Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells.

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

National Experiences from 30 Years of Provider-Mediated Cascade Testing in Lynch Syndrome Families-The Danish Model.

Cascade genetic testing and surveillance reduce morbidity and mortality in Lynch syndrome. However, barriers to conveying information about genetic disorders within families result in low uptake of genetic testing. Provider-mediated interventions may increase uptake but raise legal and ethical concerns.

Tralokinumab Effectively Disrupts the IL-13/IL-13Rα1/IL-4Rα Signaling Complex but Not the IL-13/IL-13Rα2 Complex.

Tralokinumab, a fully human mAb specifically targeting the IL-13 cytokine, has demonstrated clinical efficacy and safety in patients with moderate-to-severe atopic dermatitis. Tralokinumab binds IL-13 with high affinity, which prevents the interaction of IL-13 with IL-13Rα1 and subsequent signaling. Similarly, tralokinumab-bound IL-13 cannot bind to IL-13Rα2, a proposed decoy receptor that is reported to bind IL-13 with extraordinarily high affinity.

From expected to actual barriers and facilitators when implementing a new screening tool: A qualitative study applying the Theoretical Domains Framework.

Aim And Objectives: To identify determinants for using a new screening tool to identify older patients eligible for targeted nurse-led intervention, as perceived by healthcare professionals implementing the tool, and to examine how these perceptions changed over time.

Design: A cross-sectoral longitudinal qualitative study based on semi-structured interviews with healthcare professionals in a Danish hospital and two collaborating municipalities.

Methods: In three focus groups, seven single interviews and a workshop, we examined the healthcare professionals' perceptions of and attitudes towards the new screening tool before, during and after the implementation.

Take-Home Naloxone Kits: Attitudes and Likelihood-Of-Use Outcomes from a European Survey of Potential Overdose Witnesses.

Background: Injectable naloxone is already provided as take-home naloxone (THN), and new concentrated intranasal naloxone is now being introduced in Europe. Despite evidence of the effectiveness and cost-effectiveness of THN, little is known about the attitudes of key target populations: people who use opioids (PWUO), family/friends, and staff. We examined the acceptability of different naloxone devices (ampoule, prefilled syringe, and concentrated nasal spray) across 5 European countries.

The functional role of the autolysis loop in the regulation of factor X upon hemostatic response.

Background: The regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity.

Objectives: To functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX.

Methods: We introduced novel N-linked glycosylations on the surface-exposed loop spanning residues 143-150 (chymotrypsin numbering) of FX.

Surveillance life and the shaping of 'genetically at risk' chronicities in Denmark.

Today, in the field of hereditary colorectal cancer in Denmark, more than 40,000 identified healthy individuals with an increased risk of cancer are enrolled in a surveillance program aimed at preventing cancer from developing, with numbers still growing. What this group of healthy individuals has in common is lifelong regular interaction with a healthcare system that has traditionally been geared towards treating the acutely and chronically ill. In this article, we explore how people living with an inherited elevated risk of colorectal cancer orient themselves towards their families' and their own predispositions as well as the lifelong surveillance trajectories that they have embarked upon - what we call surveillance life.

"It is two worlds" cross-sectoral nurse collaboration related to care transitions: A qualitative study.

Aims And Objectives: To explore how the hospital and home care nurses talk about and experience cross-sectoral collaboration related to the transitional care of frail older patients.

Background: Effective communication and collaboration between nurses involved in care transition are crucial for a safe patient handover. Organisational systems to support cross-sectoral collaboration have been developed but do not always promote the intended dialogue and precise and useful exchange of information.

Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes.

Dissemination of information on a genetically increased risk should according to guidelines primarily be family-mediated. Incomplete and incorrect information spread has, however, been documented and implies missed possibilities for prevention. In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer.

Nurses' perception of how an e-message system influences cross-sectoral communication: A qualitative study.

Aim: To investigate hospital and home care nurses' experiences on how an e-message system influences cross-sectoral communication 2 years after introduction.

Background: Cross-sectoral communication is identified as the main barrier for high quality in transitional care. An e-message system was introduced to ensure dialogue and precise and useful information exchange.

TFPIα interacts with FVa and FXa to inhibit prothrombinase during the initiation of coagulation.

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry.

Monoclonal antibodies targeting the disintegrin-like domain of ADAMDEC1 modulates the proteolytic activity and enables quantification of ADAMDEC1 protein in human plasma.

Decysin-1 (ADAMDEC1) is an orphan ADAM-like metalloprotease with unknown biological function and a short domain structure. ADAMDEC1 mRNA has previously been demonstrated primarily in macrophages and mature dendritic cells. Here, we generated monoclonal antibodies (mAbs) against the mature ADAMDEC1 protein, as well as mAbs specific for the ADAMDEC1 pro-form, enabling further investigations of the metalloprotease.

Nurses' perspectives on how an e-message system supports cross-sectoral communication in relation to medication administration: A qualitative study.

Aims And Objectives: To describe nurses' perspectives on how an e-message system supports communication between hospital and home care nurses in relation to medication administration.

