Quality, acceptability and usability of self-sampling kits used by non-healthcare professionals for STI diagnosis in Spain: a single-blind study.

OBJECTIVES: Sexually transmitted infections (STIs) have markedly increased over the last decade in Spain, calling for prevention and control innovative approaches. While there is evidence indicating the effectiveness of self-sampling for STI diagnosis, no kits for this purpose have been authorised in Spain. METHODS: A prospective single-blind cross-sectional study carried out between November and December 2022 in an STI clinic in Madrid, Spain, to determine the validity, feasibility and acceptability of self-sampling kits used by non-healthcare professionals from vagina, pharynx, rectum and urethra to diagnose Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Self-samples were compared with samples collected by healthcare professional (HC samples) and analysed by PCR. Frequency of CT and NG diagnosis by sample type was compared using McNemar's test for paired data. Sensitivity and specificity of self-samples for CT and NG diagnosis were also calculated. RESULTS: 306 self-samples from 51 participants were analysed. 80% were men with median age of 33 (IQR: 28-38) years. Self-samples and HC samples showed no significant statistical differences in CT and NG diagnosis. Self-samples had a sensitivity of 81% for CT and 93% for NG, with a specificity of 97% for CT and 95% for NG. More than 90% of participants had no difficulty understanding the kit instructions and 71% expressed high levels of satisfaction with the self-sampling kit. CONCLUSION: Self-sampling kits for CT and NG diagnosis can be safely and effectively used by non-healthcare professionals in Spain. National strategies for STI prevention and control should prioritise self-sampling strategies.

Lipid-based nanosystems: the next generation of cancer immune therapy.

Immunotherapy has become an important part of the oncotherapy arsenal. Its applicability in various cancer types is impressive, as well as its use of endogenous mechanisms to achieve desired ends. However, off-target or on-target-off-tumor toxicity, limited activity, lack of control in combination treatments and, especially for solid tumors, low local accumulation, have collectively limited clinical use thereof. These limitations are partially alleviated by delivery systems. Lipid-based nanoparticles (NPs) have emerged as revolutionary carriers due to favorable physicochemical characteristics, with specific applications and strengths particularly useful in immunotherapeutic agent delivery. The aim of this review is to highlight the challenges faced by immunotherapy and how lipid-based NPs have been, and may be further utilized to address such challenges. We discuss recent fundamental and clinical applications of NPs in a range of areas and provide a detailed discussion of the main obstacles in immune checkpoint inhibition therapies, adoptive cellular therapies, and cytokine therapies. We highlight how lipid-based nanosystems could address these through either delivery, direct modulation of the immune system, or targeting of the immunosuppressive tumor microenvironment. We explore advanced and emerging liposomal and lipid nanoparticle (LNP) systems for nucleic acid delivery, intrinsic and extrinsic stimulus-responsive formulations, and biomimetic lipid-based nanosystems in immunotherapy. Finally, we discuss the key challenges relating to the clinical use of lipid-based NP immunotherapies, suggesting future research directions for the near term to realize the potential of these innovative lipid-based nanosystems, as they become the crucial steppingstone towards the necessary enhancement of the efficacy of immunotherapy.

[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Foxp3 inhibitory peptide encapsulated in a novel CD25-targeted nanoliposome promotes efficient tumor regression in mice.

