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BACKGROUND: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). METHODS: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. RESULTS: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). CONCLUSIONS: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. CLINICAL TRIALS REGISTRATION: NCT03572049.

Aims: To determine the risk factors associated with amputations in hospitalized patients with diabetic foot infection. Methods: this is a prospective study conducted at a tertiary care hospital in Panama between January 2010 and December 2016. We included all patients admitted to the hospital with diabetes and diabetic foot infection. A total of 351 patients were included, and a survey to assess for demographic and clinical factors was completed prospectively until discharge. The outcome was lower limb amputation. Results: Sixty-one participants (17.4 %) required a lower limb amputation, and 22 (36.1 %) were major amputations. Several factors were associated with amputation in the univariate analysis: history of foot infection, history of amputation, peripheral arterial disease, a major index ulcer area, duration of the index ulcer >30 days, Grade III 3D severity according to Texas scale, a greater IDSA classification, the presence of necrosis and osteomyelitis. Nevertheless, multiple logistic regression revealed significant relationships between amputations and necrosis (P

Abstract Background The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers’ (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. Methods HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March–April 2023. Findings Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% “other”). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term “antibiotic stewardship”. Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (

Abstract The food and culinary heritage with medicinal uses are a fascinating field that combines history, culture, and health through food. Over the centuries, various cultures have developed knowledge and practices related to the use of specific ingredients and culinary preparations with medicinal properties. In the Pungalá parish in Ecuador, these generational knowledge and traditions form a valuable biocultural heritage that helps us understand the close relationship between food and traditional medicine. Through qualitative and documentary research, interviews and community workshops are conducted to gather information using different techniques. Among the findings regarding the food and culinary heritage of Pungalá are extinct culinary traditions, as well as important culinary techniques and processes that play a role in nutrition and medicine, valuing traditional and ancestral knowledge as part of their culture. The inventory includes 22 plants used in Andean medicine and 38 preparations, including beverages, porridges, stews, soups, and wrapped dishes that become an integral part of everyday routines, dietary habits, and festive traditions. It is concluded that this knowledge constitutes a valuable food and culinary heritage, and its biocultural is based on ancestral knowledge of the healing properties of local plants and foods, contributing to the health and identity of the community. Measures should be taken to preserve and promote this heritage in the face of current challenges.

Whole-body vibration (WBV) therapy is a way of passive exercise in which subjects are exposed to mild and well-controlled mechanical vibrations through a vibrating platform. For a long time, studies have focused on the effects and applications of WBV to enhance musculoskeletal performance in athletes and patients suffering from musculoskeletal disorders. Recent evidence points toward the positive effect of WBV on the brain and its therapeutic potential in brain disorders. Research being done in the field gradually reveals cellular and molecular mechanisms underlying WBV affecting the body and brain. Particularly, the influence of WBV on immune and brain function is a growing field that warrants an up-to-date and integrated review. Immune function is closely intertwined with brain functioning and plays a significant role in various brain disorders. Dysregulation of the immune response is linked to conditions such as neuroinflammation, neurodegenerative diseases, and mood disorders, highlighting the crucial connection between the immune system and the brain. This review aims to explore the impact of WBV on the cellular and molecular pathways involved in immune and brain functions. Understanding the effects of WBV at a cellular and molecular level will aid in optimizing WBV protocols to improve its therapeutic potential for brain disorders.

Summary: The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants underlie the neurodevelopmental disorder (NDD) ‘Intellectual Disability, Autosomal Dominant 57’ (MRD57), characterized by intellectual disability and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown. A male patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency was determined to have a heterozygous TLK1 variant (c.1435C>G, p.Q479E), as well as a mutation in MDM1 (c.1197dupT, p.K400∗). Cells expressing TLK1 p.Q479E exhibited reduced cytokine responses and elevated DNA damage, but not increased radiation sensitivity or DNA repair defects. The TLK1 p.Q479E variant impaired kinase activity but not proximal protein interactions. Our study provides the first functional characterization of NDD-associated TLK1 variants and suggests that, such as TLK2, TLK1 variants may impact development in multiple tissues and should be considered in the diagnosis of rare NDDs.

