Usability, Appeal, and Relevance of Music and Wellbeing Training for Carers of People with Dementia: A Think-Aloud Study.

Background: Personalized music listening can be highly effective in supporting people experiencing changes in mood and behavior due to Alzheimer's disease and other conditions causing dementia. However, a lack of staff education can be a barrier to effective use of music in residential aged care. Objective: This study investigates the usability, appeal and relevance of an online training course designed to help care staff develop personalized music programs for people living with dementia in their care. Methods: A mixed methods approach was taken in which 13 participants took part in a think-aloud session while using the training. Qualitative data from the think-aloud session and interviews were triangulated with results of a survey evaluation of the training. Results: Themes relating to Engagement, Usability and Appeal, Pedagogical Design and Content, and Transfer, Impact and Barriers to Uptake were discussed. Results indicated that participants regarded the virtual environment and pedagogical design as of high quality, although some minor issues in navigability were identified. Participants also found the training to be highly relevant to their roles as caregivers and reported ways they would incorporate key concepts into care practices. However, ongoing barriers to implementation of such training were identified including systemic issues that contribute to a culture of focus on physical care. Conclusions: Consistency of navigation and clear instructions for interacting with content are important in training of time-poor care staff. Linking training to industry standards can provide important motivation for implementation of training, although systemic barriers can impede real-world change.

Urease-powered nanobots for radionuclide bladder cancer therapy.

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.

Biomarkers of axonal damage to favor early diagnosis in variant transthyretin amyloidosis (A-ATTRv).

Early identification of ATTRv amyloidosis disease onset is still often delayed due to the lack of validated biomarkers of this disease. Light chain neurofilament (NfL) have shown promising results in early diagnosis in this disease, but data is still needed, including with alternative measuring methods. Our aim was to study the levels of NfL measured by ELISA. Furthermore, interstitial matrix metalloproteinase type 1 (MMP-1) serum levels were measured as a potential new biomarker in ATTRv. Serum NfL and MMP-1 were measured using ELISA assays in 90 participants (29 ATTR-V30M patients, 31 asymptomatic V30M-TTR variant carriers and 30 healthy controls). Median NfL levels among ATTRv amyloidosis patients were significantly higher (116 pg/mL vs 0 pg/mL in both comparison groups). The AUC comparing ATTRv amyloidosis patients and asymptomatic carriers was 0.90 and the NfL concentration of 93.55 pg/mL yielded a sensitivity of 79% and a specificity of 87%. NfL levels had a significant positive correlation with NIS values among patients. We found a negative significant correlation between eGFR and NfL levels. Finally, MMP1 levels were not different between groups. Evidence of NfL use for early diagnosis of ATTR-PN amyloidosis is growing. ELISA seems a reliable and available technique for it quantification. Decreased GFR could influence NfL plasma levels.

The High Plasticity of Nonpathogenic Mycobacterium brumae Induces Rapid Changes in Its Lipid Profile during Pellicle Maturation: The Potential of This Bacterium as a Versatile Cell Factory for Lipid Compounds of Therapeutic Interest.

The immunomodulatory potential of mycobacteria to be used for therapeutic purposes varies by species and culture conditions and is closely related to mycobacterial lipid composition. Although the lipids present in the mycobacterial cell wall are relevant, lipids are mainly stored in intracellular lipid inclusions (ILIs), which have emerged as a crucial structure in understanding mycobacteria-host interaction. Little is known about ILI ultrastructure, production, and composition in nonpathogenic species. In this study, we compared the lipid profiles of the nonpathogenic immunomodulatory agent Mycobacterium brumae during pellicle maturation under different culture conditions with qualitative and quantitative approaches by using high-resolution imaging and biochemical and composition analyses to understand ILI dynamics. The results showed wax esters, mainly in early stages of development, and acylglycerols in mature ILI composition, revealing changes in dynamics, amount, and morphometry, depending on pellicle maturation and the culture media used. Low-glycerol cultures induced ILIs with lower molecular weights which were smaller in size in comparison with the ILIs produced in glycerol-enriched media. The data also indicate the simple metabolic plasticity of lipid synthesis in M. brumae, as well as its high versatility in generating different lipid profiles. These findings provide an interesting way to enhance the production of key lipid structures via the simple modulation of cell culture conditions.

