Duration of CPR: How Long is Too Long? A Positive Outcome After 90 Minutes of CPR

INTRODUCTION: Survival and neurologic function following prolonged cardiopulmonary resuscitation (CPR) are often poor and currently there lacks a formal recommendation for the maximum duration of resuscitative efforts. However, there have been multiple case reports of positive neurological outcomes following prolonged CPR. This case presentation helps to support and encourage the continuation of CPR in the appropriate setting and with available resources including intra-arrest percutaneous intervention (PCI) and extracorporeal membrane oxygenation (ECMO). CONCLUSION: Prolonged CPR can result in favorable patient outcomes if done promptly and effectively, utilizing all available resources including intra-arrest PCI and ECMO

Scenario planning: An alternative approach to European Commission for combating antimicrobial resistance by 2050

Aim: Antimicrobial resistance (AMR) is one of the major health challenges of the future, but the concrete impact of counteracting measures is still unclear. To study possible outcomes within the European Union, a scenario analysis for the year 2050 was performed on the possible influence of the European Commission (EC). Methods: Scenario planning and development of strategies based on different scenarios. Results: Rational use of antimicrobials in animals and humans, surveillance and monitoring, new antimicrobial therapies, travel and globalization, exposure to the environment, and awareness were recognized as the main driving elements. Four Scenarios were developed: An efficient and impli-cated EC sorts out AMR; An implicated but unsuccessful EC withstands AMR; AMR is managed regardless of the EC disinterest; and A neutral and inefficient EC fails to manage AMR. Conclusion: All the strategies developed on the basis of the four scenarios probe for an increase in European Union's dedication to achieve positive outcomes. These include the development of effective legislation and international coordination. Acknowledgment: Peter Schröder-Bäck, Helmut Brand and Kiranjeet Kaur’s contribution is co-funded through a grant of the European Commission within the Erasmus+ programme (Project: Prevent it. Project reference: 598515-EPP-1-2018-1-IN-EPPKA2-CBHE-JP). Conflict of interests: None declared

Scenario planning: An alternative approach to European Commission for combating antimicrobial resistance by 2050

Aim: Antimicrobial resistance (AMR) is one of the major health challenges of the future, but the concrete impact of counteracting measures is still unclear. To study possible outcomes within the European Union, a scenario analysis for the year 2050 was performed on the possible influence of the European Commission (EC). Methods: Scenario planning and development of strategies based on different scenarios. Results: Rational use of antimicrobials in animals and humans, surveillance and monitoring, new antimicrobial therapies, travel and globalization, exposure to the environment, and awareness were recognized as the main driving elements. Four Scenarios were developed: An efficient and impli-cated EC sorts out AMR; An implicated but unsuccessful EC withstands AMR; AMR is managed regardless of the EC disinterest; and A neutral and inefficient EC fails to manage AMR. Conclusion: All the strategies developed on the basis of the four scenarios probe for an increase in European Union's dedication to achieve positive outcomes. These include the development of effective legislation and international coordination. Acknowledgment: Peter Schröder-Bäck, Helmut Brand and Kiranjeet Kaur’s contribution is co-funded through a grant of the European Commission within the Erasmus+ programme (Project: Prevent it. Project reference: 598515-EPP-1-2018-1-IN-EPPKA2-CBHE-JP). Conflict of interests: None declared

An integrated systems approach for understanding cellular responses to gamma radiation

Cellular response to stress entails complex mRNA and protein abundance changes, which translate into physiological adjustments to maintain homeostasis as well as to repair and minimize damage to cellular components. We have characterized the response of the halophilic archaeon Halobacterium salinarum NRC-1 to (60)Co ionizing gamma radiation in an effort to understand the correlation between genetic information processing and physiological change. The physiological response model we have constructed is based on integrated analysis of temporal changes in global mRNA and protein abundance along with protein–DNA interactions and evolutionarily conserved functional associations. This systems view reveals cooperation among several cellular processes including DNA repair, increased protein turnover, apparent shifts in metabolism to favor nucleotide biosynthesis and an overall effort to repair oxidative damage. Further, we demonstrate the importance of time dimension while correlating mRNA and protein levels and suggest that steady-state comparisons may be misleading while assessing dynamics of genetic information processing across transcription and translation

Converging endometrial and ovarian tumorigenesis in Lynch syndrome : Shared origin of synchronous carcinomas

