Effect of AT1 receptor blockade on cardiovascular outcome after cardiac arrest: an experimental study in rats.

Angiotensin II receptor 1(AT1) antagonists are beneficial in focal ischemia/reperfusion (I/R). However, in cases of global I/R, such as cardiac arrest (CA), AT1 blocker's potential benefits are still unknown. Wistar male rats were allocated into four groups: Control group (CG)-animals submitted to CA by ventricular fibrillation induced by direct electrical stimulation for 3 min, and anoxia for 5 min; Group AT1 (GAT1)-animals subjected to CA and treated with 0.2 mg/kg of candesartan diluted in dimethylsulfoxide (DMSO) (0.1%); Vehicle Group (VG): animals subjected to CA and treated with 0.2 ml/kg of DMSO and Sham group (SG)-animals submitted to surgical interventions, without CA. Cardiopulmonary resuscitation consisted of group medications, chest compressions, ventilation, epinephrine (20 mcg/kg) and defibrillation. The animals were observed up to 4 h after spontaneous circulation (ROSC) return, and survival rates, hemodynamic variables, histopathology, and markers of tissue injury were analyzed. GAT1 group had a higher rate of ROSC (62.5% vs. 42.1%, p < 0.0001), survival (100% vs. 62.5%, p = 0.027), lower incidence of arrhythmia after 10 min of ROSC (10% vs. 62.5%, p = 0.000), and lower neuronal and cardiac injury scores on histology evaluation (p = 0.025 and p = 0.0052, respectively) than GC group. The groups did not differ regarding CA duration, number of adrenaline doses, or number of defibrillations. AT1 receptor blockade with candesartan yielded higher rates of ROSC and survival, in addition to neuronal and myocardial protection.

Perezone and its phenyl glycine derivative induce cytotoxicity via caspases on human glial cancer cells.

The new phenyl glycine derivative of perezone was obtained in a single reaction step in ca. 80% yield which showed remarkable cytotoxic activity against the astrocytoma U-251 cell line. After 24 h of exposure, both perezone (IC50 = 6.83 ± 1.64 µM) and its phenyl glycine derivative (2.60 ± 1.69 µM) showed cytotoxic effect on U-251 cells but were five times less cytotoxic on the non-tumoral SVGp12 cell line (IC50 = 28.54 ± 1.59 and 31.87 ± 1.54 µM respectively). Both compounds induced cellular morphological changes (pyknosis or cytoplasmic vacuolization) and increased the expression of caspases 3, 8, and 9 genes related to apoptosis. In the acute toxicity study, phenyl glycine perezone (DL50 = 2000 mg/Kg) demonstrated to be less toxic than perezone (DL50 = 500 mg/Kg). Phenylglycine-perezone can envisage a beneficial therapeutic potential.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Erratum: Physiological lentiviral vectors for the generation of improved CAR-T cells.

[This corrects the article DOI: 10.1016/j.omto.2022.05.003.].

Physiological lentiviral vectors for the generation of improved CAR-T cells.

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor α (EF1α)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-α) and interferon (IFN)-É£ after efficient destruction of CD19+ lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19+ pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AW-LVs for the generation of improved CAR-T products.

Estudio comparativo del tiempo de pantallas recreativas en los trastornos del neurodesarrollo / A comparative study of recreational screen time in neurodevelopmental disorders