P60, a Foxp3 inhibitory peptide, can hinder the regulatory T cell (Treg) activity and impair tumor proliferation. However, low systemic stability and poor specificity have led to daily dosing to achieve therapeutic effect. Therefore, this study aims to improve P60 stability and specific delivery through its encapsulation in liposomes targeting CD25, constitutively expressed in Tregs. P60 liposomes formulated with DSPE-PEG750 or DSPE-PEG2000 were incubated with DSPE-PEG2000-Maleimide micelles conjugated to Fab' fragments of anti-CD25 to develop two targeted formulations or immunoliposomes (IL): IL-P602000 (DSPE-PEG2000 only) and IL-P60750 (combining DSPE-PEG750 and DSPE-PEG2000). P60 encapsulation efficiency was 50%-60% irrespective of PEG chain length. Treg uptake was 2.5 and 14 times higher for IL-PEG750 compared with IL-PEG2000 and non-targeted liposomes, respectively, in in-vitro assays. In fact, IL-P60750 allowed CD8+  T cells ex-vivo proliferation in presence of Treg at doses 10-20 times lower than for free P60. Antitumor response of P60 and IL-P60750 in monotherapy and combined with anti-PD-1 was evaluated in MC38 and LLCOVA tumor bearing mice. In MC38 model, IL-P60750 monotherapy induced total tumor regression in 40% of mice reaching 100% for anti-PD-1 combination. This effect was associated with a significant increase in activated CD8+ T cells in tumors. Notably, IL-P60750 also inhibited human Treg in ex-vivo assay, showing the translational capability of this formulation. In conclusion, IL-P60750 formulated with different PEG chain lengths, has demonstrated antitumor efficacy by selective inhibition of Treg activity and enhances the effect of anti-PD1. Altogether, this novel IL represents a promising nanoplatform for cancer immunotherapies.

Retrospective registry of patients with locally advanced/metastatic HR+/HER2- breast cancer treated in clinical practice in Andalusia.

BACKGROUND: Limited data are available regarding the real-world effectiveness and safety of Cyclin Dependent Kinase 4/6 inhibitor (CDK4/6i) (palbociclib/ribociclib) just as a first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2‒) metastatic breast cancer (MBC). OBJECTIVE: To assess whether clinical or demographic characteristics limit access to first-line CDK4/6i treatment in clinical practice in the Autonomous Community of Andalusia (Spain) between November 2017 and April 2020. In addition, effectiveness will be described in an exploratory analysis. METHODS: Physicians from 12 centers participated in selecting demographic and clinical characteristics, treatment, and outcome data from women with HR + /HER2- MBC treated with or without CDK4/6i in addition to hormonal in the first-line setting, in a 3:1 proportion. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs). RESULTS: A total of 212 patients were included, of whom 175 (82.5%) were in the CDK4/6i treatment group and 37 (17.5%) were in the non-CDK4/6i treatment group (control group). Patients in the CDK 4/6i treatment group were younger (p = 0.0011), the biopsies of the metastatic site at the moment of the relapse were most commonly performed (p = 0.0454), and had multiple metastatic sites (p = 0.0025). The clinical benefit rate (CBR) was 82.3% in the CDK4/6i group and 67.8% in the control group. Median time to a progression event or death (PFS) was 20.4 months (95%CI 15.6-28) in the CDK4/6i group and 12.1 months (95%CI 7.9-not reached) in the control group. CONCLUSIONS: Younger patients, biopsies of metastatic disease and with multiple metastatic sites were more frequently treated with CDK4/6i in our daily clinical practice.

Prevalence of crystal deposits in asymptomatic hyperuricemia according to different scanning definitions: A comparative study.

BACKGROUND/AIM: The appropriate sonographic protocol for assessing urate crystal deposits in asymptomatic hyperuricemia (AH) is undefined, as well as how the choice would impact on deposit rates and accompanying sonographic, clinical and laboratory features. METHODS: Patients with AH (serum urate ≥7 mg/dL) underwent musculoskeletal ultrasound of 10 locations for OMERACT elementary gout lesions (double contour [DC] signs, tophi, aggregates). Different definitions for AH with deposits were applied, varying according to deposits (any deposits; only DC and/or tophi); gradation (any grade; only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and 1MTPs; >1 location with deposits), or pre-defined definitions (DC sign in femoral condyles/1MTP and/or tophi in 1MTP). We evaluated crystal deposits rates and compared between other sonographic features, clinical and laboratory variables. RESULTS: Seventy-seven participants with AH showed a median 1 location (IQR 0-2) with tophi, 1 (IQR 1-2) with aggregates, and 0 locations (IQR 0-1) with DC sign. The deposition rate ranged from 23.4% (in >1 location with grade 2-3 DC or tophi) to 87.0% (in any deposit in all 10 locations). Accompanying inflammation - assessed by a positive power-Doppler (PD) signal - and erosions were found in 19.5% and 28.4% of participants, respectively. Positive PD signal was better discriminated by criteria requiring grade 2-3 or >1 location with lesions. Erosions and the different clinical and laboratory variables were similar among protocols. CONCLUSION: Rates of sonographic deposition in AH varied dramatically among studied protocols, while some could discriminate accompanying inflammation, all highlighting the need for a validated, consensus-based definition.

