Deep Learning-based Segmentation of CT Scans Predicts Disease Progression and Mortality in IPF.

RATIONALE: Despite evidence demonstrating a prognostic role for CT scans in IPF, image-based biomarkers are not routinely used in clinical practice or trials. OBJECTIVES: Develop automated imaging biomarkers using deep learning based segmentation of CT scans. METHODS: We developed segmentation processes for four anatomical biomarkers which were applied to a unique cohort of treatment-naive IPF patients enrolled in the PROFILE study and tested against a further UK cohort. The relationship between CT biomarkers, lung function, disease progression and mortality were assessed. MEASUREMENTS AND MAIN RESULTS: Data was analysed from 446 PROFILE patients. Median follow-up was 39.1 months (IQR 18.1-66.4) with cumulative incidence of death of 277 over 5 years (62.1%). Segmentation was successful on 97.8% of all scans, across multiple imaging vendors at slice thicknesses 0.5-5mm. Of 4 segmentations, lung volume showed strongest correlation with FVC (r=0.82, p<0.001). Lung, vascular and fibrosis volumes were consistently associated across cohorts with differential five-year survival, which persisted after adjustment for baseline GAP score. Lower lung volume (HR 0.98, CI 0.96-0.99, p=0.001), increased vascular volume (HR 1.30, CI 1.12-1.51, p=0.001) and increased fibrosis volume (HR 1.17, CI 1.12-1.22, p=<0.001) were associated with reduced two-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR 3.41; 95% CI 1.36-8.54; p=0.009) and increasing fibrosis volume (HR 2.23; 95% CI 1.22-4.08; p=0.009) were associated with differential survival. CONCLUSIONS: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Interventional treatments for low back pain due to sacroiliac joint dysfunction: a systematic review of the literature.

PURPOSE: This systematic review aimed to report the current evidence in the literature about the efficacy of interventional treatments in the management of low back pain (LBP) due to sacroiliac joint dysfunction. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, EMBASE, Scopus, CINAHL, Cochrane Library, and CENTRAL bibliographic databases were searched. The search was performed from October to December 2021, and articles from the inception of the database to December 2021 were searched. RESULTS: Fourteen studies were included for qualitative synthesis. Five studies used the traditional radiofrequency approach (tRF), five studies used cooled radiofrequency approach (cRF), one study used botulinum toxin (BT), two studies used steroid injection, triamcinolone (TA) and local anesthetics injections, and one study used pulsed radiofrequency (PRF) denervation. Two studies used sham as a comparator. CONCLUSIONS: Cooled radiofrequency seems to be the most effective treatment in improving pain and functionality, while intra-articular injections are helpful only as diagnostic tools. However, due to the lack of high-quality studies, it was not possible to draw significant conclusions.

Vascular Thrombosis in Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Multicenter Study.

