Summary
Esophageal atresia (EA) is a congenital defect of the esophagus involving the interruption of the esophagus with or without connection to the trachea (tracheoesophageal fistula TEF). EA/TEF ...may occur as an isolated anomaly, may be part of a complex of congenital defects (syndromic), or may develop within the context of a known syndrome or association. The molecular mechanisms underlying the development of EA are poorly understood. It is supposed that a combination of multigenic factors and epigenetic modification of genes play a role in its etiology.
The aim of our work was to assess the human gene expression microarray study in esophageal tissue samples. Total RNA was extracted from 26 lower pouches of esophageal tissue collected during thoracoscopic EA repair in neonates with the isolated (IEA) and the syndromic form (SEA).
We identified 787 downregulated and 841 upregulated transcripts between SEA and controls, and about 817 downregulated and 765 upregulated probes between IEA and controls. Fifty percent of these genes showed differential expression specific for either IEA or SEA. Functional pathway analysis revealed substantial enrichment for Wnt and Sonic hedgehog, as well as cytokine and chemokine signaling pathways. Moreover, we performed reverse transcription polymerase chain reaction study in a group of SHH and Wnt pathways genes with differential expression in microarray profiling to confirm the microarray expression results. We verified the altered expression in SFRP2 gene from the Wnt pathway as well as SHH, GLI1, GLI2, and GLI3 from the Sonic hedgehog pathway. The results suggest an important role of these pathways and genes for EA/TEF etiology.
Summary
Esophageal atresia (EA) is a congenital developmental defect of the alimentary tract concerning the interruption of the esophagus with or without connection to the trachea. The incidence of ...EA is 1 in 3000–3500 of live‐born infants, and occurs in both isolated and syndromic (in combination with abnormalities in other organ systems) forms. The molecular mechanisms underlying the development of EA are poorly understood. Knockout studies in mice indicate that genes like Sonic hedgehog, Gli2, and Gli3 play a role in the etiology of EA. These facts led us to hypothesize that Sonic hedgehog‐GLI gene rearrangements are associated with EA in humans. To test this hypothesis, we screened patients with isolated and syndromic EA for GLI2 and/or GLI3 microrearrangements using methods to estimate the copy number (Multiplex Ligation‐dependent Probe Amplification, real‐time polymerase chain reaction). To our best knowledge this is the first study assessing copy number of GLI2 and GLI3 genes in patients with EA.
Organic cation transporters play a critical role in the elimination of therapeutic compounds in the liver and the kidney.
We used computational quantitative structure activity approaches to predict ...molecular features that influence interaction
with the human ortholog of the organic cation transporter (hOCT1). 3 Htetraethylammonium uptake in HeLa cells stably expressing hOCT1 was inhibited to varying extents by a diverse set of 30
molecules. A subset of 22 of these was used to produce, using Catalyst, a pharmacophore that consisted of three hydrophobic
features and a positive ionizable feature. The correlation coefficient of observed versus predicted IC 50 was 0.86 for this training set, which was superior to calculated logP alone ( r = 0.73) as a predictor of hOCT1 inhibition. A descriptor-based quantitative structure-activity relationship study using Cerius 2 resulted in an equation relating five molecular descriptors to log IC 50 with a correlation coefficient of 0.95. Furthermore, a group of phenylpyridinium and quinolinium compounds were used to investigate
the spatial limitations of the hOCT1 binding site. The affinity for hOCT was higher for 4-phenylpyridiniums > 3-phenylpyridiniums
> quinolinium, indicating that substrate affinity was influenced by the distribution of hydrophobic mass. In addition, supraplanar
hydrophobic mass was found to increase the affinity for binding hOCT1. These results indicate how a combination of computational
and in vitro approaches may yield insight into the binding affinity of transporters and may be applicable to predicting these
properties for new therapeutics.
2-Acetamido-2-deoxy-
d-glucose hydrochloride (
d-glucosamine hydrochloride) has been used for the preparation of 1,3,4,6-tetra-
O-acetyl-2-deoxy-2-trifluoroacetamido-β- (
4) and ...2-tetrachlorophthalimido-α,β-
d-glucopyranose (
6), which have been transformed into the appropriate bromides and the chloride. Both bromo and chloro sugars were used as a glycosyl donors for the glycosylation of diosgenin (25
R)-spirost-5-en-3β-ol. These condensations were conducted under mild conditions, using silver triflate as a promoter, and gave diosgenyl glycosides
9 and
12. Each of them was converted into diosgenyl 2-amino-2-deoxy-β-
d-glucopyranoside hydrochloride (
11) and
N-acylamido derivatives. The structures of all new glycosides were established by
1H and
13C NMR spectroscopy. These diosgenyl glycosides are the first saponins containing the
d-glucosamine residue that have been synthesized. These compounds show promising antitumor activities. The synthetic saponins increase the number of apoptotic B cells, in combination with cladribine (2-CdA), that are isolated from chronic lymphotic leukemia (B-CLL) patients.
