Clinical case report of intractable paroxysmal sympathetic hyperactivity in TANGO2 deficiency disorder.

TANGO2 deficiency disorder (TDD) is a neurodegenerative disease characterized by a broad and variable spectrum of clinical manifestations, even among individuals sharing the same pathogenic variants. Here, we report a severely affected individual with TDD presenting with intractable paroxysmal sympathetic hyperactivity (PSH). While progressive brain atrophy has been observed in TDD, PSH has not been reported. Despite comprehensive workup for an acute trigger, no definite cause was identified, and pharmacological interventions were ineffective to treat PSH. Ultimately care was redirected to comfort measures. This article expands the clinical phenotype of patients with TDD, highlights the possibility of PSH in these patients, and the need for continued research for better treatments of TDD.

L-PRF Secretome from Both Smokers/Nonsmokers Stimulates Angiogenesis and Osteoblast Differentiation In Vitro.

Leukocyte and Platelet-Rich Fibrin (L-PRF) is part of the second generation of platelet-concentrates. L-PRF derived from nonsmokers has been used in surgical procedures, with its beneficial effects in wound healing being proven to stimulate biological activities such as cell proliferation, angiogenesis, and differentiation. Cigarette smoking exerts detrimental effects on tissue healing and is associated with post-surgical complications; however, evidence about the biological effects of L-PRF derived from smokers is limited. This study evaluated the impact of L-PRF secretome (LPRFS) derived from smokers and nonsmokers on angiogenesis and osteoblast differentiation. LPRFS was obtained by submerging L-PRF membranes derived from smokers or nonsmokers in culture media and was used to treat endothelial cells (HUVEC) or SaOs-2 cells. Angiogenesis was evaluated by tubule formation assay, while osteoblast differentiation was observed by alkaline phosphatase and osterix protein levels, as well as in vitro mineralization. LPRFS treatments increased angiogenesis, alkaline phosphatase, and osterix levels. Treatment with 50% of LPRFS derived from smokers and nonsmokers in the presence of osteogenic factors stimulates in vitro mineralization significantly. Nevertheless, differences between LPRFS derived from smokers and nonsmokers were not found. Both LPRFS stimulated angiogenesis and osteoblast differentiation in vitro; however, clinical studies are required to determine the beneficial effect of LPRFS in smokers.

De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features.

FRY-like transcription coactivator (FRYL) belongs to a Furry protein family that is evolutionarily conserved from yeast to humans. The functions of FRYL in mammals are largely unknown, and variants in FRYL have not previously been associated with a Mendelian disease. Here, we report fourteen individuals with heterozygous variants in FRYL who present with developmental delay, intellectual disability, dysmorphic features, and other congenital anomalies in multiple systems. The variants are confirmed de novo in all individuals except one. Human genetic data suggest that FRYL is intolerant to loss of function (LoF). We find that the fly FRYL ortholog, furry (fry), is expressed in multiple tissues, including the central nervous system where it is present in neurons but not in glia. Homozygous fry LoF mutation is lethal at various developmental stages, and loss of fry in mutant clones causes defects in wings and compound eyes. We next modeled four out of the five missense variants found in affected individuals using fry knockin alleles. One variant behaves as a severe LoF variant, whereas two others behave as partial LoF variants. One variant does not cause any observable defect in flies, and the corresponding human variant is not confirmed to be de novo, suggesting that this is a variant of uncertain significance. In summary, our findings support that fry is required for proper development in flies and that the LoF variants in FRYL cause a dominant disorder with developmental and neurological symptoms due to haploinsufficiency.

Validation of an instrument to measure knowledge, attitudes and skills towards Evidence-Based Practice in nursing students in Colombia.

