"Letting Go and Staying Connected": Substance Use Outcomes from a Developmentally Targeted Intervention for Parents of College Students.

We present results of a randomized, controlled, efficacy trial of a handbook intervention for parents of first-year college students. The aim of the interactive intervention was to decrease risk behaviors by increasing family protective factors. The handbook, based in self-determination theory and the social development model, provided evidence-based and developmentally targeted suggestions for parents to engage with their students in activities designed to support successful adjustment to college. We recruited 919 parent-student dyads from incoming students enrolled at a university in the U.S. Pacific Northwest and randomly assigned them to control and intervention conditions. We sent handbooks to intervention parents in June before students' August matriculation. Research assistants trained in motivational interviewing contacted parents to encourage use of the handbook. Control parents and students received treatment as usual. Participants completed baseline surveys during their final semester in high school (time 1) and their first semester at college (time 2). Self-reported frequency of alcohol, cannabis, and simultaneous use increased across both handbook and control students. In intent-to-treat analyses, odds of increased use were consistently lower and of similar magnitude for students in the intervention condition than in the control condition, and odds of first-time use were also lower in the intervention condition. Contact from research assistants predicted parents' engagement, and parent and student report of active engagement with handbook predicted lower substance use among intervention than control students across the transition to college. We developed a low-cost, theory-based handbook to help parents support their young adult children as they transition to independent college life. Students whose parents used the handbook were less likely to initiate or increase substance use than students in the control condition during their first semester in college.ClinicalTrials.gov Identifier: NCT03227809.

Octreotide and pasireotide effects on medullary thyroid carcinoma (MTC) cells growth, migration and invasion.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine neoplasm of the parafollicular thyroid C cells. Although somatostatin receptors are expressed by MTCs, treatment with octreotide has shown poor efficacy, whereas recently pasireotide has demonstrated antiproliferative effects in persistent postoperative MTCs. Aim of this study was to test the effects of octreotide and pasireotide on MTC cells proliferation, cell cycle proteins expression, MAPK activation, apoptosis, calcitonin secretion, migration and invasion in TT cell line as well as in primary MTC cultured cells. Our results showed that both octreotide and pasireotide reduced TT cell proliferation (-35.2 ± 12.1%, p < 0.001, and -25.3 ± 24.8%, p < 0.05, at 10-8 M, respectively), with concomitant inhibition of ERK phosphorylation and cyclin D1 expression. This cytostatic effect was accompanied by a proapoptotic action, with an increase of caspase3/7 activity of 1.5-fold. Moreover, both octreotide and pasireotide inhibited cell migration (-50.9 ± 11.3%, p < 0.01, and -40.5 ± 17%, p < 0.05, respectively) and invasion (-61.3 ± 35.1%, p < 0.05, and -49.7 ± 18%, p < 0.01, respectively). No effect was observed on calcitonin secretion. We then tried to extend these observations to primary cultures (n = 5). Octreotide and/or pasireotide were effective in reducing cells proliferation in 3 out of 5 tumors, and to induce cell apoptosis in 1 out of 3 MTCs. Both octreotide and pasireotide were able to reduce cell migration in all MTC tested. SST2, SST3 and SST5 were expressed in all MTC, with a tendency to increased expression of SST2 in RET mutated vs wild type MTCs. In agreement, inhibition of mutated RET in TT cells reduced SST2 expression. In conclusion, we demonstrated that octreotide and pasireotide inhibited cell proliferation and invasiveness in a subset of MTC, supporting their potential use in the control of tumor growth.

The cytoskeleton actin binding protein filamin A impairs both IGF2 mitogenic effects and the efficacy of IGF1R inhibitors in adrenocortical cancer cells.

Adrenocortical carcinomas (ACCs) overexpress insulin-like growth factor 2 (IGF2), that drives a proliferative autocrine loop by binding to IGF1R and IR, but IGF1R/IR-targeted therapies failed in ACC patients. The cytoskeleton actin-binding protein filamin A (FLNA) impairs IR signalling in melanoma cells. Aims of this study were to test FLNA involvement in regulating IGF1R and IR responsiveness to both IGF2 and inhibitors in ACC. In ACC cells H295R and SW13 and primary cultures (1ACC, 4 adenomas) we found that IGF1R and IR interacted with FLNA, and FLNA silencing increased IGF1R and reduced IR expression, with a downstream effect of increased cell proliferation and ERK phosphorylation. In addition, FLNA knockdown potentiated antiproliferative effects of IGF1R/IR inhibitor Linsitinib and IGF1R inhibitor NVP-ADW742 in H295R. Finally, Western blot showed lower FLNA expression in ACCs (n = 10) than in ACAs (n = 10) and an inverse correlation of FLNA/IGF1R ratio with ERK phosphorylation in ACCs only. In conclusion, we demonstrated that low FLNA levels enhance both IGF2 proliferative effects and IGF1R/IR inhibitors efficacy in ACC cells, suggesting FLNA as a new factor influencing tumor clinical behavior and the response to the therapy with IGF1R/IR-targeted drugs.

Monte Carlo implementation of new algorithms for the evaluation of averaged-dose and -track linear energy transfers in 62 MeV clinical proton beams.

We exploited the power of the Geant4 Monte Carlo toolkit to study and validate new approaches for the averaged linear energy transfer (LET) calculation in 62 MeV clinical proton beams. The definitions of the averaged LET dose and LET track were extended, so as to fully account for the contribution of secondary particles generated by target fragmentation, thereby leading to a more general formulation of the LET total. Moreover, in the proposed new strategies for the LET calculation, we minimised the dependencies in respect to the transport parameters adopted during the Monte Carlo simulations (such as the production cut of secondary particles, voxel size and the maximum steplength). The new proposed approach was compared against microdosimetric experimental spectra of clinical proton beams, acquired at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) from two different detectors: a mini-tissue equivalent proportional chamber (TEPC), developed at the Legnaro National Laboratories of the National Institute for Nuclear Physics (LNL-INFN) and a silicon-on-insulator (SOI) microdosimeter with 3D sensitive volumes developed by the Centre for Medical Radiation Physics of Wollongong University (CMRP-UoW). A significant increase of the LET in the entrance region of the spread out Bragg peak (SOBP) was observed, when the contribution of the generated secondary particles was included in the calculation. This was consistent with the experimental results obtained.

Microdosimetry of a therapeutic proton beam with a mini-TEPC and a MicroPlus-Bridge detector for RBE assessment.

Proton beams are widely used worldwide to treat localized tumours, the lower entrance dose and no exit dose, thus sparing surrounding normal tissues, being the main advantage of this treatment modality compared to conventional photon techniques. Clinical proton beam therapy treatment planning is based on the use of a general relative biological effectiveness (RBE) of 1.1 along the whole beam penetration depth, without taking into account the documented increase in RBE at the end of the depth dose profile, in the Bragg peak and beyond. However, an inaccurate estimation of the RBE can cause both underdose or overdose, in particular it can cause the unfavourable situation of underdosing the tumour and overdosing the normal tissue just beyond the tumour, which limits the treatment success and increases the risk of complications. In view of a more precise dose delivery that takes into account the variation of RBE, experimental microdosimetry offers valuable tools for the quality assurance of LET or RBE-based treatment planning systems. The purpose of this work is to compare the response of two different microdosimetry systems: the mini-TEPC and the MicroPlus-Bridge detector. Microdosimetric spectra were measured across the 62 MeV spread out Bragg peak of CATANA with the mini-TEPC and with the Bridge microdosimeter. The frequency and dose distributions of lineal energy were compared and the different contributions to the spectra were analysed, discussing the effects of different site sizes and chord length distributions. The shape of the lineal energy distributions measured with the two detectors are markedly different, due to the different water-equivalent sizes of the sensitive volumes: 0.85 µm for the TEPC and 17.3 µm for the silicon detector. When the Loncol's biological weighting function is applied to calculate the microdosimetric assessment of the RBE, both detectors lead to results that are consistent with biological survival data for glioma U87 cells. Both the mini-TEPC and the MicroPlus-Bridge detector can be used to assess the RBE variation of a 62 MeV modulated proton beam along its penetration depth. The microdosimetric assessment of the RBE based on the Loncol's weighting function is in good agreement with radiobiological results when the 10% biological uncertainty is taken into account.