Remodeling the bladder tumor immune microenvironment by mycobacterial species with changes in their cell envelope composition.

Intravesical BCG instillation after bladder tumor resection is the standard treatment for non-muscle invasive bladder cancer; however, it is not always effective and frequently has undesirable side effects. Therefore, new strategies that improve the clinical management of patients are urgently needed. This study aimed to comprehensively evaluate the bladder tumor immune microenvironment profile after intravesical treatment with a panel of mycobacteria with variation in their cell envelope composition and its impact on survival using an orthotopic murine model to identify more effective and safer therapeutic strategies. tumor-bearing mice were intravesically treated with a panel of BCG and M. brumae cultured under different conditions. Untreated tumor-bearing mice and healthy mice were also included as controls. After mycobacterial treatments, the infiltrating immune cell populations in the bladder were analysed by flow cytometry. We provide evidence that mycobacterial treatment triggered a strong immune infiltration into the bladder, with BCG inducing higher global absolute infiltration than M. brumae. The induced global immune microenvironment was strikingly different between the two mycobacterial species, affecting both innate and adaptive immunity. Compared with M. brumae, BCG treated mice exhibited a more robust infiltration of CD4+ and CD8+ T-cells skewed toward an effector memory phenotype, with higher frequencies of NKT cells, neutrophils/gMDSCs and monocytes, especially the inflammatory subset, and higher CD4+ TEM/CD4+ Treg and CD8+ TEM/CD4+ Treg ratios. Conversely, M. brumae treatment triggered higher proportions of total activated immune cells and activated CD4+ and CD8+ TEM cells and lower ratios of CD4+ TEM cells/CD4+ Tregs, CD8+ TEM cells/CD4+ Tregs and inflammatory/reparative monocytes. Notably, the mycobacterial cell envelope composition in M. brumae had a strong impact on the immune microenvironment, shaping the B and myeloid cell compartment and T-cell maturation profile and thus improving survival. Overall, we demonstrate that the bladder immune microenvironment induced by mycobacterial treatment is species specific and shaped by mycobacterial cell envelope composition. Therefore, the global bladder immune microenvironment can be remodelled, improving the quality of infiltrating immune cells, the balance between inflammatory and regulatory/suppressive responses and increasing survival.

Creativity in lockdown: Understanding how music and the arts supported mental health during the COVID-19 pandemic by age group.

Recent research has indicated that many people around the world turned to artistic creative activities (ACAs) to support their mental health during COVID-19 lockdowns. However, studies have also shown that the negative psychosocial impacts of the pandemic have disproportionately affected young people, suggesting that the use of ACAs to support mental health in lockdown may have varied across age groups. This study investigated how Australians in four different age groups (18-24, 25-34, 35-54, and 55+) engaged in ACAs to support their mental health during the 2020 pandemic lockdowns. Participants (N = 653) recruited from the general public completed an online survey between May and October 2020, in which they reported which ACAs they had undertaken during the pandemic using an established list. Participants subsequently ranked undertaken ACAs in terms of effectiveness at making them "feel better," and those who had engaged in musical ACAs also completed the Musical Engagement Questionnaire (MusEQ). Additionally, ratings of anxiety (GAD7) and depression (PHQ9) symptoms were obtained and examined for potential variations across four diverse variables: age, exercise, gender and state/territory of residence. ACA rankings showed that younger participants overwhelmingly rated musical activities as most effective, while, with the exception of singing, those aged 55+ rated non-musical activities as being most effective. These differences were further supported by ratings for all six MusEQ subscales, with responses strongly indicating that the youngest participants (aged 18-24) used music in significantly different ways during the pandemic than participants in all other age groups. Specifically, these youngest participants were more likely to integrate music into daily life, use music for emotion regulation, respond to music in embodied ways, and use music to perform a social identity. In line with prior research, further analyses indicated that symptoms of anxiety and depression were lessened for older participants, as well for those who reported exercising more during the lockdowns. These findings provide insight into how ACAs can support mental health during a pandemic crisis for specific age groups, which may inform future policy directions, and suggestions for how this can be done are provided.

