A Bacillus megaterium plasmid system for the production, export, and one-step purification of affinity-tagged heterologous levansucrase from growth medium

A multiple vector system for the production and export of recombinant affinity-tagged proteins in Bacillus megaterium was developed. Up to 1 mg/liter of a His(6)-tagged or Strep-tagged Lactobacillus reuteri levansucrase was directed into the growth medium, using the B. megaterium esterase LipA signal peptide, and recovered by one-step affinity chromatography

A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection

SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. After vaccination of mice, the MVA/SdFCS vaccine induced eightfold higher neutralizing antibodies compared with MVA/S, which expressed spike without FCS inactivation, and protected against the Beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, and rectum) that neutralized the homologous (WA-1/2020) and heterologous VOCs, including Delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both spike- and nucleocapsid-specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared with IM vaccination. After challenge with the SARS-CoV-2 Delta variant, the IM route induced robust protection, the BU route induced moderate protection, and the SL route induced no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination

Geklebte modulare Zwischendecken aus Kleintafeln zur Altbaumodernisierung

Viele Wohnungsaltbauten weisen häufig sehr massive Außenwände, jedoch nur gering tragfähige Zwischendecken auf. Bei der Sanierung solcher Zwischendecken mit voller Grundriss-Spannweite ist die Zugänglichkeit durch Türen, Tore oder Fenster für viele größere Formate (z. B. lange Träger) oft eingeschränkt oder sogar unmöglich. Ein neuer Ansatz zum Austausch der alten Zwischendecke durch eine moderne tragfähige Decke analog einer vorgefertigten Fertighaus-Decke (Großtafel in Holzbauweise) stellt die modular aufgebaute Zwischendecke aus Kleintafeln in Holzbauweise dar. Diese bestehen wie die Großtafeln hauptsächlich aus Konstruktionsvollholz und Holzwerkstoffplatten und haben Möbelabmessungen, um die vorhandenen Zugangswege in das Gebäude zu nutzen. Zur thermischen Isolierung und Verbesserung des Schallschutzes werden neuartige Holzwerkstoffe aus 100 % Holz (Holzschaum) und für den Trittschallschutz relativ dünne faserverstärkte Textilbetonplatten integriert. Für eine sichere und steife Verbindung der Module werden Fügetechniken aus dem Holzbau mit neuartigen Schnellklebtechniken mit elektrisch beheizbarer Klebfuge kombiniert, um einen schnellen Baufortschritt zu ermöglichen

Discrete choice experiment on educating value-based healthcare

Introduction Identifying costs and values in healthcare interventions as well as the ability to measure and consider costs relative to value for patients are pivotal in clinical decision-making and medical education. This study explores residents' preferences in educating value-based healthcare (VBHC) during postgraduate medical education. Exploring residents' preferences in VBHC education, in order to understand what shapes their choices, might contribute to improved medical residency education and healthcare as a whole.Methods A discrete choice experiment (DCE) examined which conditions for educating VBHC are preferred by residents. DCE gives more insight into the trade-off's residents make when choosing alternatives, and which conditions for educating VBHC have the most influence on residents' preference.Results This DCE shows that residents prefer knowledge on both medical practice as well as the process of care-to be educated by an expert on VBHC together with a clinician. They prefer limited protected time to conduct VBHC initiatives (thus while at work) and desire the inclusion of VBHC in formal educational plans.Conclusion When optimising graduate and postgraduate medical education curricula, these preferences should be considered to create necessary conditions for the facilitation and participation of residents in VBHC education and the set-up of VBHC initiatives

How Do Attending Physicians Prepare Residents to Deliver High-Value, Cost-Conscious Care?

Purpose An estimated 20% of health care expenditures are wasteful. Educational interventions aimed at reducing waste by delivering high-value, cost-conscious care (HV3C) often focus on the role of the physician. This study sought to understand how attending physicians, who have a central role in the workplace, prepare residents to provide HV3C. Method Researchers from Maastricht University in Maastricht, the Netherlands, conducted semistructured interviews between September 2016 and August 2017 with 12 attending physicians who supervise residents in the workplace. Participants were purposefully sampled from 5 institutions throughout the Netherlands to include surgical and nonsurgical attending physicians and hospital- and nonhospital-based physicians. Data collection and analysis were iterative, using principles of grounded theory. Results The attending physician's approach to providing HV3C was an important factor in preparing residents in the workplace. Three differences became apparent: priority of HV3C training, feedback on HV3C, and obstacles to HV3C delivery. Results indicate that attending physicians use 3 teaching methods to teach HV3C delivery: Socratic questioning, role modeling, and setting limits. Training was often implicit and ad hoc. Conclusions How attending physicians deal with HV3C themselves influences how they prepare residents in the workplace. To optimize resident training, it may be important to create a supportive environment for HV3C delivery and training. Delivery could be supported by making HV3C a shared goal for attending physicians and residents, thereby providing insight into clinical practice behavior and minimizing the influence of obstacles. Training could be optimized by supporting a variety of teaching methods suitable for daily teaching to stimulate continuous learning in residents

Prevalence of sexual dysfunctions and other sexual disorders in adults with attention-deficit/hyperactivity disorder compared to the general population

Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and/or hyperactivity and impulsivity that lead to dysfunctioning in daily life. One of the affected areas of life that has so far not been studied in ADHD is sexual functioning. The goal of this study was to assess prevalence of sexual dysfunctions and other sexual disorders among adults with ADHD. A total of n = 136 adult patients treated in a Dutch outpatient ADHD clinic filled out two questionnaires to screen for sexual dysfunctions and other sexual disorders. We compared the prevalence of sexual dysfunctions and other sexual disorders in our ADHD patient population to results from two large surveys among the general Dutch population. We found that 39% of the male and 43% of the female ADHD patients had symptoms of a sexual dysfunction, and 17% of the male and 5% of the female ADHD patients had symptoms of any other sexual disorder. Only one male patient had received a diagnosis of a sexual disorder at this clinic prior to study participation. In conclusion, sexual dysfunctions and other sexual disorders are highly prevalent in adults with ADHD. Screening for sexual disorders should be therefore standard procedure during diagnostic assessment