La teoría de las transiciones como paradigma de apoyo al automanejo en personas con condiciones crónicas / Transitions theory as a paradigm for supporting self-management in people with chronic conditions / A teoria das transições como paradigma para apoiar a autogestão em pessoas com condições crónicas

Resumen Introducción: La experiencia de vivir con una enfermedad crónica no es una tarea sencilla, se requiere de herramientas que permitan aumentar el grado de conciencia para enfrentar las necesidades y superar desafíos sobre el estado de salud y enfermedad. En los últimos años, se ha instaurado el apoyo al automanejo, con la finalidad de potenciar las habilidades en personas con este tipo de afecciones. Resulta trascendental considerar como desde enfermería se puede contribuir al logro de aquello. El objetivo del presente ensayo es reflexionar acerca de la teoría de las transiciones de Meléis como paradigma de apoyo al automanejo en personas con condiciones crónicas. Desarrollo: La teoría de las transiciones de Meléis establece que las personas están en constante cambio, tal como ocurre en el proceso de transición de salud-enfermedad. Recibir el diagnóstico de una enfermedad crónica, conlleva una serie de procesos complejos para la persona, debido a la multiplicidad de variables que ello implica. La teoría de Meléis entrega lineamientos para orientar a la persona profesional de enfermería sobre elementos claves e interrelacionados, como la concepción previa de la naturaleza de la transición y sus condiciones, lo que servirá para la planificación de modalidades de intervención congruentes con las experiencias de la persona y su evaluación en el transcurso del proceso de salud y enfermedad. Conclusión: El paradigma ofrecido por Meléis puede ser considerado un enfoque clave para emprender el proceso de cuidado de enfermería tendiente a apoyar a las personas con enfermedad crónica en el logro del automanejo.

Abstract Introduction: The experience of living with a chronic disease is not a simple task, since it requires tools that allow increasing the degree of awareness to face the needs and overcome challenges about the state of health and disease. In recent years, support for self-management has been established, with the aim of enhancing the skills of people with this type of condition. It is important to consider how the nursing discipline can contribute to achieve this. The aim of this paper is to reflect on Meléis' theory of transitions as a paradigm to support self-management in people with chronic conditions. Development: Meléis' theory of transitions establishes that people are in constant change, as occurs in the health-illness transition process. Receiving the diagnosis of a chronic disease involves a series of complex processes for the person, due to the multiplicity of variables involved. Meléis' theory provides guidelines to orient the nursing professional on key and interrelated elements, such as the previous conception of the nature of the transition and its conditions, which will serve for the planning of intervention modalities congruent with the person's experiences and their evaluation in the course of the health and disease process. Conclusion: The paradigm offered by Meléis can be considered a key approach to undertake the nursing care process aimed at supporting people with chronic illness in achieving self-management.

