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Abstract BamA is the central component of the essential β-barrel assembly machine (BAM), a conserved multi-subunit complex that dynamically inserts and folds β-barrel proteins into the outer membrane of Gram-negative bacteria. Despite recent advances in our mechanistic and structural understanding of BamA, there are few potent and selective tool molecules that can bind to and modulate BamA activity. Here, we explored in vitro selection methods and different BamA/BAM protein formulations to discover peptide macrocycles that kill Escherichia coli by targeting extreme conformational states of BamA. Our studies show that Peptide Targeting BamA-1 (PTB1) targets an extracellular divalent cation-dependent binding site and locks BamA into a closed lateral gate conformation. By contrast, PTB2 targets a luminal binding site and traps BamA into an open lateral gate conformation. Our results will inform future antibiotic discovery efforts targeting BamA and provide a template to prospectively discover modulators of other dynamic integral membrane proteins.

Background: Listening difficulties may frequently occur in school settings, but so far there were no tools to identify them for both hearing and hearing-impaired Italian students. This study performed cross-cultural adaptation and validation of the Listening Inventory for Education-Revised for Italian students (LIFE-R-ITA). Methods: The study procedure followed the stages suggested by the Guidelines for the Process of Cross-cultural Adaptation of Self-Report Measures. For the content validation, six cochlear implanted students (8–18 years old) pre-tested the initial version. Whenever any situation did not occur in Italy, the item was adapted to more typical listening situations in Italy. The final version of LIFE-R-ITA was administered to a sample of 223 hearing students from different school settings and educational degrees in order to collect normative data. Results: For the LIFE-R-ITA, hearing students showed an average score of 72.26% (SD = 11.93), reflecting some listening difficulties. The subscales (LIFE total, LIFE class, and LIFE social) indicated good internal consistency. All items were shown to be relevant. Most challenging situations happened when listening in large rooms, especially when other students made noise. LIFE social scores were significantly worse than those of LIFE class (p < 0.001). Conclusions: The present study provides cross-cultural adaptation and validation for the LIFE-R-ITA along with the normative data useful to interpret the results of students with hearing loss. The LIFE-R-ITA may support teachers and clinicians in assessing students’ self-perception of listening at school. Such understanding may help students overcome their listening difficulties, by planning and selecting the most effective strategies among classroom interventions.

Abstract Background The case describes a successful endovascular thrombectomy using the ClotTriever System for an acute subclavian thrombosis in venous thoracic outlet syndrome. To the best of our knowledge, this is the first case report on use of Inari ClotTriever for acute upper extremity deep venous thrombosis due to venous thoracic outlet syndrome. The rapid technical and clinical success of our intervention may be an interesting cue for interventional radiologist colleagues. Case presentation Upper extremity deep vein thrombosis in the setting of venous thoracic outlet syndrome generally occurs in young adults after excessive arm activity and can sometimes be managed with anticoagulation. In this case, a 29-year-old male diagnosed with acute effort-induced thrombosis of the left subclavian vein and persistent symptoms following low-molecular-weight heparin therapy underwent mechanical thrombectomy. Successful thrombectomy was completed with > 90% thrombus burden reduction and no complication. The patient experienced immediate symptom relief and vein patency was confirmed via imaging 3 months post procedure. Conclusions Mechanical thrombectomy is a promising treatment technique for thrombosis associated with venous thoracic outlet syndrome.

Whereas economists do not traditionally address social harmony, and sociologists or political scientists do not usually tackle economic development, the interaction of social harmony and economic development has recently become an object of intense concern. In their aim to foster evolved rather than uprooted cultural values, the authors of this research note suggest an educational approach to promote the concept and the implementation of what they refer to as "authentic development." They propose interdisciplinary courses that include notions of history, sociology and economy. Their methodology is based on two main resources: (1) a textbook providing a broad historical survey tracing the development of 28 nations in the Americas; and (2) analytical parameters related to the extent of social interaction and income generation. Students carry out digital and group research and elaborate the conditions that generate social harmony, economic well-being and a better balance between them. The authors have already piloted their educational approach in four secondary schools in Antigua, Guatemala with 50 students aged 17-19. Most of them are now enrolled at local universities, but the impact of this course on their performance will only emerge over time.

Nowadays, organizations are very interested to gather data for strategic decision-making. Data are disposable in operational sources, which are distributed, heterogeneous, and autonomous. These data are gathered through ETL processes, which occur traditionally in a pre-defined time, that is, once a day, once a week, once a month or in a specific period of time. On the other hand, there are special applications for which data needs to be obtained in a faster way and sometimes even immediately after the data are generated in the operation data sources, such as health systems and digital agriculture. Thus, the conventional ETL process and the disposable techniques are incapable of making the operational data delivered in real-time, providing low latency, high availability, and scalability. As our proposal, we present an innovative architecture, named Data Magnet, to cope with real-time ETL processes. The experimental tests performed in the digital agriculture domain using real and synthetic data showed that our proposal was able to deal in real-time with the ETL process. The Data Magnet provided great performance, showing an almost constant elapsed time for growing data volumes. Besides, Data Magnet provided significant performance gains over the traditional trigger technique.