In soil radon anomalies and volcanic activity on Mt. Etna (Italy).

We present here the first attempt to understand the fast dynamics of an active basaltic volcano, namely Mt. Etna using soil gas radon measured in some sites located in strategic places around the volcano. Data were measured continuously from July 2015 to February 2017 and the raw signals were treated in order to filter out all possible periodic components that are normally due to non-volcanic factors, applying a method that does not require acquisition of other parameters, which are not always available. The residual signals highlighted seven anomalous changes, with radon values reaching levels from 2 to 5 times higher than the normal background. In six out of seven cases, anomalies were almost contemporaneous in all or almost all of the sites, indicating a common source for the observed radon variations. The pattern of anomalies suggests a transient wave-like propagation in the space/time domain, compatible with pressure-induced displacement of the gas. The observed patterns are most probably caused by the rapid upward motion of gas-rich magma into the volcano conduits, as almost all anomalies precede or accompany major volcanic events. In some cases, an alternative explanation could be the strong and sudden strain releases through earthquakes swarms, with consequent variations in the permeability of rocks at a large scale, given the apparent correlation between those anomalies and intense seismicity.

Transversal dose profile reconstruction for clinical proton beams: A detectors inter-comparison.

PURPOSE: The main purpose of this work is the inter-comparison between different devices devoted to the transversal dose profile recostruction for daily QA tests in proton therapy. METHODS: The results obtained with the EBT3 radiochromic films, used as a reference, and other common quality control devices, have been compared with those obtained with a beam profiling system developed at the "Laboratori Nazionali del Sud" of Italian Institute for Nuclear Physics (INFN-LNS, Catania, Italy). It consists of a plastic scintillator screen (thickness 1 mm), mounted perpendicularly to the beam axis and coupled with a highly sensitive CCD detector in a light-tight box. RESULTS AND CONCLUSION: The tests, carried out both at the INFN-LNS and Trento Proton Therapy Center facilities, show, in general, a good agreement between the different detectors. The beam profiling system, in particular, appears to be a promising quality control device for 2-D relative dosimetry, because of its linear response in a dose rate range useful for proton therapy treatments, its high spatial resolution and its short acquisition and processing time.

Cofilin is a mediator of RET-promoted medullary thyroid carcinoma cell migration, invasion and proliferation.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that originates from parafollicular thyroid C cells and accounts for 5% of thyroid cancers. In inherited cases of MTC, and in about 40% of sporadic cases, activating mutations of the receptor tyrosine kinase proto-oncogene RET are found. Constitutively active RET triggers signaling pathways involved in cell proliferation, survival and motility, but the mechanisms underlying malignant transformation of C-cells have been only partially elucidated. Cofilin is a key regulator of actin cytoskeleton dynamics. A crucial role of cofilin in tumor development, progression, invasion and metastasis has been demonstrated in different human cancers, but no data are available in MTC. Interestingly, RET activation upregulates cofilin gene expression. The aim of this study was to investigate cofilin contribution in invasiveness and growth of MTC cells, and its relevance in the context of mutant RET signaling. We found that cofilin transfection in human MTC cell line TT significantly increased migration (178 ±â€¯44%, p < 0.001), invasion (165 ±â€¯28%, p < 0.01) and proliferation (146 ±â€¯18%, p < 0.001), accompanied by an increase of ERK1/2 phosphorylation (2.23-fold) and cyclin D1 levels (1.43-fold). Accordingly, all these responses were significantly reduced after genetic silencing of cofilin (-55 ±â€¯10% migration, p < 0.001, -41 ±â€¯8% invasion, p < 0.001, -17 ±â€¯3% proliferation, p < 0.001). These results have been confirmed in primary cells cultures obtained from human MTCs. The inhibition of constitutively active RET in TT cells by both the RET pharmacological inhibitor RPI-1 and the transfection of dominant negative RET mutant (RETΔTK) resulted in a reduction of cofilin expression (-37 ±â€¯8%, p < 0.001 and -31 ±â€¯16%, p < 0.01, respectively). Furthermore, RPI-1 inhibitory effects on TT cell migration (-57 ±â€¯13%, p < 0.01), but not on cell proliferation, were completely abolished in cells transfected with cofilin. In conclusion, these data indicate that an unbalanced cofilin expression, induced by oncogenic RET, contributes to promote MTC invasiveness and growth, suggesting the possibility of targeting cofilin pathway for more effective treatment of MTC.

