prevalent (in mmHg: stage 1 = 15 center dot 9; stage 2 = 15 center dot 2, stage 4 = 14 center dot 7), with scores from 0-3 on the Oxford scale. The pelvic floor musculature strength did not differ in relation to maternal age, skin colour, conjugal status, dyspareunia, stool characteristics, type of delivery, or conditions of the perineum. An interaction between maternal nutritional state and newborn`s weight may affect the pelvic floor musculature strength (manova: p = 0 center dot 04). Conclusion. Pregnancy and childbirth did not reduce significantly pelvic floor musculature strength. The perineometry and digital vaginal palpation used to assess the pelvic floor musculature strength were well accepted by the women. Relevance to clinical practice. In clinical practice, digital vaginal palpation is effective for supporting the diagnosis of urinary, intestinal and sexual dysfunctions. Perineometry use is particularly important together with the performance of perineal exercises with biofeedback in the treatment these disorders.

Analgesic Effects of Sweet-Tasting Solutions for Infants: Current State of Equipoise

OBJECTIVE: The goal was to review published studies of analgesic effects of sweet solutions, to ascertain areas with sufficient evidence of effectiveness and areas of uncertainty. METHODS: Databases searched included Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature database, and PsycINFO, using the terms pain*, infant*, neonat*, newborn*, sucrose, glucose, and alternative sugars. Publications were sorted according to type, year, painful procedure studied, placebo/no-treatment groups, population studied, and country of publication. RESULTS: A total of 298 relevant unique publications involving human infants were identified; 125 (42%) were primary research studies, of which 116 (93%) were randomized controlled trials. Healthy preterm or term newborns were included in 82 studies (65%), and sick or very low birth weight infants were included in 22 (18%). Most studies included single episodes of painful procedures, with only 3 (2%) conducted over long periods. Procedures investigated most frequently were heel lance (49%), venipuncture (14%), and intramuscular injection (14%). Placebo or no-treatment groups were included in 111 studies (89%); in 103 (93%) of those studies, sweet solutions reduced behavioral responses, compared with placebo/no treatment. CONCLUSION: Clinical equipoise relating to analgesic effects of sweet solutions no longer exists for single episodes of procedures for healthy preterm and term newborn infants. Uncertainties include outcomes after prolonged use of sweet solutions, concomitant use of other analgesics, and effectiveness beyond the newborn period. Future research should focus on addressing these knowledge and research gaps. Pediatrics 2010;126:894-902

Women`s feelings about early contact with their infants on the labour ward

Objectives: to identify women`s feelings after early contact with their newborn infants in the delivery room, and to identify how health professionals involved in mother and infant care behave in the intrapartum setting. Design: a qualitative approach using semi-structured interviews and observation. Content analysis was used to derive the three themes that emerged from the interviews. Setting and participants: 23 postpartum women and their caregivers in a public maternity hospital in Ribeirao Preto, Brazil. Findings: three thematic categories emerged from the interviews: heightened fear, severe pain and intense conflict. The professionals` actions revealed that they have theoretical and practical abilities for humanisation of care, but their actions are fragmented. Final considerations: women can feel lonely, fearful and conflicted in the delivery room, and they also experience pain. Giving birth is a major event in a woman`s life, so it is important to facilitate a positive experience. Health professionals were found to display interventionist and impersonal attitudes; these influenced the potential choices of women at their first contact with their infant. Implications for practice: the focus of health care needs to extend beyond the institution. This means fewer normative actions performed by health professionals, enabling women to enjoy their early contact with their newborn infants. (C) 2010 Elsevier Ltd. All rights reserved.

Variability on red blood cell transfusion practices among Brazilian neonatal intensive care units

BACKGROUND: Guidelines for red blood cell (RBC) transfusions exist; however, transfusion practices vary among centers. This study aimed to analyze transfusion practices and the impact of patients and institutional characteristics on the indications of RBC transfusions in preterm infants. STUDY DESIGN AND METHODS: RBC transfusion practices were investigated in a multicenter prospective cohort of preterm infants with a birth weight of less than 1500 g born at eight public university neonatal intensive care units of the Brazilian Network on Neonatal Research. Variables associated with any RBC transfusions were analyzed by logistic regression analysis. RESULTS: Of 952 very-low-birth-weight infants, 532 (55.9%) received at least one RBC transfusion. The percentages of transfused neonates were 48.9, 54.5, 56.0, 61.2, 56.3, 47.8, 75.4, and 44.7%, respectively, for Centers 1 through 8. The number of transfusions during the first 28 days of life was higher in Center 4 and 7 than in other centers. After 28 days, the number of transfusions decreased, except for Center 7. Multivariate logistic regression analysis showed higher likelihood of transfusion in infants with late onset sepsis (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8-4.4), intraventricular hemorrhage (OR, 9.4; 95% CI, 3.3-26.8), intubation at birth (OR, 1.7; 95% CI, 1.0-2.8), need for umbilical catheter (OR, 2.4; 95% CI, 1.3-4.4), days on mechanical ventilation (OR, 1.1; 95% CI, 1.0-1.2), oxygen therapy (OR, 1.1; 95% CI, 1.0-1.1), parenteral nutrition (OR, 1.1; 95% CI, 1.0-1.1), and birth center (p < 0.001). CONCLUSIONS: The need of RBC transfusions in very-low-birth-weight preterm infants was associated with clinical conditions and birth center. The distribution of the number of transfusions during hospital stay may be used as a measure of neonatal care quality.