BACKGOUND: Evidence-Based Practice (EBP) is crucial for the nursing profession, as it helps professionals make informed clinical decisions based on the best available evidence. Most EBP competency assessment tools focus on specific technical knowledge or skill components, and most have been tested on medical students. The Evidence-Based Practice Competence Questionnaire (EBP-COQ-E) is an instrument that assesses the competence in EBP in nursing students. The objective of the article was to evaluate the psychometric properties of the EBP-COQ-E instrument in final year nursing students in Colombia. DESIGN: A validation study was conducted using a cross-sectional design. METHODS: The population included nursing students from 19 programs in Colombia, who were selected during the years 2020 and 2021 based on their university enrollment in the last year of training in nursing programs with current qualified registration by the Ministry of Education and who had attended the least one subject related to research. The data were collected through a virtual platform and the researchers consolidated it into a general database. The EBP-COQ-E instrument consists of 25 items grouped into three factors: attitude towards EBP, skills for EBP and knowledge about EBP. The items were answered on a Likert-type scale from 1 to 5. An exploratory factor analysis was performed and an internal consistency analysis of the instrument. RESULTS: A total of 1021 final year students from 19 university nursing programs participated, with a mean age of 23 years and where 83% identified themselves as female. The results showed good internal consistency and construct validity for the instrument, with a Cronbach's alpha of 0.89. In the exploratory factor analysis, 3 factors were found that explained 51% of the variance of the data. Together these three factors had statistically significant positive correlations. CONCLUSION: The study contributes to the validation of the Evidence-Based Practice Competence Questionnaire (EBP-COQ-E) which is a valid and reliable tool to assess knowledge, attitudes and skills in EBP in nursing students in the Colombian context. Training in EBP is crucial to guarantee the quality of performance of future professionals in care practice and the EBP-COQ-E can be useful and applicable where it is necessary to evaluate this competence in training processes.

Clinical and cost-effectiveness of DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives) for people living with dementia and their carers: a study protocol for a parallel multicentre randomised controlled trial.

INTRODUCTION: Many people living with dementia experience sleep disturbance and there are no known effective treatments. Non-pharmacological treatment options should be the first-line sleep management. For family carers, relatives' sleep disturbance leads to interruption of their sleep, low mood and breakdown of care. Our team developed and delivered DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives), a multimodal non-pharmacological intervention, showing it to be feasible and acceptable. The aim of this randomised controlled trial is to establish whether DREAMS START is clinically cost-effective in reducing sleep disturbances in people living with dementia living at home compared with usual care. METHODS AND ANALYSIS: We will recruit 370 participant dyads (people living with dementia and family carers) from memory services, community mental health teams and the Join Dementia Research Website in England. Those meeting inclusion criteria will be randomised (1:1) either to DREAMS START or to usual treatment. DREAMS START is a six-session (1 hour/session), manualised intervention delivered every 1-2 weeks by supervised, non-clinically trained graduates. Outcomes will be collected at baseline, 4 months and 8 months with the primary outcome being the Sleep Disorders Inventory score at 8 months. Secondary outcomes for the person with dementia (all proxy) include quality of life, daytime sleepiness, neuropsychiatric symptoms and cost-effectiveness. Secondary outcomes for the family carer include quality of life, sleep disturbance, mood, burden and service use and caring/work activity. Analyses will be intention-to-treat and we will conduct a process evaluation. ETHICS AND DISSEMINATION: London-Camden & Kings Cross Ethics Committee (20/LO/0894) approved the study. We will disseminate our findings in high-impact peer-reviewed journals and at national and international conferences. This research has the potential to improve sleep and quality of life for people living with dementia and their carers, in a feasible and scalable intervention. TRIAL REGISTRATION NUMBER: ISRCTN13072268.

The Potential of Microalgae-Bacteria Consortia to Restore Degraded Soils.

Soil restoration is one of the biggest challenges of this century. Besides the negative impacts of climate change, the current increase in food demands has put severe pressure on soil resources, resulting in a significant area of degraded land worldwide. However, beneficial microorganisms, such as microalgae and plant growth-promoting bacteria, have an outstanding ability to restore soil health and fertility. In this mini-review, we summarize state-of-the-art knowledge on these microorganisms as amendments that are used to restore degraded and contaminated soils. Furthermore, the potential of microbial consortia to maximize beneficial effects on soil health and boost the production of plant-growth-promoting compounds within a mutualistic interaction is discussed.

