Spanish adaptation of meaning-centered psychotherapy for participants with cancer: Study protocol of a randomized control Trial

Background: Meaning-Centered Psychotherapy (MCP) is effective in improving meaning in life, hope, optimism, self-efficacy, well-being, and quality of life, and in reducing stress in people with cancer. However, all the studies on the application of MCP in cancer patients have been carried out in Anglo-Saxon samples. Therefore, it is necessary to adapt and verify the efficacy of MCP in populations that speak languages other than English, such as Spanish. Moreover, to expand the data supporting the efficacy of MCP for cancer patients, it would be necessary to compare MCP to other active therapies such as Cognitive Behavioral Therapy (CBT). Methods: The aims of the proposed study are: the first objective is to verify the efficacy of the MCP intervention for Spanish participants with cancer in a randomized control trial (RCT) comparing it to CBT. The second objective is to analyze the feasibility and acceptance of MCP in Spanish participants with cancer. The third objective is to analyze whether the changes produced in the meaning in life dimensions (presence, search, comprehension, purpose, and mattering) will predict changes in anxiety, depression, quality of life, etc. Our research team adapted MCP for Spanish participants with cancer. This paper presents the study protocol. The study design consists of a two-arm RCT with two conditions: MCP and CBT, where participants will be randomized to one of the two groups. Eligible participants will be adults with stage I, II, and III cancer who were treated with curative intent and had completed their main medical treatment (surgery, radiotherapy, or chemotherapy). Participants will be assessed at pretreatment, post-treatment, and 6-month follow-up. The intention-to-treat principle will be used when analyzing data, using mixed-effects models with full information and maximum likelihood estimation. Discussion: This study will provide results that confirm the efficacy of the MCP in Spanish participants with cancer. Trial Registration: ClinicalTrials.gov; https://register.clinicaltrials.gov/prs/app/template/Home.vm?uid=U0005WS9&ts=4&sid=S000BOTT&cx=bvr2ue, identifier NCT0519734

One Health Approach: Invasive California Kingsnake (Lampropeltis californiae) as an Important Source of Antimicrobial Drug-Resistant Salmonella Clones on Gran Canaria Island

The increase in the reptile population has led to a rise in the number of zoonotic infections due to close contact with reptiles, with reptile-associated salmonellosis being particularly relevant. California kingsnake invasion not only threatens the endemic reptile population of the island of Gran Canaria (Spain) but also poses serious public health problems by spreading zoonotic pathogens and their antimicrobial resistance (AMR) to the environment. Thus, the aim of this study was to assess the occurrence, genetic diversity, and AMR among Salmonella spp. strains isolated from California kingsnakes in Gran Canaria Island (Spain). Of 73 invasive individuals captured, 20.5% carried Salmonella spp., belonging to different subspecies and serovars, with subsp. salamae as the most abundant. Pulsed-field electrophoresis showed high genetic diversity among subsp. salamae isolates, and among these, 73.3% showed resistance to at least one of the antimicrobials tested. In conclusion, the present study revealed the importance of wild invasive California kingsnakes as reservoirs of drug-resistant Salmonella spp. that could pose a direct threat to livestock and humans. Identification of drug-resistant Salmonella strains in wildlife provides valuable information on potential routes of transmission that involve risks to public and animal health.This study was supported by the project “POSTLIFE+ Lampropeltis para el control de la culebra real de California en Gran Canaria (LIFE10/NAT/ES/656)” financed by the Government of Canary Islands, Cabildo of Gran Canaria and Universidad Cardenal Herrera-CEU (IDOC 19/15, and INDI 20-21, INDI 22-34).info:eu-repo/semantics/publishedVersio

One Health Approach : Invasive California Kingsnake (Lampropeltis californiae) as an Important Source of Antimicrobial Drug-Resistant Salmonella Clones on Gran Canaria Island

The aim of this study was to investigate the invasive species Lampropeltis californiae (California kingsnake) as a reservoir of Salmonella and its ability to spread different clones of the bacterium with zoonotic potential into the environment, as well as study its antimicrobial resistance patterns in Gran Canaria (Spain). The main results showed that a high diversity of Salmonella subsp. salamae strains circulate in Gran Canaria with a high prevalence of resistance shown for antimicrobials of public health importance, as summarised in the European Decision 2013/652/EU. The increase in the reptile population has led to a rise in the number of zoonotic infections due to close contact with reptiles, with reptile-associated salmonellosis being particularly relevant. California kingsnake invasion not only threatens the endemic reptile population of the island of Gran Canaria (Spain) but also poses serious public health problems by spreading zoonotic pathogens and their antimicrobial resistance (AMR) to the environment. Thus, the aim of this study was to assess the occurrence, genetic diversity, and AMR among Salmonella spp. strains isolated from California kingsnakes in Gran Canaria Island (Spain). Of 73 invasive individuals captured, 20.5% carried Salmonella spp., belonging to different subspecies and serovars, with subsp. salamae as the most abundant. Pulsed-field electrophoresis showed high genetic diversity among subsp. salamae isolates, and among these, 73.3% showed resistance to at least one of the antimicrobials tested. In conclusion, the present study revealed the importance of wild invasive California kingsnakes as reservoirs of drug-resistant Salmonella spp. that could pose a direct threat to livestock and humans. Identification of drug-resistant Salmonella strains in wildlife provides valuable information on potential routes of transmission that involve risks to public and animal health

Non-traditional small companion mammals in Spain as reservoirs of antimicrobial-resistant Staphylococci

IntroductionThe increasing prevalence of antimicrobial resistance (AMR) and multidrug resistance (MDR) in microorganisms poses a significant concern in both human and veterinary medicine. Non-traditional companion animals (NTCAs), particularly popular amongst households with children, play a crucial role in AMR epidemiology due to their rising population. Indeed, it is known that some of these animals may act as reservoirs of zoonotic pathogens and thus be able to spread and transmit them to family members, along with their AMR, through their shared environment. It is therefore imperative to address this concern with the involvement of human, animal and environmental health professionals. This pilot study aimed to assess the prevalence and AMR patterns of Staphylococcus spp. strains obtained from commensal mucosal and skin infection samples in NTC small mammals, with a focus on strains like methicillin-resistant Staphylococcus spp. (MRS) that are critical in public health.MethodsFor this purpose, 81 animals of different small mammal species were sampled, assessing antimicrobial susceptibility to 27 relevant antimicrobial agents (AMAs) in human health using minimum inhibitory concentration assays, and interpreting them according to EUCAST and CLSI guidelines. The isolated Staphylococci strains were identified by MALDI-TOF, with the predominant species being Mammalicoccus sciuri and Staphylococcus aureus.Results and discussionIncluding all strains isolated, AMR was observed against all 27 AMAs, including six last-resort AMAs in human medicine. Additionally, over 85% of the strains exhibited MDR. These findings underscore the need to monitor AMR and MDR trends in companion animals and emphasise the potential role of NTCAs in spreading resistance to humans, other animals, and their shared environment, calling for a comprehensive “One Health” approach

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease