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Isomeric coordination complexes of different configurations (hour-glass and double-decker) but prepared from regioisomeric tridentate ligands are described.

Self-assembled coordination complexes prepared from a combination of Pd(II) components with one or more types of high-symmetry or low-symmetry bis/tris/tetrakis-monodentate ligands are considered in this review. The structures of these complexes are viewed in terms of the presence of a metallo-macromonocycle or conjoined metallo-macromonocycles/metallocages in the frameworks. Analysis of the typical molecular structures revealed an open truth that one or more units of metallo-macromonocycles can be conjoined to afford planar or non-planar systems. In the same line, the enveloping surface of a 3D cage can be considered as a multiple number of conjoined metallomacrocycles that embrace a 3D space from all directions. However, two or more units of cages are conjoined in a multi-3D-cavity cage system and such a system is considered as a conjoined cage. Construction of such conjoined cages having a finite but multiple number of 3D-cavities unified in a single molecular architecture is a challenging task when compared to that of single-3D-cavity based compounds. Conjoining of as many as four units of 3D cages is known so far. Single- as well as multi-cavity cages of lower symmetry have become a very recent trend in this regard where low-symmetry ligands or mixed ligand ensembles are crafted in the framework of the cages. Other structural diversities like helicity in cages, and supramolecular isomerism are also included in this assorted literature work. Although isomerism in classical coordination complexes is well known, it is very less studied in self-assembled coordination complexes. Ligand isomerism is one such feature that is reviewed here. The dynamic behavior of the cages results in interesting reactivity aspects. A large variety of dynamic processes are collected under an umbrella

Papaya is reported to trigger food and respiratory allergy. Here, we identified chymopapain Cari p 2 as an allergen that can sensitize atopic individuals through fruit consumption followed by respiratory hazards through pollen exposure. Recombinant Cari p 2 displayed IgE-reactivity with 78% of papaya allergic sera. rCari p 2 also displayed allergenic activity through basophil degranulation. rCari p 2 is correctly folded and showed irreversible denaturation in the melting curve. rCari p 2 displayed IgE-cross-reactivity with homologous cysteine proteases from kiwi and pineapple. Cari p 2 transcript was also detected in papaya pulps. rCari p 2 was resistant to pepsin digestion and retained IgE-reactivity after 60 minutes of pepsin digestion. In mouse model, rCari p 2 was found to elicit inflammatory responses in the lung and gastrointestinal epithelium. Hence, Cari p 2 is a newly characterized allergen with diagnostic and immunotherapeutic potential for managing allergic disorders in papaya sensitized individuals.

Mesendoderm cells are key intermediate progenitors that form at the early primitive streak (PrS) and give rise to mesoderm and endoderm in the gastrulating embryo. We have identified an interaction between CNOT3 and the cell cycle kinase Aurora B that requires sequences in the NOT box domain of CNOT3 and regulates MAPK/ERK signaling during mesendoderm differentiation. Aurora B phosphorylates CNOT3 at two sites located close to a nuclear localization signal and promotes localization of CNOT3 to the nuclei of mouse embryonic stem cells (ESCs) and metastatic lung cancer cells. ESCs that have both sites mutated give rise to embryoid bodies that are largely devoid of mesoderm and endoderm and are composed mainly of cells with ectodermal characteristics. The mutant ESCs are also compromised in their ability to differentiate into mesendoderm in response to FGF2, BMP4, and Wnt3 due to reduced survival and proliferation of differentiating mesendoderm cells. We also show that the double mutation alters the balance of interaction of CNOT3 with Aurora B and with ERK and reduces phosphorylation of ERK in response to FGF2. Our results identify a potential adaptor function for CNOT3 that regulates the Ras/MEK/ERK pathway during embryogenesis.