Introducción: En poblaciones infantiles, el tiempo de consumo de pantallas recreativas se ha estudiado ampliamente, pero se dispone de menos información en niños con trastornos del neurodesarrollo. Nuestro principal objetivo era estudiar las características de uso de las pantallas recreativas (televisión y videojuegos) en niños con trastornos del neurodesarrollo. Sujetos y métodos: Realizamos un estudio de casos y controles, comparando niños con y sin trastornos del neurodesarrollo menores de 6 años. A través de un cuestionario rellenado por los progenitores, se analizó el tiempo de exposición diaria a pantallas recreativas, las características sociodemográficas y ambientales, los hábitos socioculturales y las actitudes relacionadas con las pantallas recreativas. Resultados: Se analizó a 61 individuos con trastorno del neurodesarrollo y a 153 controles. Los casos pasaron más tiempo mirando la televisión (124,4 ± 83,4 frente a 71,5 ± 47,4 minutos/día; p < 0,001), mientras que el tiempo de videojuegos fue similar en ambos grupos (37,6 ± 39, 6 frente a 31,7 ± 32,6 minutos/día; p = 0,138). Los niños con trastorno del neurodesarrollo empezaron a una edad más temprana a ver televisión. No hubo diferencias relevantes entre los dos grupos en características sociodemográficas, socioculturales, ambientales y de actitud relacionadas con las pantallas recreativas. Conclusiones: Los niños con trastorno del neurodesarrollo empiezan a ver la televisión a una edad más temprana y consumen más tiempo que sus coetáneos sanos. Nuestros hallazgos indican que los niños con trastornos del neurodesarrollo son más vulnerables al abuso de la televisión, por lo que consideramos relevante ofrecer una guía anticipada a sus progenitores.(AU)

Introduction: Digital screen time has been largely studied in children populations, but few have focused on children with neurodevelopmental disorders. Our main objective was to study the characteristics of use of recreational screens (television (TV) and video games), in children with neurodevelopmental disorders. Subjects and methods: We conducted a case-control study in which children with neurodevelopmental disorders under the age of 6 were compared with controls of the same age range. We analysed TV and video game exposure through a designed questionnaire for parents that included daily time exposure, sociodemographic characteristics, home media environment, sociocultural habits, attitudes and beliefs about TV. Results: Sixty-one individuals with developmental and 153 controls were enrolled. Children with developmental problems spend more time watching TV than controls (124,4 ± 83,4 vs 71,5 ± 47,4 min / day p <0,001), while video game time was similar in both groups (37,6 ± 39, 6 vs 31,7 ± 32,6 min / day p = 0,138). Children with neurodevelopmental disorders began earlier to watch TV than controls. There were no relevant differences between groups in demographics, Sociocultural, environmental and attitudinal and belief variables. Conclusions: Children with neurodevelopmental disorders start watching TV at an earlier age and consume more screen time than healthy children. Our findings indicate that Children with neurodevelopmental disorders are more vulnerable to screen abuse, and stress the importance to offer anticipatory guidance to their parents.(AU)

[A comparative study of recreational screen time in neurodevelopmental disorders]. / Estudio comparativo del tiempo de pantallas recreativas en los trastornos del neurodesarrollo.

INTRODUCTION: Digital screen time has been largely studied in children populations, but few have focused on children with neurodevelopmental disorders. Our main objective was to study the characteristics of use of recreational screens (television (TV) and video games), in children with neurodevelopmental disorders. SUBJECTS AND METHODS: We conducted a case-control study in which children with neurodevelopmental disorders under the age of 6 were compared with controls of the same age range. We analysed TV and video game exposure through a designed questionnaire for parents that included daily time exposure, sociodemographic characteristics, home media environment, sociocultural habits, attitudes and beliefs about TV. RESULTS: Sixty-one individuals with developmental and 153 controls were enrolled. Children with developmental problems spend more time watching TV than controls (124,4 ± 83,4 vs 71,5 ± 47,4 min / day p <0,001), while video game time was similar in both groups (37,6 ± 39, 6 vs 31,7 ± 32,6 min / day p = 0,138). Children with neurodevelopmental disorders began earlier to watch TV than controls. There were no relevant differences between groups in demographics, Sociocultural, environmental and attitudinal and belief variables. CONCLUSIONS: Children with neurodevelopmental disorders start watching TV at an earlier age and consume more screen time than healthy children. Our findings indicate that Children with neurodevelopmental disorders are more vulnerable to screen abuse, and stress the importance to offer anticipatory guidance to their parents.