Mycobacterial surface characters remodeled by growth conditions drive different tumor-infiltrating cells and systemic IFN-γ/IL-17 release in bladder cancer treatment.

The mechanism of action of intravesical Mycobacterium bovis BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation of BCG-unresponsive patients, who have scarce further therapeutic options. BCG is grown under diverse culture conditions worldwide, which can impact the antitumor effect of BCG strains and could be a key parameter of treatment success. Here, BCG and the nonpathogenic Mycobacterium brumae were grown in four culture media currently used by research laboratories and BCG manufacturers: Sauton-A60, -G15 and -G60 and Middlebrook 7H10, and used as therapies in the orthotopic murine BC model. Our data reveal that each mycobacterium requires specific culture conditions to induce an effective antitumor response. since higher survival rates of tumor-bearing mice were achieved using M. brumae-A60 and BCG-G15 than the rest of the treatments. M. brumae-A60 was the most efficacious among all tested treatments in terms of mouse survival, cytotoxic activity of splenocytes against tumor cells, higher systemic production of IL-17 and IFN-É£, and bladder infiltration of selected immune cells such as ILCs and CD4TEM. BCG-G15 triggered an antitumor activity based on a massive infiltration of immune cells, mainly CD3+ (CD4+ and CD8+) T cells, together with high systemic IFN-É£ release. Finally, a reduced variety of lipids was strikingly observed in the outermost layer of M. brumae-A60 and BCG-G15 compared to the rest of the cultures, suggesting an influence on the antitumor immune response triggered. These findings contribute to understand how mycobacteria create an adequate niche to help the host subvert immunosuppressive tumor actions.

Developing online training in using music for carers of people with dementia: A focus group study.

OBJECTIVE: This study aimed to identify the core content and design issues in developing an online training course in the effective use of music for people with dementia. METHODS: A co-design approach was taken in which focus groups were conducted with aged care staff and family caregivers (n = 17; 76.5% female). A general inductive approach was taken to data analysis. The consolidated criteria for reporting qualitative research (COREQ) guidelines were followed to ensure rigour in this study. RESULTS: Participants identified five core concepts for inclusion in the training program including the benefits of music, the need to assess for vulnerability to negative responses, music selection strategies, timing of use and equipment selection. Themes on design and implementation such as the need for role-specific content for care staff at all levels and scenario-based learning were identified. CONCLUSIONS: The development of online training in music use for carers of people with dementia needs to consider the demands on carers and develop training that is informative and engaging without placing large time demands on the user. Support at a management and executive level will be important to the implementation of such training in residential aged care contexts.

Encouraging help-seeking and engagement in a mental health app: What young people want.

Although many young people evince a preference for digital mental health support over face to face, engagement with smartphone apps for mental health remains relatively low, particularly in young people not accessing professional support services. While some of this can be attributed to stigma or embarrassment, there is also a need for developers and researchers to investigate features which promote long-term usage. MoodyTunes is a music-based smartphone app that has been co-designed with young people to help them develop effective self-management strategies for mood through music listening. Four focus groups with young people (N = 24, aged 13-25) were conducted to workshop how MoodyTunes could promote help-seeking behaviours and long-term engagement with the app. Online discussions following a broad topic guide were held in groups of 4-7 in which participants explored topics including the use of social features, promoting help-seeking behaviour, gamification and mood tracking. Participants also viewed visual materials and offered ideas about visual design both verbally and on paper. A general inductive approach was taken to analysis of qualitative data. Three primary themes were identified in the data: privacy; user empowerment; and engagement vs. achievement. Participants voiced a strong desire to remain anonymous and to feel empowered to make their own decisions about accessing professional help. Sensitive use of language was noted as critical, with some participants noting that the use of more directive language could have a negative impact on their mental health and that motivational features should focus on engagement with the primary aim of the app rather than rewarding achievement. Findings highlight the benefits of a co-design approach and provide key insights into how mental health apps may be able to improve long-term user engagement with young people.

