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The bi-thiophene-vinylene-benzothiazole (bTVBT4) ligand developed for Alzheimers disease (AD)-specific detection of amyloid tau has been studied by a combination of several theoretical methods and experimental spectroscopies. With reference to the cryo-EM tau structure of the tau protofilament (Nature 2017, 547, 185), a periodic model system of the fibril was created, and the interactions between this fibril and bTVBT4 were studied with nonbiased molecular dynamics simulations. Several binding sites and binding modes were identified and analyzed, and the results for the most prevailing fibril site and ligand modes are presented. A key validation of the simulation work is provided by the favorable comparison of the theoretical and experimental absorption spectra of bTVBT4 in solution and bound to the protein. It is conclusively shown that the ligand-protein binding occurs at the hydrophobic pocket defined by the residues Ile360, Thr361, and His362. This binding site is not accessible in the Picks disease (PiD) fold, and fluorescence imaging of bTVBT4-stained brain tissue samples from patients diagnosed with AD and PiD provides strong support for the proposed tau binding site. Funding Agencies|European CommissionEuropean CommissionEuropean Commission Joint Research Centre [765739]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2018-4343, 2016-07213]; Swedish e-Science Research Centre (SeRC); German Research FoundationGerman Research Foundation (DFG) [KO 5423/1-1]; U.S. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [UO1NS110437]

The title compound was made by the reaction of the CpCo-complex of 2,3,7,8-tetrakis(trimethylsilyl) linear [3]phenylene, in which the metal coordinates one of the cyclobutadiene rings, with CpCo(C2H4)2. Because of its relative stability, a syn-dicobalt-bound configuration is indicated rather than its anti alternative.

BACKGROUND Technological advancements have opened the path for many technology providers to easily develop and introduce eHealth tools to the public. The use of these tools is increasingly recognized as a critical quality driver in health care; however, choosing a quality tool from the myriad of tools available for a specific health need does not come without challenges. OBJECTIVE This review aimed to systematically investigate the literature to understand the different approaches and criteria used to assess the quality and impact of eHealth tools by considering sociotechnical factors (from technical, social, and organizational perspectives). METHODS A structured search was completed following the participants, intervention, comparators, and outcomes framework. We searched the PubMed, Cochrane, Web of Science, Scopus, and ProQuest databases for studies published between January 2012 and January 2022 in English, which yielded 675 results, of which 40 (5.9%) studies met the inclusion criteria. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions were followed to ensure a systematic process. Extracted data were analyzed using NVivo (QSR International), with a thematic analysis and narrative synthesis of emergent themes. RESULTS Similar measures from the different papers, frameworks, and initiatives were aggregated into 36 unique criteria grouped into 13 clusters. Using the sociotechnical approach, we classified the relevant criteria into technical, social, and organizational assessment criteria. Technical assessment criteria were grouped into 5 clusters: technical aspects, functionality, content, data management, and design. Social assessment criteria were grouped into 4 clusters: human centricity, health outcomes, visible popularity metrics, and social aspects. Organizational assessment criteria were grouped into 4 clusters: sustainability and scalability, health care organization, health care context, and developer. CONCLUSIONS This review builds on the growing body of research that investigates the criteria used to assess the quality and impact of eHealth tools and highlights the complexity and challenges facing these initiatives. It demonstrates that there is no single framework that is used uniformly to assess the quality and impact of eHealth tools. It also highlights the need for a more comprehensive approach that balances the social, organizational, and technical assessment criteria in a way that reflects the complexity and interdependence of the health care ecosystem and is aligned with the factors affecting users’ adoption to ensure uptake and adherence in the long term.

ZusammenfassungWie kann eine Führungskraft vom Subsidiary Governance Modell und diesem Handbuch profitieren? Eine Möglichkeit besteht darin, die eigene Qualität der Subsidiary Governance innerhalb dieser sechs Bereiche zu messen. Die Ausführungen über die Bestandteile des Subsidiary Governance Modells und Beispiele in Kap. 4 verleiten hoffentlich dazu, die eigenen Governance-Praktiken selbstkritisch zu reflektieren. Im letzten Teil des Buches stehen hierfür eine Checkliste und ein Praxisbeispiel bereit.

