Birth weight in relation to endometrial and breast cancer risks in Swedish women

An examination of birth weight in a Swedish cohort study of 38 566 women showed no significant association between birth weight and endometrial cancer, but supported a protective role for low birth weight for premenopausal breast cancer

Ownership-dependent mating tactics of minor males of the beetle Librodor japonicus (Nitidulidae) with intra-sexual dimorphism of mandibles

Intra-sexual dimorphism is found in the weapons of many male beetles. Different behavioral tactics to access females between major and minor males, which adopt fighting and alternative tactics, respectively, are thought to maintain the male dimorphism. In these species major males have enlarged weapons that they use in fights with rival males. Minor males also have small weapons in some of these species, and it is unclear why these males possess weapons. We examined the hypothesis that minor males might adopt a fighting tactic when their status was relatively high in comparison with that of other males (e.g., ownership of a territory). We observed the behavioral tactics of major and minor males of the beetle Librodor japonicus, whose males have a dimorphism of their mandibles. Major males fought for resources, whereas minor males adopted two status-dependent tactics, fighting and sneaking, to access females, depending on their ownership of a sap site. We suggest that ownership status-dependent mating tactics in minor males may maintain the intra-sexual dimorphism in this beetle.</p

Intestinal ischemia after cardiac surgery: analysis of a large registry.

Intestinal ischemia after cardiac surgery is a rare but severe complication with a high mortality. Early surgery can be lifesaving. The aim was to analyze the incidence, outcome, and risk factors for these patients

The Periotest Method: Implant-Supported Framework Precision of Fit Evaluation

: In this study, the Periotest instrument was used to measure the precision of fit between cast high noble-metal frameworks and the supporting implants in a patient-simulation model. Three framework conditions and three implant-location variables were used to evaluate the rigidity of the assembly as measured by the Periotest method. The framework variables were (1) one-piece castings (OPC); (2) sectioned-soldered inaccurate castings (SSIC); and (3) sectioned-soldered accurate castings (SSAC). The implant-location variables were right anterior (RA), center (C), and left anterior (LA). Materials and Methods : The patient simulation model used consisted of three self-tapping BrÅnemark implants in a reasonable arch curvature in bovine bone. Three working casts were fabricated from the patient-simulation model using polyvinyl siloxane and tapered impression copings. From the working casts, three sets of three frameworks were fabricated as OPCs, SSICs, and SSACs using type 3 high noble alloy. The SSICs were fabricated with a quantitative misfit of 101.6 Μm at the facial surface, between the abutment-to-gold cylinder interface at the C implant location. Periotest value (PTV) measurements were made at the midfacial surface of the frameworks directly above each abutment-to-gold cylinder interface. Three measurements were made for each test condition. The data were analyzed to compare framework condition(s) and implant location(s) using ANOVA and Fisher's Protected Least Significant Difference Comparison Test. Results : The ANOVA showed that significant differences exist between the mean PTV data for framework condition and for implant location (p < .01). Significant differences were shown between the mean PTV data for the SSAC assemblies and the OPC and SSIC assemblies. The SSICs displayed a more positive (+) mean PTV than the OPCs. The OPC assemblies had a more positive mean PTV than the SSAC assemblies. The mean PTV data for the SSAC assemblies had a significantly different PTV (p < .01) than the other two framework condition assemblies. The OPC and the SSIC assemblies had PTVs that were not significantly different. The C implant location was significantly different from the RA and the LA implant locations (p < .01). The RA and the LA implant locations were not significantly different from each other. The C implant location always demonstrated the most positive mean PTV regardless of the framework condition being tested. Conclusions : The Periotest instrument quantified differences in the precision of fit between three framework conditions. The SSAC assemblies were significantly more rigid than the OPC and SSIC assemblies. The OPC and SSIC assemblies' mean PTVs were not significantly different. The mean PTVs for the C implant location and the RA and LA implant locations were significantly different (p < .01). The mean PTVs of the RA and LA implant locations were not significantly different. The implant-location PTVs followed the same rank order for all three framework conditions. The procedures used to fabricate a more precise fit between the framework and the supporting implants is influenced by the skill of the clinician and technician.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75096/1/j.1532-849X.1996.tb00298.x.pd

Longitudinal Evaluation of the Hypothalamic-Pituitary-Testicular Function in 8 Boys with Adrenal Hypoplasia Congenita (AHC) Due to NR0B1 Mutations

BACKGROUND:Boys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC) and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH) and primary defects in spermatogenesis. METHODS:We analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function. RESULTS:The first symptoms appeared in the neonatal period (n = 5) or between 6 months and 8.7 years (n = 3). Basal plasma adrenocorticotrophic hormone (ACTH) concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH) test (n = 2), and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein. CONCLUSIONS:The decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility

Computer-Based Interventions for Problematic Alcohol Use:a Review of Systematic Reviews