Cytoskeleton actin-binding proteins in clinical behavior of pituitary tumors.

Although generally benign, pituitary tumors are frequently locally invasive, with reduced success of neurosurgery and unresponsive to pharmacological treatment with somatostatin or dopamine analogues. The molecular basis of the different biological behavior of pituitary tumors are still poorly identified, but a body of work now suggests that the activity of specific cytoskeleton proteins is a key factor regulating both the invasiveness and drug resistance of these tumors. This review recapitulates the experimental evidence supporting a role for the actin-binding protein filamin A (FLNA) in the regulation of somatostatin and dopamine receptors expression and signaling in pituitary tumors, thus in determining the responsiveness to currently used drugs, somatostatin analogues and dopamine receptor type 2 agonists. Regarding the regulation of invasive behavior of pituitary tumoral cells, we bring evidence to the role of the actin-severing protein cofilin, whose activation status may be modulated by dopaminergic and somatostatinergic drugs, through FLNA involvement. Molecular mechanisms involved in the regulation of FLNA expression and function in pituitary tumors will also be discussed.

cAMP/PKA-induced filamin A (FLNA) phosphorylation inhibits SST2 signal transduction in GH-secreting pituitary tumor cells.

An efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors requires filamin A (FLNA). Since cAMP pathway plays an important role in GH-secreting pituitary tumors pathogenesis and FLNA is phosphorylated by PKA on S2152, aim of this study was to investigate in tumoral somatotrophs the impact of cAMP pathway activation and SSA stimulation on FLNA phosphorylation and the consequences on SST2 function. We found a PKA-mediated increase (2-fold) and SST2 agonist-induced decrease (-50%) of FLNA phosphorylation in GH3, GH4C1 and primary somatotroph tumor cells. This modification regulates FLNA function. Indeed, phosphomimetic S2152D FLNA mutant, but not phosphodeficient S2152A, abolished the known SSA antitumoral effects, namely: 1) inhibition of cell proliferation, reduction of cyclin D3 and increase of p27; 2) increase of cell apoptosis; 3) inhibition of cell migration via RhoA activation and cofilin phosphorylation. Coimmunoprecipitation and immunofluorescence assays showed that S2152A FLNA was recruited to activated SST2, whereas S2152D FLNA constitutively bound SST2 on the plasma membrane, but prevented Gαi proteins recruitment to SST2. In conclusion, we demonstrated that FLNA phosphorylation, promoted by cAMP pathway activation and inhibited by SSA, prevented SST2 signaling in GH-secreting tumoral pituitary cells.

A novel pathway activated by somatostatin receptor type 2 (SST2): Inhibition of pituitary tumor cell migration and invasion through cytoskeleton protein recruitment.

