The NDR/LATS protein kinases in immunology and cancer biology

Publication date: Available online 1 June 2017
Source:Seminars in Cancer Biology
Author(s): Ahmad A.D. Sharif, Alexander Hergovich
The NDR (nuclear Dbf2-related)/LATS (large tumour suppressor) family of kinases represents a subclass of the AGC (protein kinase A (PKA)/PKG/PKC-like) group of serine/threonine protein kinases. Members of the NDR/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. In particular, the central involvement of NDR/LATS as YAP/TAZ kinases in the Hippo tissue growth control pathway has gained much interest. In this review, we summarize the roles of mammalian NDR1/2 (aka STK38/STK38L) and LATS1/2 in immunity and cancer biology. We also discuss the activation mechanisms of NDR/LATS involving Ste20-like kinases and the MOB1 signal transducer, followed by an overview of NDR/LATS knockout mouse models. We further review the mutation and expression status of NDR/LATS in human cancers and their possible predictive and/or prognostic value in cancer treatment.



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Robotic Pancreatoduodenectomy Biotissue Curriculum has Validity and Improves Technical Performance for Surgical Oncology Fellows

Publication date: Available online 1 June 2017
Source:Journal of Surgical Education
Author(s): Vernissia Tam, Mazen Zenati, Stephanie Novak, Yong Chen, Amer H. Zureikat, Herbert J. Zeh, Melissa E. Hogg
ObjectiveObtaining the proficiency on the robotic platform necessary to safely perform a robotic pancreatoduodenectomy is particularly challenging. We hypothesize that by instituting a proficiency-based robotic training curriculum we can enhance novice surgeons' skills outside of the operating room, leading to a shorter learning curve.DesignA biotissue curriculum was designed consisting of sewing artificial organs to simulate a hepaticojejunostomy (HJ), gastrojejunostomy (GJ), and pancreaticojejunostomy (PJ). Three master robotic surgeons performed each biotissue anastomosis to assess validity. Using video review, trainee performance on biotissue drills was evaluated for time, errors and objective structured assessment of technical skills (OSATS) by 2 blinded graders.SettingThis study is conducted at the University of Pittsburgh Medical Center (Pittsburgh, PA), a tertiary care academic teaching hospital.ParticipantsIn total, 14 surgical oncology fellows completed the biotissue curriculum.ResultsFourteen fellows performed 196 anastomotic drills during the first year: 66 (HJ), 64 (GJ), and 66 (PJ). The fellows' performances were analyzed as a group by attempt. The attendings' first attempt outperformed the fellows' first attempt in all metrics for every drill (all p < 0.05). More than 5 analyzed attempts of the HJ, there was improvement in time, errors, and OSATS (all p < 0.01); however, no metric reached attending performance. For the GJ, time, errors, and OSATS all improved more than 5 attempts (all p < 0.01), whereas only errors and OSATS reached proficiency. For the PJ, errors and OSATS both improved over attempts (p < 0.01) and reached proficiency; however, time did not statistically improve nor reach proficiency. The graders scoring correlated for errors and OSATS (p < 0.0001).ConclusionA pancreatoduodenectomy biotissue curriculum has face and construct validity. The curriculum is feasible and improves errors and technical performance. Time is the most difficult technical parameter to improve. This curriculum is a valid tool for teaching robotic pancreatoduodenectomies with established milestones for reaching optimum performance.