ZusammenfassungDurch die zunehmende Internationalisierung von Unternehmen wird das Führen über die Landesgrenzen hinaus immer wichtiger. Internationalisierung ist heutzutage für Unternehmen unabhängig von ihrer Größe beinahe eine Grundvoraussetzung, um erfolgreich zu sein. Ziele, die ein Unternehmen mit der Internationalisierung verfolgt, sind bspw. Wachstum durch Erschließung neuer Märkte oder das Auslagern von Teilen der Wertkette und damit die Konzentration auf Kernkompetenzen. Die Digitalisierung bzw. digitale Transformation hat die Möglichkeiten zur Internationalisierung noch stark vergrößert. Zur Erreichung dieser Ziele werden ausländische Niederlassungen (englisch: subsidiaries) gegründet oder Partnerschaften mit Unternehmen anderer Länder eingegangen.

ZusammenfassungSubsidiary Governance baut nicht auf der grünen Wiese auf – viele international tätige Unternehmen sind in vielen der behandelten Themen bereits aktiv, auf gezielte oder teilweise auch zufällige Art und Weise. Das nachfolgende Kapitel soll Leserinnen und Leser aus der Praxis in der Anwendung des Subsidiary Governance Modells unterstützen. Dazu wird einleitend eine (reale) Fallstudie dargestellt. Eine Checkliste fasst die behandelten Bereiche oder Indikatoren zusammen und dient als Diskussionsgrundlage oder um Prioritäten zu setzen. Den Abschluss bilden verschiedene Szenarien (sogenannte Anwendungsarten), wie das Subsidiary Governance Modell sinnvoll in reale Führungsprozesse eingebettet werden kann.

ZusammenfassungDas Subsidiary Governance Modell besteht aus den sechs Inhaltsmodulen System, Mission, Integrität, Stakeholder, Risiko und Audit. System-Management beschäftigt sich mit dem ganzheitlichen Verständnis des Unternehmens, seiner Umwelt, der Anspruchsgruppen und des Kontexts. Die Kenntnis der Zusammenhänge innerhalb eines Systems (Strukturen, Prozesse, Abhängigkeiten, Rollen) und der Positionierung von Mutterhaus und Tochtergesellschaft intern und gegenüber der Umwelt ist entscheidend für eine zielorientierte Subsidiary Governance. Mission Management befasst sich mit Strategie, Struktur und Kultur – Elemente, die Ordnung ins System Unternehmen bringen. Integritätsmanagement beschäftigt sich mit den Werten guter Zusammenarbeit. Durch Bewusstseinsförderung und das Einrichten von Prozessen und Instrumenten können Compliance und ethisches Verhalten sichergestellt und Reputationsverluste vermieden werden. Stakeholdermanagement besteht aus Definition, Identifizierung, Management und Kontrolle der Stakeholder. Risikomanagement beinhaltet den gesamten Risikomanagementprozess, von der Risikodefinition über die Bewertung der hierarchiestufengerechten Risiken bis hin zur Schulung spezifischer Risiken. Audit Management beschäftigt sich sowohl mit den gesetzlichen Anforderungen als auch mit der Effektivität, Effizienz, Erfolgsrelevanz und Rolle interner und externer Audits.

ZusammenfassungDas Subsidiary Governance Modell (Abb. 2.1) besteht aus sechs Inhaltsmodulen und sechs resultatorientierten Modulen. Die sechs Inhaltsmodule bestimmen den Inhalt bzw. die Grundlage der Subsidiary Governance, weshalb man sie auch „Grundlagenmodule“ nennen kann. Sie beantworten die Frage, welche Themen für gute Führung und Kontrolle einer Subsidiary fundamental und wichtig sind und liefern somit eine Aussage über die Qualität dessen, was in einem Unternehmen vorhanden ist oder nicht. Mit anderen Worten: Die Steuerung und Kontrolle von Niederlassungen muss die Bereiche System, Mission, Integrität, Anspruchsgruppen, Risiko und Audit umfassen. Ohne diese inhaltliche Konkretisierung bleibt Subsidiary Governance ein schwer greifbarer Begriff.

