Health Technologies

Medical devices designed for use in low-resource settings require unique and thoughtful design considerations to facilitate successful implementation and adoption. Usability testing is critical for good design but conducting research in international locations with intended target users is challenging and costly. Proxy user groups have been proposed as a reasonable solution when travel is impractical or wholly restricted, as it was during the Covid-19 pandemic. This study explored the viability of utilizing a proxy user group in Houston, TX, USA, to represent nurses in Blantyre, Malawi, to assess the usability of neonatal medical devices designed for use in sub-Saharan Africa. Seven devices were tested with 13 clinicians in Houston, Texas, and 17 clinicians in Blantyre, Malawi. Participants in Houston were carefully selected to mirror Malawi's expected demographics, particularly educational background and years of experience. This analysis compared the rates and types of use errors that occurred within each group. Results indicated that the Houston nurses recruited were an insufficient proxy to represent Malawian nurses in usability studies, with only 53.7% of errors observed in both groups. Furthermore, common errors identified tended to be more severe in Blantyre than in Houston, indicating that caution should be exercised when relying on proxy users. Future work should explore these observed differences further, and larger sample sizes should be utilized to assess the viability of a proxy group. Although proxy usability testing can be advantageous, testing with target users remains the gold standard.

The exposome accelerates the skin aging process, highlighting the need to use cosmetics capable of repairing the damage and maintaining the skin's physiological conditions. Thus, the present study aims to evaluate the potential anti-inflammatory and protective action of a dermocosmetic formulation combination of vitamins. For this, a gel-cream formulation added or not with 3% of ascorbyl tetraisopalmitate and 1% of D-panthenol was developed. The stability and sensory properties of these formulations were evaluated. In addition, a short-term clinical efficacy study of the formulations was carried out for 7 days. After this period, measurements were taken in terms of transepidermal water loss and blood microcirculation by Laser Doppler at the initial time and after the application of methyl nicotinate. The results showed that the formulations remained stable during the study period and showed pseudoplastic non-Newtonian behavior. In addition, the association of vitamins was effective in the protection of the skin against the effects of methyl nicotinate by reducing blood microcirculation, which suggests that the active substances in combination can have an anti-inflammatory and protective action on the skin barrier function.

ABSTRACT The Artificial Gravity Bed Rest – European Space Agency (AGBRESA) study was the first joint bed rest study by ESA, DLR, and NASA that examined the effect of simulated weightlessness on the human body and assessed the potential benefits of artificial gravity as a countermeasure in an analog of long-duration spaceflight. In this study, we investigated the impact of simulated microgravity on the gut microbiome of 12 participants during a 60-day head-down tilt bed rest at the :envihab facilities. Over 60 days of simulated microgravity resulted in a mild change in the gut microbiome, with distinct microbial patterns and pathway expression in the feces of the countermeasure group compared to the microgravity simulation-only group. Additionally, we found that the countermeasure protocols selectively increased the abundance of beneficial short-chain fatty acids in the gut, such as acetate, butyrate, and propionate. Some physiological signatures also included the modulation of taxa reported to be either beneficial or opportunistic, indicating a mild adaptation in the microbiome network balance. Our results suggest that monitoring the gut microbial catalog along with pathway clustering and metabolite profiling is an informative synergistic strategy to determine health disturbances and the outcome of countermeasure protocols for future space missions.

In recent years, the field of radiotherapy has witnessed remarkable advancements with the integration of artificial intelligence (AI) technologies into clinical practice.
 Traditionally, radiotherapy treatment planning has been a labor-intensive process, requiring meticulous manual segmentation and optimization. With the advent of AI, particularly deep learning algorithms, the accuracy and efficiency of target delineation and organ-at-risk segmentation have significantly improved. AI-driven algorithms analyze voluminous medical imaging data, enabling rapid and precise contouring, thus expediting the planning phase and reducing inter-observer variability.
 Furthermore, AI's role extends to treatment plan optimization, where it intelligently explores vast parameter spaces to generate optimal plans tailored to individual patients. This not only saves dosimetrists' time but also enhances plan quality by accounting for complex anatomical variations and personalized clinical goals.
 In the realm of treatment delivery, AI-powered real-time image guidance enhances the accuracy of patient positioning, ensuring precise radiation targeting. Adaptive radiotherapy, enabled by AI, allows on-the-fly plan modifications in response to anatomical changes, significantly improving treatment accuracy in scenarios like tumor shrinkage or weight loss.
 Beyond planning and delivery, AI algorithms contribute to outcome prediction by analyzing historical patient data and treatment responses. This predictive capability aids clinicians in making informed decisions and refining treatment strategies for better prognoses.
 Despite the revolutionary potential, challenges remain in seamlessly integrating AI into clinical workflows. Ethical considerations, data privacy, and algorithm interpretability necessitate cautious implementation. Additionally, fostering interdisciplinary collaboration between AI experts and radiation oncologists is imperative to harness the technology's full potential.
 This paper explores the impact of AI in four key areas of radiotherapy: automated segmentation, dosimetric and machine quality assurance, adaptive radiation therapy, and clinical outcome prediction.