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Clinical Skills Passport: A Method to Increase Participation in Clinical Skills by Medical Students During a Surgery Clerkship

Publication date: Available online 1 June 2017
Source:Journal of Surgical Education
Author(s): Thomas E. Read
ObjectiveTo prospectively evaluate the effect of introducing a clinical skills "passport" on medical students' reporting of their experience with basic clinical skills.DesignA prospective longitudinal intervention study was conducted. Medical students were administered a questionnaire at the conclusion of their 12-week surgery clerkship regarding their experience with 15 clinical skills, inquiring whether they had "learned on surgery clerkship", "learned before surgery clerkship", or "not learned". Preintervention baseline data were obtained for 2 consecutive academic years (n = 213 students). In the third year, students (n = 124) were given a clinical skills passport to document performance of 8 of the 15 skills under the supervision of a surgical resident or faculty member. After excluding from analysis those students who learned a skill before their surgery clerkship, the fraction of students who reported learning clinical skills during their surgery clerkship before and after the introduction of the clinical skills passport was compared using Fisher exact test and chi-squared test, where appropriate (p ≤ 0.003 was considered significant; Bonferroni correction for multiple comparisons).SettingWashington University School of Medicine.ParticipantsA total of 337 medical students completing the junior surgery clerkship over a 3-year period were included in the study.ResultsAll 337 students completed a survey. Considering each skill individually, survey response rate was 5045/5055 (99.8%). Combining all responses for all skills, the fraction of students reporting that skills were learned on the surgery clerkship increased after the introduction of the clinical skills passport (1498/1938 [77%] preintervention vs. 974/1109 [88%] postintervention, p < 0.0001, chi square). After the introduction of the clinical skills passport, the fraction of students reporting that a skill was "learned on surgery clerkship" significantly increased for the 8 skills listed on the passport (1026/1699 [83%] preintervention vs. 685/714 [96%] postintervention, p < 0.0001, chi square), but did not increase for the 7 skills not listed on the passport (472/695 [68%] preintervention vs. 289/395 [73%] postintervention, p = 0.08, chi square). Considering each skill individually, after the introduction of the clinical skills passport, the fraction of students reporting that a skill was "learned on surgery clerkship" significantly increased for 4/15 skills (all listed on the clinical passport) and decreased for 0/15 skills (p < 0.003, Fisher exact test, 2 tailed).ConclusionsInstitution of a clinical skills passport system during a surgery clerkship increased medical student reporting of their performance of basic clinical skills.



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Family Home Food Environment and Nutrition-Related Parent and Child Personal and Behavioral Outcomes of the Healthy Home Offerings via the Mealtime Environment (HOME) Plus Program: A Randomized Controlled Trial

Publication date: Available online 1 June 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Jayne A. Fulkerson, Sarah Friend, Melissa Horning, Colleen Flattum, Michelle Draxten, Dianne Neumark-Sztainer, Olga Gurvich, Ann Garwick, Mary Story, Martha Y. Kubik
BackgroundResearch has demonstrated a significant positive association between frequent family meals and children's dietary intake; however, the promotion of healthful family meals has not been rigorously tested for key food environment and nutrition-related behavioral outcomes in a randomized trial.ObjectiveTo describe family home food environment and nutrition-related parent and child personal and behavioral outcomes of the Healthy Home Offerings via the Mealtime Environment Plus program, the first rigorously tested family meals intervention targeting childhood obesity prevention.DesignRandomized controlled trial. Baseline, postintervention (12 months, 93% retention), and follow-up (21 months, 89% retention) data (surveys and dietary recalls) were collected.Participants/settingChildren aged 8 to 12 years (N=160) and their parents were randomized to intervention (n=81) or control (n=79) groups.InterventionThe intervention included five parent goal-setting calls and 10 monthly sessions delivered to families in community settings that focused on experiential nutrition activities and education, meal planning, cooking skill development, and reducing screen time.Main outcome measuresFamily home food environment outcomes and nutrition-related child and parent personal and behavioral outcomes.Statistical analyses performedAnalyses used generalized linear mixed models. Primary comparisons were contrasts between intervention and control groups at postintervention and follow-up, with adjustments for child age and parent education.ResultsCompared with control parents, intervention parents showed greater improvement over time in scores of self-efficacy for identifying appropriate portion sizes, with significant differences in adjusted means at both post-intervention (P=0.002) and follow-up (P=0.01). Intervention children were less likely to consume at least one sugar-sweetened beverage daily at post-intervention than control children (P=0.04).ConclusionsThe Healthy Home Offerings via the Mealtime Environment Plus program involved the entire family and targeted personal, behavioral, and environment factors important for healthful changes in the home food environment and children's dietary intake. The intervention improved two nutrition-related behaviors and this may inform the design of future family meal interventions.