Identification of Two Homozygous Variants in MYBPC3 and SMYD1 Genes Associated with Severe Infantile Cardiomyopathy.

Mutations in cardiac genes are one of the primary causes of infantile cardiomyopathy. In this study, we report the genetic findings of two siblings carrying variations in the MYBPC3 and SMYD1 genes. The first patient is a female proband exhibiting hypertrophic cardiomyopathy (HCM) and biventricular heart failure carrying a truncating homozygous MYBPC3 variant c.1224-52G>A (IVS13-52G>A) and a novel homozygous variant (c.302A>G; p.Asn101Ser) in the SMYD1 gene. The second patient, the proband's sibling, is a male infant diagnosed with hypertrophic cardiomyopathy and carries the same homozygous MYBPC3 variant. While this specific MYBPC3 variant (c.1224-52G>A, IVS13-52G>A) has been previously reported to be associated with adult-onset hypertrophic cardiomyopathy, this is the first report linking it to infantile cardiomyopathy. In addition, this work describes, for the first time, a novel SMYD1 variant (c.302A>G; p.Asn101Ser) that has never been reported. We performed a histopathological evaluation of tissues collected from both probands and show that these variants lead to myofibrillar disarray, reduced and irregular mitochondrial cristae and cardiac fibrosis. Together, these results provide critical insight into the molecular functionality of these genes in human cardiac physiology.

Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients.

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD. METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review. RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at the time of data collection was 9.0 years (interquartile range = 5.3-15.9 years, range = fetal to 31.8 years). A total of 24 different TANGO2 alleles were observed. Patients showed normal development in early infancy, with progressive delay in developmental milestones thereafter. Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years. A total of 46/71 (65%) patients suffered metabolic crises, and of those, 30 (65%) developed cardiac crises. Metabolic crises were significantly decreased after the initiation of B-complex or multivitamin supplementation. CONCLUSION: We provide the most comprehensive review of natural history of TDD and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.

Validation to Spanish of nursing assessment scale for early diagnosis of delirium - Nu-DESC.

Objective: This work aimed to determine the validity and reliability of the Colombian Spanish version of the Nursing Delirium Screening Scale (Nu-DESC). Methods: A psychometric study was conducted to achieve the goal of this study, which measured face validity, content validity, sensitivity, specificity and predictive values of the Nu-DESC. Results: . Face validity obtained a total Aiken V of 0.89, and content validity showed a modified Lawshe index of 0.92. When Nu-DESC was applied to 210 adult patients hospitalized in the Intensive Care Unit, it was found that 14.2% had suspected delirium. The instrument showed a sensitivity of 91.6%, specificity of 95.6%, positive predictive value of 73.3%, negative predictive value of 98.8%, good internal consistency with Cronbach's α of 0.8 and good concordance according to Cohen's Kappa index of 0.788. Conclusion: The Spanish version of the Nu-DESC scale for Colombia has appropriate psychometric values for assessing delirium risk. In addition, this scale is easy to apply, so the adaptation of nursing personnel for its employability favors routine monitoring and timely detection of delirium.

Transiciones en sobrevivientes de cáncer de mama frente al reintegro laboral: revisión integrativa / Transitions in breast cancer survivors regarding work return: integrative review

INTRODUCCIÓN: El cáncer de mama es una de las enfermedades más comunes entre las mujeres en todo el mundo. El tratamiento del cáncer de mama a menudo implica cirugía, radioterapia, quimioterapia y/o terapia hormonal, tratamientos que a largo plazo pueden generar efectos en las mujeres. Estas mujeres que han sido tratadas por cáncer de mama pueden enfrentar situaciones diversas al decidir retornar a su trabajo, debido entre otros a que pueden ser percibidas como menos productivas. OBJETIVO: Describir las transiciones que experimentan las sobrevivientes de cáncer de mama frente al reintegro laboral a través de una revisión integrativa. MATERIALES Y MÉTODOS: revisión integrativa de alcance descriptivo, a través de la identificación del problema, búsqueda de literatura, evaluación de datos, análisis de datos y presentación de resultados. Los términos de búsqueda utilizados fueron: "breast neoplasms" "breast cancer" "breast cancer survivor and, or y not "return to work". Las bases de datos utilizadas fueron Scielo, Pubmed, Scopus, según criterios de inclusión implementados en la búsqueda de literatura se encontraron 22 artículos que cumplieron con ello. RESULTADOS: Se identificaron temáticas que van en relación con las sobrevivientes de cáncer de mama que planean reincorporarse laboralmente, por lo general no se identifica un momento ni tiempo específico para que la sobreviviente tome la decisión de volver al trabajo después de pasar la enfermedad. CONCLUSIÓN: Es importante generar estudios donde el abordaje de los factores asociados al retorno laboral pueda ocasionar un impacto sobre la calidad de vida de la mujer sobreviviente y su relación con el retorno al trabajo, sobre todo aspectos relacionados con los efectos de los tratamientos.