Background Beta-hCG can be detected in post-menopausal women, who also demonstrate an increased cancer risk. Whether ovarian hormones mediate cytotoxic effects on beta-hCG-responsive tumor cells, whether beta-hCG exerts enhanced pro-tumorigenic effects in the absence of ovarian steroids, and whether steroid administration can have restorative effects on tumor molecular profiles and progression, remain unaddressed. Methods The effect of ovarian steroids on the proliferation, viability and apoptosis of beta-hCG responsive LLC1 tumor cells were assessed. Involvement of nuclear/non-nuclear steroid receptors was evaluated by assessing presence and employing receptor antagonists, by cAMP measurements, and by assessing MAP kinase activation. LLC1 tumor cells were implanted in female non-transgenic mice, in beta-hCG transgenic mice and in ovariectomized beta-hCG transgenic mice; progesterone was additionally administered to the latter two groups. Tumor volumes were measured, and RNA-seq, qPCR and immunohistochemistry were employed to characterize tumor molecular profiles. TCGA databases for lung adenocarcinoma, colon adenocarcinoma and glioblastoma were probed with human orthologs of newly-identified genes to reveal clinically-relevant associations, with a focus on the post-menopausal state. Results Ovarian steroids demonstrated anti-tumor effects in vitro; progesterone caused tumor cell apoptosis via non-nuclear receptors and the phosphorylation of p38. Beta-hCG, particularly in absence of the ovaries (a mimic of the post-menopausal state), constituted an aggravated pro-tumorigenic signal for implanted LLC1 tumor cells. Progesterone dampened aggravated tumor growth in ovariectomized mice. RNA-seq on excised tumors identified genes associated with enhanced beta-hCG-mediated tumor growth in ovariectomized mice, as well as with the anti-tumor effects of progesterone. TCGA analysis revealed correlations between the expression of several newly-identified, progesterone-influenced genes (and of intra-tumoral beta-hCG) and poor patient prognosis, specifically in post-menopausal women. Conclusion This study describes a previously-unidentified interplay between progesterone and beta-hCG in the regulation of tumorigenesis. Murine tumor-associated gene signatures, combined with queries on aggressive human tumors reveal, for the first time, that beta-hCG acts as an additionally potent pro-tumorigenic signal when the ovaries are quiescent. Associations of progesterone-influenced genes (and intra-tumoral beta-hCG) with prognosis were revealed. Intra-tumoral / extra-tumoral beta-hCG may be a useful prognostic indicator in post-menopausal women with cancer, and progesterone may constitute a potential therapeutic in such cases.

In this paper two types of synthetic wind power time series are used to assess the effect of wind variability in the long-term voltage stability assessment of a power system. A wind power time series is generated using the wind simulation tool CorWind, which is based on power spectral density. This time series is then used as input to develop a Markov model for wind power simulation. Both the CorWind time series and randomly generated time series using the Markov model are then applied to a simple power system and the effect of wind variability on the maximum power transfer to a remote load is investigated.

The beta subunit of human chorionic gonadotropin (βhCG) is secreted by various tumors, and its presence associated with poor prognosis. Though exogenous hCG elicits the synthesis of molecules associated with angiogenesis, invasion, immune suppression and chemoresistance from responsive tumor cells in vitro, the influence of cell-extrinsic βhCG on tumorigenesis in vivo has not been adequately explored. Female C57BL/6−/− × FVBβhCG/− F1 transgenic mice demonstrated ovarian hyperplasia and pituitary adenomas; transcripts of hCG-driven, tumor-associated molecules were heightened in the pituitary. Upon the implantation of Lewis Lung Carcinoma cells (murine lung tumor cells derived from C57BL/6 mice) in transgenic mice, tumor incidence and volume were enhanced, and increased transcription and expression of hCG-driven, tumor-associated molecules was observed in excised tumors. While treatment of these mice with Cabergoline (a potent dopamine receptor agonist) had no significant effects, ovariectomy resulted in a reduction in the lag phase, accompanied by an increase in tumor incidence and volume upon Lewis Lung Carcinoma cell implantation. In tumors derived from Lewis Lung Carcinoma cell-implanted ovariectomized, transgenic mice, the transcription and expression of hCG-driven, tumor-associated molecules remained elevated and enhanced animal mortality was observed. Cell-extrinsic βhCG can therefore induce pro-tumorigenic effects in vivo (even on tumor lineages not part of the reproductive axis), with ovarian products mediating an ameliorating influence.

Anion induced twisted disposition of four units of a bidentate ligand around two palladium(II) centers in the cage of [Pd2L4](ClO4)4 formulation resulted in a helical structure. The crystal structure reveals the existence of both M and P enantiomers. The disposition of one of the arms is noticeably different from the other three, hence the molecular symmetry of the helicate is lowered. The encapsulation of perchlorate anion within the cage pocket with H-bonding interactions provided the driving force for the helicity. However, the analogues complex [Pd2L4](NO3)4 with nitrate as counter anion is nonhelical. Formation of helical and nonhelical Pd2L4 arrangement by mere change of counter anion was not reported hence it is a new finding.