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Development of a Spanish Food Exchange List: Application of Statistical Criteria to a Rationale Procedure

Publication date: Available online 2 June 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Iva Marques-Lopes, Susana Menal-Puey, J. Alfredo Martínez, Giuseppe Russolillo




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2015 Evidence Analysis Library Evidence-Based Nutrition Practice Guideline for the Management of Hypertension in Adults

Publication date: Available online 1 June 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Shannon L. Lennon, Diane M. DellaValle, Susan G. Rodder, Melissa Prest, Rachel C. Sinley, M. Katherine Hoy, Constantina Papoutsakis
Hypertension (HTN) or high blood pressure (BP) is among the most prevalent forms of cardiovascular disease and occurs in approximately one of every three adults in the United States. The purpose of this Evidence Analysis Library (EAL) guideline is to provide an evidence-based summary of nutrition therapy for the management of HTN in adults aged 18 years or older. Implementation of this guideline aims to promote evidence-based practice decisions by registered dietitian nutritionists (RDNs), and other collaborating health professionals to decrease or manage HTN in adults while enhancing patient quality of life and taking into account individual preferences. The systematic review and guideline development methodology of the Academy of Nutrition and Dietetics were applied. A total of 70 research studies were included, analyzed, and rated for quality by trained evidence analysts (literature review dates ranged between 2004 and 2015). Evaluation and synthesis of related evidence resulted in the development of nine recommendations. To reduce BP in adults with HTN, there is strong evidence to recommend provision of medical nutrition therapy by an RDN, adoption of the Dietary Approaches to Stop Hypertension dietary pattern, calcium supplementation, physical activity as a component of a healthy lifestyle, reduction in dietary sodium intake, and reduction of alcohol consumption in heavy drinkers. Increased intake of dietary potassium and calcium as well as supplementation with potassium and magnesium for lowering BP are also recommended (fair evidence). Finally, recommendations related to lowering BP were formulated on vitamin D, magnesium, and the putative role of alcohol consumption in moderate drinkers (weak evidence). In conclusion, the present evidence-based nutrition practice guideline describes the most current recommendations on the dietary management of HTN in adults intended to support the practice of RDNs and other health professionals.



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Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women’s cancers

Abstract

Purpose

Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance.

Methods

To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters.

Results

Clearance (6.8 L/h) and volume (33 L) estimates were comparable with literature. The only significant covariate was the presence of carboplatin on olaparib clearance, consistent with published noncompartmental PK and in vitro data.

Conclusions

Simulations predicted lower steady-state peak/trough olaparib exposure through 24–36 h post carboplatin pre-treatment, but this effect was lost by day 2 and thus no dose adjustment is recommended.

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Comprehensive Mapping of HIV-1 Escape from a Broadly Neutralizing Antibody

Publication date: Available online 1 June 2017
Source:Cell Host & Microbe
Author(s): Adam S. Dingens, Hugh K. Haddox, Julie Overbaugh, Jesse D. Bloom
Precisely defining how viral mutations affect HIV's sensitivity to antibodies is vital to develop and evaluate vaccines and antibody immunotherapeutics. Despite great effort, a full map of escape mutants has not been delineated for an anti-HIV antibody. We describe a massively parallel experimental approach to quantify how all single amino acid mutations to HIV Envelope (Env) affect neutralizing antibody sensitivity in the context of replication-competent virus. We apply this approach to PGT151, a broadly neutralizing antibody recognizing a combination of Env residues and glycans. We confirm sites previously defined by structural and functional studies and reveal additional sites of escape, such as positively charged mutations in the antibody-Env interface. Evaluating the effect of each amino acid at each site lends insight into biochemical mechanisms of escape throughout the epitope, highlighting roles for charge-charge repulsions. Thus, comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization.