INTRODUCTION: Breast cancer is one of the most common diseases among women worldwide. Breast cancer treatment often involves surgery, radiotherapy, chemotherapy and/or hormone therapy, treatments that can have long-term effects on women. These women who have been treated for breast cancer may face different situations when deciding to return to work, due to the fact that they may be perceived as less productive, among others. OBJECTIVE: To describe the transitions experienced by breast cancer survivors when faced with reemployment through an integrative review. MATERIALS AND METHODS: integrative review of descriptive scope, through the identification of the problem, literature search, data evaluation, data analysis and presentation of results. The search terms used were "breast neoplasms" "breast cancer" "breast cancer survivor and, or and not "return to work". The databases used were Scielo, Pubmed, Scopus, according to the inclusion criteria implemented in the literature search, 22 articles were found that complied with it. RESULTS: Themes that are related to breast cancer survivors who plan to return to work were identified, in general, a specific moment or time is not identified for the survivor to make the decision to return to work after passing the disease. CONCLUSION: It is important to generate studies where the approach to the factors associated with the return to work may have an impact on the quality of life of the surviving woman and its relationship with the return to work, especially aspects related to the effects of the treatments.

A 25 años de la implementación del identificador de objeto digital / Twenty-five years after the implementation of the Digital Object Identifier

RESUMEN El identificador de objeto digital, conocido en inglés como digital object identifier y abreviado DOI, surgido en 1997, es una cadena alfanumérica única que identifica un contenido electrónico y proporciona un enlace permanente a su ubicación en internet. A 25 años de la implementación de esta herramienta, todavía quedan muchas revistas con un impacto considerable que no cuentan con DOI. Cuba no lo tiene porque le es negado por las grandes agencias registradoras. Fue objetivo de los autores de esta comunicación destacar la importancia del DOI como herramienta básica para el control de la documentación digital. Se concluyó que su principal aporte es asegurar la identificación persistente y unívoca de un documento, a través de un registro sistemático central de sus metadatos. Se recomienda que siempre que esté disponible el DOI en línea, se utilice en la cita bibliográfica, para mejorar la visibilidad de las revistas y los propios investigadores.

ABSTRACT The Digital Object Identifier, abbreviated as DOI and emerged in 1997, is a unique alphanumeric string that identifies electronic content and provides a permanent link to its location on the Internet. Twenty-five years after the implementation of this tool, there are still many journals with a considerable impact which do not have DOIs. Cuba does not have it because it is denied by the big registration agencies. The objective of this article was to highlight the importance of the DOI as a basic tool for the control of digital documentation. We concluded that its main contribution is to ensure the persistent and unique identification of a document, through a central systematic record of its metadata. It is recommended that whenever the DOI is available online, it is used in the bibliographic citation, to improve the visibility of the journals and the researchers themselves.

Natural history of propionic acidemia in the Amish population.