Microarray data analysis is one of the major area of research in the field computational biology. Numerous techniques like clustering and biclustering are often applied to microarray data to extract meaningful outcomes which play key roles in practical healthcare affairs like disease identification, drug discovery, etc. But these techniques become obsolete when time as an another factor is considered for evaluation in such data. This problem motivates to use triclustering method on gene expression 3D microarray data. In this article, a new methodology based on coarse-grained parallel genetic approach is proposed to locate meaningful triclusters in gene expression data. The outcomes are quite impressive as they are more effective as compared to traditional state-of-the-art genetic approaches previously applied for triclustering of 3D GCT microarray data.

Mesendoderm cells are key intermediate progenitors that form at the early primitive streak (PrS) and give rise to mesoderm and endoderm in the gastrulating embryo. We have identified an interaction between CNOT3 and the cell cycle kinase Aurora B, which requires sequences in the NOT box domain of CNOT3, and regulates MAPK/ERK signalling during mesendoderm differentiation. Aurora B phosphorylates CNOT3 at two sites located close to a nuclear localization signal and promotes localization of CNOT3 to the nuclei of mouse ES cells (ESCs) and metastatic lung cancer cells. ESCs that have both sites mutated give rise to embryoid bodies that are largely devoid of mesoderm and endoderm and are composed mainly of ectoderm. The mutant ESCs are also compromised in their ability to differentiate into mesendoderm in response to FGF2, BMP4 and Wnt3. The double mutation affects interaction of CNOT3 with Aurora B and with ERK and reduces phosphorylation of ERK in response to FGF2, impacting on survival of the differentiated ME cells. Our results identify an adaptor function for CNOT3 that regulates a key pathway in embryogenesis and cancer.

Clinical and mycological features of onychomycosis show variation with time and place. Onychomycosis is a major public health problem with high incidence, associated morbidity and long lasting treatment with anti-fungal agents. A study was carried out on 118 patients having clinical diagnosis of onychomycosis, attending the dermatology out-patient department of R. G. Kar Medical College, Kolkata. Nail clippings were subjected to direct microscopy and cultured on Sabouraud's Dextrose Agar with antibiotics. The commonest age group affected was 21-40 years with a female preponderance and housewives were most commonly affected group. Finger nail involvement were more frequent and distolateral subungal onychomycosis (DLSO) was the most common clinical type observed . Out of 118 cases total KOH positivity was in 72 (61.01%) and culture positivity was in 62 (52.54%). Total culture positive cases were 62 and total number of fungi identified were 66 as dual pathogen had been identified in four cases . Among 66 culture positive isolates dermatophytes were 30 ( 45.55%), candida 21(31.82%) and non-dermatophyte moulds (NDM) 15 ( 22.73%) . T. rubrum was the commonest etiological agent. Among dermatophytes, Trichophyton rubrum, and among NDM, Fusarium moniliforme, were the most common isolates identified in our study.

This paper investigates how current-limited converters influence system stability. An improved approach for assessing voltage stability is introduced, which determines the maximum deliverable power to a load by accounting for changes in the Thevenin voltages. The new approach is able to detect voltage instability well before the traditional approach based on Thevenin impedance matching. A new stability boundary is discovered that describes the aperiodic small signal stability boundary for current-limited converters. The improved approach was modified to account for current-limited converters. The detection of voltage and rotor angle instability during current limitation were demonstrated on a seven bus system, where test cases were performed. The test cases showed that voltage instability can lead to aperiodic small signal instability, when the converter has reached its current limit and loss of synchronism in the unstable region during current-limitation causes the system voltages to collapse.

Accumulating evidence indicates that immune cells in the microenvironment play a significant role in tumor progression. Understanding the dynamic interplay between tumor cells and the host immune system is therefore of critical importance. While some immunotherapeutic strategies aim to specifically overcome hyporesponsiveness to tumor-associated antigens, others seek to nonspecifically activate the immune system; efficacy and toxicity are overriding, and often conflicting, concerns. This chapter, while occasionally providing brief historical perspectives, describes ongoing efforts in the area, including strategies for anticancer vaccination and adoptive cell transfer, the use of cytokines and development of oncolytic viruses, and the administration of checkpoint inhibitors. While significant successes have been achieved, the field is also characterized by notable failure, an indication that much remains unknown about factors that trigger and promote tumorigenesis, about current limitations in the effective delivery of therapeutic moieties, and about the workings of the immune system.

Due to characteristics of wind which is inherently variable, active power production from wind power plants fluctuates over time. Reactive power capability of wind power plant is dependent on active power production. This paper investigates the impact of active power fluctuations on reactive power capability of wind power plants and quantifies the impact. For this purpose time series data of active power production with fluctuations from aggregated wind power plant is simulated. This time series is then used to calculate reactive power capability time series of the aggregated wind power plant. Different time periods have been used for calculating mean values of reactive power capability. Then, ramp rates has been calculated to quantify mean value changes between two consecutive time periods. From the case study performed, it is observed that active power fluctuation has an impact on reactive power capability - increasing the averaging time period increases the ramp rate of reactive power capability.