Resumo Introdução: A experiênca de viver com uma doença crônica não é uma tarefa simple, pois requer ferramentas que permitam aumentar o nível de consciência para enfrentar as necessidades e superar desafios relativos ao estado de saúde e doença. Nos últimos anos, foi estabelecido o apoio à autogestão, com o objetivo de melhorar as habilidades das pessoas com este tipo de condições. É transcendental considerar como a disciplina de Enfermagem pode contribuir para isso. O objetivo deste ensaio é refletir sobre a teoria das transições de Meleis como paradigma de apoio à autogestão em pessoas com condições crônicas. Desenvolvimento: A teoria das transições de Meléis estabelece que as pessoas estão em constante mudança, como acontece no processo de transição saúde-doença. Receber o diagnóstico de uma doença crónica implica uma série de processos complexos para a pessoa, devido à multiplicidade de variáveis envolvidas. A teoria de Meléis fornece directrizes para orientar o profissional de enfermagem sobre elementos-chave e inter-relacionados, como a conceção prévia da natureza da transição e das suas condições, que servirão para o planeamento de modalidades de intervenção congruentes com as experiências da pessoa e a sua avaliação no decurso do processo saúde-doença. Conclusão: O paradigma oferecido por Meleis pode ser considerado uma abordagem chave para empreender o processo de cuidado de enfermagem que visa apoiar as pessoas com doenças crônicas no alcance do autogerenciamento.

Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit.

AIMS: Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. METHODS: The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414). RGS14414 is an ORM enhancer and therefore used here as a gain-in-function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits. RESULTS: An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2-fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14414 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit. CONCLUSIONS: These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised.

[Main Types of Cysts in Dermatopathology: Part 2]. / Principales tipos de quistes en dermatopatología: Parte 2.

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts.

How effective are mobile apps in managing people with type 2 diabetes mellitus? A systematic literature review protocol.

INTRODUCTION: The rise of new technologies in the field of health is yielding promising results. In certain chronic conditions such as type 2 diabetes mellitus, which ranks among the top five causes of global mortality, it could be useful in supporting patient management. MATERIALS AND METHODS: A systematic review will be conducted on scientific publications from the last 5 years (January 2019 to October 2023) to describe the effect of mobile app usage on glycated hemoglobin for the management of adult patients with type 2 diabetes mellitus who participated in randomized controlled clinical trials. The search will be carried out in the databases of MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), CENTRAL, WoS, Scopus, Epistemonikos, and LILACS. The search strategy will be constructed using both controlled and natural language. Additionally, the Cochrane filter will be applied to identify randomized controlled trials. The review will include scientific articles reporting studies that present results from randomized controlled trials, with texts in Spanish, English, or French, utilizing mobile applications for the management of adult individuals (over 18 years) with type 2 diabetes mellitus, and whose outcomes report the effects on glycated hemoglobin. The Cochrane Risk of Bias Tool will be used to assess the quality of the studies, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology will be implemented to evaluate the certainty of the evidence. RESULTS: The analysis will be conducted by observing the value of the glycated hemoglobin levels of the participants. Given that this data is a quantitative and continuous value, it facilitates the identification of the effects of the mobile applications used for the management of type 2 diabetes mellitus (T2DM) in adults. Furthermore, if sufficient data are available, a meta-analysis will be conducted using IBM-SPSS. The effect of the intervention will be estimated by the mean difference. All point estimates will be accompanied by 95% confidence intervals. A random effects model will be used. The heterogeneity of the results will be assessed using Cochrane's Q and I2 statistics. DISCUSSION: Considering that the quality of content and functionality of certain applications in the healthcare field is highly variable, it is necessary to evaluate the scientific evidence reported on the effect of the use of this type of technology in people with T2DM.

Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.

Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) - study protocol.

INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

Advanced Periocular Basal Cell Carcinoma with Orbital Invasion: Update on Management and Treatment Advances.