TITLE: Estudio comparativo del tiempo de pantallas recreativas en los trastornos del neurodesarrollo.Introducción. En poblaciones infantiles, el tiempo de consumo de pantallas recreativas se ha estudiado ampliamente, pero se dispone de menos información en niños con trastornos del neurodesarrollo. Nuestro principal objetivo era estudiar las características de uso de las pantallas recreativas (televisión y videojuegos) en niños con trastornos del neurodesarrollo. Sujetos y métodos. Realizamos un estudio de casos y controles, comparando niños con y sin trastornos del neurodesarrollo menores de 6 años. A través de un cuestionario rellenado por los progenitores, se analizó el tiempo de exposición diaria a pantallas recreativas, las características sociodemográficas y ambientales, los hábitos socioculturales y las actitudes relacionadas con las pantallas recreativas. Resultados. Se analizó a 61 individuos con trastorno del neurodesarrollo y a 153 controles. Los casos pasaron más tiempo mirando la televisión (124,4 ± 83,4 frente a 71,5 ± 47,4 minutos/día; p menor de 0,001), mientras que el tiempo de videojuegos fue similar en ambos grupos (37,6 ± 39, 6 frente a 31,7 ± 32,6 minutos/día; p = 0,138). Los niños con trastorno del neurodesarrollo empezaron a una edad más temprana a ver televisión. No hubo diferencias relevantes entre los dos grupos en características sociodemográficas, socioculturales, ambientales y de actitud relacionadas con las pantallas recreativas. Conclusiones. Los niños con trastorno del neurodesarrollo empiezan a ver la televisión a una edad más temprana y consumen más tiempo que sus coetáneos sanos. Nuestros hallazgos indican que los niños con trastornos del neurodesarrollo son más vulnerables al abuso de la televisión, por lo que consideramos relevante ofrecer una guía anticipada a sus progenitores.

El ejercicio físico multicomponente como herramienta de mejora de la fragilidad en personas mayores / Multi-component physical exercise as a tool to improve frailty in older people

Introducción:La fragilidad, entendida como un estado de vulnerabilidad y prediscapacidad en el paciente geriátrico, lleva asociada un aumento significativo del riesgo de morbimortalidad y, con ello, un impacto importante en la calidad de vida y la funcionalidad de las personas mayores con enfermedades crónicas y/o degenerativas. En este sentido, se ha constatado como el ejercicio físico aparece como una herramienta óptima no farmacológica para preservar y/o mejorar la calidad de vida de las personas mayores. Objetivos: Analizar la influencia de la práctica de ejercicio físico multicomponente en la mejora del estado de fragilidad de las personas mayores inscritas en clases de gimnasia de mantenimiento. Metodología: Estudio transversal y analítico que evaluó (pre- y posprograma) el nivel de fragilidad, la condición física y las constantes vitales de 118 personas mayores. Todos los participantes recibieron un entrenamiento de ejercicio físico multicomponente durante 12 semanas con una frecuencia de 3 días por semana con 1 h de duración. Resultados: Los datos muestran mejora en la condición física tras el programa de intervención con independencia del nivel físico de partida. Por otro lado, se observó una disminución del número de personas prefrágiles tras el programa. Conclusiones: los programas de ejercicio físico multicomponente optimizan la calidad de vida, mejoran la salud, y previenen la fragilidad de las personas mayores (AU)

Introduction: Frailty, understood as a state of vulnerability and prediscapability in the geriatric patient, is associated with a significant increase in the risk of morbidity and mortality, and with it an important impact on the quality of life and functionality of elderly with chronic diseases and/or degenerative. In this sense, it has been verified how physical exercise appears as an optimal non-pharmacological tool to preserve and / or improve the quality of life of the elderly. Objectives: To analyze the influence of the practice of multicomponent physical exercise in improving the frailty state of the elderly enrolled in maintenance gym classes. Methods: Crosssectional and analytical study that evaluated (pre- and postprogram) the level of frailty, physical condition and vital signs of 118 elderly people. All participants received 12-week multicomponent physical exercise training 3 hours a week, lasting one hour. Results: Data show improvement in physical condition after the intervention program regardless of the starting physical level. On the other hand, a decrease in the number of pre-fragile people was observed after the program. Conclusions: Multicomponent physical exercise programs optimize quality of life, improve health, and prevent frailty in the elderly (AU)

High Yield Synthesis of Curcumin and Symmetric Curcuminoids: A "Click" and "Unclick" Chemistry Approach.