Papaya has been reported to elicit IgE-mediated hypersensitivity via pollen inhalation and fruit consumption. Certain papaya sensitive patients with food allergy were found to experience recurrent respiratory distresses even after quitting the consumption of fruits. This observation prompted us to investigate the allergens commonly present in fruits and pollen grains of papaya. A discovery approach consisting of immunoproteomic detection followed by molecular characterization led to the identification of a novel papaya allergen designated as Cari p 1. This allergen was detected as a 56 kDa IgE-reactive protein from pollen as well as fruit proteome through serological analysis. The protein was identified as an endopolygalacturonase by tandem mass spectrometry. Full length Cari p 1 cDNA was isolated from papaya pollen, cloned in expression vector, and purified as recombinant allergen. The recombinant protein was monomeric and displayed pectinolytic activity. Recombinant Cari p 1 reacted with IgE-antibodies of all the papaya sensitized patient sera. In addition to IgE-reactivity, rCari p 1 displayed allergenic activity by stimulating histamine release from IgE-sensitized granulocytes. CD-spectroscopy of rCari p 1 revealed the presence of predominantly β-sheet characters. The melting curve of the allergen showed partial refolding from a fully denatured state indicating the possible presence of conformational IgE-epitopes characteristic of inhalant allergens in addition to the linear IgE-epitopes of food allergens. The expression of this allergen in papaya fruits was detected by immunoblot with anti-Cari p 1 rabbit IgG and reconfirmed by PCR. In an in vivo mouse model, rCari p 1 exhibited a comparable level of inflammatory responses in the lung and duodenum tissues explaining the dual role of Cari p 1 allergen in respiratory sensitization via pollen inhalation and sensitization of gut mucosa via fruit consumption. Purified rCari p 1 can be used a marker allergen for component-resolved molecular diagnosis. Further immunological studies on Cari p 1 are warranted to design immunotherapeutic vaccine for the clinical management of papaya allergy.

DEAD box protein family of RNA helicases are vital players of RNA metabolism, and constitute the largest family of RNA helicases. Members of this family share nine conserved motifs including an Asp-Glu-Ala-Asp motif, giving this family its characteristic name as DEAD box RNA helicases. These conserved motifs confer RNA binding and RNA unwinding properties. Besides functioning in RNA metabolism, emerging evidences suggests several DEAD box RNA helicases to possess potential roles in regulating gene expression by acting as a transcriptional co-activator. Many of them are deregulated in cancers, and are implicated in possessing oncogenic potential. On the contrary, each of them also possesses tumor suppressive property in a context dependent manner. In this review, we discuss the mechanistic insights of gene regulation by DEAD box RNA helicases, and their significance in cancers.

Increased abundance of proto-oncogene AKT and reduced expression of tumor suppressor Forkhead box O3 (FOXO3a), the downstream target of AKT, is frequent in carcinogenesis. Mechanistic insights of AKT gene regulation are limited. DEAD box RNA helicase p68 is overexpressed in various cancers and acts as a transcriptional co-activator of several transcription factors, including β-catenin. Here, we report a novel mechanism of p68-mediated transcriptional activation of AKT, and its ensuing effect on FOXO3a, in colon carcinogenesis. Interestingly, we found that the expression of p68 and AKT exhibits strong positive correlation in normal and colon carcinoma patient samples. In addition, p68 increased both AKT messenger RNA (mRNA) and protein, enhanced AKT promoter activity in multiple colon cancer cell lines. Conversely, p68 knockdown led to reduced AKT mRNA and protein, diminished AKT promoter activity. Here, we demonstrated that p68 occupies AKT promoter with β-catenin as well as nuclear factor-κB (NF-κB)and cooperates with these in potentiating AKT transcription. Furthermore, p68 and FOXO3a expression followed inverse correlation in the same set of colon carcinoma samples. We observed that p68 significantly reduced FOXO3a protein level in an AKT-dependent manner. Studies in primary tumors and metastatic lung nodules generated in mice colorectal allograft model, using syngeneic cells stably expressing p68, corroborated our in vitro findings. Hence, a new mechanism of oncogenesis is attributed to p68 by upregulation of AKT and consequent nuclear exclusion and degradation of tumor suppressor FOXO3a.