Abstract Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients. Brain organoids from CTD donors had reduced creatine uptake compared with those from healthy donors. The expression of neural progenitor cell markers SOX2 and PAX6 was reduced in CTD derived organoids, while GSK3β, a key regulator of neurogenesis, was up-regulated. Shotgun proteomics combined with integrative bioinformatic and statistical analysis identified changes in abundance of proteins associated with intellectual disability, epilepsy, and autism. Re-establishment of the expression a functional SLC6A8 in CTD-derived organoids restored creatine uptake and normalized the expression of SOX2, GSK3β and other key proteins associated with clinical features of CTD patients. Our brain organoid model opens new avenues for further characterizing the CTD pathophysiology and supports the concept that reinstating creatine levels in patients with CTD could result in therapeutic efficacy.

Introduction:Mental health disorders are common in cancer patients. However, these disorders are still underestimated in oncology. The aim of the present study is to examine the effect of breast cancer and gynecological cancer on mental health disorders in women who have undergone nonsurgical antineoplastic treatment for gyneco-mammary cancer and to investigate the predictors of these mental disorders.Material and Methods:A cross-sectional study was carried out on Moroccan women treated with nonsurgical treatment for breast or gynecological cancer (N=200). The Hospital Anxiety and Depression Scale, Body Image Scale, Pittsburgh Sleep Quality Index, Rosenberg’s Self-Esteem Scale, and Multidimensional Scale of Perceived Social Support, were used.Results:The type of cancer had a significant effect on mental health disorders but not the age. Women with breast cancer had significantly more mental health problems than women with gynecological cancer (P-values ​​<0.01). The predictive model of anxiety included the effects of the following variables: having a lower school level and an advanced tumor stage. While the predictive model of depression included advanced tumor stage and disease recurrence. For poor sleep quality, the variables included were: not having an occupation and having a lower monthly income. The variables that predicted body image dissatisfaction were: being younger, being unmarried, and living in a rural area.Conclusion:High mental distress in women with breast cancer and gynecological cancer is favored by several predictive factors. The implementation of a protocol for the assessment and management of distress is necessary in oncology departments.

FLT3 mutations are found in 30% of AML cases and are actionable by tyrosine kinase inhibitors. Here, we discovered that C/EBPα regulates FA biosynthesis and protection from lipid redox stress downstream mutant-FLT3 signaling, which confers a vulnerability to ferroptosis upon FLT3 inhibition with therapeutic potential in AML. This article is highlighted in the In This Issue feature, p. 1501.

Research on graphene based nanomaterials has flourished in the last decade due their unique properties and emerging socio-economic impact. In the context of their potential exploitation for biomedical applications, there is a growing need for the development of more efficient imaging techniques to track the fate of these materials. Herein we propose the first correlative imaging approach based on the combination of radioimaging and mass spectrometry imaging for the detection of Graphene Oxide (GO) labelled with carbon-14 in mice. In this study, 14C-graphene oxide nanoribbons were produced from the oxidative opening of 14C-carbon nanotubes, and were then intensively sonicated to provide nano-size 14C-GO flakes. After Intravenous administration in mice, 14C-GO distribution was quantified by radioimaging performed on tissue slices. On the same slices, MS-imaging provided a highly resolved distribution map of the nanomaterial based on the detection of specific radical anionic carbon clusters ranging from C2˙- to C9˙- with a base peak at m/z 72 (12C) and 74 (14C) under negative laser desorption ionization mass spectrometry (LDI-MS) conditions. This proof of concept approach synergizes the strength of each technique and could be advantageous in the pre-clinical development of future Graphene-based biomedical applications.

Chemotherapy is almost exclusively administered via theintravenous(IV) route, which has serious limitations (e.g., patient discomfort,long hospital stays, need for trained staff, high cost, catheter failures,infections). Therefore, the development of effective and less costlychemotherapy that is more comfortable for the patient would revolutionizecancer therapy. While subcutaneous (SC) administration has the potentialto meet these criteria, it is extremely restrictive as it cannot beapplied to most anticancer drugs, such as irritant or vesicant ones,for local toxicity reasons. Herein, we report a facile, general, andscalable approach for the SC administration of anticancer drugs throughthe design of well-defined hydrophilic polymer prodrugs. This wasapplied to the anticancer drug paclitaxel (Ptx) as a worst-case scenariodue to its high hydrophobicity and vesicant properties (two factorspromoting necrosis at the injection site). After a preliminary screeningof well-established polymers used in nanomedicine, polyacrylamide(PAAm) was chosen as a hydrophilic polymer owing to its greater physicochemical,pharmacokinetic, and tumor accumulation properties. A small libraryof Ptx-based polymer prodrugs was designed by adjusting the natureof the linker (ester, diglycolate, and carbonate) and then evaluatedin terms of rheological/viscosity properties in aqueous solutions,drug release kinetics in PBS and in murine plasma, cytotoxicity ontwo different cancer cell lines, acute local and systemic toxicity,pharmacokinetics and biodistribution, and finally their anticancerefficacy. We demonstrated that Ptx-PAAm polymer prodrugs could besafely injected subcutaneously without inducing local toxicity whileoutperforming Taxol, the commercial formulation of Ptx, thus openingthe door to the safe transposition from IV to SC chemotherapy.