Vulnerable Phase Research Articles

‘Something about X-rays for everyone:’ emerging technologies and open communities

This paper argues that the contemporary category of ‘emerging technology’ has probative value for historians of technology, because the vulnerable transitional phase the term is understood to refer to is also when actors outside of the traditional dyad of users and innovators can be most influential. In the case of X-ray generating apparatuses at the turn of the twentieth century, their success cannot be accounted for by the relatively small coterie of physicians who were both wealthy and technically sophisticated enough to purchase one, nor from any overwhelming medical utility. Rather, a diverse and diffuse community ranging from electrical hobbyists to photographers not only influenced the form and function of the artifact, making it more accessible to physicians, but also brought public attention to the technology, rendering it more commercially viable.

Drawing a fine line on endogenous retroelement activity.

Endogenous retroelements (EREs) are essential motors of evolution yet require careful control to prevent genomic catastrophes, notably during the vulnerable phases of epigenetic reprogramming that occur immediately after fertilization and in germ cells. Accordingly, a variety of mechanisms restrict these mobile genetic units. Previous studies have revealed the importance of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor, KAP1, in the early embryonic silencing of endogenous retroviruses and so-called SVAs, but the implication of this transcriptional repression system in the control of LINE-1, the only known active autonomous retrotransposon in the human genome, was thought to be marginal. Two recent studies straighten the record by revealing that the KRAB/KAP system is key to the control of L1 in embryonic stem (ES) cells, and go further in demonstrating that DNA methylation and KRAB/KAP1-induced repression contribute to this process in an evolutionally dynamic fashion. These results shed light on the delicate equilibrium between higher vertebrates and endogenous retroelements, which are not just genetic invaders calling for strict control but rather a constantly renewed and nicely exploitable source of evolutionary potential.

Effects of different temperature regimes on flower development, microsporogenesis and fertility in bolting garlic (Allium sativum).

Garlic (Allium sativum L.) cultivars do not develop fertile flowers and seeds. Therefore, garlic production and improvement depend exclusively on vegetative propagation. Recent advances in garlic research have enabled fertility restoration and the discovery of fertile and male-sterile genotypes; however, the environmental regulation of the reproductive process is still not clear. Garlic seeds are successfully produced in the Mediterrenean region, where the photoperiod is relatively short, whereas spring and summer temperatures are high. We hypothesise that, in bolting garlic, various stages of florogenesis are differentially regulated by temperature and that high temperatures might obstruct pollen production. The effects of eight combinations of controlled growth temperatures on fertile and male-sterile garlic clones were studied. In both genotypes, a gradual temperature increase before and during anthesis favoured intact flower development. Surprisingly, continuous exposure to moderate temperatures during the entire growth period resulted in poor flowering, anther abortion and reduced pollen production. In the male-sterile genotype, no growth regime improved pollen production, which is controlled by genetic mechanisms. In the male-fertile genotype, gradual temperature increase supported pollen production but a sharp transition to high temperatures resulted in rapid flower senescence and pollen abortion, thus supporting our research hypothesis. In both fertile and male-sterile plants, the most vulnerable phase of microsporogenesis is the unicellular microspore stage. Tapetal malformation is the major cause for malnutrition of the microspores, with consequent production of nonviable pollen grains.

Abstract 12797: Temporal Changes in Mortality Risk Post-Discharge After Hospitalization for Heart Failure

Importance: In observational studies, the risk for adverse events among patients admitted for heart failure (HF) is highest immediately post-discharge and declines over time. This ‘vulnerable phase’ concept has led to research and quality of care initiatives focusing primarily on early post-discharge period. However, whether this risk trajectory represents lowering of individual patient risk or changes in the population risk profile is not known. Methods: Survival and longitudinal models were used to assess temporal changes in mortality risk post-discharge in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Post hoc analysis of EVEREST included 4017 patients >18 years old discharged alive after hospitalization for HF with an ejection fraction of <40% at 359 sites from 2003-2006 and randomized to receive oral tolvaptan or placebo. Results: After a median of 9.8 months, 971 patients died (24.2%). Mortality at 1 year was 24.2%. Cumulative mortality rate declined from 15.9/100 patient-years immediately post-discharge to 13.4 at 30 days and 12.8 at 90 days; it rose steadily thereafter. The risk variation between quintiles of baseline risk was considerably larger than the temporal variation within risk strata. In a longitudinal model assessing updated mortality risk after each follow up visit, mortality risk increased during the 90 days preceding readmission and then followed a trajectory similar to the index admission. The net increase in mortality attributable to readmission was ~37%. Conclusions and Relevance: Among hospitalized HF patients, although there is a transiently elevated risk in 90 days before and after discharge, the patient’s clinical risk profile rather than temporal change remains the main determinant of mortality risk.