The interaction between alprazolam (Alp) and bovine serum albumin (BSA) has been investigated under physiological conditions by UV–vis, steady state as well as time-resolved fluorescence, circular dichroism (CD) spectroscopic and molecular docking studies. The binding constant K of Alp to BSA was found to be 1.8×105 L mol−1 from absorption data. Fluorometric studies suggested the formation of the Alp–BSA complex, while time-resolved fluorescence studies showed that the binding of Alp by BSA was mainly static and the effective rate constant is found to be 2.33×1013 L mol−1 s−1. According to the modified Stern–Volmer equation, the Stern–Volmer quenching constants (KSV) between Alp and BSA at four different temperatures 295, 303, 308, 313 K were obtained to be 1.19×105, 1.05×105, 0.99×105 and 0.90×105 L mol−1, respectively. The change in enthalpy (ΔH) and entropy (ΔS) were calculated to be −11.66 and 57.64 J mol−1 K−1, respectively, indicating that the interaction was hydrophobic in nature. Site marker competitive experiments suggested that the binding of Alp to BSA primarily took place in sub-domain IIA, whereas the binding distance (r) between Alp and the tryptophan residue of BSA was obtained to be 1.87 nm by Forster's theory of non-radiative energy transfer. The conformational studies by CD spectroscopy showed that the presence of Alp decreased the α-helical content of BSA and induced the unfolding of the polypeptide of the protein. The change in conformation was also supported by excitation–emission matrix spectroscopy (EEMS) studies. The molecular docking experiment supports the above results and effectively proves the binding of Alp to BSA.

A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum β-lactamases (CTX-M E. coli ) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for bla CTX-M , bla TEM , and bla SHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli ) and uninfected controls. Of 575 patients with ESBL-producing E. coli , 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli ( n = 51 [16%]) and non-CTX-M E coli ( n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially bla CTX-M-15 type, represented the most common ESBL determinants from ESBL-producing E. coli , the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms.

Increasing penetration of converter-based generations in power system has led to new system challenges. Short circuit power response from converter-based generations is different from that of traditional synchronous generators. Power electronic converters can be designed for over-current only up to 1.1-1.25 times of its nominal value. Low availability of short circuit power can cause many challenges such as misoperation of distance relays. The aim of this paper is to investigate the effect of converter dominated systems on performance of distance relays. Backup functionality of the distance relay is major concern as miscoordination of backup relays in case of cascading faults can lead to severe stress in system, which can develop into blackout. In this paper, response of relays in traditional system is compared with response of relays in low short-circuit-current power systems. Impact of converter controls on fault current response of converter-based generations is also investigated. Index Terms—Converter control, distance relays, power system protection, system modelling.

DEAD box RNA helicase p68 acts as a transcriptional coactivator of several oncogenic transcription factors apart from being a vital player of RNA metabolism. Signal transducer and activator of transcription 3 (Stat3) is a major oncogenic contributor of diverse cancers, including that of colon. Deciphering the mechanistic insights of coactivation of Stat3 transcriptional activity may aid in improved therapeutic strategies. Here we report for the first time a novel mechanism of alliance between p68 and Stat3 in stimulating transcriptional activity of Stat3. Interestingly, we observed that the expression of p68 and Stat3 bears strong positive correlation and significant colocalization in normal and colon carcinoma patient samples. We demonstrated that p68 directly interacts with Stat3 in HEK293 cells as well as multiple colon cancer cell lines. Additionally, p68 positively modulated both mRNA and protein expression levels of Stat3 target genes; promoter activity of Stat3 target gene Mcl-1 in multiple colon cancer cell lines. Also, p68 occupied the promoters of multiple Stat3 target genes in enhancing Stat3-dependent transcription. Moreover, the strong positive correlation between the abundance of p68 and Stat3 target genes in the same set of colon carcinoma samples further supported our observations. Enhanced expression levels of Stat3 target genes observed in primary tumors and metastatic lung nodules, generated in mice colorectal allograft model using syngeneic cells stably expressing p68, further reinforced our in vitro findings. Hence, this study unravels novel modes of p68-mediated oncogenesis through coactivation of Stat3 and enhancing Stat3 signaling.