OBJECTIVES: Coronavirus disease 2019 has been reported to be a prothrombotic condition; however, multicenter data comparing this with other viral pneumonias in those requiring extracorporeal membrane oxygenation are lacking. We conducted a multicenter study using whole-body CT to examine the prevalence, severity, and nature of vascular complications in coronavirus disease 2019 in comparison with patients with other viral pneumonias. DESIGN: We analyzed whole-body CT scans for the presence of vascular thrombosis (defined as pulmonary artery thrombus, venous thrombus, systemic arterial thrombus, or end-organ infarct). The severity, distribution, and morphology of pulmonary artery thrombus were characterized. Competing risk cumulative incidence analysis was used to compare survival with discharge. SETTING: Three centers of the English national extracorporeal membrane oxygenation service. PATIENTS: Consecutive patients admitted with either coronavirus disease 2019 or noncoronavirus disease 2019 viral pneumonia admitted from January 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred thirty-six patients (45.2 ± 10.6 yr old, 39/146 [27%] female) requiring extracorporeal membrane oxygenation support underwent whole-body CT scans at admission. Of these, 86 had coronavirus disease 2019 pneumonia, and 50 had noncoronavirus disease 2019 viral pneumonia. Vascular thrombosis was seen more often in patients with coronavirus disease 2019 (odds ratio, 12.9 [95% CI 4.5-36.8]). In those with coronavirus disease 2019, 57 (73%) demonstrated pulmonary artery thrombus or pulmonary perfusion defects. Eighty-two percent of thrombus exhibited emboli-like morphology. The location of pulmonary artery thrombus and parenchymal perfusion defects was only concordant in 30% of cases. The risk of mortality was higher in those with coronavirus disease 2019 compared with noncoronavirus disease 2019 pneumonia (χ2 = 3.94; p = 0.047). Mortality was no different in coronavirus disease 2019 patients with or without vascular thrombosis (χ2 = 0.44; p = 0.51). CONCLUSIONS: In patients who received extracorporeal membrane oxygenation, coronavirus disease 2019 is associated with a higher prevalence of vascular thrombosis compared with noncoronavirus disease viral pneumonias. The pattern of pulmonary vascular changes suggests concurrent embolic disease and small vessel disease. Despite this, vascular thrombosis was not linked to poorer short-term prognosis in those with coronavirus disease 2019.

A Musculoskeletal Multibody Algorithm Based on a Novel Rheonomic Constraints Definition Applied to the Lower Limb.

In this paper, a multibody model was developed in the framework of biotribology of lower limb artificial joints. The presented algorithm performs the inverse dynamics of musculoskeletal systems with the aim to achieve a tool for the calculation of the joint reaction forces. The revolute joint, the cam joint, the spherical joint and the free joint were considered in the analyzed lower limb system by introducing a novel analytical formulation of the rheonomic constraint equations based on the quaternions theory. Within the kinematical analysis, the curved muscle paths were modeled by simulating their geodesic wrapping over bony surfaces while the muscle actuations were formulated through the Hill muscle model. The developed theoretical model was developed in matlab environment allowing to follow the classical musculoskeletal analysis pipeline: kinematical analysis, inverse dynamics, and static optimization, applied to the lower limb during the gait kinematics. The validation of the results was obtained by comparing the calculated hip joint reactions with the ones obtained in vivo by Bergmann and calculated by Opensim software, showing a satisfactory agreement. The proposed model and algorithm represent a fully open and controllable synovial joint tribological configuration generator tool, useful to be coupled with numerical lubrication/contact models in the framework of the in silico artificial joints tribological optimization.

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis.

BACKGROUND: In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). OBJECTIVE: To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I-II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. RESULTS: Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). CONCLUSION: CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

Functional respiratory imaging identifies redistribution of pulmonary blood flow in patients with COVID-19.

An increasing observation is that some patients with COVID-19 have normal lung compliance but significant hypoxaemia different from typical acute respiratory distress syndrome (ARDS). We hypothesised that changes in pulmonary blood distribution may be partially responsible and used functional respiratory imaging on CT scans to calculate pulmonary blood volume. We found that patients with COVID-19 had significantly reduced blood volume in the smaller calibre blood vessels (here defined as <5 mm2 cross-sectional area) compared with matched ARDS patients and healthy controls. This suggests that using high levels of PEEP may not alone be enough to oxygenate these patients and that additional management strategies may be needed.

Computed Tomography and Magnetic Resonance Imaging.

Imaging in Oncology is rapidly moving from the detection and size measurement of a lesion to the quantitative assessment of metabolic processes and cellular and molecular interactions. Increasing insights into cancer as a complex disease with involvement of the tumor stroma in tumor pathobiological processes have made it clear that for successful control of cancer, treatment strategies should not only be directed at the cancer cells but should also take aspects of the tumor microenvironment into account. This requires an understanding of the complex molecular and cellular interactions in cancer tissue. Recent developments in imaging technology have increased the possibility to image various pathobiological processes in cancer development and response to treatment. For computed tomography (CT) and magnetic resonance imaging (MRI) various improvements in hardware, software, and imaging probes have lifted these modalities from classical anatomical imaging techniques to techniques suitable to image and quantify various physiological processes and molecular and cellular interactions. Next to a more general overview of possible imaging targets in oncology, this chapter provides an overview of the various developments in CT and MRI technology and some specific applications.