ZusammenfassungWas ist der Nutzen guter Subsidiary Governance? Im vorhergehenden Kapitel wurden die sogenannten Inhaltsmodule beschrieben. Diese schaffen – wie im Kap. 2 aufgezeigt – Voraussetzungen für mehrere zentrale Eigenschaften erfolgreicher Unternehmen, nämlich für Wettbewerbsstärke, Innovationsfähigkeit, Nachhaltigkeit, Führung (im Sinne von Führungsstärke), digitale Reife und Umsetzungsexzellenz. Im Subsidiary Governance Modell (vgl. Abb. 2.1) sind dies die sogenannten Resultatmodule. Mit anderen Worten: Die Inhaltsmodule liefern zentrale Grundlagen für die Resultatmodule, weshalb erstere auch Grundlagenmodule genannt werden. In diesem Kapitel werden nun die Resultatmodule vorgestellt und die Verbindungen zu den bisherigen Konzepten aufgezeigt.

The intersection between the human oral microbiome and oral health is an emerging area of study which has gained momentum over the last decade. This momentum has motivated a search for associations between the oral microbiome and oral cancer, in hopes of identifying possible biomarkers that facilitate earlier diagnosis and improved prognosis for patients with that disease. The present study examined the relationship between the microbiome in the human oral cavity and oral squamous cell carcinoma (OSCC). We searched the literature for case-control studies which focused on the relationship between the human oral microbiome and OSCC. We aggregated three types of data from these studies: bacteriome data at the genus level, predicted functional pathway data, and gene abundance data. From these data, we noted several microbial genera which may be associated with oral cancer status, including Fusobacterium. We also identified functional pathways which merit further investigation, including RNA degradation (ko03018) and primary immunodeficiency (ko05340). In addition, our analysis of gene abundance data identified the gene K06147 (ATP-binding cassette, subfamily B, bacterial) as being over abundant in OSCC samples. Our results are generalizations which identified some currents that we believe could guide further research. Our work faced several limitations related to the heterogeneity of the available data. Wide variation in methods for sample collection, methods for controlling for known behavioral risk factors, computing platform choice, and methods for case-control design all posed confounding factors in this work. We examined the current methods of data collection, data processing, and data reporting in order to offer suggestions toward the establishment of best practices within this field. We propose that these limitations should be addressed through the implementation of standardized data analytic practices that will conform to the rigor and reproducibility standards required of publicly funded research.

The mechanisms by which the complexes CpCoL2 (Cp = C5H5; L = CO or CH2=CH2) mediate the cycloisomerizations of α,δ,ω-enynenes containing allylic ether linkages are probed by DFT methods. The outcomes corroborate experimental results and provide energetic and structural details of the trajectories leading to 3-(oxacyclopentyl or cycloalkyl)furans via the intermediacy of isolable CpCo-η 4-dienes. They comprise initial stereoselective complexation of one of the double bonds and the triple bond, rate-determining oxidative coupling to a triplet 16e cobalta-2-cyclopentene, and terminal double bond docking, followed by stereocontrolled insertion to assemble intermediate cis- and trans-fused triplet cobalta-4-cycloheptenes. A common indicator of the energetic facility of the latter is the extent of parallel alignment of the alkene moiety and its target Co–Cα bond. The cobalta-4-cycloheptenes transform further by β-hydride elimination–reductive elimination to furnish CpCo-η 4-dienes, which are sufficiently kinetically protected to allow for their experimental observation. The cascade continues through cobalt-mediated hydride shifts and dissociation of the aromatic furan ring. The findings in silico with respect to the stereo-, regio-, and chemoselectivity are in consonance with those obtained in vitro.

Context We describe a participatory framework that enhanced and implemented innovative changes to an existing distributed health data network (DHDN) infrastructure to support linkage across sectors and systems. Our processes and lessons learned provide a potential framework for other multidisciplinary infrastructure development projects that engage in a participatory decision-making process. Program The Childhood Obesity Data Initiative (CODI) provides a potential framework for local and national stakeholders with public health, clinical, health services research, community intervention, and information technology expertise to collaboratively develop a DHDN infrastructure that enhances data capacity for patient-centered outcomes research and public health surveillance. CODI utilizes a participatory approach to guide decision making among clinical and community partners. Implementation CODI's multidisciplinary group of public health and clinical scientists and information technology experts collectively defined key components of CODI's infrastructure and selected and enhanced existing tools and data models. We conducted a pilot implementation with 3 health care systems and 2 community partners in the greater Denver Metro Area during 2018-2020. Evaluation We developed an evaluation plan based primarily on the Good Evaluation Practice in Health Informatics guideline. An independent third party implemented the evaluation plan for the CODI development phase by conducting interviews to identify lessons learned from the participatory decision-making processes. Discussion We demonstrate the feasibility of rapid innovation based upon an iterative and collaborative process and existing infrastructure. Collaborative engagement of stakeholders early and iteratively was critical to ensure a common understanding of the research and project objectives, current state of technological capacity, intended use, and the desired future state of CODI architecture. Integration of community partners' data with clinical data may require the use of a trusted third party's infrastructure. Lessons learned from our process may help others develop or improve similar DHDNs.