Aim: The TWEAK and T-ACE screening tools are validated methods of identifying problem drinking in a pregnant population. The objective of this study was to compare the effectiveness of the TWEAK and T-ACE screening tools in identifying problem drinking using traditional cut-points (CP). Methods: Study participants consisted of women calling the Motherisk Alcohol Helpline for information regarding their alcohol use in pregnancy. In this cohort, concerns surrounding underreporting are not likely as women self-report their alcohol consumption. Participant’s self-identification, confirmed by her amount of alcohol use, determined whether she was a problem drinker or not. The TWEAK and T-ACE tools were administered on both groups and subsequent analysis was done to determine if one tool was more effective in predicting problem drinking. Results: The study consisted of 75 problem and 100 non-problem drinkers. Using traditional CP, the TWEAK and T-ACE tools both performed similarly at identifying potential at-risk women (positive predictive value = 0.54), with very high sensitivity rates (100–99% and 100–93%, respectively) but poor specificity rates (36–43% and 19–34%, respectively). Upon comparison, there was no statistical difference in the effectiveness for one test performing better than next using either CP of 2 ( P = 0.66) or CP of 3 ( P = 0.38). Conclusion: Despite the lack of difference in performance, improved specificity associated with TWEAK suggests that it may be better suited to screen at-risk populations seeking advice from a helpline.

Background Debate has recently arisen about the safety of paroxetine use in pregnancy, prompted by reports of increased risks for cardiac defects following first trimester exposure. Methods We conducted a meta-analysis of nine studies. Results Three case-control studies (N = 30 247) found no increased risk of congenital malformations associated with paroxetine (OR = 1.18; 95% CI 0.88–1.59). Cardiac malformation rates were similar (1.1% each) and within population norms (0.7–1.2%). Six cohort studies (N = 66 409) found a non-significant weighted average difference of 0.3% (95% CI -0.1–0.7%; P = 0.19). Conclusion First-trimester exposure to paroxetine does not appear to be associated with increased rates of cardiac malformations. This information should be reassuring to prescribing physicians and women who require treatment with paroxetine in pregnancy.

Background: Menstruation and menstrual practices are still clouded by taboos and socio-cultural restrictions resulting in adolescent girls remaining ignorant of the scientific facts and hygienic health practices, which sometimes result into adverse health outcomes. Objectives: (i) To elicit the beliefs, conception and source of information regarding menstruation among the study population and (ii) to find out the status of menstrual hygiene among adolescent girls. Materials and Methods: A descriptive, cross-sectional study was conducted among 160 adolescent girls of a secondary school situated in the field practice area of Rural Health Unit and Training Center, Singur, West Bengal, with the help of a pre-designed and pre-tested questionnaire. Data were analyzed statistically by simple proportions. Results: Out of 160 respondents, 108 (67.5%) girls were aware about menstruation prior to attainment of menarche. Mother was the first informant regarding menstruation in case of 60 (37.5%) girls. One hundred and thirty-eight (86.25%) girls believed it as a physiological process. Seventy-eight (48.75%) girls knew the use of sanitary pad during menstruation. Regarding practices, only 18 (11.25%) girls used sanitary pads during menstruation. For cleaning purpose, 156 (97.5%) girls used both soap and water. Regarding restrictions practiced, 136 (85%) girls practised different restrictions during menstruation. Conclusions: Menstrual hygiene, a very important risk factor for reproductive tract infections, is a vital aspect of health education for adolescent girls. Educational television programmes, trained school nurses/health personnel, motivated school teachers and knowledgeable parents can play a very important role in transmitting the vital message of correct menstrual hygiene to the adolescent girl of today.

Introduction Nuclear accumulation of β-catenin is important for cancer development and it is found to overlap with p68 (DDX5) immunoreactivity in most breast cancers, as indicated by both clinical investigations and studies in cell lines. In this study, we aim to investigate the regulation of p68 gene expression through β-catenin/transcription factor 4 (TCF4) signaling in breast cancer. Methods Formalin-fixed paraffin-embedded sections derived from normal human breast and breast cancer samples were used for immunohistochemical analysis. Protein and mRNA expressions were determined by immunoblotting and quantitative RT-PCR respectively. Promoter activity of p68 was checked using luciferase assay. Occupancy of several factors on the p68 promoter was evaluated using chromatin immunoprecipitation. Finally, a syngeneic mouse model of breast cancer was used to assess physiological significance. Results We demonstrated that β-catenin can directly induce transcription of p68 promoter or indirectly through regulation of c-Myc in both human and mouse breast cancer cells. Moreover, by chromatin immunoprecipitation assay, we have found that both β-catenin and TCF4 occupy the endogenous p68 promoter, which is further enhanced by Wnt signaling. Furthermore, we have also established a positive feedback regulation for the expression of TCF4 by p68. To the best of our knowledge, this is the first report on β-catenin/TCF4-mediated p68 gene regulation, which plays an important role in epithelial to mesenchymal transition, as shown in vitro in breast cancer cell lines and in vivo in an animal breast tumour model. Conclusions Our findings indicate that Wnt/β-catenin signaling plays an important role in breast cancer progression through p68 upregulation. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0496-5) contains supplementary material, which is available to authorized users.