HerzMobil Tirol network: rationale for and design of a collaborative heart failure disease management program in Austria.

Heart failure (HF) is approaching epidemic proportions worldwide and is the leading cause of hospitalization in the elderly population. High rates of readmission contribute substantially to excessive health care costs and highlight the fragmented nature of care available to HF patients. Disease management programs (DMPs) have been implemented to improve health outcomes, patient satisfaction, and quality of life, and to reduce health care costs. Telemonitoring systems appear to be effective in the vulnerable phase after discharge from hospital to prevent early readmissions. DMPs that emphasize comprehensive patient education and guideline-adjusted therapy have shown great promise to result in beneficial long-term effects. It can be speculated that combining core elements of the aforementioned programs may substantially improve long-term cost-effectiveness of patient management.We introduce a collaborative post-discharge HF disease management program (HerzMobil Tirol network) that incorporates physician-controlled telemonitoring and nurse-led care in a multidisciplinary network approach.

Exotic invaders gain foraging benefits by shoaling with native fish.

Freshwater habitats are under increasing threat due to invasions of exotic fish. These invasions typically begin with the introduction of small numbers of individuals unfamiliar with the new habitat. One way in which the invaders might overcome this disadvantage is by associating with native taxa occupying a similar ecological niche. Here we used guppies (Poecilia reticulata) from a feral population in Mexico to test the prediction that exotic shoaling fish can associate with heterospecifics, and that they improve their foraging efficiency by doing so. Guppies have invaded the Mexican High Plateau and are implicated in the declines of many native topminnow (Goodeinae) species. We show that heterospecific associations between guppies and topminnows can deliver the same foraging benefits as conspecific shoals, and that variation in foraging gains is linked to differences in association tendency. These results uncover a mechanism enabling founding individuals to survive during the most vulnerable phase of an invasion and help explain why guppies have established viable populations in many parts of Mexico as well in every continent except Antarctica.

Characterization of Inhibitory GABA-A Receptor Activation during Spreading Depolarization in Brain Slice

Spreading depolarization (SD) is a slowly propagating wave of near complete depolarizations of neurons and glia. Previous studies have reported large GABA releases during SD, but there is limited understanding of how GABA release and receptor activation are regulated and influence the propagating SD wavefront, as well as an excitatory phase immediately following the passage of SD. The present study characterized GABA-A type receptor (GABAAR) currents during SD generated by KCl microinjection in acute hippocampal slices from adult mice. Spontaneous GABAAR-mediated currents (sIPSCs) were initially enhanced, and were followed by a large outward current at the wavefront. sIPSC were then transiently supressed during the late SD phase, resulting in a significant reduction of the sIPSC/sEPSC ratio. The large outward current generated during SD was eliminated by the GABAAR antagonist gabazine, but the channel potentiator/agonist propofol failed to potentiate the current, likely because of a ceiling effect. Extracellular Cl− decreases recorded during SD were reduced by the antagonist but were not increased by the potentiator. Together with effects of GABAAR modulators on SD propagation rate, these results demonstrate a significant inhibitory role of the initial GABAAR activation and suggest that intracellular Cl− loading is insufficient to generate excitatory GABAAR responses during SD propagation. These results provide a mechanistic explanation for facilitating effects of GABAAR antagonists, and the lack of inhibitory effect of GABAAR potentiators on SD propagation. In addition, selective suppression of GABA transmission in the late SD period and the lack of effect of GABAA modulators on the duration of SD suggests that GABA modulation may not be effective approach to protect neurons during the vulnerable phase of SD.

Asthma and obesity in children: current evidence and potential systems biology approaches.

Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities; however, their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health. This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison with current approaches in 'difficult-to-treat' childhood asthma. Finally, the authors propose hypotheses for future research from a systems-based perspective.

