Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients.

C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough

Invertibility Conditions for Floating-Point Formulae

Automated reasoning procedures are essential for a number of applications that involve bit-exact floating-point computations. This paper presents conditions that characterize when a variable in a floating-point constraint has a solution, which we call invertibility conditions. We describe a novel workflow that combines human interaction and a syntax-guided synthesis (SyGuS) solver that was used for discovering these conditions. We verify our conditions for several floating-point formats. One implication of this result is that a fragment of floating-point arithmetic admits compact quantifier elimination. We implement our invertibility conditions in a prototype extension of our solver CVC4, showing their usefulness for solving quantified constraints over floating-points

Combining Decision Procedures for Sorted Theories

Abstract. The Nelson-Oppen combination method combines decision procedures for theories satisfying certain conditions into a decision pro-cedure for their union. While the method is known to be correct in the setting of unsorted first-order logic, some current implementations of it appear in tools that use a sorted input language. So far, however, there have been no theoretical results on the correctness of the method in a sorted setting, nor is it obvious that the method in fact lifts as is to logics with sorts. To bridge this gap between the existing theoretical results and the current implementations, we extend the Nelson-Oppen method to (order-)sorted logic and prove it correct under conditions sim-ilar to the original ones. From a theoretical point of view, the extension is relevant because it provides a rigorous foundation for the application of the method in a sorted setting. From a practical point of view, the extension has the considerable added benefits that in a sorted setting the method’s preconditions become easier to satisfy in practice, and the method’s nondeterminism is generally reduced.

Lesions associated with mineral deposition in the lymph nodes and lungs of cattle: a case-control study of environmental health hazard.

This report focuses on the state of health of the cattle raised in the district of Taranto - city of Italy rated as environmentally at risk. Representative samples of lungs, bronchial and mediastinal lymph nodes of cattle from district of Taranto's slaughterhouses were collected. After a macroscopic examination, samples with marked lesions were processed for light microscopy. Samples were also observed with polarized light microscopy, scanning electron microscopy and with microanalysis. The macroscopic examination revealed that 60 out of 183 samples showed marked lesions. Lung alterations were characterized by thickening of the alveolar septa and by the latter's modifying action on the alveolar spaces, foci of fibrosis and bronchopulmonary inflammation. For 51 out of the 60 samples observed, the histological examination confirmed the presence of pneumoconiosis and lymph nodal anthracosis. Energy-dispersive X-ray microanalysis of lung samples identified a wide range of elements including silicon, aluminium, titanium, iron, carbon and small amount of the other metals. In the lymph-nodes the same kind of metals with a different levels of distribution was observed. Our survey on cattle farmed in areas at high risk of pollution may be helpful to the estimation of the exposure risk for man to environmental contaminants and to the evaluation of the occurrence of the pathological manifestations as well

Auditory time thresholds in the range of milliseconds but not seconds are impaired in ADHD

The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. A sample of 40 children/adolescents (20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds in the milliseconds (0.25–1 s) and seconds (0.75–3 s) ranges. Results showed a severe impairment in ADHD for milliseconds thresholds (Log10BF = 1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. In the seconds range, thresholds were indistinguishable between the two groups (Log10BF = − 0.5) and not correlated with milliseconds thresholds. Our results largely confirm previous evidence suggesting partially separate mechanisms for time perception in the ranges of milliseconds and seconds. Moreover, since the evidence suggests that time perception of milliseconds stimuli might load relatively less on cognitive control and working memory, compared to longer durations, the current results are consistent with a pure timing deficit in individuals with ADHD

Interleukin-6, interleukin-1β, and tumor necrosis factor α in menstrual effluents as biomarkers of chronic endometritis.

Objective: To assess the relationship between chronic endometritis (CE) and proin␣ammatory cytokine levels in menstrual ef␣uents and to develop a simple noninvasive test for screening CE. Design: Case-control study. Setting: Academic center. Patient(s): Sixty-four women referred to our center for infertility. Intervention(s): Of␣ce hysteroscopy; endometrial biopsy; collection of menstrual blood at subsequent cycle. Main Outcome Measure(s): Interleukin (IL) 6, IL-1b, and tumor necrosis factor (TNF) a concentrations in menstrual ef␣uents. Result(s): Thirty-sixoutof64infertilewomenhadhistologicallyprovenCE.Theremaining28womenwereincludedascontrols.IL-6, IL-1b, and TNF-a levels were markedly higher in menstrual ef␣uents of women with CE compared with control subjects. Receiver operating characteristic curve analysis revealed a good CE screening capacity for all of the cytokines. The combined evaluation of either IL-6/TNF-a or IL-6/IL-1b increased the diagnostic capacity of the test, which reached a 100% sensitivity and a negative predictive value of 100 when at least one cytokine was found to exceed its cutoff value; it also reached a 100% speci␣city and a positive predictive value of 100 in cases of positivity of both cytokines. Logistic regression analysis con␣rmed the IL-6/TNF-a– based model as a signi␣cant predictor of CE. Conclusion(s): Proin␣ammatorycytokinelevelsareincreasedinmenstrualef␣uentsofwomen with CE. A test dosing IL-6 and TNF-a seems to have a high screening capacity for CE. (Fertil Steril! 2014;101:242–7. !2014 by American Society for Reproductive Medicine.