As part of the Canadian Association of Paediatric Health Centres Taskforce on FASD Screening commitment to further pilot, validate and evaluate the multiple components of the Canadian FASD Screening Tool Kit, it was deemed necessary that recent developments and/or improvements in FASD screening were identified and considered. In 2008 a literature review of methods for screening for FASD was published until 2006 and identified five tools which met pre-set criteria. A review of all new papers was published from the period January 2006 until July 1, 2013. Out of 1392 papers, two new screening methods met the inclusion criteria: Clarren et al's new norms for palpebral fissure length by age in Canada; and Breiner et al's extension of the Neurobehavioral Screening Test (NST) to age 4 years. Further work is needed to validate these methods in other settings.

Despite recent advances in medicine, 30-40% of patients with breast cancer show recurrence underscoring the need for improved effective therapy. In this study, by in vitro screening we have selected a novel synthetic indole derivative 2,2'-diphenyl-3,3'-diindolylmethane (DPDIM) as a potential anti- breast cancer agent. DPDIM induces apoptosis both in vitro in breast cancer cells MCF7, MDA-MB 231 and MDA-MB 468 and in vivo in 7,12-dimethylbenz[α]anthracene (DMBA) induced Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show that DPDIM exerts apoptotic effect by negatively regulating the activity of EGFR and its downstream molecules like STAT3, AKT and ERK1/2 which are involved in the proliferation and survival of these cancer cells. In silico predictions also suggest that DPDIM may bind to EGFR at its ATP binding site. DPDIM furthermore inhibits EGF induced increased cell viability. We have also shown decreased expression of pro-survival factor Bcl-XL as well as increase in the level of pro-apoptotic proteins like Bax, Bad, Bim in DPDIM treated cells in vitro and in vivo. Our results further indicate that the DPDIM induced apoptosis is mediated through mitochondrial apoptotic pathway involving the caspase-cascade. To the best of our knowledge this is the first report of DPDIM for its anticancer activity. Altogether this report suggests that DPDIM could be an effective therapeutic agent for breast cancer.

The National Taskforce for the development of screening tools for FASD has identified maternal drinking as a critical area that should be screened. We describe the steps of development and implementation of a knowledge translation program for health care providers. The slide presentation is attached in English and French to allow its maximal use.In 2010, the National Taskforce for the development of screening tools for FASD identified maternal drinking as a critical area that should be screened. The systematic review and associated recommendations have been published and were included in the toolkit developed by the Canadian Association of Paediatric Health Centres with funding support from the Public Health Agency of Canada. Effective inquiry of maternal drinking can be conducted at three levels: Primary level, as part of practice-based screening; Level 2 use of structured questionnaires; and Level 3 laboratory-based screening.It was acknowledged that most physicians do not ask women of reproductive age questions regarding their drinking habits, and the Taskforce was seriously concerned that even an effective guide may not change practice at the primary level. To that end, the Taskforce developed a three phase Knowledge Translation plan, to ensure that the educational program developed will be optimally effective for Canadian healthcare providers.

Background Given the known link between vancomycin-resistant Enterococcus faecalis (VREF) and vancomycin-resistant Staphylococcus aureus (VRSA), the recent increase in prevalence of VREF in southeast Michigan has raised concerns about the presence of a large "community" reservoir of VREF. Efforts to control its spread face some important challenges. Methods Patients with clinical isolates of community-onset (CO) VREF (cases) were compared with matched uninfected controls (study 1) and patients with hospital-onset (HO) VREF (study 2). Here, CO was defined as a hospital stay of ≤2 days before VRE isolation. Results Independent predictors for the isolation of CO-VREF compared with uninfected controls were nonhome residence; chronic skin ulcers; previous invasive procedures/surgery; exposure to cephalosporin, penicillin, and/or vancomycin; immunosuppressive status; and the presence of indwelling devices. Independent predictors for isolation of CO-VREF compared with HO-VREF included no stay in an intensive care unit in the previous 3 months and recent hospitalization. VREF isolation from wounds and aminoglycoside exposure were inversely associated with isolation of CO-VREF. Conclusions Health care–related exposures and antimicrobial exposures are risk factors for the isolation of CO-VREF. Regional infection control practices are imperative in controlling CO-VREF, in addition to the emergence and spread of VRSA.