Graphical abstract

Teaser

Dingens et al. developed a massively parallel approach to quantify how all mutations to HIV Env affect antibody neutralization in the context of replication-competent virus. They applied this approach to the antibody PGT151, validated the results with neutralization assays, and explored the biochemical basis of HIV escape from this antibody.


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Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages

Publication date: Available online 1 June 2017
Source:Cell Host & Microbe
Author(s): Ching-On Wong, Steven Gregory, Hongxiang Hu, Yufang Chao, Victoria E. Sepúlveda, Yuchun He, David Li-Kroeger, William E. Goldman, Hugo J. Bellen, Kartik Venkatachalam
Clearance of bacteria by macrophages involves internalization of the microorganisms into phagosomes, which are then delivered to endolysosomes for enzymatic degradation. These spatiotemporally segregated processes are not known to be functionally coupled. Here, we show that lysosomal degradation of bacteria sustains phagocytic uptake. In Drosophila and mammalian macrophages, lysosomal dysfunction due to loss of the endolysosomal Cl⁻ transporter ClC-b/CLCN7 delayed degradation of internalized bacteria. Unexpectedly, defective lysosomal degradation of bacteria also attenuated further phagocytosis, resulting in elevated bacterial load. Exogenous application of bacterial peptidoglycans restored phagocytic uptake in the lysosomal degradation-defective mutants via a pathway requiring cytosolic pattern recognition receptors and NF-κB. Mammalian macrophages that are unable to degrade internalized bacteria also exhibit compromised NF-κB activation. Our findings reveal a role for phagolysosomal degradation in activating an evolutionarily conserved signaling cascade, which ensures that continuous uptake of bacteria is preceded by lysosomal degradation of microbes.

Graphical abstract

Teaser

Macrophages clear bacteria by phagosomal internalization and subsequent lysosomal degradation of the microbes. Wong et al. find that defective lysosomal degradation attenuates further phagocytosis, resulting in elevated bacterial load. Cytosolic pattern recognition receptors and NF-κB signal to couple phagolysosomal degradation to sustained phagocytic bacterial clearance.


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Gene expression profiles in mouse cumulus cells derived from in vitro matured oocytes with and without blastocyst formation

Publication date: Available online 2 June 2017
Source:Gene Expression Patterns
Author(s): Yixin Xu, Tuanping Zhou, Li Shao, Zhang Bei, Kailu Liu, Chao Gao, Li Gao, Jiayin Liu, Yugui Cui, Ri-Cheng Chian
Cumulus cells (CCs) are considered as an important source to predict oocyte quality. Despite numerous candidate genes in CCs have been identified for embryonic developmental competence, the results are inconsistent. The next generation RNA-sequencing was used to investigate the transcriptomic differences in CCs from in vitro matured oocytes did or did not develop to blastocyst stage following in vitro fertilization (IVF). In our study, the corresponding mouse oocytes were traced using a single-cell tracking system, and CCs were pooled into groups based on the embryonic developmental outcomes. In vivo matured oocytes with blastocyst development were set as a reference group. The transcriptomic differences in mouse CCs from in vitro maturated oocytes with or without blastocyst formation were tested by RNA-sequencing. Real-time PCR was used to verify the expression levels of those candidate genes. A total of 103 transcripts were significantly up-regulated, and 97 down-regulated, in the CCs with the oocytes developed to blastocyst stage. The bioinformatics study showed that those genes were involved in tube morphogenesis, cell-cell signaling and cell projection formation. Nine genes were selected from the most significantly changed transcripts after comparison with the reference group: Arrb1, Atp2c1, Cdh5, Cntnap1, Mkln1, Lgr4, Rhobtb1, Smc2 and Six2, as the candidate target genes. They were associated with the regulation of G-protein coupled receptors, Wnt and MAPK signaling, actin filaments and cell adhesion. Real-time PCR verified the up-regulation of all 9 genes, and significantly increased of Rhobtb1, Mkln1, Smc2, Arrb1, Atp2c1, Cdh5 and Lgr4. Based on RNA-sequencing, we found the changes in gene transcription of mouse CCs that were critical for the communication between CCs and oocytes. The results could provide novel insights on non-invasively predicting the oocyte quality and improving developmental competence.



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SERPINB2 is regulated by dynamic interactions with pause-release proteins and enhancer RNAs

Publication date: August 2017
Source:Molecular Immunology, Volume 88
Author(s): Lihua Shii, Li Song, Kelly Maurer, Zhe Zhang, Kathleen E. Sullivan
The SERPINB2 gene is strongly upregulated in inflammatory states. In monocytes, it can constitute up to 1% of total cellular protein. It functions in protection from proteotoxic stress and plays a role in angioedema. The purpose of this study was to define the roles of enhancer RNAs embedded in the SERPIN gene complex. We found that the upstream enhancer RNAs upregulated SERPINB2 and the enhancer RNAs were expressed prior to those of SERPINB2 mRNA. Studies of the SERPINB2 promoter demonstrated the presence of an RNA polymerase II pause-inducing protein, NELF. Stimulation with LPS led to recruitment of the pause-releasing kinase P-TEFb and departure of the pause-inducing protein NELF. RNA immunoprecipitation revealed that NELF and the CDK9 component of P-TEFb bound to the enhancer RNAs after stimulation with distinct kinetics. Knock-down of the enhancer RNAs compromised stimulus induction of promoter and enhancer chromatin changes. Conversely, over-expression was associated with enhanced recruitment of c-JUN and increased expression of SERPINB2 mRNA expression. This study is the first to associate enhancer RNAs with SERPINB2 and is the first demonstration of acquisition of NELF binding by enhancer RNAs on chromatin.

Graphical abstract

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No prolongation of skin allograft survival by immunoproteasome inhibition in mice

Publication date: August 2017
Source:Molecular Immunology, Volume 88
Author(s): Sarah Mundt, Michael Basler, Birgit Sawitzki, Marcus Groettrup
The immunoproteasome, a distinct class of proteasomes, which is inducible under inflammatory conditions and constitutively expressed in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Moreover, inhibition of the immunoproteasome subunit LMP7 ameliorates clinical symptoms of autoimmune diseases in vivo and was shown to suppress the development of T helper cell (Th) 1 and Th17 cells and to promote regulatory T-cell (Treg) generation independently of its function in antigen processing. Since Th1 and Th17 cells are detrimental and Treg cells are critical for transplant acceptance, we investigated the influence of the LMP7-selective inhibitor ONX 0914 in a mixed lymphocyte reaction (MLR) in vitro as well as on allograft rejection in a MHC-disparate (C57BL/6 to BALB/c) and a multiple minor histocompatibility antigen (miHA)-disparate (B10.Br to C3H) model of skin transplantation in vivo. Although we observed reduced allo-specific IL-17 production of T cells in vitro, we found that selective inhibition of LMP7 had neither an influence on allograft survival in an MHC-mismatch model nor in a multiple minor mismatch skin transplantation model. We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation.



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Cyr61/CCN1 induces CCL20 production by keratinocyte via activating p38 and JNK/AP-1 pathway in psoriasis