The Role of Artistic Creative Activities in Navigating the COVID-19 Pandemic in Australia.

During the COVID-19 pandemic some Australians turned to artistic creative activities (ACAs) as a way of managing their own mental health and well-being. This study examined the role of ACAs in regulating emotion and supporting mental health and well-being during the COVID-19 pandemic, and also attempted to identify at-risk populations. We proposed that (1) participants would use ACAs as avoidance-based emotion regulation strategies; and (2) music engagement would be used for emotion regulation. Australian participants (N = 653) recruited from the general public completed an online survey, which included scales targeting anxiety (GAD7 scale), depression (PHQ9 scale) and loneliness (two UCLA Loneliness Scales, referring to "Before" and "Since" COVID-19). Participants reported which ACAs they had undertaken and ceased during the pandemic using an established list and ranked their undertaken ACAs in terms of effectiveness at making them "feel better." For their top-ranked ACA, participants then completed the Emotion Regulation Scale for Artistic Creative Activities (ERS-ACA), and if participants had undertaken any musical ACAs, also the Musical Engagement Questionnaire (MusEQ). The results supported both hypotheses. ANOVAs indicated that participants ranked significantly higher on the "avoidance" ERS-ACA subscale than the other subscales, and that participants ranked significantly higher on the emotion regulation and musical preference MusEQ subscales than the other subscales. Additionally, while ACAs such as "Watching films or TV shows" and "Cookery or baking" were common, they ranked poorly as effective methods of emotion regulation, whereas "Listening to music" was the second-most frequently undertaken ACA and also the most effective. "Singing" and "Dancing" were among the most ceased ACAs but also ranked among the most effective for emotion regulation, suggesting that support for developing pandemic-safe approaches to these ACAs may provide well-being benefits in future crises. Additionally, correlation analyses showed that younger participants, those who took less exercise during the pandemic, and those with the highest musical engagement reported the poorest well-being. We conclude that ACAs provided an important resource for supporting mental health and well-being during the COVID-19 pandemic in Australia and could potentially support mental health and well-being in future crises.

Benefits, Challenges and Solutions for Implementing Personalised Music Playlist Programs in Residential Aged Care in Australia.

INTRODUCTION: Residential aged care facilities face the immense challenge of adapting to the increasingly high needs of their residents, while delivering personalised, holistic care. There is considerable evidence that music can provide an affordable, accessible way to reduce changes in behaviour associated with dementia, in order to meet these standards of care. However, a number of barriers exist to the effective implementation of music programs in long-term aged care facilities. METHODS: This study involved focus groups with 17 participants including staff in residential aged care facilities and family caregivers to investigate the benefits of music programs, as well as the challenges and possible solutions to them. A general inductive approach was taken to data analysis. RESULTS: A number of benefits of music programs were identified, including improvements to the wellbeing of both residents of aged care facilities and their caregivers. However, an ingrained culture within residential aged care of focusing on physical care rather than thinking holistically about wellbeing was identified as a significant barrier. DISCUSSION: These findings revealed that education is a key component of changing ingrained cultures of task-driven care at both a managerial level and in care staff, so that attention can be given to psychological and emotional needs as well as the physical.

Swarming behavior and in vivo monitoring of enzymatic nanomotors within the bladder.

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either 124I on gold nanoparticles or 18F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors' self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications.

Analysis of the Lipid Composition of Mycobacteria by Thin Layer Chromatography.