Experimental Comparison on Dental BioTribological Pairs Zirconia/Zirconia and Zirconia/Natural Tooth by Using a Reciprocating Tribometer.

The application of tribology in dentistry is growing rapidly, intense research has been conducted to develop an understanding of dental tribology for better selection of artificial materials and dental implant design. Dental biotribology, has been one of the most important branches in biotribology in recent years. The aim of this research is to investigate the tribological performances in the tooth-to-tooth contact and material-to-natural tooth contact (zirconia vs. zirconia and natural tooth vs. zirconia). The presented research was carried out by testing the above mentioned tribological pairs with the use of a reciprocating tribometer under lubricated conditions (artificial saliva). The normal force used in the tests was 20 N the time for each test was of 60 min. The stroke length was 2 mm, according to the range of displacement used in scientific literature. The wear mass loss evaluation was evaluated by using a gravimetric method. In order to characterize the wear mechanisms, present in the worn surfaces after each of tribo-tests, a topographic analysis was carried with a 3D non-contact optical profiler. The results show that the minimum value of the COF is obtained in the case of Zirconia vs. Zirconia tribo-couple. The results on the wear mass loss show a very low wear rate when coupling in tribological condition natural tooth with a ceramic restoration (a mean value of 0.5 mg was found). This rate is even lower when the contact is between two artificial zirconia teeth.

Evaluation of the Applicability of 3d Models as Perceived by the Students of Health Sciences.

The methodology and style of teaching anatomy in the faculties of Health Sciences is evolving due to the changes being introduced as a result of the application of new technologies. This brings a more positive attitude in the students, enabling an active participation during the lessons. One of these new technologies is the creation of 3D models that reliably recreates the anatomical details of real bone pieces and allow access of anatomy students to bone pieces that are not damaged and possess easily identifiable anatomical details. In our work, we have presented previously created 3D models of skull and jaw to the students of anatomy in the Faculties of Health Sciences of the University of Salamanca, Spain. The faculties included were odontology, medicine, occupational therapy nursing, health sciences and physiotherapy. A survey was carried out to assess the usefulness of these 3D models in the practical study of anatomy. The total number of students included in the survey was 280.The analysis of the results presents a positive evaluation about the use of 3D models by the students studying anatomy in different Faculties of Health Sciences.

Different Digitalization Techniques for 3D Printing of Anatomical Pieces.

The use of different technological devices that allow the creation of three-dimensional models is in constant evolution, allowing a greater application of these technologies in different fields of health sciences and medical training. The equipment for digitalization is becoming increasingly sophisticated allowing obtaining three-dimensional which are more defined and similar to real image and original object. In this work, different modalities of designing 3D anatomical models of bone pieces are presented, for use by students of different disciplines in Health Sciences. To do this we digitalized bone pieces, with different models of scanners, producing images that can be transformed for 3D printing, with a Colido X 3045 printer by digital treatment with different software.

Tribocorrosion of 3D printed dental implants: An overview.

With the advancements in dental science and the growing need for improved dental health, it has become imperative to develop new implant materials which possess better geometrical, mechanical, and physical properties. The oral environment is a corrosive environment and the relative motion between the teeth also makes the environment more hostile. Therefore, the combined corrosion and tribology commonly known as tribocorrosion of implants needs to be studied. The complex shapes of the dental implants and the high-performance requirements of these implants make manufacturing difficult by conventional manufacturing processes. With the advent of additive manufacturing or 3D-printing, the development of implants has become easy. However, the various requirements such as surface roughness, mechanical strength, and corrosion resistance further make the manufacturing of implants difficult. The current paper reviews the various studies related to3D-printed implants. Also, the paper tries to highlight the role of 3D-Printing can play in the area of dental implants. Further studies both experimental and numerical are needed to devise optimized conditions for 3D-printing implants to develop implants with improved mechanical, corrosion, and biological properties.