Concerns about climate change have boosted the massive introduction of renewable energy into electric power systems. Renewable generators can mitigate pollution by replacing fuel-based energy with clean energy. However, these generators displace conventional synchronous ones. This changes power system dynamics and can lead to a less stable operation. To face this emerging problem, many approaches have been proposed in order to enable renewable generators and consumers to provide ancillary services. Nevertheless, if renewable generators adjust their production to support grid ancillary services, all the primary energy resources cannot be optimally used. This work proposes a way for railway systems to contribute to primary and supplementary frequency control and to relieve renewable generation from frequency control tasks. Furthermore, a tuning control method is introduced. Due to the high stochasticity of railway system operation, a method for selecting local optimum parameters is proposed. The frequency control scheme is set and tested in simulation, and experimentally validated by means of Hardware In the Loop tests with a real micro controller. The results demonstrate, first, the capacity of railway systems to manage a certain quantity of frequency deviations and, second, the feasibility of implementing the proposed control strategy in real time. This work broadens the framework of railway-based demand response approaches.

The relevance of the Franciscan community is reflected in the San Francisco church in Quito, which was built between 1535 and 1755. This architectural work belonging to the Franciscan complex was implanted on a plot of land with an area of 3.5 hectares and was one of the first buildings in the Audience of Quito. Eleven mortar samples that covered the walls of the central nave and side chapels were taken from the church’s main temple. The procedure proposed by the authors is based on a combined methodology following the standards and protocols for the less-invasive extraction of heritage samples. Tests included X-ray diffraction, petrography, and scanning electron microscopy with a microanalysis of the samples. Mortars with a rustic composition and rough manufacturing were identified to differentiate two types of mortar, one of earthen with volcanic aggregates and another of lime with volcanic aggregates. The mining data validated the existing historical documentation, the imaginary process, and the stages of the established constructions.

Introduction: Despite the highly favorable prognosis, mortality occurs in nearly 2% of patients with cerebral venous thrombosis (CVT), in which decompressive craniectomy (DC) may be the only way to save the patient's life. The aim of this report is to describe the risk factors, neuroimaging features, in-hospital complications and functional outcome of severe CVT in patients treated with DC. Materials and methods: Consecutive malignant CVT cases treated with DC from a retrospective third-level hospital database were analyzed. Demographic, clinical, and functional outcomes were analyzed. Results: Twenty-six patients were included (20 female, age 35.4 ± 12.1 years); 53.8% of the patients had acute CVT, with neurological focalization as the most common symptom in 92.3% of the patients. Superior sagittal sinus thromboses were found in 84.6% of cases. Bilateral lesions were present in 10 patients (38.5%). Imaging on admission showed a parenchymal lesion (venous infarction ± hemorrhagic lesion) > 6 cm measured along the longest diameter in 25 patients (96.2%). Mean duration of clinical neurological deterioration was 3.5 days; eleven patients (42.3%) died during hospitalization. Conclusion: In patients with severe forms of CVT, we found higher mortality than previously reported. DC is an effective life-saving treatment with acceptable functional prognosis for survivors. Resumen: Introducción: A pesar del pronóstico favorable en pacientes con trombosis venosa cerebral (TVC), cerca de un 2% de estos pacientes fallecen, para los cuales la craniectomía descompresiva (CD) puede ser una opción terapéutica. El objetivo de este artículo es describir los factores de riesgo, las características de las neuroimágenes, complicaciones hospitalarias y evolución funcional, de pacientes con TVC severa tratados con CD. Materiales y métodos: Se analizaron características demográficas, clínicas y funcionales de casos consecutivos de TVC severa tratados con CD, a partir de una base de datos retrospectiva de un hospital de tercer nivel. Resultados: Veintiséis pacientes fueron incluidos (20 mujeres, media de edad 35,4 ±12,1 años); un 53,8% de los pacientes presentaron una TVC aguda, con manifestaciones neurológicas focales como el síntoma más frecuente en el 92,3% de los casos. La trombosis del seno sagital superior estuvo presente en el 84,6% y se presentaron lesiones bilaterales parenquimatosas en 10 pacientes (38,5%). La imagen al ingreso demostró lesiones parenquimatosas (infarto venoso ± lesión hemorrágica) > 6 cm (medida en el mayor diámetro de la misma), en 25 pacientes (96,2%). La duración media del deterioro neurológico fue de 3,5 días; 11 pacientes (42,3%) murieron durante la hospitalización. Conclusión: En pacientes con formas severas de TVC encontramos una mayor mortalidad que la publicada previamente; la CD podría ser una opción terapéutica en ese grupo de pacientes.