The pharmacological therapy of GH-secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of our study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA). Our data revealed that SST2 agonist BIM23120 significantly reduced GH3 cells migration (-22% ± 3.6%, p < 0.001) and invasion on collagen IV (-31.3% ± 12.2%, p < 0.01), both these effects being reproduced by octreotide and pasireotide. Similar results were obtained in primary cultured cells from human GH-secreting tumors. These inhibitory actions were accompanied by a marked increase in RhoA/ROCK-dependent cofilin phosphorylation (about 2.7-fold in GH3 and 2.1-fold in human primary cells). Accordingly, the anti-invasive effect of the SS analog was mimicked by the overexpression in GH3 cells of the S3D phosphomimetic cofilin mutant, and abolished by both phosphodeficient S3A cofilin and a specific ROCK inhibitor that prevented cofilin phosphorylation. Moreover, FLNA silencing and FLNA dominant-negative mutants FLNA19-20 and FLNA21-24 transfection demonstrated that FLNA plays a scaffold function for SST2-mediated cofilin phosphorylation. Accordingly, cofilin recruitment to agonist-activated SST2 was completely lost in FLNA silenced cells. In conclusion, we demonstrated that SST2 inhibits rat and human tumoral somatotrophs migration and invasion through a molecular mechanism that involves FLNA-dependent cofilin recruitment and phosphorylation.

Cofilin is a cAMP effector in mediating actin cytoskeleton reorganization and steroidogenesis in mouse and human adrenocortical tumor cells.

cAMP pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). cAMP-induced steroidogenesis is preceded by actin cytoskeleton reorganization, a process regulated by cofilin activity. In this study we investigated cofilin role in mediating cAMP effects on cell morphology and steroidogenesis in adrenocortical tumor cells. We demonstrated that forskolin induced cell rounding and strongly reduced phosphorylated (P)-cofilin/total cofilin ratio in Y1 (-52 ± 16%, p < 0.001) and human CPA cells (-53 ± 18%, p < 0.05). Cofilin silencing significantly reduced both forskolin-induced morphological changes and progesterone production (1.3-fold vs 1.8-fold in controls, p < 0.05), whereas transfection of wild-type or S3A (active), but not S3D (inactive) cofilin, potentiated forskolin effects on cell rounding and increased 3-fold progesterone synthesis with respect to control (p < 0.05). Furthermore, cofilin dephosphorylation by a ROCK inhibitor potentiated forskolin-induced cell rounding and steroidogenesis (2-fold increase vs forskolin alone). Finally, we found a reduced P-cofilin/total cofilin ratio and increased cofilin expression in CPA vs endocrine inactive adenomas by western blot and immunohistochemistry. Overall, these results identified cofilin as a mediator of cAMP effects on both morphological changes and steroidogenesis in mouse and human adrenocortical tumor cells.

Reproductive suppression follows threats to child survival.

Natural selection presumably conserved mechanisms that allow females to block or terminate gestation when environmental circumstances threaten the survival of offspring. One example of this adaptive reproductive suppression, the Bruce effect, has been identified in several species, both in the laboratory and in the wild. Although descriptive epidemiology reports low fertility among women experiencing stressful circumstances, attempts to detect a Bruce effect in humans have been rare and limited. We contribute to this limited work by examining the relationship between the odds of child death and the sex ratio at birth in Sweden for the years 1751-1840. We find evidence of a generalized Bruce effect in humans in that unexpected changes in child mortality predict opposite unexpected changes in the secondary sex ratio in the following year, even after adjusting for period life expectancy. Our analysis broadens the scope of the Bruce effect literature to include humans, suggesting that women, through noncognitive decisional biology, adjust reproductive strategies and investments in response to changing environmental conditions.