2D materials for Tribo-corrosion and -oxidation protection: A review.

The recent rise of 2D materials has extended the opportunities of tuning a variety of properties. Tribo-corrosion, the complex synergy between mechanical wear and chemical corrosion, poses significant challenges across numerous industries where materials are subjected to both tribological stressing and corrosive environments. This intricate interplay often leads to accelerated material degradation and failure. This review critically assesses the current state of utilizing 2D nanomaterials to enhance tribo-corrosion and -oxidation behavior. The paper summarizes the fundamental knowledge about tribo-corrosion and -oxidation mechanisms before assessing the key contributions of 2D materials, including graphene, transition metal chalcogenides, hexagonal boron nitride, MXenes, and black phosphorous, regarding the resulting friction and wear behavior. The protective roles of these nanomaterials against corrosion and oxidation are investigated, highlighting their potential in mitigating material degradation. Furthermore, we delve into the nuanced interplay between mechanical and corrosive factors in the specific application of 2D materials for tribo-corrosion and -oxidation protection. The synthesis of key findings underscores the advancements achieved through integrating 2D nanomaterials. An outlook for future research directions is provided, identifying unexplored avenues, and proposing strategies to propel the field forward. This analysis aims at guiding future investigations and developments at the dynamic intersection of 2D nanomaterials, tribo-corrosion, and -oxidation protection.

Laparoscopic-Guided Transversus Abdominis Plane (TAP) Block Combined with Port-Site Infiltration (PSI) for Laparoscopic Sleeve Gastrectomy in an ERABS Pathway: A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Patients undergoing laparoscopic sleeve gastrectomy (LSG) commonly experience moderate to severe postoperative pain. We conducted a randomized, prospective double-blind placebo-controlled study to evaluate the analgesic effect of laparoscopic-guided TAP (LG-TAP) block after LSG in a high-volume bariatric center, applying an enhanced recovery after bariatric surgery (ERABS) pathway. MATERIAL AND METHODS: One hundred ten patients were randomly allocated to receive LG-TAP block with local anesthetic (LA) or saline solution (placebo), both combined with port-site infiltration with LA (LA-PSI). Primary outcome was pain score measured in post-anesthesia care unit (PACU) and at 6, 12, and 24 h after surgery. Secondary outcomes included postoperative nausea and/or vomiting (PONV), analgesic requirement, time to walking, time to flatus, length of hospital stay (LOS), and surgical complications. RESULTS: No significant differences were observed between LG-TAP and placebo groups in postoperative analgesia, with a median (IQR) NRS of 2 (4.75-0) vs. 2 (5.25-0) in PACU, 5.5 (7-3) vs. 6 (7-4) at 6 h, 2 (6-0) vs. 3 (5.25-1.75) at 12 h, and 2 (3.75-0) vs. 1 (2-0) at 24 h; all p > 0.05. A significant difference was found in PONV in PACU (LG-TAP, 46%; placebo, 25%, p-value, 0.019) and at 6 h postoperatively (LG-TAP, 69%, placebo, 41%, p-value, 0.003). No differences were observed as regards other secondary outcomes. CONCLUSION: Our results suggest that LG-TAP block is not related to more effective postoperative analgesia compared to placebo when LA-PSI is performed.

Intrathecal dexamethasone as an adjuvant for spinal anesthesia: a systematic review.