Abstract Background To address the evolving needs and context changes due to the COVID-19 pandemic, we adapted Connect for Health, an evidence-based, primary care, pediatric weight management intervention. The objective of this study is to describe the planned adaptation process to ensure continued and equitable program uptake during the pandemic. Methods Guided by adaptation frameworks, we identified the core functions and forms of Connect for Health and then adapted the intervention in response to a changing healthcare context. We engaged stakeholders and surveyed parents of children with a BMI ≥ 85th percentile and pediatric clinicians and examined their experiences using telehealth for pediatric weight management and needs and preferences. Using multivariable logistic regression, we examined the preferences of parents with limited English proficiency regarding key aspects of pediatric weight management. Results We surveyed 200 parents and 43% had a primary language of Spanish. Parents wanted care to be a combination of in-person and virtual visits (80%). We found that parents with limited English proficiency had a higher odds ratio of affirming in-person visits are better than virtual visits for ensuring their child’s health concern can be taken care of (OR: 2.91; 95% CI: 1.36, 6.21), feeling comfortable when discussing personal information (OR: 3.91; 95% CI: 1.82, 8.43), talking about healthy behaviors and setting goals (OR: 3.09; 95% CI: 1.39, 6.90), and talking about mental health and overall well-being (OR: 4.02; 95% CI: 1.83, 8.87) than parents without limited English proficiency. We surveyed 75 clinicians and 60% felt telehealth was a useful tool to provide care for pediatric weight management. Clinicians felt virtual visits did not pose barriers to all aspects of care. Informed by the surveys and stakeholder input, we made clinician- and family-level adaptations while retaining the program’s function. Conclusions By engaging stakeholders and adapting the program for telehealth, we optimized the reach and fit of Connect for Health to ensure its continued uptake. We have provided a real-world example of how clinical innovations can evolve and how to systematically plan adaptations in response to changing healthcare contexts. Trial registration Clinicaltrials.gov (NCT04042493), Registered on August 2, 2019.

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke.

Background: Numerous research studies have delved into the biomechanics of walking, focusing on the spine and lower extremities. However, understanding the symmetry of walking in individuals without health issues poses a challenge, as those with normal mobility may exhibit uneven movement patterns due to inherent functional differences between their left and right limbs. The goal of this study is to examine the three-dimensional kinematics of gait symmetry in the spine and lower body during both typical and brisk overground walking in healthy individuals. The analysis will utilize statistical methods and symmetry index approaches. Furthermore, the research aims to investigate whether factors such as gender and walking speed influence gait symmetry. Methods: Sixty young adults in good health, comprising 30 males and 30 females, underwent motion capture recordings while engaging in both normal and fast overground walking. The analysis focused on interlimb comparisons and corresponding assessments of side-specific spine and pelvis motions. Results: Statistical Parametric Mapping (SPM) predominantly revealed gait symmetries between corresponding left and right motions in the spine, pelvis, hip, knee, and ankle during both normal and fast overground walking. Notably, both genders exhibited asymmetric pelvis left-right obliquity, with women and men showing an average degree of asymmetry between sides of 0.9 ± 0.1° and 1.5 ± 0.1°, respectively. Furthermore, the analysis suggested that neither sex nor walking speed appeared to exert influence on the 3D kinematic symmetry of the spine, pelvis, and lower body in healthy individuals during gait. While the maximum normalized symmetry index (SInorm) values for the lower thorax, upper lumbar, lower lumbar, pelvis, hip, knee, and ankle displayed significant differences between sexes and walking speeds for specific motions, no interaction between sex and walking speed was observed. Significance: The findings underscore the potential disparities in data interpretations between the two approaches. While SPM discerns temporal variations in movement, these results offer valuable insights that may enhance our comprehension of gait symmetry in healthy individuals, surpassing the limitations of straightforward discrete parameters like the maximum SInorm. The information gleaned from this study could serve as reference indicators for diagnosing and evaluating abnormal gait function.