Purpose: Basal cell carcinoma (BCC) is the most frequent malignant periocular tumor. It is associated with exposure to ultraviolet radiation, and its incidence is gradually increasing. It may occasionally display more aggressive behavior and result in orbital or intracranial invasion. Mortality from periocular BBC with orbital invasion is very low, but the associated morbidity can be significant, from disfigurement to blindness. Traditionally, these cases have been treated with orbital exenteration or with radiotherapy (RT), but in recent years, hedgehog pathway inhibitors (HPIs) have emerged, are effective in more serious cases, and are used primarily or combined with surgery, changing our perspective on the management of these patients. Methods: We studied 24 cases of periocular BCC with orbital invasion, some primary and others recurrent, which were treated between 2011 and 2021 in the same hospital. All patients had clinical or radiological evidence of orbital invasion. Orbital exenteration was performed on 9/24 of the patients (1 received vismodegib after surgery), and 12/24 were treated, surgically preserving the eyeball, with 3 of them receiving adjuvant vismodegib. Three of the twenty-four patients were treated exclusively with vismodegib (Erivedge®, Genentech). Results: One patient died due to poor tumor evolution, but the rest evolved favorably and they have had no recurrences. Vismodegib was generally well tolerated, except for in one patient who discontinued treatment due to the side effects. Conclusions: In advanced BBC with orbital invasion, mutilating surgical treatments such as exenteration or potentially vision-threatening treatments such as RT remain as options. In recent years, however, very promising new medical therapies have emerged, such as HPI, which can be used effectively instead of surgery or in combination with it, preserving the eye and vision, which implies a new approach to treatment.

[Main Types of Cysts in Dermatopathology: Part 1]. / Principales tipos de quistes en dermatopatología: parte 1.

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones.

Neurons regulate the esterification of bioactive lipid mediators in the brain of acid sphingomyelinase deficient mice.

Acid sphingomyelinase deficiency is a neurodegenerative lysosomal storage disorder caused by mutations in the sphingomyelin-degrading enzyme acid sphingomyelinase (ASM) gene. Upregulated neuroinflammation has been well-characterized in an ASM knockout mouse model of acid sphingomyelinase deficiency disease, but lipid mediator pathways involved in 'mediating' inflammation and inflammation-resolution have yet to be characterized. In this study, we 1) measured free (bioactive) and esterified (inactive) lipid mediators involved in inflammation and inflammation resolution in cerebellum and neuronal cultures of ASM knockout (ASMko) mice and wildtype (WT) controls, and 2) quantified the esterification of labeled pro-resolving free d11-14(15)-epoxyeicosatrienoic acid in cultured neurons from ASMko and WT mice. We found elevated concentrations of esterified pro-resolving lipid mediators and hydroxyeicosatrienoic acids typically destined for pro-resolving lipid mediator synthesis (e.g. lipoxins) in the cerebellum and neurons of ASMko mice compared to controls. Free d11-14(15)-epoxyeicosatrienoic acid esterification within neurons of ASMko mice was significantly elevated compared to WT. Our findings show evidence of increased inactivation of free pro-resolving lipid mediators through esterification in ASMko mice, suggesting impaired resolution as a new pathway underlying ASM deficiency pathogenesis.

The differential sensitivity of the hypothalamic-hypophysial-ovarian axis to 5-hydroxytryptophan alters the secretion of estradiol.

Serotonin [5-hydroxytryptamine (5-HT)] modulates ovarian function. The precursor of 5-HT, 5-hydroxytryptophan (5-HTP), has been used to treat depression. However, the effects of 5-HTP on ovarian and reproductive physiology remain unknown. In this research, we analysed the impact of 5-HTP on the monoaminergic system and its interactions with the reproductive axis and ovarian estradiol secretion when administered by distinct routes. Female rats 30 days of age were injected with 5-HTP i.p. (100 mg/kg), into the ovarian bursa (1.5 µg/40 µL) or into the median raphe nucleus (20 µg/2.5 µL) and were killed 60 or 120 min after injection. As controls, we used rats of the same age injected with vehicle (0.9% NaCl). Monoamine, gonadotrophin and steroid ovarian hormone concentrations were measured. The injection of 5-HTP either i.p. or directly into the ovarian bursa increased the concentrations of 5-HT and the metabolite 5-hydroxyindole-3-acetic acid in the ovary. For both routes of administration, the serum concentration of estradiol increased. After i.p. injection of 5-HTP, the concentrations of luteinizing hormone were decreased and follicle-stimulating hormone increased after 120 min. Micro-injection of 5-HTP into the median raphe nucleus increased the concentrations of 5-HT in the anterior hypothalamus and dopamine in the medial hypothalamus after 120 min. Our results suggest that the administration of 5-HTP either i.p. or directly into the ovarian bursa enhances ovarian estradiol secretion.