Background: Medication administration is a complex process involving a high risk of error. Unclear communication and lack of updated information about medication have been identified as the leading cause of medication errors during care transitions.

Stuck in tradition-A qualitative study on barriers for implementation of evidence-based nutritional care perceived by nursing staff.

Aims And Objectives: To explore the barriers for nutritional care as perceived by nursing staff at an acute orthopaedic ward, aiming to implement evidence-based nutritional care.

Background: Previous studies indicate that nurses recognise nutritional care as important, but interventions are often lacking. These studies show that a range of barriers influence the attempt to optimise nutritional care.

Laparoscopic and robotic nephroureterectomy: does lymphadenectomy have an impact on the clinical outcome?

Purpose: To evaluate the effect of lymphadenectomy (LND) in conjunction with nephroureterectomy on cancer-specific mortality (CSM) and overall survival (OS) for patients with muscle-invasive UTUC.

Methods: A retrospective, multicenter study of patients with UTUC, clinical stage N0M0, who underwent nephroureterectomy between January 2008 and December 2014 was conducted. Outcome measures were OS and CSM.

Barriers and facilitators for implementing a new screening tool in an emergency department: A qualitative study applying the Theoretical Domains Framework.

Aim: The aim was to identify the factors that were perceived as most important as facilitators or barriers to the introduction and intended use of a new tool in the emergency department among nurses and a geriatric team.

Background: A high incidence of functional decline after hospitalisation for acute medical illness has been shown in the oldest patients and those who are physically frail. In Denmark, more than 35% of older medical patients acutely admitted to the emergency department are readmitted within 90 days after discharge.

Evidence for restricted reactivity of ADAMDEC1 with protein substrates and endogenous inhibitors.

ADAMDEC1 is a proteolytically active metzincin metalloprotease displaying rare active site architecture with a zinc-binding Asp residue (Asp-362). We previously demonstrated that substitution of Asp-362 for a His residue, thereby reconstituting the canonical metzincin zinc-binding environment with three His zinc ligands, increases the proteolytic activity. The protease also has an atypically short domain structure with an odd number of Cys residues in the metalloprotease domain.

[Hygiene communication - conditions for change].

The article focuses on strengths and weaknesses of the local hygiene communication in a hospital ward. Efficient change communication consists of central and local communication activities. The hygiene coordinator is an important local "change agent", but in practice the role is difficult.

Balancing life with an increased risk of cancer: lived experiences in healthy individuals with Lynch syndrome.

Possibilities to undergo predictive genetic testing for cancer have expanded, which implies that an increasing number of healthy individuals will learn about cancer predisposition. Knowledge about how an increased risk of disease influences life in a long-term perspective is largely unknown, which led us to explore lived experiences in healthy mutation carriers with Lynch syndrome. Individual interviews were subjected to descriptive phenomenological analysis.

Cross-sector problems of collaboration in psychiatry.

Introduction: Some mental health service users need support from both hospital-based and community-based services. Treatment requires well-functioning collaboration practices between different mental health organizations and professions. However, serious cross-sector problems of collaboration have existed in Danish psychiatry since the 1980s when mental health service provisions were split into two psychiatric systems.

Sense of coherence and self-concept in Lynch syndrome.

Objective: Most individuals who learn about hereditary cancer manage well, but identification of subgroups who find this knowledge burdening would allow psychosocial intervention. The objective of the study was to assess sense of coherence (SOC) in individuals with Lynch syndrome with comparison to a general population and correlation to self-concept.

Methods: A total of 345 individuals with Lynch syndrome completed the 13-item SOC scale and the 20-item Lynch syndrome self-concept scale.

ADAMDEC1 is a metzincin metalloprotease with dampened proteolytic activity.

ADAMDEC1 (Decysin-1) is a putative ADAM (a disintegrin and metalloprotease)-like metalloprotease with an unknown physiological role, selectively expressed in mature dendritic cells and macrophages. When compared with other members of the ADAM family, ADAMDEC1 displays some unusual features. It lacks the auxiliary cysteine-rich, EGF, and transmembrane domains, as well as the cytoplasmic tail.

100 years Lynch syndrome: what have we learned about psychosocial issues?

In the care of patients with Lynch Syndrome (LS), a range of psychosocial issues are encountered, which significantly affect patient outcomes. A brief historical background of 'psycho-onco-genetics' (the domain where psychology, oncology and genetics meet) in relation to LS is presented, followed by an overview of important psychosocial issues identified in the past 20 years. The identification of mismatch repair genes in 1993-1994 made possible genetic counseling and testing for patients who had cancer and for potentially high-risk relatives without cancer.

Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model.

Hemophilia is treated by IV replacement therapy with Factor VIII (FVIII) or Factor IX (FIX), either on demand to resolve bleeding, or as prophylaxis. Improved treatment may be provided by drugs designed for subcutaneous and less frequent administration with a reduced risk of inhibitor formation. Tissue factor pathway inhibitor (TFPI) down-regulates the initiation of coagulation by inhibition of Factor VIIa (FVIIa)/tissue factor/Factor Xa (FVIIa/TF/FXa).