AbstractObjective The diagnosis of carcinoma in both the uterus and the ovary simultaneously is not uncommon and raises the question of synchronous primaries vs. metastatic disease. Targeted sequencing of sporadic synchronous endometrial and ovarian carcinomas has shown that such tumors are clonally related and thus represent metastatic disease from one site to the other. Our purpose was to investigate whether or not the same applies to Lynch syndrome (LS), in which synchronous cancers of the gynecological tract are twice as frequent as in sporadic cases, reflecting inherited defects in DNA mismatch repair (MMR). Methods MMR gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nationwide registry. Endometrial (n = 35) and ovarian carcinomas (n = 23), including 13 synchronous carcinoma pairs, were collected as well as endometrial hyperplasias (n = 56) and normal endometria (n = 99) from a surveillance program over two decades. All samples were studied for MMR status, ARID1A and L1CAM protein expression and tumor suppressor gene promoter methylation, and synchronous carcinomas additionally for somatic mutation profiles of 578 cancer-relevant genes. Results Synchronous carcinomas were molecularly concordant in all cases. Prior or concurrent complex (but not simple) endometrial hyperplasias showed a high degree of concordance with endometrial or ovarian carcinoma as the endpoint lesion. Conclusions Our investigation suggests shared origins for synchronous endometrial and ovarian carcinomas in LS, in analogy to sporadic cases. The similar degrees of concordance between complex hyperplasias and endometrial vs. ovarian carcinoma highlight converging pathways for endometrial and ovarian tumorigenesis overall.Peer reviewe

Structure, function and mechanism of N-glycan processing enzymes : endo-α-1,2-mannanase and endo-α-1,2-mannosidase

While most glycosidases that act on N-linked glycans remove a single sugar residue at a time, endo-α-1,2-mannosidases and endo-α-1,2-mannanases of glycoside hydrolase family GH99 cut within a chain and remove two or more sugar residues. They are stereochemically retaining enzymes that use an enzymatic mechanism involving an epoxide intermediate. Human endo-α-1,2-mannosidase (MANEA) trims glucosylated mannose residues; the endomannosidase pathway provides a glucosidase-independent pathway for glycoprotein maturation. Cell-active MANEA inhibitors alter N-glycan processing and reduce infectivity of dengue virus, demonstrating that MANEA has potential as a host-directed antiviral target. Sequence-related enzymes from gut Bacteroides spp. exhibit endo-α-1,2-mannosidase activity and are a fruitful test bed for structure-guided inhibitor development. The genes encoding the Bacteroides spp. enzymes sit within polysaccharide utilization loci and are preferential endo-α-1,2-mannanases

Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue

Omomyc; Mass spectrometry; Protein therapeuticsOmomyc; Espectrometría de masas; Terapéutica de proteínasOmomyc; Espectrometria de masses; Terapèutica de proteïnesMYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.This research has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 872212 and from the Ministerio de Ciencia e Innovacion under grant no. RTC2019-007067-1

Does regulating the sale of high-strength beer and cider impact hospital admissions with decompensated alcohol-related liver disease: A retrospective cohort study

Objective ‘Sensible on Strength’ (SoS), a local public health initiative, is aimed at reducing high-strength beer and cider availability. The objective of this study was to assess its impact on local hospital admissions with alcohol-related liver disease (ALD) and on drinking behaviour. Design This was a retrospective cohort study in patients admitted with decompensated ALD, 3 years before and 3 years after the introduction of the SoS initiative. Hospital records of 143 index admissions with decompensated ALD were reviewed. Outcomes measures were the severity of liver disease on admission and mortality (inpatient and long-term), and change (if any) in alcohol drinking behaviour. Results Comparing patients admitted in both phases, there were no significant differences in liver prognostic scores, liver-related complications, length of stay and inpatient/long-term mortality (p>0.05). However, the SoS initiative was associated with a 33% move away from beer and cider consumption (36.3% vs 54.0%; p=0.034), but without a significant change in units of alcohol consumed. The Model for End-stage Liver Disease (MELD) score was the only independent predictor of inpatient mortality (odds ratio 1.25; p=0.025). Conclusion Despite having no apparent impact on the clinical spectrum of local ALD admissions, it is conceivable that longer follow-up is needed to determine the true impact of this initiative