PURPOSE: The aim of this review is to provide an overview of knowledge and knowledge gaps in the field of computer-based alcohol interventions by (1) collating evidence on the effectiveness of computer-based alcohol interventions in different populations and (2) exploring the impact of four specified moderators of effectiveness: therapeutic orientation, length of intervention, guidance and trial engagement.  METHODS: A review of systematic reviews of randomized trials reporting on effectiveness of computer-based alcohol interventions published between 2005 and 2015.  RESULTS: Fourteen reviews met the inclusion criteria. Across the included reviews, it was generally reported that computer-based alcohol interventions were effective in reducing alcohol consumption, with mostly small effect sizes. There were indications that longer, multisession interventions are more effective than shorter or single session interventions. Evidence on the association between therapeutic orientation of an intervention, guidance or trial engagement and reductions in alcohol consumption is limited, as the number of reviews addressing these themes is low. None of the included reviews addressed the association between therapeutic orientation, length of intervention or guidance and trial engagement.  CONCLUSIONS: This review of systematic reviews highlights the mostly positive evidence supporting computer-based alcohol interventions as well as reveals a number of knowledge gaps that could guide future research in this field

Prospects and Bottlenecks of Reciprocal Partnerships Between the Private and Humanitarian Sectors in Cash Transfer Programming for Humanitarian Response

As an alternative to commodity-based programming (in-kind aid), Cash Transfer Programming is attracting both humanitarian organizations' and institutional donors' attention. Unlike in-kind aid, Cash Transfer Programming transfers purchasing power directly to beneficiaries in the form of currency or vouchers for them to obtain goods and/or services directly from the local market. In distributing currency to beneficiaries, the private sector, especially financial service providers, plays a prominent role, due to the humanitarian sector's limited relevant resources. The present work unveils challenges for the private and humanitarian sectors, which hinder implementing Cash Transfer Programming. Based on primary and secondary qualitative data, the paper presents the main characteristics and the mechanisms of Cash Transfer Programming to explore how the private sector is involved with Cash Transfer Programming. Then, this study presents bottlenecks of reciprocal relationships between financial service providers and humanitarian organizations in Cash Transfer Programming

EBV-Encoded LMP1 Upregulates Igκ 3′Enhancer Activity and Igκ Expression in Nasopharyngeal Cancer Cells by Activating the Ets-1 through ERKs Signaling

Accumulating evidence indicates that epithelial cancer cells, including nasopharyngeal carcinoma (NPC) cells, express immunoglobulins (Igs). We previously found that the expression of the kappa light chain protein in NPC cells can be upregulated by the EBV-encoded latent membrane protein 1 (LMP1). In the present study, we used NPC cell lines as models and found that LMP1-augmented kappa production corresponds with elevations in ERKs phosphorylation. PD98059 attenuates LMP1-induced ERKs phosphorylation resulting in decreased expression of the kappa light chain. ERK-specific small interfering RNA blunts LMP1-induced kappa light chain gene expression. Luciferase reporter assays demonstrate that immunoglobulin κ 3′ enhancer (3′Eκ) is active in Igκ-expressing NPC cells and LMP1 upregulates the activity of 3′Eκ in NPC cells. Moreover, mutation analysis of the PU binding site in 3′Eκ and inhibition of the MEK/ERKs pathway by PD98059 indicate that the PU site is functional and LMP1-enhanced 3′Eκ activity is partly regulated by this site. PD98059 treatment also leads to a concentration-dependent inhibition of LMP1-induced Ets-1 expression and phosphorylation, which corresponds with a dose-dependent attenuation of LMP1-induced ERK phosphorylation and kappa light chain expression. Suppression of endogenous Ets-1 by small interfering RNA is accompanied by a decrease of Ig kappa light chain expression. Gel shift assays using nuclear extracts of NPC cells indicate that the transcription factor Ets-1 is recruited by LMP1 to the PU motif within 3′Eκ in vitro. ChIP assays further demonstrate Ets-1 binding to the PU motif of 3′Eκ in cells. These results suggest that LMP1 upregulates 3′Eκ activity and kappa gene expression by activating the Ets-1 transcription factor through the ERKs signaling pathway. Our studies provide evidence for a novel regulatory mechanism of kappa expression, by which virus-encoded proteins activate the kappa 3′ enhancer through activating transcription factors in non-B epithelial cancer cells

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydroxysteroid oxidoreductase and 3α(β)-hydroxysteroid oxidoreductases in tumorigenic (MCF-7, MDA-MB-231, T-47D) and nontumorigenic (MCF-10A) human breast cancer cells