La inclusión laboral de las personas con discapacidad y la integración de la docencia, investigación y vinculación con la sociedad son actividades básicas de las universidades ecuatorianas. El artículo expone los resultados de experiencias pedagógicas desarrolladas por los estudiantes de Administración de Empresas de la Universidad Laica Eloy Alfaro de Manabí, extensión Pedernales en la Fundación Simón Palacios, en el marco de la ejecución del proyecto de investigación: Gestión Empresarial Sostenible para personas con discapacidad en el cantón Pedernales. Se empleó el enfoque cuali-cuantitativo transversal correlacional, usando los métodos inductivo, analítico e histórico. Se aplicaron encuestas a familias de las personas con discapacidad y entrevistas a técnicos de la Fundación Simón Palacios. Como resultado se obtuvo la articulación de las funciones sustantivas de la Universidad, lo cual es posible al contar la misma con un modelo pedagógico orientado a la solución de problemas y necesidades de los pueblos y una epistemología de la construcción del saber y del trabajo laboral. Se concluye que las principales acciones desarrolladas como parte de la ejecución del proyecto, los talleres de capacitación y el acompañamiento brindado a las familias, permitieron el vínculo directo y empoderamiento de la Universidad en la vida de la Fundación.

Las bacterias Burkholderia glumae, Burkholderia gladiolii y Burkholderia plantarii son importantes en el cultivo de arroz, por provocar manchado y tizón del grano. El objetivo de esta investigación fue identificar fenotípicamente mecanismos de resistencia de B. gladiolii, B. plantarii y sensibilidad in vitro a bactericidas de uso agrícola. Los aislados bacterianos de B. gladiolii y B. plantarii fueron proporcionados por el laboratorio de Microbiología Vegetal de la Universidad Nacional Agraria, Nicaragua. La identificación de mecanismo de resistencia y sensibilidad a bactericidas de uso agrícola se realizó por el método de Bauer –Kirby (difusión en agar), se midió el tamaño de los halos de inhibición, se observó el tamaño y forma de los halos de inhibición producidos por la sinergia entre los discos de antibióticos. Se identificaron seis aislados con mecanismo de resistencia AmpC derreprimida, de estos, cuatro fueron de B. gladiolii y dos de B. plantarii; se identificó un aislado multirresistente con presencia de AmpC y cinco que no manifestaron mecanismos de resistencia. Los aislados bacterianos de Burkholderia gladiolii (D4 y M4) fueron sensibles al ácido oxolínico en comparación con los aislados (V5, D2I, V2, T5 y D3) y el aislados de B. plantarii (T5II). El aislado M4 de B. gladiolii fue susceptible al ácido oxolínico más gentamicina, mientras que los aislados de Burkholderia gladiolii (D4, D2I y D3) y el aislado de Burkholderia plantarii (T5II) fueron poco susceptible, a diferencia de los aislado bacteriano de B. gladiolii (T5 y V2) que no mostraron sensibilidad a dicho producto comercial. La dosis comercial 1.5 kg ha-1 de ácido oxolínico inhibió el mayor número de aislados en comparación con la dosis 1 kg ha-1. El producto biológico a base de Bacillus subtillis y el producto formulado sulfato de estreptomicina más oxitetraciclina no ejercieron efecto inhibitorio sobre los aislados de Burkholderia gladiolii y Burkholderia plantarii.