Abstract 5054: Smoking prevention intervention with school classes at a university hospital by thoracic surgeon und pulmonologist

Abstract Purpose: Smoking prevention in schoolchildren with the aim to inform and prevent smoking initiation has been widely studied and has shown variable results. Interventions provided by physicians in a hospital setting have been rarely reported. Here we show the feasibility and gain of knowledge of our smoking prevention project in a hospital setting. Methods: Interventions performed from November 2009 - February 2013 were evaluated. Overall 470 children participated in our preventive intervention. A 7-item questionnaire was provided to the school classes (Grades 6 to 10) before and after a two-hour smoking prevention intervention consisting of anatomical models, oral presentations, videos, patient interviews and hands-on lung function tests. The goal was to show the anatomical and physiological basics as well as age-based information about the harms of smoking. During the intervention the children have been motivated to be actively involved. Class selection has been performed for groups of children in a highly vulnerable phase of age before smoking initiation. Results: The baseline questionnaire was completed by 457 children, the one after intervention by 426. The knowledge about which organs are affected by smoking increased from 6.8-99.6% to 65.5-99.5% (p<0.01). While only 59.5% knew that only a minority of people is able to quit smoking successfully, 94.1% answered the question correctly after intervention (p<0.001). Prior to the intervention only 78.1% believed that minor tobacco consumption is not damaging which increased to 89.4% after the teaching session (p<0.05). Smoking hookah was believed to be less harmful than cigarettes by 30.2% of children decreasing to 7.7% after the intervention (p<0.001). Conclusion: Information on health effects provided by lung specialists in the hospital leads to a statistically significant increase in knowledge as assessed by a short questionnaire. The intervention is feasible and well received. This kind of interventions might help to prevent schoolchildren from smoking in a highly vulnerable phase of age. Citation Format: Sandra Tomaszek, Macé M. Schuurmans, Didier Schneiter, Walter Weder, Sven Hillinger. Smoking prevention intervention with school classes at a university hospital by thoracic surgeon und pulmonologist. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5054. doi:10.1158/1538-7445.AM2014-5054

Problemas Emocionais e de Comportamento e Clima Familiar em Adolescentes e seus Pais

Adolescence is a period of many changes and a vulnerable phase for the development of emotional and behavioral problems (EBP). These may happen due to family crises, considered as risk factors. This study investigated EBP and their relation with family climate in the view of 187 adolescents and their mothers and fathers. The youngsters were students from public schools in Rio Grande do Sul. The used instruments were Youth Self-Report [YSR], Adult Self-Report [ASR] and Family Climate Inventory. The results of the participants’ perceptions, considering internalizing and externalizing symptoms, indicated a relation between mothers and fathers’ and mothers and children’s descriptions, but not between fathers and children’s. The maternal internalizing problems were positively correlated with the perceived Hierarchy of adolescents and negatively with Affection; the externalizing problems were positively correlated with Conflict and Hierarchy, and negatively with Cohesion and Affection.

Gender medicine. Sex- and gender-specific aspects of clinical medicine

Gender medicine studies sex- and gender-based differences in the development and prevention of diseases, the awareness and presentation of symptoms, and the effectiveness of therapy. Gender medicine is part of personalized medicine, considering differences in biological and psychosocial factors individually. There are differences in genes, chromosomes, hormones, and metabolism as well as differences in culture, environment, and society. Lifelong interactions between physical and psychosocial factors will influence the health and ill-health of men and women in different ways. Epigenetic modifications provide evidence of the impact of environment and lifestyle during vulnerable phases on biological processes, effecting future generations. Maternal lifestyle and environmental factors during pregnancy can impact the health of offspring in later life already in utero in a sex-specific way. Pain, stress, and coping styles differ between men and women. Women experience more dramatic physical changes during their lifetime, which are associated with specific burdens and psychosocial alterations. Women with multiple roles and responsibilities suffering from stress develop depression more frequently. However, men are often not diagnosed and treated appropriately in cases of depression or osteoporosis, diseases that are typically considered "female." There are prominent differences between men and women in medicine regarding the immune system, inflammation, and noncommunicable diseases such as obesity, type 2 diabetes, hypertension, and cardiovascular disease. Women experience more often autoimmune diseases and suffer more frequently from (chronic) pain, neurodegenerative changes, and functional disabilities. Men have shorter life expectancy but relatively more healthy years of life, which is in greater part ascribed to psychosocial determinants. State-of-the-art clinical medicine comprises individual risk factors based on sex- and gender-sensitive health programs in order to improve the health-related quality of life for men and women.