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.

Evaluation of the operational conditions in the production and morphology of Chlorella sp / Avaliação das condições operacionais na produção e morfologia de Chlorella sp

Abstract It was evaluated the effect of operational conditions in the production of Chlorella sp. after its selection from genus Chlorella sp., Scenedesmus sp., Nannochloris sp., Tetraselmis sp. and Dunaliella salina. Microalgae were inoculated in drinking water with addition of NPK fertilizer (N 24%, P 24%, K 18%), at a concentration of 0.5 g/L, agitation of 150 rpm, temperature 25 °C, light intensity of 1680 lumens at a color temperature of 6400K, without pH control for 8 days. The cellular concentrations obtained were 3.72x107 (Chlorella sp.), 1.36x107 (Scenedesmus sp.), 3.55x107 (Tetraselmis sp.), 5.74x107 (Nannochloris sp.) and 3.45x106 (Dunaliella salina), where the microalgae Chlorella sp., shows invasive capacity in drinking water cultivations. Applying the 2n-p fractional factorial design concept for the elemental composition of the microalgae and the cellular morphology, it was obtained 44.33% of C, 7.09% of H, 8.53% of N and 0.84% ​​of S for the Chlorella sp.

Resumo Foi avaliado o efeito das condições operacionais na produção de Chlorella sp. após a seleção do gênero Chlorella sp., Scenedesmus sp., Nannochloris sp., Tetraselmis sp. e Dunaliella salina. Microalgas foram inoculadas em água potável com adição de fertilizante NPK (N 24%, P 24% e K 18%), na concentração de 0,5 g/L, agitação de 150 rpm, temperatura de 25 °C, intensidade luminosa de 1.680 lúmens para uma temperatura de cor de 6.400 K, sem controle de pH por 8 dias. As concentrações celulares obtidas foram de 3,72 x 107 (Chlorella sp.), 1,36 x 107 (Scenedesmus sp.), 3,55 x 107 (Tetraselmis sp.), 5,74 x 107 (Nannochloris sp.) e 3,45 x 106 (Dunaliella salina), em que a microalga Chlorella sp. mostrou capacidade invasiva em cultivos de água potável. Aplicando o conceito de projeto fatorial fracionado 2n-p para a composição elementar da microalga e a morfologia celular, foram obtidos 44,33% de C, 7,09% de H, 8,53% de N e 0,84% de S para a Chlorella sp.

Evaluation of the operational conditions in the production and morphology of Chlorella sp.

It was evaluated the effect of operational conditions in the production of Chlorella sp. after its selection from genus Chlorella sp., Scenedesmus sp., Nannochloris sp., Tetraselmis sp. and Dunaliella salina. Microalgae were inoculated in drinking water with addition of NPK fertilizer (N 24%, P 24%, K 18%), at a concentration of 0.5 g/L, agitation of 150 rpm, temperature 25 °C, light intensity of 1680 lumens at a color temperature of 6400K, without pH control for 8 days. The cellular concentrations obtained were 3.72x107 (Chlorella sp.), 1.36x107 (Scenedesmus sp.), 3.55x107 (Tetraselmis sp.), 5.74x107 (Nannochloris sp.) and 3.45x106 (Dunaliella salina), where the microalgae Chlorella sp., shows invasive capacity in drinking water cultivations. Applying the 2n-p fractional factorial design concept for the elemental composition of the microalgae and the cellular morphology, it was obtained 44.33% of C, 7.09% of H, 8.53% of N and 0.84% ​​of S for the Chlorella sp.

Using Gene Editing Approaches to Fine-Tune the Immune System.