Update on the management of elderly patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.

Influence of Dietary Lipid Source Supplementation on Milk and Fresh Cheese from Murciano-Granadina Goats.

This study analyzes the influence of the incorporation of flaked linseed and fish oil in the diet on the resulting milk and cheese. Three dietary treatments were assayed in 350 milking Murciano-Granadina multiparous goats in full-lactation: a control diet and two experimental diets, one including flaked linseed (FL) at 3.88% of dry matter, and the other containing salmon oil (SO) at 2.64% of dry matter for three periods of 21 d. None of the dietary treatments affected the daily milk yield, cheese yield, or the physicochemical parameters of the milk and cheese. Regarding the fatty acid profile (FA), the milk and cheese from animals whose diets were supplemented with SO had a higher percentage of fatty acids than those obtained with the FL-supplemented diet, except for C18:0, C18:1, C18:2 n-6, trans-9, trans-12 C18:2, cis-9, trans-11 C18:2, C18:3, and C19:0, which reached their highest levels in milk obtained with the diet supplemented with FL. The decrease in the percentage of C16:0 was greater in the milk derived from the FL diet than from the SO diet. The FL-supplemented diet improved the nutritional value of milk due to a reduction in saturated fatty acids (SFAs) and increases in polyunsaturated fatty acids (PUFAs) and conjugated linoleic acid (CLA). The decrease in n-6/n-3 in the observed milk was more pronounced with the FL diet. No differences in the sensory profile were found for the milk and cheese derived from the different dietary treatments. Dietary n-3 treatments modified the fatty acid profile without making any sensory difference to milk and fresh cheese, accompanied by marginal modifications to the physicochemical profile. We conclude that dietary supplementation with flaked linseed or fish oil produces milk and cheese from Murciano-Granadina goats with a higher nutritional quality without modifying the sensory profile of the corresponding products obtained from animals that were fed a routine diet.

Association of interleukin-13 gene single nucleotide polymorphism rs1800925 with allergic asthma in Asian population: A meta-analysis.

Background: The interleukin-13 (IL-13) gene has been associated with allergic asthma pathogenesis due to its role in IgE synthesis. The IL-13 single nucleotide polymorphism (SNP) rs1800925 has been implicated in exacerbated allergic asthma symptoms in different ethnicities. Objectives: To determine the association of IL-13 SNP rs1800925 with allergic asthma symptoms in the Asian population. Methods: Major databases were searched for studies on the association of IL-13 rs1800925 with allergic asthma in various Asian populations published between 2010 and February 2022. The odds ratio with 95% CI was obtained from included studies, and the association was evaluated using different genetic models. Heterogeneity was explored by subgroup analyses and I2 statistic evaluation. Results: Eleven studies with a total of 2895 cases and 2914 controls were included in this meta-analysis. The majority of the cases exhibited CC genotype (n = 1897), followed by CT genotype (n = 852), and TT genotype (n = 146). IL-13 rs1800925 was significantly associated with increased allergic asthma risk in the Asian population under the recessive model (TT vs CT/CC: OR, 1.48; 95% CI, 1.14-1.93; P = 0.37; I2 = 08%). Subgroup analyses by ethnicity showed an elevated risk of allergic asthma in West Asians (Iranian and Saudi Arabian) followed by East Asians (Chinese and Japanese) using the recessive model. Both age groups (adults and children) exhibited an increased risk of allergic asthma. Conclusion: This meta-analysis provides evidence that IL-13 SNP rs1800925 is a risk factor for allergic asthma in the Asian Population. It also suggests that rs1800925 is a risk factor present in both adult and children population.