(+)-and (-)-Phenazocine enantiomers: Evaluation of their dual opioid agonist/σ1 antagonist properties and antinociceptive effects.

cis-N-Substituted N-normetazocine enantiomers possess peculiar pharmacological profiles. Indeed, dextro enantiomers bind with high affinity σ1 receptor while opposite enantiomers bind opioid receptors. In spite of their stereochemistry, cis-N-2-phenylethyl N-normetazocine (phenazocine) enantiomers showed mixed opioid/σ1 receptor profiles and a significant in vivo analgesia. To the best of our knowledge, there is no information available regarding the evaluation of σ1 pharmacological profile in the antinociceptive effects of (+)- and (-)-phenazocine. Therefore, the present study was designed to ascertain this component by in vitro and in vivo studies. In particular, we tested the σ1 affinity of both enantiomers by a predictive binding assay in absence or presence of phenytoin (DPH). Our results showed that DPH (1 mM) did not increase the σ1 receptor affinity of (+)-and (-)-phenazocine (Ki = 3.8 ± 0.4 nM, Ki = 85 ± 2.0 nM, respectively) suggesting a σ1 antagonist profile of both enantiomers. This σ1 antagonistic component of two phenazocine enantiomers was corroborated by in vivo studies in which the selective σ1 receptor agonist PRE-084, was able to unmask their σ1 antagonistic component associated with the opioid activity. The σ1 antagonistic component of (+)- and (-)-phenazocine may justify their analgesic activity and it suggests that they may constitute useful lead compounds to develop new ligands with this dual activity.

Mechanisms linking high school graduation to health disparities in young adulthood: a longitudinal analysis of the role of health behaviours, psychosocial stressors, and health insurance.

OBJECTIVES: This study examined three competing mechanisms in the link between educational attainment and health among young adults: (a) a health behaviour mechanism; (b) a psychosocial stressor mechanism; and (c) a health insurance mechanism. The central research question was the pervasiveness and specificity of these mechanisms in the link between low educational attainment and health outcomes during young adulthood. STUDY DESIGN: A prospective longitudinal study was conducted with 808 men and women followed to age 33 years in the USA. METHODS: Health outcomes included major depressive disorder, obesity, chronic health conditions, and self-rated health. The focal predictor was educational attainment at age 21. The roles of the health behaviour mechanism (heavy episodic drinking, cigarette smoking, and meeting physical activity guidelines), the psychosocial stressor mechanism (stressful life events, perceived financial stress, and lack of control at work), and having health insurance (either through their employer or union or via family members) in the link between education and varying health outcomes were assessed using path analyses. RESULTS: Lack of health insurance emerged as a statistically significant explanatory factor underlying the association of education with depression and self-rated health. Health behaviours, specifically smoking and physical activity, were statistically significant intervening factors for obesity and self-rated health. CONCLUSIONS: The processes linking educational attainment to health inequalities begin unfolding during young adulthood. The salience of different mechanisms is specific to a health outcome rather than pervasive across multiple health outcomes. Public health policies with a broad spectrum of components, particularly focussing on smoking, physical activity, and lack of health insurance, are recommended to promote educational equalities in multiple health outcomes among young adults.

Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants.

OBJECTIVE: To determine the association between antenatal steroids administration and intraventricular hemorrhage rates. METHODS: We used cross-sectional data from the California Perinatal Quality Care Collaborative during 2007 to 2013 for infants ⩽32 weeks gestational age. Using multivariable logistic regression, we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by gestational age. RESULTS: In 25 979 very-low-birth weight infants, antenatal steroid use was associated with a reduction in incidence of any grade of intraventricular hemorrhage (odds ratio=0.68, 95% confidence interval: 0.62, 0.75) and a reduction in incidence of severe intraventricular hemorrhage (odds ratio=0.51, 95% confidence interval: 0.45, 0.58). This association was seen across gestational ages ranging from 22 to 29 weeks. CONCLUSIONS: Although current guidelines recommend coverage for preterm birth at 24 to 34 weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even before 24 weeks of gestational age.

Topical hemostasis in laparoscopic surgery.