Publication date: Available online 1 June 2017
Source:Journal of Dermatological Science
Author(s): Huidan Li, Haichuan Li, Rongfen Huo, Pinru Wu, Zhengyu Shen, Hui Xu, Baihua Shen, Ningli Li
BackgroundPsoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood.ObjectiveIn this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte.Methodsand results: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion. Furthermore, in vivo, blocking or knockdown CCN1 expression ameliorated skin inflammation and reduced the expression of CCL20 in both imiquimod and IL-23-induced psoriasis-like mouse models, which indicated that CCN1 might be involved in the regulation of CCL20 production in psoriasis. Next, in vitro, we stimulated primary normal human epidermal keratinocyte (NHEK) with exogenous protein CCN1 and found that CCN1 directly upregulated CCL20 production independent of TNF-α, IL-22 and IL-17 pathway. Lastly, the signaling pathway study showed that CCN1 enhanced the binding of AP-1 to the CCL20 promoter via crosstalk with p38 and JNK.ConclusionsOur study demonstrates that CCN1 stimulates CCL20 production in vitro and in vivo, and thus supports the notion that overexpressed CCN1 in hyperproliferating keratinocyte is functionally involved in the recruitment of inflammatory cells to skin lesions affected by psoriasis.



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Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online

The online platform for Taylor & Francis Online content New for Atmospheric and Oceanic Science Letters and online now on Taylor & Francis Online: Original Articles Uncertainty in hottest years ranking: analysis of Tibetan Plateau surface air temperature | Wei HUA, Kai-Qin YANG & Guang-Zhou FAN Pages: 1-5 | DOI: 10.1080/16742834.2017.1330646 Two anomalous convective systems in the tropical western Pacific and their influences on the East Asian summer monsoon | Feng XUE, Xiao DONG & Ren-Ping LIN Pages: 1-6 | DOI: 10.1080/16742834.2017.1328969 Read selected content from the Journal of Structural Integrity and Maintenance for free! http://ift.tt/2coiFom To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Association between biochemical hyperandrogenism parameters and Ferriman–Gallwey score in patients with polycystic ovary syndrome: a systematic review and meta-regression analysis

Abstract

Background and Objective

A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism (HA). This study aimed to evaluate the association between biochemical hyperandrogenism parameters (BHPs) and Ferriman–Gallwey (FG) score in patients with polycystic ovary syndrome (PCOS).

Methods

We searched PubMed, Scopus, Google Scholar, ScienceDirect and Web of Sciences databases (2000 to 2015) to identify studies investigating clinical and biochemical parameters of HA in PCOS patients. In this meta-analysis, both fixed and random effect models were applied to estimate pooled effect size. To assess the relationships between BHPs and FG score, meta-regression analysis was used.

Results

Fifty-five study groups with a total of 6593 PCOS patients were analyzed. Meta-regression analysis of pooled data from all eligible studies showed significant positive relationships of FG score with androstenedione (A4) (p= 0.034) and dehydroepiandrosterone sulfate (DHEAS) (p=0.012), whereas it showed no association with total testosterone (tT), free testosterone (fT), sex hormone bonding globulin (SHBG) and free androgen index (FAI). The results did not change after adjusting for quality assessment or method of assay. Nor did the associations between A4 and FG score remain after adjusting for age and BMI, diagnostic criteria for PCOS and study design or the association between DHEAS and FG score remain after adjusting for ethnicity.

Conclusion

This meta-analysis confirmed the associations of some BHPs, including A4 and DHEAS with FG score, indicating that measurement of these parameters can be useful for managing PCOS patients with hirsutism.

This article is protected by copyright. All rights reserved.

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Mortality rates are lower in siad, than in hypervolaemic or hypovolaemic hyponatraemia; results of a prospective observational study

Abstract

Objective

Hyponatremia is associated with increased mortality, but the mortality associated specifically with SIAD is not known. We hypothesised that mortality in SIAD was elevated, but that it was less than in hypervolemic(HEN) or hypovolemic(HON) hyponatremia.

Design

Mortality rates are presented as risk ratios(RR),with 95% confidence intervals (CI), and compared to normonatremic controls(NN).

Methods

Prospective, single center, non-interventional study of all patients with hyponatremia(≤ 130 mmol/l) admitted to hospital.