The decomposition of leaf litter of four selected dominant tree species, Vatica lanceaefolia, Artocarpus chaplasha, Lagerstroemia speciosa and Magnolia hookeri was studied during July 2011-June 2012 in a semievergreen forest of Assam, North East India. The weight loss pattern and concentration of N, P and K were evaluated. The annual decomposition constant (k) ranged from 3.23 to 7.8 year -1 and was positively correlated with rainfall, soil temperature, soil moisture content and total N. Litter quality and initial chemistry affected the rate of decomposition. L. speciosa having highest initial N, decomposed at a relatively faster rate. Rapid weight loss was observed during the monsoon period. The present findings indicate that rapid nutrient cycling is enhanced by fairly high decay rates of the dominant tree species maintaining proper nutrient cycling in this tropical semi-evergreen forest ecosystem.

Background. The objective was to determine whether relationships exist between the methylene-tetrahydrofolate reductase (MTHFR) polymorphisms and risk of colorectal cancer (CRC) and examine whether the risk is modified by level of folate intake.Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012 using the terms “folic acid,” “folate,” “colorectal cancer,” “methylenetetrahydrofolate reductase,” “MTHFR.” Observational studies were included which (1) assessed the risk of CRC for each polymorphism and/or (2) had defined levels of folate intake for each polymorphism and assessed the risk of CRC.Results. From 910 references, 67 studies met our criteria; hand searching yielded 10 studies. The summary risk estimate comparing the677CT versus CC genotype was 1.02 (95% CI 0.95–1.10) and for677TT versus CC was 0.88 (95% CI 0.80–0.96) both with heterogeneity. The summary risk estimates for A1298C polymorphisms suggested no reduced risk. The summary risk estimate for high versus low total folate for the677CC genotype was 0.70 (95% CI 0.56–0.89) and the677TT genotype 0.63 (95% CI 0.41–0.97).Conclusion. These results suggest that the677TT genotype is associated with a reduced risk of developing CRC, under conditions of high total folate intake, and this associated risk remains reduced for bothMTHFR 677CC and TT genotypes.

Wnt/β-catenin and EGFR pathways are important in cancer development and often aberrantly activated in human cancer. However, it is very important to understand the mechanism responsible for this activation and the relation between them. Here, we report the mechanism of EGFR expression by transcriptionally active β-catenin in GSK3β-inactivated prostate cancer cells that eventually leads to its enhanced proliferation and survival. Expressions of β-catenin and EGFR are elevated in various cancers specifically in prostate cancer cells, DU145. When GSK3β is inactivated in these cells, β-catenin gets stabilized, phosphorylated at Ser-552 by protein kinase A, accumulates in the nucleus, and regulates the expression of its target genes that include EGFR. Chromatin immunoprecipitation (ChIP) and promoter analysis revealed that the EGFR promoter gets occupied by transcriptionally active β-catenin when elevated in GSK3β-inactivated cells. This phenomenon not only leads to increased expression of EGFR but also initiates the activation of its downstream molecules such as ERK1/2 and Stat3, ultimately resulting in up-regulation of multiple genes involved in cell proliferation and survival.

OBJECTIVE: Because there are no studies available on the safety of venlafaxine during pregnancy, the authors’ goal in this study was to determine whether venlafaxine increases the risk for major malformations. METHOD: Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. CONCLUSIONS: These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%–3%.

Introduction : Folic acid fortification and supplementation to prevent neural tube defects has led to concerns regarding increased risk of colorectal cancer. The results of existing studies have been inconclusive. The purpose was to examine the relationship between level of folate intake and the incidence of colorectal cancer. Methods : A systematic review and meta analysis were conducted. MEDLINE, Embase, and SCOPUS were searched from inception to October 2009 with the following search terms "folic acid," "folate", "colorectal cancer," "colon neoplasms," rectal neoplasms." Observational studies in adult populations were included that defined levels of folate intake and incidence of colorectal cancer. Result : Out of 6427 references, 27 studies met our inclusion criteria. The summary risk estimate for case control studies comparing high versus low total folate intake was 0.85 (CI 95% 0.74–0.99) with no significant heterogeneity among studies. Similarly, for cohort studies, the resulting summary risk estimate for high versus low dietary folate intake was 0.92 (CI 95% 0.81–1.05) with no significant heterogeneity. However, defining what represents a higher intake of folic acid is difficult as there is variability in the upper limit of folic acid intake used in the studies. Discussion : These results suggest that higher folate intake levels offer a reduction in one of the perceived risks associated with developing colorectal cancer. These data can serve to help reassure women planning a pregnancy to increase folic intake during the preconception period to levels sufficient to prevent neural tube defects.