Global network analysis in Schizosaccharomyces pombe reveals three distinct consequences of the common 1-kb deletion causing juvenile CLN3 disease

Juvenile CLN3 disease is a recessively inherited paediatric neurodegenerative disorder, with most patients homozygous for a 1-kb intragenic deletion in CLN3. The btn1 gene is the Schizosaccharomyces pombe orthologue of CLN3. Here, we have extended the use of synthetic genetic array (SGA) analyses to delineate functional signatures for two different disease-causing mutations in addition to complete deletion of btn1. We show that genetic-interaction signatures can differ for mutations in the same gene, which helps to dissect their distinct functional effects. The mutation equivalent to the minor transcript arising from the 1-kb deletion (btn1102–208del) shows a distinct interaction pattern. Taken together, our results imply that the minor 1-kb deletion transcript has three consequences for CLN3: to both lose and retain some inherent functions and to acquire abnormal characteristics. This has particular implications for the therapeutic development of juvenile CLN3 disease. In addition, this proof of concept could be applied to conserved genes for other mendelian disorders or any gene of interest, aiding in the dissection of their functional domains, unpacking the global consequences of disease pathogenesis, and clarifying genotype–phenotype correlations. In doing so, this detail will enhance the goals of personalised medicine to improve treatment outcomes and reduce adverse events

Uterine fibroid pseudocapsule studied by transmission electronmicroscopy.

OBJECTIVE: The fibroid pseudocapsule is a structure which surrounds the uterine fibroid, separates it from the uterine tissue and contains a vascular network rich in neurotransmitters like a neurovascular bundle. The authors examined the composition of the fibroid pseudocapsule using electron microscopy. STUDY DESIGN: Twenty non-pregnant patients were submitted to laparoscopic myomectomy by the intracapsular method and samples of the removed pseudocapsules were analyzed using transmission electron microscopy. RESULTS: At the ultrastructural level the pseudocapsule cells have the features of smooth muscle cells similar to the myometrium. So, the pseudocapsules are part of the myometrium which compresses the leiomyoma. CONCLUSION: This ultrastructural feature suggests that when removing fibroids their pseudocapsules should be preserved. This study confirms preliminary evidence that pseudocapsules contain neuropeptides together with their related fibers, as a neurovascular bundle. The surgeon's behavior should be directed to carefully control and spare this muscular surrounding tissue during fibroid excision, in order to preserve the myometrium as much as possible

The Biological Relevance of NHERF1 Protein in Gynecological Tumors

Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types

Inflammation and Neurotransmission of the Vescico-Uterine Space in Cesarean Sections:

Collagen IV and laminin play a key role in regulating stiffness, elasticity and flexibility of the vescico-uterine space (VUS) tissue. The neurotensin (NT), the neuropeptide tyrosine (NPY) and the protein gene product 9.5 (PGP 9.5) possessing vasorelaxation and tissue vascularization activities, play key roles in cervical ripening, scar innervations and pain control. We propose that the integrity of these substances in VUS tissue is compromised after Cesarean section (CS), since wound healing disturbances and pelvic pain, as well as pregnancy and delivery complications, are related with lower uterine segment dysfunctions after CS. Therefore, the contents of collagen IV, laminin, NT, NPY and PGP 9.5 nerve fibres from the VUS tissue samples obtained during the first CS and the repeated CS were comparatively studied. VUS specimens were collected from 104 patients during CS and evaluated by immunohistochemistry. Collagen IV and laminin were mostly found in the vascular membrane bounds and their images were quantitatively evaluated by Quantimet Leica analyzer software. Differences of collagen IV, laminin, NT, NPY and PGP 9.5 values in VUS tissue between the first CS and the repeat CS samples were calculated by Student's Mest. Reduced laminin and increased collagen IV values were observed in the VUS scar tissue after the repeated CS in comparison with those of VUS intact tissue obtained during the first CS. Significantly higher values of nerve fibres, containing NT, NPY and PGP 9.5 were registered in intact VUS tissue samples, respectively 5±0.7, 7±0.6 and 5±0.9 CU, than those of VUS scar tissue samples obtained during the repeated CS, respectively 3±0.6,2±0.4 and 3±0.7 CU (p<0.05). The authors observed increased collagen IV and reduced laminin values after the repeated CS which might be the key signs of inflammatory damage of VUS scar tissue by CS. These findings were strengthened by the registration of decreased NT, NPY and PGP 9.5 values in the same samples, which are important neurotransmitters and are responsible for optimal wound healing, pain control and lower uterine segment functions