The
N-trifluoroacetyl- and
N-tetrachlorophthaloyl-protected bromides and chloride of
d-glucosamine have been used as glycosyl donors for the glycosylation of diosgenin (25
R)-spirost-5-en-3β-ol. These glycosides were converted into diosgenyl 2-amino-2-deoxy-β-
d-glucopyranoside and its derivatives, which showed promising antitumor activities. The structures of all new glycosides were established by
1H and
13C NMR spectroscopy. The synthetic saponins increase the number of apoptotic B cells, in combination with cladribine (2-CdA), that were isolated from chronic lymphotic leukemia (B-CLL) patients.
Epidemiologic data suggest that in 2007 the number of HIV infected people in Poland is nearly 11000. The purpose of the study was to assess the psychosexual problems in HIV infected patients.
The ...reaserch was based on personal questionnaire. To assess psychical wellness GHQ-28 scale was used, to assess the sexual problems we used Mell-Krat scale and BSP questionnaire.
Mean age was 36,2 years, most of respondents were men (75%), average infection period was 8,2 years and most of respondents (37,5%) didn’t know how they had become infected. Most of them were coinfeced with HCV (81.25%). Antiretrovirusal therapy was used with most of patients (51%). The mean result obtained in Mell Krat scale was 35,3 for men (opimal is 39), women result was 46,25 (opimal for women is 55). Mell Krat scale is used to assess the sexual needs and rections. We obtained following mean results in GHQ-28 scale: somatic symptoms - 13,06, anxietyinsomn nia - 10,7, social dysfunction - 11,5, severe depression - 7,38, and were similar in women and men. Most of respondents had permanent partners (81%), in most cases partners were infected with HIV (57%). For nearly 50% patients sex plays a very important thing in their life.
The preliminary study seems to approve our hipothesis about psychosexual disturbances in HIV infected people. The group of 16 patients is to small to draw a conclusions thus study on bigger group (150 patients) are going to be performed.
Sexually transmitted diseases (STDs) are ones of the most frequent among infectious diseases. In pathogenesis of the diseases that can be transmitted during the sexual practices between women, the ...most important is the problem of infected cervicovaginal secretions’transfer. That transfer may happen directly during the vagina's mucosa contact or indirectly by digital-vaginal sexual practices or sex toys sharing. The task of the studies was to show risk awareness and STDs’knowledge among women having sex with other women.
To describe the problem the studies were done on 259 women group, of which 56% names themselves as homosexual, and 32% as bisexual. The survey was carried out using internet, through the web page for lesbians. The research was based on personal questionnaire; concerning socio-demographical data, question about sexuality and knowledge of STD.
Almost half of the women participating in the studies considered the level of their knowledge of STDs infection prevention is good. Most of them (80%) reported that has never suffered on STD before. About 50% of the participants had problems to define infection risk in different sexual practices correctly, as well as to point out infection tracts and gates. The biggest problem for them was to connect typical symptoms with particular disease. However almost all participants assumed any STD's symptom appearance as an indication for immediate medical consultation.
Although the prevailing part of the participants were convinced to be well-informed about STDs, their knowledge was not very deeP - what can increase STDs infection risk.
Abstract Numerous series, propensity matched trials and meta-analyses suggest appropriate use of extracorporeal cardiopulmonary resuscitation (E-CPR) for in-hospital cardiac arrest (IHCA) can be ...lifesaving. Even with antecedent CPR durations in excess of 45 minutes, 30-day survival with favourable neurologic outcome using E-CPR is approximately 35 to 45%. Survival may be related to age, duration of CPR or etiology. Associated complications include sepsis, renal failure, limb and neurologic complications, hemorrhage and thrombosis. However, methodological biases including small sample sizes, selection bias, publication bias and inability to control for confounders in these series prevent definitive conclusions. As such, the 2015 American Heart Association Advanced Cardiac Life Support (ACLS) guidelines update recommended E-CPR as a Level of Evidence IIb recommendation in appropriate cases. The absence of high quality evidence presents an opportunity for clinician-scientists to generate practice-defining data via collaborative investigation and prospective trials. A multidisciplinary dialogue is required to standardize the field and promote multicenter investigation of E-CPR with data sharing and the development of a foundation for high-quality trials. The objectives of this review are to: (1) provide an overview of the strengths and limitations of currently-available studies investigating the use of E-CPR in patients with IHCA and highlight knowledge gaps; (2) create a framework for the standardization of terminology, clinical practice, data collection and investigation of E-CPR for patients with IHCA that will help to ensure congruence in future work in this area; (3) propose suggestions to guide future research by the cardiovascular community in order to advance this important field.
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