Results

1323 admissions with hyponatremia were prospectively evaluated and 1136 contemporaneous NN controls. 431(32.6%) hyponatraemic patients had HON, 573(43.3%) had SIAD and 275(20.8%) patients had HEN. In patient mortality was higher in hyponatremia than NN (9.1% v 3.3%, p<0.0001). The RRs for in-hospital mortality compared to NN were: SIAD, 1.76 (95% CI 1.08-2.8, p=0.02), HON 2.77 (95% CI 1.8-4.3, p<0.0001) and HEN, 4.9 (95% CI 3.2-7.4, p<0.0001). The mortality rate was higher in HEN (RR 2.85; 95% CI 1.86-4.37, p<0.0001) and in HON, (RR 1.6; 95% CI 1.04-2.52; p=0.03), when compared to SIAD. The Charlson Comorbidity Index was lower in SIAD than in eunatraemic patients(p<0.0001). 9/121(7.4%) patients died with plasma sodium <125 mmol/l and 4(3.3%) with plasma sodium <120 mmol/l. However, 69/121(57%) patients died with a plasma sodium above 133 mmol/l.

Conclusions

We confirmed higher all-cause mortality in hyponatremia than in NN. Mortality was higher in SIAD than in normonatraemia, and was not explained on the basis of co-morbidities. Mortality was higher in HON and HEN than in SIAD. Mortality rates reported for all-cause hyponatremia in the medical literature are not applicable to SIAD.

This article is protected by copyright. All rights reserved.

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Datasets on the genomic positions of the MLL1 morphemes, the ZFP57 binding site, and ZFBS-Morph overlaps in the build mm9 of the mouse genome

Publication date: August 2017
Source:Data in Brief, Volume 13
Author(s): Minou Bina, Phillip Wyss, Xiaohui C. Song
While MLL1 activates gene expression in most tissues, ZFP57 represses transcription. MLL1 selectively interacts with a group of nonmethylated DNA sequences known as the MLL1 morphemes. ZFP57 associates with a methylated hexamer (ZFBS), dispersed in the genomic DNA segments known as Imprinted Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs), to maintain allele-specific gene repression. We have identified a set of composite DNA elements (ZFBS-Morph overlaps) that provides the sequence context of ZFBS in the canonical ICRs/gDMRs. This report provides tables listing the nucleotide sequences of the MLL1 morphemes and ZFBS-Morph overlaps. The report also offers links to the data repository at Purdue University, for downloading the positions of the MLL1 morphemes, the ZFP57 binding site, and the ZFBS-Morph overlaps in the mouse genome.



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Bank blood shortage, transfusion containment and viscoelastic point-of-care coagulation testing in cardiac surgery

In January 2017, many Italian hospitals (including my own institution) were forced to reduce the number of major surgical operations because of a severe shortage of packed red blood cells (RBCs). Blood banks warned that donors with blood group O (both O+ and O–) were scarce, and imposed that units of RBCs of this group were to be reserved for non-postponable major surgeries. Subsequently, other blood groups were affected by the shortage. On January 12, 2017 the National Blood Center warned that about 2600 RBC units were lacking in nine Italian regions. This emergency, resulting from the combination of Christmas holidays and an outbreak of influenza, came to an end by the end of January.

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Hydrogen peroxide: more harm than good?

Editor—Hydrogen peroxide remains a frequently used agent in operating theatres despite its marginal benefits and potential for serious complications. We are writing to remind anaesthetists of the risks of hydrogen peroxide use and pose the question: does hydrogen peroxide cause more harm than good?

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More or less? The Goldilocks Principle as it applies to red cell transfusions

The quest for the optimal haemoglobin threshold (previously referred to as 'trigger') for red blood cell transfusion seems a never-ending journey. As if we are chasing a mirage, the closer we seem to think we get to the 'just right' haemoglobin level, the further it seems to move away. Applying the 'Goldilocks Principle' to transfusion of red cells, regardless of the population queried, appears to yield results that satisfy some investigators but leave many practitioners still wondering what is best for the patient.

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