INTRODUCTION: Spinal anesthesia is a common anesthetic technique for lower limb and abdominal surgery. Despite its efficacy, its use is limited because of its duration and potential severe side effects, especially in high-risk patients undergoing major surgery. Adjuvants such as dexamethasone offer the potential to prolong the anesthetic effect and reduce the need for local anesthetics while reducing the incidence of serious adverse events. The purpose of this systematic review is to evaluate the efficacy of dexamethasone as an intrathecal adjuvant in prolonging anesthetic duration, delaying pain onset, and minimizing adverse events (PROSPERO registration: CRD42022350218). EVIDENCE ACQUISITION: We included randomized controlled trials conducted in adult patients undergoing spinal anesthesia for lower limb or abdominal surgery and comparing the performance of dexamethasone with alternative spinal treatments. A comprehensive systematic search was conducted on PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL, and Cochrane Library from February to June 2023 without language restriction. Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2). EVIDENCE SYNTHESIS: Ten studies, nine of which were at high risk of bias, were included (N.=685 patients). Overall, intrathecal dexamethasone was associated with a longer duration of sensory block, improvement in the duration or extent of postoperative analgesia, and significant shortening of block onset. The role of dexamethasone in prolonging motor block was not clear. The incidence of adverse events was low. Intrathecal dexamethasone has been shown to be a potentially valuable adjuvant to prolong the duration of sensory block and improve postoperative analgesia without increasing adverse events. CONCLUSIONS: Given the wide heterogeneity of methodological approaches, further investigation is needed. Considering the limitations of the included studies and awaiting more conclusive evidence, the prudent use of dexamethasone could be recommended in those specific situations where general anesthesia or higher local anesthetics should be avoided.

Rectus sheath block added to parasternal block may improve postoperative pain control and respiratory performance after cardiac surgery: a superiority single-blinded randomized controlled clinical trial.

BACKGROUND: The population undergoing cardiac surgery confronts challenges from uncontrolled post-sternotomy pain, with possible adverse effects on outcome. While the parasternal block can improve analgesia, its coverage may be insufficient to cover epigastric area. In this non-blinded randomized controlled study, we evaluated the analgesic and respiratory effect of adding a rectus sheath block to a parasternal block. METHODS: 58 patients undergoing cardiac surgery via median sternotomy were randomly assigned to receive parasternal block with rectus sheath block (experimental) or parasternal block with epigastric exit sites of chest drains receiving surgical infiltration of local anesthetic (control). The primary outcome of this study was pain at rest at extubation. We also assessed pain scores at rest and during respiratory exercises, opiate consumption and respiratory performance during the first 24 hours after extubation. RESULTS: The median (IQR) maximum pain scores (on a 0-10 Numeric Rate Scale (NRS)) at extubation were 4 (4, 4) in the rectus sheath group and 5 (4, 5) in the control group (difference 1, p value=0.03). Rectus sheath block reduced opioid utilization by 2 mg over 24 hours (IC 95% 0.0 to 2.0; p<0.01), reduced NRS scores at other time points, and improved respiratory performance at 6, 12, and 24 hours after extubation. CONCLUSION: The addition of a rectus sheath block with a parasternal block improves analgesia for cardiac surgery requiring chest drains emerging in the epigastric area. TRIAL REGISTRATION NUMBER: NCT05764616.

Lateral Femoral Cutaneous Nerve Block or Wound Infiltration Combined with Pericapsular Nerve Group (PENG) Block for Postoperative Analgesia following Total Hip Arthroplasty through Posterior Approach: A Randomized Controlled Trial.