Propionic acidemia (PA) in the Amish is caused by a homozygous pathogenic variant (c.1606A>G; p.Asn536Asp) in the PCCB gene. Amish patients can have borderline or normal newborn screening (NBS) results and symptoms can present at any time from early childhood to mid-adulthood. Early diagnosis and initiation of treatment for PA in the non-Amish population improves patient outcomes. Here, we present data from a retrospective chart review of Amish patients diagnosed with PA from three different medical centers in order to document its natural history in the Amish and determine the influence of treatment on outcomes in this population. A total of 38 patients with average current age 19.9 years (range 4y-45y), 57.9% males, were enrolled in the study. Fourteen patients (36.8%) were diagnosed with a positive newborn screening (NBS) while 24 patients (63.2%) had negative or inconclusive NBS or had no record of NBS in their charts. These 24 patients were diagnosed by screening after a family member was diagnosed with PA (14; 58.3%), following a hospitalization for metabolic acidosis (5; 20.8%), hospitalization for seizures (3; 12.5%) or via cord blood (2; 8.3%). The majority of patients were prescribed a protein restricted diet (32; 84.2%), including metabolic formula (29; 76.3%). Most were treated with carnitine (35; 92.1%), biotin (2; 76.3%) and/or Coenzyme Q10 (16; 42.1%). However, treatment adherence varied widely among patients, with 7 (24.1%) of the patients prescribed metabolic formula reportedly nonadherent. Cardiomyopathy was the most prevalent finding (22; 63.2%), followed by developmental delay/intellectual disability (15; 39.5%), long QT (14; 36.8%), seizures (12; 31.6%), failure to thrive (4; 10.5%), and basal ganglia strokes (3; 7.9%). No difference in outcome was obvious for those diagnosed by NBS and treated early with dietary and supplement management, especially for cardiomyopathy. However, this is a limited retrospective observational study. A prospective study with strict documentation of treatment adherence and universal screening for cardiomyopathy and long QT should be conducted to better study the impact of early detection and treatment. Additional treatment options such as liver transplantation and future therapies such as mRNA or gene therapy should be explored in this population.

ITCH deficiency clinical phenotype expansion and mitochondrial dysfunction.

Autoimmune Disease, Multisystem, with Facial Dysmorphism (ADMFD) is an autosomal recessive disorder due to pathogenic variants in the ITCH gene. It is characterized by failure to thrive, dysmorphic facial features, developmental delay, and systemic autoimmunity that can manifest variably with autoimmune hepatitis, thyroiditis, and enteropathy, among other organ manifestations. It was originally described in 10 consanguineous Old Order Amish patients, and more recently in two patients of White British and Black German ethnicities. While the role of ITCH protein in apoptosis and inflammation has previously been characterized, a defect in cellular bioenergetics has not yet been reported in ITCH deficiency. Here we present a Caucasian female originally evaluated for possible mitochondrial respiratory chain deficiency, who ultimately was found to have two novel variants in ITCH with absence of ITCH protein in patient derived fibroblasts. Clinical studies of patient muscle showed mitochondrial DNA copy number of 57% compared to controls. Functional studies in skin fibroblasts revealed decreased activity of mitochondrial fatty acid oxidation and oxidative phosphorylation, and decreased overall ATP production. Our findings confirm mitochondrial energy dysfunction in a patient with ITCH deficiency offering the opportunity to assess alternative therapeutic options.

Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is caused by deficient glycine cleavage enzyme activity and characterized by elevated brain glycine. Metabolism of glycine is connected enzymatically to serine through serine hydroxymethyltransferase and shares transporters with serine and threonine. We aimed to evaluate changes in serine and threonine in NKH patients, and relate this to clinical outcome severity. Age-related reference values were developed for cerebrospinal fluid (CSF) serine and threonine from 274 controls, and in a cross-sectional study compared to 61 genetically proven NKH patients, categorized according to outcome. CSF d-serine and l-serine levels were stereoselectively determined in seven NKH patients and compared to 29 age-matched controls. In addition to elevated CSF glycine, NKH patients had significantly decreased levels of CSF serine and increased levels of CSF threonine, even after age-adjustment. The CSF serine/threonine ratio discriminated between NKH patients and controls. The CSF glycine/serine aided in discrimination between severe and attenuated neonates with NKH. Over all ages, the CSF glycine, serine and threonine had moderate to fair correlation with outcome classes. After age-adjustment, only the CSF glycine level provided good discrimination between outcome classes. In untreated patients, d-serine was more reduced than l-serine, with a decreased d/l-serine ratio, indicating a specific impact on d-serine metabolism. We conclude that in NKH the elevation of glycine is accompanied by changes in l-serine, d-serine and threonine, likely reflecting a perturbation of the serine shuttle and metabolism, and of one-carbon metabolism. This provides additional guidance on diagnosis and prognosis, and opens new therapeutic avenues to be explored.