Admission plasma neutrophil gelatinase associated lipocalin (NGAL) predicts worsening renal function during hospitalization and post discharge outcome in patients with acute heart failure.

Abstract Background: The role of neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF), however less data are available in patients admitted for acute HF. We evaluated the role of NGAL in predicting in-hospital worsening renal function (WRF) and post-discharge follow-up during six months period in patients with acute HF. All patients were submitted to creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and B-type natriuretic peptide (BNP) measurement during hospitalization and before discharge. Patients with chronic kidney dysfunction (CKD) demonstrated higher NGAL respect to subject with preserved renal function (241 ± 218 and 130 ± 80 ng/ml; P = 0.0001). In subgroup that developed WRF during hospitalization, NGAL levels were significantly increased respect to patients without WRF (272 ± 205 versus 136 ± 127 ng/ml; P = 0.0001). A cut off of 134 ng/ml has been related to WRF with good sensibility and specificity (92% and 71% AUC 0.83; P = 0.001). Multivariable Cox regression analysis showed that cut-off of 134 ng/ml was the only marker related to death (HR: 1.75; 95% CI: 1.24-2.45; P < 0.001). Follow-up analysis confirmed that NGAL > 130 ng/ml was associated with adverse events during a six-month period. Admission NGAL measurement appears a sensible tool for in-hospital WRF prediction as well as an early marker for adverse outcome during post discharge vulnerable phase.

Top 10 Review Tips

Carol Rauen,rn, ms, ccns, ccrn, pccn, cen, rn-bc, the department editor, is an independent clinical nurse specialist in The Outer Banks of North Carolina. Carol welcomes feedback from readers and practice questions from potential contributors at rauen.carol104@gmail.com.RAUENMary Beth Flynn Makic,rn, phd, cns, ccns, is a research nurse scientist in critical care at University of Colorado Hospital and an associate professor adjoint at the University of Colorado College of Nursing. She contributed the PCCN-specific questions.MAKICLisa M. Soltis,msn, aprn, pccn, ccrn-csc, ccns, is a cardiovascular/critical care clinical nurse specialist for Wake Med Health & Hospital in Raleigh, North Carolina. She contributed the CCRN questions.SOLTISThe television show Late Night With David Letterman may not have invented the top 10 list, but the show certainly made it more popular. Here is a top 10 list for preparing to take an acute or critical care certification examination.Asphyxiation or aspiration can occur if the tube migrates and occludes the airway. A pair of scissors must be at the bedside so that the 3 balloon lumens can be cut if needed. Calling a respiratory therapist (A) or giving supplemental oxygen (B) will not treat the acute emergency, and a delay in treatment could worsen the situation and cause irreversible damage. The situation does not involve a patient who is coding, so beginning CPR (D) would not be required.Pancreatitis is commonly diagnosed on the basis of laboratory values. The most classic findings are elevated levels of 2 of the enzymes made in the pancreas: serum amylase and lipase. Two other common findings are hypocalcemia and hyperglycemia.The increased production of ADH causes decreased urinary output and fluid overload resulting in a serum hyponatremia and low osmolality. The fluid overload state would cause hypokalemia and low osmolality.Physiologic dead space will occur when there is poor perfusion but adequate ventilation with a pulmonary embolism. Intrapulmonary shunt (A) occurs when there is poor ventilation but adequate perfusion (acute respiratory distress syndrome [ARDS], pneumonia). A silent unit (B) is when there is no perfusion and no ventilation (cardiac arrest), and a Pao2:Fio2 ratio (C) is used to predict shunting and hypoxemia.The patient has rib fractures with decreased breath sounds and signs of respiratory distress. Chest tube placement can help with potential hemo/pneumothorax, oxygen would be indicated, and a fluid bolus would be the first-line treatment for hypotension. The chest tube placement will essentially provide a thoracentesis (A) and allow for continuous draining. Although intubation (C) and pericardiocentesis (D) might be required in a person with blunt chest trauma, the immediate priority will be the insertion of the chest tube.QT measurements reflect the duration of ventricular repolarization. Lengthening of QT interval is associated with arrhythmias, adverse cardiac events, and increased mortality because a longer QT duration places the vulnerable ventricular repolarization phase close to the next depolarization, increasing the likelihood of R-on-T. The most common arrhythmia that occurs with prolonged QTc is torsades de pointes. Atrial fibrillation, sinus bradycardia, and third-degree heart block are not typically associated with prolonged ventricular repolarization (QTc >0.50 seconds).Based on the ABG analysis, the patient is experiencing a respiratory acidosis with hypoxemia most likely due to the pneumonia. A pH of 7.19 indicates acidosis; a Paco2 of 68 mm Hg is elevated and a cause of acidosis; an HCO3− of 32 mmol/L indicates renal compensation; a Pao2 of 52 mm Hg indicates hypoxemia.Gentamicin is a nephrotoxic agent that places patients at risk for acute kidney injury, and this risk is increased in older patients. Acute delirium (A), liver failure (C), and sepsis (D) are all complications that could occur in an older adult with an infection but would not be caused by the administration of an antibiotic.Older patients are at increased risk for delirium during acute hospitalization. Interventions to manage acute delirium include removing or camouflaging tubes, removing unnecessary equipment, frequently reorienting the patient, and ensuring that the call bell is consistently within reach, assessing and treating pain effectively, and encouraging mobility and involvement in activities of daily living. Restraining the patient is contraindicated in the care of patients with delirium.The stroke protocol should be activated as soon as signs of stroke are identified in a patient. Initial signs of stroke include facial droop, arm down drift, and garbled speech. For best outcomes, the time elapsed between initials signs of stroke and treatment must be as short as possible.AACN Certcorp publishes a study bibliography that identifies the sources from which items are validated. The document may be found in the AACN Certification exam handbook. The contributor of each question written for this column has listed the source used in developing each item.