Genome editing technologies not only provide unprecedented opportunities to study basic cellular system functionality but also improve the outcomes of several clinical applications. In this review, we analyze various gene editing techniques used to fine-tune immune systems from a basic research and clinical perspective. We discuss recent advances in the development of programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases. We also discuss the use of programmable nucleases and their derivative reagents such as base editing tools to engineer immune cells via gene disruption, insertion, and rewriting of T cells and other immune components, such natural killers (NKs) and hematopoietic stem and progenitor cells (HSPCs). In addition, with regard to chimeric antigen receptors (CARs), we describe how different gene editing tools enable healthy donor cells to be used in CAR T therapy instead of autologous cells without risking graft-versus-host disease or rejection, leading to reduced adoptive cell therapy costs and instant treatment availability for patients. We pay particular attention to the delivery of therapeutic transgenes, such as CARs, to endogenous loci which prevents collateral damage and increases therapeutic effectiveness. Finally, we review creative innovations, including immune system repurposing, that facilitate safe and efficient genome surgery within the framework of clinical cancer immunotherapies.

Non-Cytotoxic Dibenzyl and Difluoroborate Curcuminoid Fluorophores Allow Visualization of Nucleus or Cytoplasm in Bioimaging.

Curcumin, the most important secondary metabolite isolated from Curcuma longa, is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono (1), di (2), tri (3), tetra (4) benzylated and dibenzyl-fluoroborate (5), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 µM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.

A meta-review of literature reviews assessing the capacity of patients with severe mental disorders to make decisions about their healthcare.

BACKGROUND: Determining the mental capacity of psychiatric patients for making healthcare related decisions is crucial in clinical practice. This meta-review of review articles comprehensively examines the current evidence on the capacity of patients with a mental illness to make medical care decisions. METHODS: Systematic review of review articles following PRISMA recommendations. PubMed, Scopus, CINAHL and PsycInfo were electronically searched up to 31 January 2020. Free text searches and medical subject headings were combined to identify literature reviews and meta-analyses published in English, and summarising studies on the capacity of patients with serious mental illnesses to make healthcare and treatment related decisions, conducted in any clinical setting and with a quantitative synthesis of results. Publications were selected as per inclusion and exclusion criteria. The AMSTAR II tool was used to assess the quality of reviews. RESULTS: Eleven publications were reviewed. Variability on methods across studies makes it difficult to precisely estimate the prevalence of decision-making capacity in patients with mental disorders. Nonetheless, up to three-quarters of psychiatric patients, including individuals with serious illnesses such as schizophrenia or bipolar disorder may have capacity to make medical decisions in the context of their illness. Most evidence comes from studies conducted in the hospital setting; much less information exists on the healthcare decision making capacity of mental disorder patients while in the community. Stable psychiatric and non-psychiatric patients may have a similar capacity to make healthcare related decisions. Patients with a mental illness have capacity to judge risk-reward situations and to adequately decide about the important treatment outcomes. Different symptoms may impair different domains of the decisional capacity of psychotic patients. Decisional capacity impairments in psychotic patients are temporal, identifiable, and responsive to interventions directed towards simplifying information, encouraging training and shared decision making. The publications complied satisfactorily with the AMSTAR II critical domains. CONCLUSIONS: Whilst impairments in decision-making capacity may exist, most patients with a severe mental disorder, such as schizophrenia or bipolar disorder are able to make rational decisions about their healthcare. Best practice strategies should incorporate interventions to help mentally ill patients grow into the voluntary and safe use of medications.

[Percutaneous tibial nerve stimulation in urge urinary incontinence: A prospective study]. / Estimulación percutánea del nervio tibial en la incontinencia urinaria de urgencia: estudio prospectivo.

OBJECTIVE: To assess the efficacy of percutaneous tibial nerve stimulation and its effectiveness over time in urge urinary incontinence. MATERIALS AND METHODS: We performed a longitudinal, observational, prospective study without a control group that included patients diagnosed with urge urinary incontinence who met the inclusion/exclusion criteria. Patients were treated with 12 sessions of percutaneous tibial nerve stimulation by electroacupuncture. Baseline and post-treatment data were collected from medical records. Patients were assessed by a telephone interview after the treatment. The variables studied were sociodemographic variables, time until interview, the Sandvick and ICIQ-SF questionnaires, daytime urinary frequency, night-time urinary frequency, use of absorbent material and drug treatment. A descriptive analysis of the variables was performed and patient outcomes were analysed with generalised linear mixed models by SPSS v. 25 statistics software. RESULTS: A total of 32 women were included (mean age 58.69±8.96). All variables significantly improved after treatment: Sandvick by 4.38 points (95% CI: 2.68-6.08, P<.001), ICIQ-SF by 8.55 points (95% CI: 5.89-11.22, P<.001), daytime urinary frequency by 2.10 points (95% CI: 1.04-3.16, P<.001) and night-time urinary frequency by 1.31 points (95%CI: 0.58-2.04, P<.001). However, 16.34±9.72 months after treatment, these improvements diminished but without reaching baseline levels. CONCLUSIONS: Percutaneous tibial nerve stimulation by electroacupuncture is effective for the treatment of urge urinary incontinence. Although its effect diminishes over time, the improvement over the baseline situation is maintained during the follow-up period.