Abstract Purpose To present our experience and provide a literature review dissertation about the use of a suture-mediated percutaneous closure device (Perclose Proglide -PP- Abbott Vascular Inc., Santa Clara, CA, USA) to achieve hemostasis for unintended subclavian arterial catheterization during central venous line placement. Materials & methods Since October 2020, we have successfully treated four consecutive patients with a central venous catheter (8 to 12 French) in the subclavian artery. In each patient, we released a PP, monitoring its efficacy by performing a subclavian angiogram and placing, as a rescue strategy, an 8 mm balloon catheter near the entry point of the misplaced catheter. Primary outcome is technical and clinical success. Technical success is defined as absence of bleeding signs at completion angiography, while clinical success is a composite endpoint defined as absence of hematoma, hemoglobin loss at 12 and 24 h, and absence of procedure-related reintervention (due to vessel stenosis, pseudoaneurysm or distal embolization). Results Technical success was obtained in 75% of cases. In one patient a mild extravasation was resolved after 3 min of balloon catheter inflation. No early complications were observed for all patients. Conclusions PP showed a safe and effective therapeutic option in case of unintentional arterial cannulation. It can be considered as first-line strategy, as it does not preclude the possibility to use other endovascular approaches in case of vascular closure device failure.

NaX is an atypical member of the voltage-gated sodium channel family that may contribute to Na+ homeostasis. Here, the authors describe the structural and functional attributes of the human NaX channel to reveal new insights into its physiology.

The voltage-gated sodium (NaV) channel NaV1.7 has been identified as a potential novel analgesic target due to its involvement in human pain syndromes. However, clinically available NaV channel-blocking drugs are not selective among the nine NaV channel subtypes, NaV1.1–NaV1.9. Moreover, the two currently known classes of NaV1.7 subtype-selective inhibitors (aryl- and acylsulfonamides) have undesirable characteristics that may limit their development. To this point understanding of the structure–activity relationships of the acylsulfonamide class of NaV1.7 inhibitors, exemplified by the clinical development candidate GDC-0310, has been based solely on a single co-crystal structure of an arylsulfonamide inhibitor bound to voltage-sensing domain 4 (VSD4). To advance inhibitor design targeting the NaV1.7 channel, we pursued high-resolution ligand-bound NaV1.7-VSD4 structures using cryogenic electron microscopy (cryo-EM). Here, we report that GDC-0310 engages the NaV1.7-VSD4 through an unexpected binding mode orthogonal to the arylsulfonamide inhibitor class binding pose, which identifies a previously unknown ligand binding site in NaV channels. This finding enabled the design of a novel hybrid inhibitor series that bridges the aryl- and acylsulfonamide binding pockets and allows for the generation of molecules with substantially differentiated structures and properties. Overall, our study highlights the power of cryo-EM methods to pursue challenging drug targets using iterative and high-resolution structure-guided inhibitor design. This work also underscores an important role of the membrane bilayer in the optimization of selective NaV channel modulators targeting VSD4.

Open Educational Resources (OER) can be adapted and combined to create new resources that better meet the specific needs of different kinds of users and scenarios. In this sense, OER strongly contributes to generating and sharing educational knowledge. Due to the possibility of creating a new OER through the revision and remix activities, the original OER and the transformation process should be adequately identified. This way, the user of the OER has enough information about the history of the resource and, thus, can use it with confidence and security. In this context, determining data provenance, which describes the history of a data from its origin to its current state, becomes very relevant. For OER, there are examples of metadata standards and digital repositories that help to obtain the data provenance. However, the information collected is insufficient to identify the entire history of the provenance of OER. This article proposes a Provenance Model for OER called the ProvOER Model, which allows the documentation and identification of the provenance of OER. For this purpose, a minimum set of metadata was defined that reflects the OER intrinsic properties and the activities that created a new OER. The experiments showed that the ProvOER Model produced a suitable representation of the provenance of OER. In addition, the ProvOER Model allowed identifying the original OER used in a revise or remix activity and the continuous stretch used to create a new resource.

The quantitative description of the supramolecular interaction occurring at the adhesion surfaces of different polymers has enabled elaborate dissections of contributions to cohesive and surface energies. An alternative analysis is proposed here based on solubility parameters and binding constants that traditionally describe the weakest and relatively larger association energies in polymer blends. The article emphasizes a feature of supramolecular polymers that has not received adequate consideration: The dynamic bond scrambling that allows a most efficient molecular recognition over significant areas of synthetic and biological surfaces.