The Aphasic Patient: Vulnerability and/or Exclusion

The aim of this article is to account for the vulnerability of the patient/subject affected by aphasia, the loss of acquired language in adults. In the case of a sudden onset of aphasia, the patient is often aware of his/her disorder from the very onset of the impairment. Vulnerability also affects patients suffering from progressive aphasia, mainly due to a collapse of the various components of memory. After describing the main types of aphasia in broad outline, the study focuses on the isolation and exclusion that they generate, starting from a brief study of the emotional impact of the impairment on the language-deprived subject. This will be related to the patient's awareness of the disorder and the notion of awareness in structuring and using language, considered as the expression of thought. Finally, given that aphasia leads to the loss of employment, patients enter a phase of social vulnerability. Their speech is perceived as strange or even "foreign" by others in ordinary communicative contexts. What solutions can be proposed to overcome this state of vulnerability and exclusion, which is often felt to be insoluble by the patients themselves?

Tricuspid valve repair in patients with mild-to-moderate tricuspid regurgitation undergoing mitral valve repair/replacement improves in-hospital outcome

Objectives: Significant tricuspid regurgitation (TR) in patients (pts) undergoing surgery for mitral valve (MV) does increase their morbidity and mortality. The early postoperative period demonstrates the most vulnerable phase for hemodynamic stabilisation at ICU after MV surgery. Does reconstruction of mild-to-moderate insufficiency of the tricuspid valve (TV) in pts undergoing MV surgery lead to a benefit in early postoperative outcome?

Processing of Diagnostic Blood Specimens: Is It Really Necessary to Mix Primary Blood Tubes after Collection with Evacuated Tube System?

The preanalytical phase is considered the most vulnerable phase in biopreservation, biobanking, and laboratory diagnostics. Accurate mixing after blood collection is claimed to be important and recommended by the manufacturers. To evaluate whether it is really necessary to mix the primary blood tubes immediately after blood collection by means of evacuated tube systems. Blood from 300 outpatients was equally and randomly divided into three groups: G1, sodium citrate vacuum tubes; G2, lithium heparin vacuum tubes; and G3, K2EDTA vacuum tubes. All vacuum tubes were processed using three different procedures. Procedure 1: Gold Standard (P1): All specimens mixed gently and carefully by inverting five times as recommended; Procedure 2: Rest time (P2): All specimens remained 5 min in the upright position, followed by gentle careful mixing by inverting five times; Procedure 3: No mix (P3): All specimens were left in upright position without mixing afterwards. The influence of the primary mixing tube procedure was evaluated for clinical chemistry, hematology, and coagulation parameters by paired t-test. The bias from the mixing procedure was also compared with quality specifications derived from biological variation. Significant differences (p<0.017) were found for: i) red blood cell count and hematocrit when P1 was compared with P2; ii) alanine aminotransferase and erythrocyte sedimentation rate when P1 was compared with P3; iii) red blood cell count, hematocrit, and hemolysis index when P2 was compared with P3. Surprisingly, clinically significant differences were found only for sodium when P1 was compared with P2, and P1 was compared with P3. No fibrin filaments or microclots were observed in any samples. Primary blood tubes mixing after collection with evacuated tube system appears to be unnecessary.