Mitochondrial dysfunction associated with TANGO2 deficiency.

Transport and Golgi Organization protein 2 Homolog (TANGO2)-related disease is an autosomal recessive disorder caused by mutations in the TANGO2 gene. Symptoms typically manifest in early childhood and include developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias, along with severe metabolic crises including hypoglycemia, lactic acidosis, and hyperammonemia. Severity varies among and within families. Previous studies have reported contradictory evidence of mitochondrial dysfunction. Since the clinical symptoms and metabolic abnormalities are suggestive of a broad dysfunction of mitochondrial energy metabolism, we undertook a broad examination of mitochondrial bioenergetics in TANGO2 deficient patients utilizing skin fibroblasts derived from three patients exhibiting TANGO2-related disease. Functional studies revealed that TANGO2 protein was present in mitochondrial extracts of control cells but not patient cells. Superoxide production was increased in patient cells, while oxygen consumption rate, particularly under stress, along with relative ATP levels and ß-oxidation of oleate were reduced. Our findings suggest that mitochondrial function should be assessed and monitored in all patients with TANGO2 mutation as targeted treatment of the energy dysfunction could improve outcome in this condition.

Prevalence of Pathogenic and Potentially Pathogenic Inborn Error of Immunity Associated Variants in Children with Severe Sepsis.

PURPOSE: Our understanding of inborn errors of immunity is increasing; however, their contribution to pediatric sepsis is unknown. METHODS: We used whole-exome sequencing (WES) to characterize variants in genes related to monogenic immunologic disorders in 330 children admitted to intensive care for severe sepsis. We defined candidate variants as rare variants classified as pathogenic or potentially pathogenic in QIAGEN's Human Gene Mutation Database or novel null variants in a disease-consistent inheritance pattern. We investigated variant correlation with infection and inflammatory phenotype. RESULTS: More than one in two children overall and three of four African American children had immunodeficiency-associated variants. Children with variants had increased odds of isolating a blood or urinary pathogen (blood: OR 2.82, 95% CI: 1.12-7.10, p = 0.023, urine: OR: 8.23, 95% CI: 1.06-64.11, p = 0.016) and demonstrating increased inflammation with hyperferritinemia (ferritin [Formula: see text] ng/mL, OR: 2.16, 95% CI: 1.28-3.66, p = 0.004), lymphopenia (lymphocyte count < 1000/µL, OR: 1.66, 95% CI: 1.06 - 2.60, p = 0.027), thrombocytopenia (platelet count < 150,000/µL, OR: 1.76, 95% CI: 1.12-2.76, p = 0.013), and CRP greater than 10 mg/dl (OR: 1.71, 95% CI: 1.10-2.68, p = 0.017). They also had increased odds of requiring extracorporeal membrane oxygenation (ECMO, OR: 4.19, 95% CI: 1.21-14.5, p = 0.019). CONCLUSION: Herein, we describe the genetic findings in this severe pediatric sepsis cohort and their microbiologic and immunologic significance, providing evidence for the phenotypic effect of these variants and rationale for screening children with life-threatening infections for potential inborn errors of immunity.

Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis.