Mycobacteria species can differ from one another in the rate of growth, presence of pigmentation, the colony morphology displayed on solid media, as well as other phenotypic characteristics. However, they all have in common the most relevant character of mycobacteria: its unique and highly hydrophobic cell wall. Mycobacteria species contain a membrane-covalent linked complex that includes arabinogalactan, peptidoglycan, and long-chains of mycolic acids with types that differ between mycobacteria species. Additionally, mycobacteria can also produce lipids that are located, non-covalently linked, on their cell surfaces, such as phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL), glycopeptidolipids (GPL), acyltrehaloses (AT), or phosphatidil-inositol mannosides (PIM), among others. Some of them are considered virulence factors in pathogenic mycobacteria, or critical antigenic lipids in host-mycobacteria interaction. For these reasons, there is a significant interest in the study of mycobacterial lipids due to their application in several fields, from understanding their role in the pathogenicity of mycobacteria infections, to a possible implication as immunomodulatory agents for the treatment of infectious diseases and other pathologies such as cancer. Here, a simple approach to extract and analyze the total lipid content and the mycolic acid composition of mycobacteria cells grown in a solid medium using mixtures of organic solvents is presented. Once the lipid extracts are obtained, thin-layer chromatography (TLC) is performed to monitor the extracted compounds. The example experiment is performed with four different mycobacteria: the environmental fast-growing Mycolicibacterium brumae and Mycolicibacterium fortuitum, the attenuated slow-growing Mycobacterium bovis bacillus Calmette-Guérin (BCG), and the opportunistic pathogen fast-growing Mycobacterium abscessus, demonstrating that methods shown in the present protocol can be used to a wide range of mycobacteria.

Music playlists for people with dementia: Qualitative evaluation of a guide for caregivers.

This study aimed to evaluate a set of guidelines for music use with people with dementia. A secondary aim was to identify challenges and barriers to implementation of music interventions by caregivers. Caregivers (n = 16) were interviewed after implementing a music listening programme based on the guidelines with 29 people with dementia in home-care and aged care facilities. Caregivers found the guidelines informative, easy to understand and use. Positive effects on mood, reduced agitation and reduced challenges to care were reported. Difficulties with technology and finding time to implement the music programme were identified. Results highlight the need for more research around appropriate technology and the streamlining of processes and procedures for aged care staff. Further iterations of the guidelines will need to address these issues and consider the differing needs of home-based carers and aged care providers separately.

BCG Substrains Change Their Outermost Surface as a Function of Growth Media.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) efficacy as an immunotherapy tool can be influenced by the genetic background or immune status of the treated population and by the BCG substrain used. BCG comprises several substrains with genetic differences that elicit diverse phenotypic characteristics. Moreover, modifications of phenotypic characteristics can be influenced by culture conditions. However, several culture media formulations are used worldwide to produce BCG. To elucidate the influence of growth conditions on BCG characteristics, five different substrains were grown on two culture media, and the lipidic profile and physico-chemical properties were evaluated. Our results show that each BCG substrain displays a variety of lipidic profiles on the outermost surface depending on the growth conditions. These modifications lead to a breadth of hydrophobicity patterns and a different ability to reduce neutral red dye within the same BCG substrain, suggesting the influence of BCG growth conditions on the interaction between BCG cells and host cells.

Music Playlists for People with Dementia: Trialing A Guide for Caregivers.

BACKGROUND: Music programs have the potential to provide an effective non-pharmacological tool for caregivers to reduce depression and agitation and increase quality of life in people with dementia. However, where such programs are not facilitated by a trained music therapist, caregivers need greater access to information about how to use music most effectively in response to key challenges to care, and how to pre-empt and manage adverse responses. OBJECTIVE: This study reports on the trial of a Guide for use of music with 45 people with dementia and their caregivers in residential care facilities and home-based care. METHODS: The study used a pre-post experimental design in which participants were randomly allocated to a treatment group or a waitlist control group. RESULTS: Improvements to quality of life were found in the experimental group over the 6-week period. Significant increases in Interest, Responsiveness, Initiation, Involvement, and Enjoyment were reported for individual listening sessions. CONCLUSION: The Guide can provide an effective protocol for caregivers to follow in selecting music to manage particular challenges to care, confirming the need for caregivers to be prepared to monitor and manage potential negative responses.

Mycobacteria-Based Vaccines as Immunotherapy for Non-urological Cancers.

The arsenal against different types of cancers has increased impressively in the last decade. The detailed knowledge of the tumor microenvironment enables it to be manipulated in order to help the immune system fight against tumor cells by using specific checkpoint inhibitors, cell-based treatments, targeted antibodies, and immune stimulants. In fact, it is widely known that the first immunotherapeutic tools as immune stimulants for cancer treatment were bacteria and still are; specifically, the use of Mycobacterium bovis bacillus Calmette-Guérin (BCG) continues to be the treatment of choice for preventing cancer recurrence and progression in non-invasive bladder cancer. BCG and also other mycobacteria or their components are currently under study for the immunotherapeutic treatment of different malignancies. This review focuses on the preclinical and clinical assays using mycobacteria to treat non-urological cancers, providing a wide knowledge of the beneficial applications of these microorganisms to manipulate the tumor microenvironment aiming at tumor clearance.

Each Mycobacterium Requires a Specific Culture Medium Composition for Triggering an Optimized Immunomodulatory and Antitumoral Effect.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) remains the first treatment option for non-muscle-invasive bladder cancer (BC) patients. In research laboratories, M. bovis BCG is mainly grown in commercially available media supplemented with animal-derived agents that favor its growth, while biomass production for patient treatment is performed in Sauton medium which lacks animal-derived components. However, there is not a standardized formulation of Sauton medium, which could affect mycobacterial characteristics. Here, the impact of culture composition on the immunomodulatory and antitumor capacity of M. bovis BCG and Mycolicibacterium brumae, recently described as efficacious for BC treatment, has been addressed. Both mycobacteria grown in Middlebrook and different Sauton formulations, differing in the source of nitrogen and amount of carbon source, were studied. Our results indicate the relevance of culture medium composition on the antitumor effect triggered by mycobacteria, indicating that the most productive culture medium is not necessarily the formulation that provides the most favorable immunomodulatory profile and the highest capacity to inhibit BC cell growth. Strikingly, each mycobacterial species requires a specific culture medium composition to provide the best profile as an immunotherapeutic agent for BC treatment. Our results highlight the relevance of meticulousness in mycobacteria production, providing insight into the application of these bacteria in BC research.

Mycolicibacterium brumae Is a Safe and Non-Toxic Immunomodulatory Agent for Cancer Treatment.

Intravesical Mycobacterium bovis Bacillus Calmette-Guérin (BCG) immunotherapy remains the gold-standard treatment for non-muscle-invasive bladder cancer patients, even though half of the patients develop adverse events to this therapy. On exploring BCG-alternative therapies, Mycolicibacterium brumae, a nontuberculous mycobacterium, has shown outstanding anti-tumor and immunomodulatory capabilities. As no infections due to M. brumae in humans, animals, or plants have been described, the safety and/or toxicity of this mycobacterium have not been previously addressed. In the present study, an analysis was made of M. brumae- and BCG-intravenously-infected severe combined immunodeficient (SCID) mice, M. brumae-intravesically-treated BALB/c mice, and intrahemacoelic-infected-Galleria mellonella larvae. Organs from infected mice and the hemolymph from larvae were processed to count bacterial burden. Blood samples from mice were also taken, and a wide range of hematological and biochemical parameters were analyzed. Finally, histopathological alterations in mouse tissues were evaluated. Our results demonstrate the safety and non-toxic profile of M. brumae. Differences were observed in the biochemical, hematological and histopathological analysis between M. brumae and BCG-infected mice, as well as survival curves rates and colony forming units (CFU) counts in both animal models. M. brumae constitutes a safe therapeutic biological agent, overcoming the safety and toxicity disadvantages presented by BCG in both mice and G. mellonella animal models.

Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update.

Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.