The effect of arousals during sleep onset on estimates of sleep onset latency

It is well established that insomniacs overestimate sleep-onset latency. Furthermore, there is evidence that brief arousals from sleep may occur more frequently in insomnia. This study examined the hypothesis that brief arousals from sleep influence the perception of sleep-onset latency. An average of four sleep onsets was obtained from each of 20 normal subjects on each of two nonconsecutive, counterbalanced, experimental nights. The experimental nights consisted of a control night (control condition) and a condition in which a moderate respiratory load was applied to increase the frequency of microarousals during sleep onset (mask condition). Subjective estimation of sleep-onset latency and indices of sleep quality were assessed by self-report inventory. Objective measures of sleep-onset latency and microarousals were assessed using polysomnography. Results showed that sleep-onset latency estimates were longer in the mask condition than in the control condition, an effect not reflected in objective sleep-stage scoring of sleep-onset latency. Furthermore, an increase in the frequency of brief arousals from sleep was detected in the mask condition, and this is a possible source for the sleep-onset latency increase perceived by the subjects. Findings are consistent with the concept of a physiological basis for sleep misperception in insomnia.

Systemic administration of antisense p75(NTR) oligodeoxynucleotides rescues axotomised spinal motor neurons

The 75 kD low-affinity neurotrophin receptor (p75(NTR)) is expressed in developing and axotomised spinal motor neurons. There is now convincing evidence that p75NTR can, under some circumstances, become cytotoxic and promote neuronal cell death. We report here that a single application of antisense p75(NTR) oligodeoxynucleotides to the proximal nerve stumps of neonatal rats significantly reduces the loss of axotomised motor neurons compared to controls treated with nonsense oligodeoxynucleotides or phosphate-buffered saline. Our investigations also show that daily systemic intraperitoneal injections of antisense p75(NTR) oligodeoxynucleotides for 14 days significantly reduce the loss of axotomised motor neurons compared to controls. Furthermore, we found that systemic delivery over a similar period continues to be effective following axotomy when intraperitoneal injections were 1) administered after a delay of 24 hr, 2) limited to the first 7 days, or 3) administered every third day. In addition, p75(NTR) protein levels were reduced in spinal motor neurons following treatment with antisense p75(NTR) oligodeoxynucleotides. There were also no obvious side effects associated with antisense p75(NTR) oligodeoxynucleotide treatments as determined by behavioural observations and postnatal weight gain. Our findings indicate that antisense-based strategies could be a novel approach for the prevention of motor neuron degeneration associated with injuries or disease. (C) 2001 Wiley-Liss, Inc.

Increased rates of ENT surgery among young children: Have clinical guidelines made a difference?

Objectives: To examine the association between introduction of paediatric ear, nose and throat (ENT) surgery guidelines and population procedure rates. To determine changes in children's risk of undergoing ENT surgery. Methods: Trend analysis of incidence of myringotomy, tonsillectomy and adenoidectomy among New South Wales (NSW) children aged 0-14 between 1981 and mid 1999. Poisson regression models were used to estimate annual rates of change pre and postguidelines introduction and age/gender specific rates, and lifetable methods to determine risk of undergoing an ENT procedure by age 15. Results: ENT surgery rates increased by 21% over the study period. Children's risk of surgery increased from 17.9% in 1981 to 20.2% in 1998/99. Guideline introduction was associated with moderate short-term decreases in rates. For tonsillectomy, rates decreased between 1981 and 1983, but then rose continually until the introduction of myringotomy guidelines in 1993, when they fell, only to recommence rising until the end of the study period. For myringotomy, rates rose annually from 1981 to 1992/93 and fell in the 3 years following guideline introduction, after which they rose again. Increases were almost exclusively restricted to children aged 0-4 and correspond with increased use of formal childcare. The prevalence of myringotomy by the age of 5 years rose from 5.6% of children born in 1988/89 to 6.4% of those born in 1994/95, and the prevalence of tonsillectomy from 2.4% to 2.7%. Conclusions: The risk of young Australian children undergoing ENT surgery increased significantly over the last two decades despite the introduction of guidelines and no evidence of an increase in otitis media, one condition prompting surgery. Surgery increased most among the very young. We hypothesize this is related to increasing use of childcare.

Achieving the millennium development goals for health - Cost effectiveness analysis of strategies for. maternal and neonatal health in developing countries

Objective To determine the costs and benefits of interventions for maternal and newborn health to assess the appropriateness of current strategies and guide future plans to attain the millennium development goals. Design Cost effectiveness analysis. Setting Two regions classified by the World Health Organization according to their epidemiological grouping: Afr-E, those countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, comprising countries in South East Asia with high adult and high child mortality. Data sources Effectiveness data from several sources, including trials, observational studies, and expert opinion. For resource inputs, quantifies came from WHO guidelines, literature, and expert opinion, and prices from the WHO choosing interventions that are cost effective database. Main outcome measures Cost per disability adjusted life year (DALY) averted in year 2000 international dollars. Results The most cost effective mix of interventions was similar in Afr-E and Sear-D. These were the community based newborn care package, followed by antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth, offering first level maternal and neonatal care around childbirth; and emergency obstetric and neonatal care around and after birth. Screening and treatment of maternal syphilis, community based management of neonatal pneumonia, and steroids given during the antenatal period were relatively less cost effective in Sear-D. Scaling up all of the included interventions to 95% coverage would halve neonatal and maternal deaths. Conclusion Preventive interventions at the community level for newborn babies and at the primary care level for mothers and newborn babies are extremely cost effective, but the millennium development goals for maternal and child health will not be achieved without universal access to clinical services as well.

Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby

Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.