Short communication: Red deer (Cervus elaphus) colostrum during its transition to milk.

We studied changes in chemical composition, somatic cell count, and immunoglobulin G (IgG) and M (IgM) content in red deer (Cervus elaphus) colostrum during the transition to milk at different times after parturition (<5 h, 24 h, 48 h, 2 wk, and 4 wk). The production level was higher at 2 and 4 wk of lactation than during the first day after parturition, with intermediate values at 48 h postpartum. Fat content did not vary during the study period. However, total protein and casein contents were particularly high in the initial 5 h after parturition, decreasing to approximately 50% after 24 h postpartum. Conversely, lactose concentration was low in the beginning (<5 h), increasing gradually throughout the study. Similarly, dry matter dropped during the first 24 h and then remained constant throughout the study. Urea content decreased during the study, showing a slight recovery at 4 wk. Somatic cell count was higher during the first hours after parturition and gradually decreased throughout the study period. The IgG content was higher before 5 h postpartum than at 24 h postpartum. After 5 h, the level of IgG decreased progressively until it reached 0.18 mg/mL at 4 wk of lactation. We observed a similar pattern for IgM content, but it decreased more quickly than IgG and was not detected after 2 wk. In the case of deer, milk should be considered transitional from 24 to 48 h after parturition, and samples collected after 2 wk can be considered mature milk.

First-line panitumumab plus docetaxel and cisplatin in advanced gastric and gastro-oesophageal junction adenocarcinoma: results of a phase II trial.

PURPOSE: Panitumumab is extensively used for RAS-WT metastatic colorectal cancer. This study assessed the efficacy and safety of panitumumab plus first-line chemotherapy [docetaxel (DOC) and cisplatin (CIS)] in treatment-naïve advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (ADC) patients. METHODS: Phase II, open-label, single-arm study includes treatment-naïve advanced gastric or GEJ-ADC patients from ten Spanish centres. Patients received panitumumab (6 mg/kg) plus DOC and CIS (50 mg/m2 both) every 2 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Primary endpoint: objective response rate (ORR); main secondary endpoints: disease control rate (DCR), duration of response (DoR), time to progressive disease (TTP), progression-free-survival (PFS), overall survival (OS), and safety. RESULTS: Forty-four patients were included; median age: 67.8 (range 43.3-82.7) years, 68.2% male. The ORR was 27.3% (95% CI 15.0, 42.8); median PFS and OS: 5.0 (95% CI 3.6, 6.9) and 7.2 (5.5, 9.0) months, respectively. Median TTP, DCR and DoR: 5.3 (range 3.8-7.0) months, 70.5% (95% CI 54.8, 83.2%), and 4.8 (1.8, NE) months. Median panitumumab treatment duration: 11.9 (range 0.1-34.9) weeks; 25.0% patients had a dose reduction and 40.9% discontinued treatment. Grade 3-4 adverse events (AEs): 68.2%/22.2% patients. Most common AEs: asthenia (75.0%) and mucosal inflammation (54.5%). Serious AEs were experienced by 54.6% patients; 9.1%, 13.6%, and 15.9% related to panitumumab, DOC, and CIS, respectively. Three (6.8%) patients died due to AEs not related to study treatment. CONCLUSIONS: The addition of panitumumab to standard chemotherapy as the first-line treatment in advanced gastric or GEJ-ADC does not appear to improve the efficacy outcomes.