BACKGROUND: Recent observations indicate that human tumorous breast tissue metabolizes progesterone differently than nontumorous breast tissue. Specifically, 5α-reduced metabolites (5α-pregnanes, shown to stimulate cell proliferation and detachment) are produced at a significantly higher rate in tumorous tissue, indicating increased 5α-reductase (5αR) activity. Conversely, the activities of 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO enzymes appeared to be higher in normal tissues. The elevated conversion to 5α-pregnanes occurred regardless of estrogen (ER) or progesterone (PR) receptor levels. To gain insight into these differences, the activities and expression of these progesterone converting enzymes were investigated in a nontumorigenic cell line, MCF-10A (ER- and PR-negative), and the three tumorigenic cell lines, MDA-MB-231 (ER- and PR-negative), MCF-7 and T-47D (ER- and PR-positive). METHODS: For the enzyme activity studies, either whole cells were incubated with [(14)C]progesterone for 2, 4, 8, and 24 hours, or the microsomal/cytosolic fraction was incubated for 15–60 minutes with [(3)H]progesterone, and the metabolites were identified and quantified. Semi-quantitative RT-PCR was employed to determine the relative levels of expression of 5αR type1 (SRD5A1), 5αR type 2 (SRD5A2), 20α-HSO (AKR1C1), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 3β-HSO (HSD3B1/HSD3B2) in the four cell lines using 18S rRNA as an internal control. RESULTS: The relative 5α-reductase activity, when considered as a ratio of 5α-pregnanes/4-pregnenes, was 4.21 (± 0.49) for MCF-7 cells, 6.24 (± 1.14) for MDA-MB-231 cells, 4.62 (± 0.43) for T-47D cells and 0.65 (± 0.07) for MCF-10A cells, constituting approximately 6.5-fold, 9.6-fold and 7.1 fold higher conversion to 5α-pregnanes in the tumorigenic cells, respectively, than in the nontumorigenic MCF-10A cells. Conversely, the 20α-HSO and 3α-HSO activities were significantly higher (p < 0.001) in MCF-10A cells than in the other three cell types. In the MCF-10A cells, 20α-HSO activity was 8-14-fold higher and the 3α-HSO activity was 2.5-5.4-fold higher than in the other three cell types. The values of 5αR:20α-HSO ratios were 16.9 – 32.6-fold greater and the 5αR:3α-HSO ratios were 5.2 – 10.5-fold greater in MCF-7, MDA-MB-231 and T-47D cells than in MCF-10A cells. RT-PCR showed significantly higher expression of 5αR1 (p < 0.001), and lower expression of 20α-HSO (p < 0.001), 3α-HSO2 (p < 0.001), 3α-HSO3 (p < 0.001) in MCF-7, MDA-MB-231 and T-47D cells than in MCF-10A cells. CONCLUSION: The findings provide the first evidence that the 5αR activity (leading to the conversion of progesterone to the cancer promoting 5α-pregnanes) is significantly higher in the tumorigenic MCF-7, MDA-MB-231 and T-47D breast cell lines than in the nontumorigenic MCF-10A cell line. The higher 5αR activity coincides with significantly greater expression of 5αR1. On the other hand, the activities of 20α-HSO and 3α-HSO are higher in the MCF-10A cells than in MCF-7, MDA-MB-231 and T-47D cells; these differences in activity correlate with significantly higher expression of 20α-HSO, 3α-HSO2 and 3α-HSO3 in MCF-10A cells. Changes in progesterone metabolizing enzyme expression (resulting in enzyme activity changes) may be responsible for stimulating breast cancer by increased production of tumor-promoting 5α-pregnanes and decreased production of anti-cancer 20α – and 3α-4-pregnenes

K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca2+ release and the associated diastolic contraction during β-adrenergic stimulation in rat ventricular cardiomyocytes

K201 has previously been shown to reduce diastolic contractions in vivo during β-adrenergic stimulation and elevated extracellular calcium concentration ([Ca2+]o). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release and contractile events in isolated rat cardiomyocytes during β-adrenergic stimulation and elevated [Ca2+]o. Parallel experiments using confocal microscopy examined spontaneous diastolic Ca2+ release events at an enhanced spatiotemporal resolution. 1.0 μmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca2+]o significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulated free Ca2+ transient amplitude was significantly reduced, but stimulated cell shortening was not significantly altered. When intracellular buffering was taken into account, K201 led to an increase in action potential-induced SR Ca2+ release. Myofilament sensitivity to Ca2+ was not changed by K201. Confocal microscopy revealed diastolic events composed of multiple Ca2+ waves (2–3) originating at various points along the cardiomyocyte length during each diastolic period. 1.0 μmol/L K201 significantly reduced the (a) frequency of diastolic events and (b) initiation points/diastolic interval in the remaining diastolic events to 61% and 71% of control levels respectively. 1.0 μmol/L K201 can reduce the probability of spontaneous diastolic Ca2+ release and their associated contractions which may limit the propensity for the contractile dysfunction observed in vivo