Nutritional status of children aged 3-6 years in a rural area of tamilnadu.

A child's entire life is determined in large measures by the food given to him during his first five years. Since childhood is the most vulnerable phase in the life of human being, nutritional inadequacies will result in the hampering of the development of the body. Future of the country is determined by the growing generation of the country. a) To assess the nutritional status of children aged 3-6 y in a rural area of TamilNadu. b) To identify the factors associated with the nutritional status of the above study population. Kuthambakkam village in Tamilnadu, Cross sectional study. Total number of children aged 3-6 y is 172 in Kuthambakkam village. The entire children aged 3-6 y was included in the study. Mothers of the children were interviewed using an interview schedule to collect information regarding the sociodemographic profile, feeding practices, and immunization status. Socio-economic status was assessed using modified BG Prasad's classification. Weight of the children was measured using a portable weighing machine. Nutritional status among 3-6 y old children was assessed by computing weight for age (standard used - National Centre For Health Statistics (NCHS) standards for weight for age) and grading of nutritional status of the children was done using the Indian Academy of Paediatrics (IAP) classification. Grade I to Grade IV nutritional grade is taken as undernourished. Statistical Analytical: Prevalence will be expressed in percentage and Chi-square test will be used to find association with factors. The prevalence of under-nutrition (≤ 80 percentage of standard weight for age) was 66.5%. The prevalence of grade 1 malnourishment was 46.2%.The prevalence of under nourishment increased with increasing age and the difference was found to be statistically significant (p< 0.05).Prevalence of under nourishment was higher among male children (76.9%)than female children (56.3%) and was statistically significant. As the socioeconomic status increased the prevalence of undernourishment decreased and the difference was found to be statistically significant(p<0.05). Duration of exclusive breast feeding had influence on the nutritional status. Community based preventive measures should be taken to allievate malnutrition. Health education to the mothers on dietary practices like feeding their children with locally available low cost but healthy food should be given. Nutritional rehabilitation centres should be established. Improving the socioeconomic standards is mandatory.

Pre- plus postnatal exposures to di-(2-ethylhexyl)-phthalate and thyroid dysfunction in prematurely born children

Thyroid dysfunction is frequently observed among comorbidities associated with prematurity. The main factors reported to affect thyroid function in preterm infants are the immaturity of the hypothalamic-pituitary-thyroid axis, immature thyroid hormone synthesis and metabolism, and insufficient or excessive exposure to iodine [1, 2], as well as drugs used to treat critically ill premature babies, such as caffeine, dopamine, morphine and glucocorticoids [3]. We propose further factors that may contribute to explaining disturbances of the hypothalamus-pituitarythyroid axis observed in preterm babies, i.e., preand postnatal exposures to environmental chemical compounds with thyroid-disrupting activity, such as phthalates. Phthalates are a group of chemicals with many commercial uses such as solvents, additives and particularly plasticizers to impart flexibility to an otherwise rigid polyvinylchloride (PVC). In particular, di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer in PVC medical devices, such as infusion systems, tracheal tubes, and blood bags [4]. It is well known that the developing fetus and the neonate are the most vulnerable phases of life for exposure to these environmental contaminants. It has also been shown that prenatal exposure to DEHP is associated with shorter pregnancy duration [5, 6]. According to Food and Drug Administration (FDA), due to their small body size, physical condition, and particularly multiple medical device DEHP-related exposure, neonates in the Neonatal Intensive Care Unit (NICU) environment are a population especially at risk [7]. In addition, it has been shown that neonates in the NICU environment are exposed to higher concentrations of DEHP than the general population [8], and their daily exposure to DEHP may increase up to 20-fold the tolerable daily intake [9]. Phthalates have also been reported to interfere with the endocrine system, especially when exposure begins early in life [6]. Several lines of evidence, mainly based on in vivo and in vitro studies, indicate that thyroid function is a further target of these compounds and that these chemicals may act through a number of potential mechanisms [10, 11]. In this regard, a recent review of the most recently published epidemiological studies reported that exposure to phthalates negatively impacts thyroid function in children [12]. Moreover, a positive relationship between urinary DEHP metabolites and thyroid-stimulating hormone levels has been reported, in both adults and adolescents from the general population [13]. Therefore, it is conceivable that prenatal and postnatal exposure to phthalates may have a role in producing thyroid hazards in exposed preterm babies. In conclusion, although alternative materials have been developed [14], only few DEHP–free medical devices are available on the market and their high cost is still a major limit to their exploitation. Therefore, research into alternatives to DEHP-containing medical devices that may come in contact with human tissues should be urgently encouraged. In the meantime, further studies are needed to evaluate the real impact of preand postnatal DEHP exposure G. Latini Division of Neonatology, Ospedale Perrino, Brindisi, Italy