Multiple Sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by Central Nervous System (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

Intervención psicoeducativa en el manejo de situaciones de incertidumbre, en mujeres sobrevivientes al cáncer de mama / Psychoeducational intervention in the management of situations of uncertainty, in women survivors of breast cancer

ntroducción: el cáncer de mama es una enfermedad catalogada como crónica, debido a los avances tecnológicos que se han presentado en los últimos años. Este tipo de cáncer implica una serie de situaciones asociadas con la incertidumbre y los tiempos de sobrevivencia. Objetivo: medir el efecto de la intervencion psicoeducativa en la disminucion de los niveles de incertidumbre en mujeres sobrevivientes al cancer de mama, en una institucion de salud de la ciudad de Cali. Método: estudio de abordaje cuantitativo, tipo cuasiexperimental, de corte longitudinal que incluye 98 pacientes sobrevivientes de cáncer de mama. Se distribuyen, aleatoriamente, en dos grupos, el grupo experimental (GE) conformado por 49 sobrevivientes que reciben la intervención de enfermería y el grupo control (GC) en el que participan 49 sobrevivientes a quienes se realiza el seguimiento de la intervención habitual. La intervención se desarrolla en seis sesiones y consiste en sesiones mediadas por las tecnologías sobre conocimiento y estrategias de afrontamiento. El estudio cuenta con aval de los comités de ética e investigación. Resultados: perfil de los participantes del GC y GE, al inicio de la intervención: la edad promedio fue de 54.3±12 años en el GE y 56.7±12 años en el GC, las mujeres pertenecían al régimen contributivo en ambos grupos (57 % experimental y 71 % control, respectivamente). Las mujeres del GE pertenecían a los estratos 2 (32,7 %), mientras que las mujeres del GC se concentraron, en su mayoría, en los estratos 2 (30, 6 %) y 3 (34,7 %). En relación con el estado civil más frecuente en ambos, grupos fue casada/unión, igualmente, en cuanto a la ocupación, el GE, en su mayoría, se dedicaba al hogar u otros, de manera similar ocurrió en el GC, donde el 42 ,9 % de las mujeres se dedicaba al hogar u otros y el 28,6 % al trabajo independiente. La intervención permitió disminuir los niveles de incertidumbre en el grupo de intervención, por ello, se consolida como una intervención considerada para ser replicada en contextos asistenciales. (Texto tomado de la fuente). 6 % al trabajo independiente. La intervención permitió disminuir los niveles de incertidumbre en el grupo de intervención, por ello, se consolida como una intervención considerada para ser replicada en contextos asistenciales. (Texto tomado de la fuente). 6 % al trabajo independiente. La intervención permitió disminuir los niveles de incertidumbre en el grupo de intervención, por ello, se consolida como una intervención considerada para ser replicada en contextos asistenciales.

Development and characterization of a mouse model for Acad9 deficiency.

Acyl CoA Dehydrogenase 9 (ACAD9) is a member of the family of flavoenzymes that catalyze the dehydrogenation of acyl-CoAs to 2,3 enoyl-CoAs in mitochondrial fatty acid oxidation (FAO). Inborn errors of metabolism of all family members, including ACAD9, have been described in humans, and represent significant causes of morbidity and mortality particularly in children. ACAD9 deficiency leads to a combined defect in fatty acid oxidation and oxidative phosphorylation (OXPHOS) due to a dual role in the pathways. In addition to its function in mitochondrial FAO, ACAD9 has a second function as one of 14 factors responsible for assembly of complex I of the electron transport chain (ETC). Considerable controversy remains over the relative role of these two functions in normal physiology and the disparate clinical findings described in patients with ACAD9 deficiency. To better understand the normal function of ACAD9 and the pathophysiology of its deficiency, several knock out mouse models were developed. Homozygous total body knock out appeared to be lethal as no ACAD9 animals were obtained. Cre-lox technology was then used to generate tissue-specific deletion of the gene. Cardiac-specific ACAD9 deficient animals had severe neonatal cardiomyopathy and died by 17 days of age. They had severe mitochondrial dysfunction in vitro. Muscle-specific mutants were viable but exhibited muscle weakness. Additional studies of heart muscle from the cardiac specific deficient animals were used to examine the evolutionarily conserved signaling Intermediate in toll pathway (ECSIT) protein, a known binding partner of ACAD9 in the electron chain complex I assembly pathway. As expected, ECSIT levels were significantly reduced in the absence of ACAD9 protein, consistent with the demonstrated impairment of the complex I assembly. The various ACAD9 deficient animals should serve as useful models for development of novel therapeutics for this disorder.