Patients and Medical Staff Attitudes Toward the Future Inclusion of eHealth in Tuberculosis Management:Perspectives From Six Countries Evaluated using a Qualitative Framework

Background: Digitally delivering healthcare services is very attractive for tuberculosis (TB) management as this disease has a complex diagnosis and lengthy management and involves multiple medical and nonmedical specialists. Especially in low- and middle-income countries, eHealth could potentially offer cost-effective solutions to bridge financial, social, time, and distance challenges. Objective: The goal of the research is to understand what would make eHealth globally applicable and gain insight into different TB situations, opportunities, and challenges. Methods: We performed focus group interviews with TB experts and patients from 6 different countries on 4 different continents. The focus group interviews followed the theory of planned behavior framework to offer structured recommendations for a versatile eHealth solution. The focus group interviews were preceded by a general demographic and technology use questionnaire Questionnaire results were analyzed using basic statistics in Excel (Microsoft Corporation). Focus group interview data were analyzed using ATLAS.ti 8 (ATLAS.ti Scientific Software Development GmbH) by assigning codes to quotations and grouping codes into the 5 domains within the framework. Results: A total of 29 patients and 32 medical staff members were included in our study. All medical staff had used the internet, whereas 31% (9/61) of patients had never been online. The codes with the most quotations were information in relation to eHealth (144 quotations) and communication (67 quotations). The consensus among all participants from all countries is that there are important communication and information gaps that could be bridged by an eHealth app. Participants from different countries also highlighted different challenges, such as a majority of asylum-seeker patients or lack of infrastructure that could be addressed with an eHealth app. Conclusions: Within the 6 countries interviewed, there is high enthusiasm toward eHealth in TB. A potential app could first target information and communication gaps in TB, with additional modules aimed at setting-specific challenges

Design of a Functionalized Metal-Organic Framework System for Enhanced Targeted Delivery to Mitochondria.

Mitochondria play a key role in oncogenesis and constitute one of the most important targets for cancer treatments. Although the most effective way to deliver drugs to mitochondria is by covalently linking them to a lipophilic cation, the in vivo delivery of free drugs still constitutes a critical bottleneck. Herein, we report the design of a mitochondria-targeted metal-organic framework (MOF) that greatly increases the efficacy of a model cancer drug, reducing the required dose to less than 1% compared to the free drug and ca. 10% compared to the nontargeted MOF. The performance of the system is evaluated using a holistic approach ranging from microscopy to transcriptomics. Super-resolution microscopy of MCF-7 cells treated with the targeted MOF system reveals important mitochondrial morphology changes that are clearly associated with cell death as soon as 30 min after incubation. Whole transcriptome analysis of cells indicates widespread changes in gene expression when treated with the MOF system, specifically in biological processes that have a profound effect on cell physiology and that are related to cell death. We show how targeting MOFs toward mitochondria represents a valuable strategy for the development of new drug delivery systems

Design of a functionalized metal-organic framework system for enhanced targeted delivery to mitochondria

Mitochondria play a key role in oncogenesis and constitute one of the most important targets for cancer treatments. Although the most effective way to deliver drugs to mitochondria is by covalently linking them to a lipophilic cation, the in vivo delivery of free drugs still constitutes a critical bottleneck. Herein, we report the design of a mitochondria-targeted metal-organic framework (MOF) that greatly increases the efficacy of a model cancer drug, reducing the required dose to less than 1% compared to the free drug and ca. 10% compared to the non-targeted MOF. The performance of the system is evaluated using a holistic approach ranging from microscopy to transcriptomics. Super-resolution microscopy of MCF-7 cells treated with the targeted MOF system reveals important mitochondrial morphology changes that are clearly associated with cell death as soon as 30 minutes after incubation. Whole transcriptome analysis of cells indicated widespread changes in gene expression when treated with the MOF system, specifically in biological processes that have a profound effect on cell physiology and that are related to cell death. We show how targeting MOFs towards mitochondria represents a valuable strategy for the development of new drug delivery systems

Keloids: Which Types Can Be Excised without Risk of Recurrence? A New Clinical Classification