A major goal during any surgical intervention is minimization of blood loss, which reduces the need for blood transfusion. In open surgery, the possibility for the surgeon to use the hands directly in contact with the bleeding tissues for hemostasis, makes mechanical methods, such as compression, ligatures or sutures, important to achieve proper hemostasis. In laparoscopic surgery, where the intervention is performed by means of small incisions through which the surgeon's hand cannot directly achieve the tissues, the problem of hemostasis is critical and needs more attention. Either in open or in laparoscopic surgery, significant bleeding during surgery is controlled through vessel ligation, suturing, and electrocautery. Topical hemostatic agents are useful adjuncts to surgical hemostasis for controlling non-specific bleeding. The introduction of different devices and topical agents has made possible to perform more complex interventions also in laparoscopy. The Authors discuss about the type, the field of application, the side effects of the hemostatic devices and of the topical hemostatic agents.

Radon transport: laboratory and model study.

In order to exploit radon profiles for geophysical purposes and also to estimate its entry indoors, it is necessary to study its transport through porous soils. The great number of involved parameters and processes affecting the emanation of radon from the soil grains and its transport in the source medium has led to many theoretical and/or laboratory studies. The authors report the first results of a laboratory study carried out at the Radioactivity Laboratory of the Department of Physics and Astronomy (University of Catania) by means of a facility for measuring radon concentrations in the sample pores at various depths under well-defined and controlled conditions of physical parameters. In particular, radon concentration vertical profiles extracted in low-moisture samples for different advective fluxes and temperatures were compared with expected concentrations, according to a three-phase transport model developed by Andersen (Risø National Laboratory, Denmark), showing, in general, a good agreement between measurements and model calculations.

15-epi-lipoxin A4 reduces the mortality of prematurely born pups in a mouse model of infection-induced preterm birth.

Preterm birth remains the leading cause of neonatal mortality and morbidity worldwide. There are currently few effective therapies and therefore an urgent need for novel treatments. Although there is much focus on trying to alter gestation of delivery, the primary aim of preterm birth prevention therapies should be to reduce prematurity related mortality and morbidity. Given the link between intrauterine infection and inflammation and preterm labour (PTL), we hypothesized that administration of lipoxins, key anti-inflammatory and pro-resolution mediators, could be a useful novel treatment for PTL. Using a mouse model of infection-induced PTL, we investigated whether 15-epi-lipoxin A4 could delay lipopolysaccharide (LPS)-induced PTL and reduce pup mortality. On D17 of gestation mice (n = 9-12) were pretreated with vehicle or 15-epi-lipoxin A4 prior to intrauterine administration of LPS or PBS. Although pretreatment with 15-epi-lipoxin A4 did not delay LPS-induced PTL, there was a significant reduction in the mortality amongst prematurely delivered pups (defined as delivery within 36 h of surgery) in mice treated with 15-epi-lipoxin A4 prior to LPS treatment, compared with those receiving LPS alone (P < 0.05). Quantitative real-time (QRT)-PCR analysis of utero-placental tissues harvested 6 h post-treatment demonstrated that 15-epi-lipoxin A4 treatment increased Ptgs2 expression in the uterus, placenta and fetal membranes (P < 0.05) and decreased 15-Hpgd expression (P < 0.05) in the placenta and uterus, suggesting that 15-epi-lipoxin A4 may regulate the local production and activity of prostaglandins. These data suggest that augmenting lipoxin levels could be a useful novel therapeutic option in the treatment of PTL, protecting the fetus from the adverse effects of infection-induced preterm birth.

Hormonal evidence of selection in utero revisited.

OBJECTIVES: Human conception cohorts in gestation during stressful times reportedly yield lower ratios of male to female live births than do other conception cohorts. Much literature attributes this phenomenon to spontaneous abortion of less fit male fetuses. Controversy remains, however, as to whether stressful times make males fetuses less fit ("Shifting Distribution" of fitness) or whether male fetuses need greater fitness to avoid spontaneous abortion during stressful times ("Shifting Criterion" for survival). METHODS: Although research using gestational hCG as a signal of fetal fitness reports support for the latter mechanism, we believe an analytic error casts doubt on those findings. Here we offered an alternative test that corrects the error. CONCLUSION: This more accurate test found similar results to those originally reported.