Background: Pericapsular nerve group (PENG) block, although effective for pain management following total hip arthroplasty (THA), does not cover skin analgesia. In this randomized controlled trial, we compared the effectiveness of PENG block combined with lateral femoral cutaneous nerve (LFCN) block or wound infiltration (WI) on postoperative analgesia and functional outcomes. Methods: Fifty patients undergoing posterior-approached THA under spinal anesthesia were randomly allocated to receive LFCN block with 10 mL of 0.5% ropivacaine or WI with 20 mL of 0.5% ropivacaine. In both groups, PENG block was performed by injecting 20 mL of 0.5% ropivacaine. Primary outcomes were static and dynamic pain scores (0-10 numeric rating scale) measured in the first 24 h after surgery. Secondary outcomes included postoperative opioid consumption, functional assessment and length of hospital stay. Results: Postoperative static NRS of patients receiving LFCN was higher than that of patients receiving WI at 6 h but lower at 24 h, with a median (IQR) of 3 (2-4) vs. 2 (1-2) (p < 0.001) and 2 (2-3) vs. 3 (3-4) (p = 0.02), respectively. Static pain scores at 12 h did not show significant differences, with an NRS of 3 (2-4) for WI vs. 3 (3-4) for LFCN (p = 0.94). Dynamic pain and range of movement followed a similar trend. No significant differences were detected in other outcomes. Conclusions: LFCN block was not inferior to WI for postoperative analgesia and functional recovery in association with PENG block during the first postoperative day, although it had worse short-term pain scores. Based on these results, it is reasonable to consider LFCN block as a valid alternative to WI or even a complementary technique added to WI to enhance skin analgesia during the first 24 h after THA. Future studies are expected to confirm this hypothesis and find the best combination between PENG block and other techniques to enhance analgesia after THA.

Computed tomography and magnetic resonance imaging.

Imaging in Oncology is rapidly moving from the detection and size measurement of a lesion to the quantitative assessment of metabolic processes and cellular and molecular interactions. Increasing insights into cancer as a complex disease with involvement of the tumor stroma in tumor pathobiological processes have made it clear that for successful control of cancer, treatment strategies should not only be directed at the tumor cells but also targeted at the tumor microenvironment. This requires understanding of the complex molecular and cellular interactions in cancer tissue. Recent developments in imaging technology have increased the possibility to image various pathobiological processes in cancer development and response to treatment. For computed tomography (CT) and magnetic resonance imaging (MRI) various improvements in hardware, software, and imaging probes have lifted these modalities from classical anatomical imaging techniques to techniques suitable to image and quantify various physiological processes and molecular and cellular interactions. Next to a more general overview of possible imaging targets in oncology this chapter provides an overview of the various developments in CT and MRI technology and some specific applications.

Homologous overexpression of RfaH in E. coli K4 improves the production of chondroitin-like capsular polysaccharide.

BACKGROUND: Glycosaminoglycans, such as hyaluronic acid, heparin, and chondroitin sulfate, are among the top ranked products in industrial biotechnology for biomedical applications, with a growing world market of billion dollars per year. Recently a remarkable progress has been made in the development of tailor-made strains as sources for the manufacturing of such products. The genetic modification of E. coli K4, a natural producer of chondroitin sulfate precursor, is challenging considering the lack of detailed information on its genome, as well as its mobilome. Chondroitin sulfate is currently used as nutraceutical for the treatment of osteoarthritis, and several new therapeutic applications, spanning from the development of skin substitutes to live attenuated vaccines, are under evaluation. RESULTS: E. coli K4 was used as host for the overexpression of RfaH, a positive regulator that controls expression of the polysaccharide biosynthesis genes and other genes necessary for the virulence of E. coli K4. Various engineering strategies were compared to investigate different types of expression systems (plasmid vs integrative cassettes) and integration sites (genome vs endogenous mobile element). All strains analysed in shake flasks on different media showed a capsular polysaccharide production improved by 40 to 140%, compared to the wild type, with respect to the final product titer. A DO-stat fed-batch process on the 2L scale was also developed for the best performing integrative strain, EcK4r3, yielding 5.3 g ∙ L(-1) of K4 polysaccharide. The effect of rfaH overexpression in EcK4r3 affected the production of lipopolysaccharide and the expression of genes involved in the polysaccharide biosynthesis pathway (kfoC and kfoA), as expected. An alteration of cellular metabolism was revealed by changes of intracellular pools of UDP-sugars which are used as precursors for polysaccharide biosynthesis. CONCLUSIONS: The present study describes the identification of a gene target and the application of a successful metabolic engineering strategy to the unconventional host E. coli K4 demonstrating the feasibility of using the recombinant strain as stable cell factory for further process implementations.