Background: A surgical team from Interplast-Germany removed 387 keloids in 302 patients during 4 visits to Goma, Democratic Republic of the Congo, from 2015-2018. Preoperative and postoperative photographs and a thorough anamnesis of keloids were done for all patients. In addition, 18 selected biopsies from 4 types of keloids were histologically examined in Germany. Methods: Treatment options were tested and keloid recurrence rates were compared with data from questionnaires, photographs, and histology. Results: Keloids were classified accordingly as follows: (1) fresh nodular (continuously growing) keloids had a 30% recurrence rate after surgery: no common adjuvant therapy but triamcinolone acetonide (TAC) injections on onset, only; (a) earlobe keloids had the lowest recurrence rate after complete excision with negative resection margins; (2) superficial spreading (or butterfly) keloids were treated with TAC injections only; (3) mature (nongrowing or burned-out) keloids had also a low recurrence rate of 4.5%, which were then treated with TAC on onset, only; and (4) multiple keloids comprise various types in different stages. Conclusions: According to this classification, about 50% of keloids may be removed surgically without risk of recurrence in the examined patient population in Africa, where only TAC injections, but no radiation, are available. Adjuvant TAC or radiation should be started at the onset of recurrence and not generally

Design of a Functionalized Metal-Organic Framework System for Enhanced Targeted Delivery to Mitochondria.

Mitochondria play a key role in oncogenesis and constitute one of the most important targets for cancer treatments. Although the most effective way to deliver drugs to mitochondria is by covalently linking them to a lipophilic cation, the in vivo delivery of free drugs still constitutes a critical bottleneck. Herein, we report the design of a mitochondria-targeted metal-organic framework (MOF) that greatly increases the efficacy of a model cancer drug, reducing the required dose to less than 1% compared to the free drug and ca. 10% compared to the nontargeted MOF. The performance of the system is evaluated using a holistic approach ranging from microscopy to transcriptomics. Super-resolution microscopy of MCF-7 cells treated with the targeted MOF system reveals important mitochondrial morphology changes that are clearly associated with cell death as soon as 30 min after incubation. Whole transcriptome analysis of cells indicates widespread changes in gene expression when treated with the MOF system, specifically in biological processes that have a profound effect on cell physiology and that are related to cell death. We show how targeting MOFs toward mitochondria represents a valuable strategy for the development of new drug delivery systems

Microelectrode Arrays for Simultaneous Electrophysiology and Advanced Optical Microscopy

Advanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At the same time, microelectrode arrays (MEAs) are indispensable in understanding the language of neurons. Here, the authors show transparent MEAs capable of recording action potentials from neurons and compatible with advanced microscopy. The electrodes are made of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) and are patterned by optical lithography, ensuring scalable fabrication with good control over device parameters. A thickness of 380 nm ensures low enough impedance and >75% transparency throughout the visible part of the spectrum making them suitable for artefact-free recording in the presence of laser illumination. Using primary neuronal cells, the arrays record single units from multiple nearby sources with a signal-to-noise ratio of 7.7 (17.7 dB). Additionally, it is possible to perform calcium (Ca2+) imaging, a measure of neuronal activity, using the novel transparent electrodes. Different biomarkers are imaged through the electrodes using conventional and super-resolution microscopy (SRM), showing no qualitative differences compared to glass substrates. These transparent MEAs pave the way for harnessing the synergy between the superior temporal resolution of electrophysiology and the selectivity and high spatial resolution of optical imaging

Microelectrode Arrays for Simultaneous Electrophysiology and Advanced Optical Microscopy.

Funder: Cambridge TrustAdvanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At the same time, microelectrode arrays (MEAs) are indispensable in understanding the language of neurons. Here, the authors show transparent MEAs capable of recording action potentials from neurons and compatible with advanced microscopy. The electrodes are made of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) and are patterned by optical lithography, ensuring scalable fabrication with good control over device parameters. A thickness of 380 nm ensures low enough impedance and >75% transparency throughout the visible part of the spectrum making them suitable for artefact-free recording in the presence of laser illumination. Using primary neuronal cells, the arrays record single units from multiple nearby sources with a signal-to-noise ratio of 7.7 (17.7 dB). Additionally, it is possible to perform calcium (Ca2+) imaging, a measure of neuronal activity, using the novel transparent electrodes. Different biomarkers are imaged through the electrodes using conventional and super-resolution microscopy (SRM), showing no qualitative differences compared to glass substrates. These transparent MEAs pave the way for harnessing the synergy between the superior temporal resolution of electrophysiology and the selectivity and high spatial resolution of optical imaging.Cambridge Trust, University of Cambridge. Wellcome Trust (065807/Z/01/Z) (203249/Z/16/Z) UK Medical Research Council (MRC) (MR/K02292X/1) Alzheimer Research UK (ARUK) (ARUK-PG013-14) Michael J Fox Foundation (16238) Infinitus China Ltd. European Union's Horizon 2020 research and innovation programme under grant agreement no. 732032 (BrainCom)