Plasticity of glutamatergic synapses in the hippocampus is believed to underlie learning and memory processes. Surprisingly, very few studies report long-lasting structural changes of synapses induced by behavioral training. It remains, therefore, unclear which synaptic changes in the hippocampus contribute to memory storage. Here, we systematically compare how long-term potentiation of synaptic transmission (LTP) (a primary form of synaptic plasticity and cellular model of memory) and behavioral training affect hippocampal glutamatergic synapses at the ultrastructural level enabled by electron microscopy. The review of the literature indicates that while LTP induces growth of dendritic spines and post-synaptic densities (PSD), that represent postsynaptic part of a glutamatergic synapse, after behavioral training there is transient (6 h) synaptogenesis and long-lasting (24 h) increase in PSD volume (without a significant change of dendritic spine volume), indicating that training-induced PSD growth may reflect long-term enhancement of synaptic functions. Additionally, formation of multi-innervated spines (MIS), is associated with long-term memory in aged mice and LTP-deficient mutant mice. Since volume of PSD, as well as atypical synapses, can be reliably observed only with electron microscopy, we argue that the ultrastructural level of analysis is required to reveal synaptic changes that are associated with long-term storage of information in the brain.

Aim: This study is carried out to determine the prevalence of nasal carriage of staphylococcus aureus among Michael Okpara University of Agriculture Umudike (MOUAU) students and determine the antibiotics susceptibility pattern. Methods: Nasal swab specimens collected from the anterior nares were cultured on mannitol salt agar. S.aureus isolates were identified by mannitol fermentation, coagulase positivity and catalase positivity. Antimicrobial susceptibility test was performed on Meuller-Hinton Agar (MHA) by modified Kirby-Bauer disc diffusion method. Result: Out of the 100 swabs collected, S.aureus was isolated from 60% of the samples. Among colonized students, 63.3% (n=38) were from male students whereas 36.7% (n=22) were from female. The antibiotic susceptibility pattern of the Staphylococcus aureus isolates indicates that Staphylococcus aureus isolates showed high rate of sensitivity towards antibiotics as follows; Gentamycin (81.67%), followed by Ciprofloxacin (80%), Levofloxacin (76.67%), Ceftriaxone (58.33%), and resistance towards antibiotics Imipenem (100%) followed by Cefotaxime (90%), Cefexime (83.33%), Cefoxitin (65%), azithromycin (55%) and cefuroxime (50%). Conclusion: This study showed a high rate of nasal carriage of Staphylococcus aureus among MOUAU students and a high incidence of antibiotics resistant Staphylococcus aureus carriage.

Cotton dust exposure has been implicated in causing diseases like byssinosis and obstructive airway diseases like COPD and asthma. Long-term exposure to cotton dust causing interstitial lung disease and pulmonary fibrosis has been sparsely reported in the literature. Here, we report a case of an individual with long-term cotton dust exposure who presented with typical symptoms of interstitial lung disease and was managed conservatively.

COVID-19 pandemic has changed the lives of many especially those living with chronic diseases. India has the highest burden of multidrug resistant tuberculosis (MDR TB) in the world. The pandemic and the lockdown created multiple bottlenecks in the provision of healthcare as well as the distribution of medications. The stigma of tuberculosis leads to mental trauma, suffering, delay in diagnosis, and non-compliance to therapy. Lockdown imposed due to COVID-19, aggravated the fears of each patient and had made medical care access difficult. Here we describe a patient with MDR TB and chronic hepatitis B and how the course of the disease and its management was affected by COVID-19.