Development of a pan-Simbu real-time reverse transcriptase PCR for the detection of Simbu serogroup viruses and comparison with SBV diagnostic PCR systems

BackgroundSchmallenberg virus (SBV), a novel orthobunyavirus of the Simbu serogroup, was first identified in October 2011 in dairy cattle in Germany, where it caused fever, diarrhea and a drop in milk yield. Since then, SBV additionally has been detected in adult sheep and goats. Although symptoms of acute infection were not observed, infection during a vulnerable phase of pregnancy caused congenital malformations and stillbirths. In view of the current situation and the possible emergence of further Simbu serogroup members, a pan-Simbu real-time reverse transcriptase (RT) PCR system for the reliable detection of Simbu serogroup viruses should be developed.MethodsIn this study a pan-Simbu real-time RT-PCR system was established and compared to several SBV real-time RT-PCR assays. All PCR-systems were tested using a panel of different Simbu serogroup viruses as well as several field samples from diseased cattle, sheep and goats originating from all over Germany. Several pan-Simbu real-time RT-PCR products were sequenced via Sanger sequencing. Furthermore, in silico analyses were performed to investigate suitability for the detection of further orthobunyaviruses.ResultsAll tested members of the Simbu serogroup (n = 14) as well as most of the field samples were successfully detected by the pan-Simbu real-time RT-PCR system. The comparison of this intercalating dye assay with different TaqMan probe-based assays developed for SBV diagnostics confirmed the functionality of the pan-Simbu assay for screening purposes. However, the SBV-TaqMan-assay SBV-S3 delivered the highest analytical sensitivity of less than ten copies per reaction for duplex systems including an internal control. In addition, for confirmation of SBV-genome detection the highly specific SBV-M1 assay was established.ConclusionThe pan-Simbu real-time RT-PCR system was able to detect all tested members of the Simbu serogroup, most of the SBV field samples as well as three tested Bunyamwera serogroup viruses with a suitable sensitivity. According to in silico analyses, this system seems to be able to detect a broad orthobunyavirus spectrum. As an additional feature of the pan-Simbu real-time RT-PCR system, subsequent species classification via sequencing is feasible. Regarding SBV diagnostics, the performance of the S-segment targeting SBV-S3 assay was superior with respect to the analytical sensitivity.

Mycotoxins and female reproduction: in vitro approaches

Exposure to mycotoxins has been linked to adverse effects on female reproduction by interfering with the synthesis, metabolism or degradation of steroid hormones, interaction with steroid receptors or impairing oocyte maturation and competence. To assess such effects, many studies initially focussed on possible endocrine actions of mycotoxins using specific cell lines known to express key enzymes involved in the synthesis of steroid hormones. Using these models, zearalenone, deoxynivalenol, ochratoxin A, T-2 and HT-2 toxins, and aflatoxin B1 were claimed to be endocrine active substances. As yet, zearalenone is the only mycotoxin for which a direct interaction with oestrogen receptors could be demonstrated, classifying this mycotoxin as an endocrine disruptor. Mycotoxin exposure of complex cell systems like ovarian follicles at the earliest (primordial) to most advanced (pre-ovulatory) stages can serve not only as the first indication of the potential of a mycotoxin to affect female reproduction, but also provides insight in specific mechanisms involved in such an effect and identifies vulnerable phases in follicle development. Zearalenone is the most widely studied mycotoxin regarding female reproduction, but effects on oocyte maturation have also been demonstrated for deoxynivalenol. Exposure to zearalenone impairs the formation of primordial, while its metabolite ?-zearalenol is more harmful to fertilised oocytes than zearalenone itself. This short overview aims to provide an introduction into the different models, such as cell lines and oocytes, commonly used to assess the potential adverse effects of mycotoxins on female reproduction.