Capsaicinoids and Their Effects on Cancer: The "Double-Edged Sword" Postulate from the Molecular Scale.

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids' pharmacological use remain subjects of discussion, since CAP also promotes epithelial-mesenchymal transition, in an ambivalence that has been referred to as "the double-edge sword". Here, we update the comparative discussion of relevant reports about capsaicinoids' bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids' immunomodulatory properties against cancer.

Pediatric perianal Crohn's disease behavior in the era of biologic therapy. / Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica.

AIM OF THE STUDY: To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. METHODS: A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. RESULTS: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CONCLUSIONS: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

OBJETIVO DEL ESTUDIO: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. METODOS: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. RESULTADOS: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. CONCLUSIONES: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by chronic hyperglycemia as a consequence of decreased insulin sensitivity, which contributes to bone demineralization and could also be related to changes in serum levels of osteocalcin and insulin, particularly when coupled with a deficiency in the daily consumption of vitamins D3 and K2. The objective of this study was to evaluate the effect of vitamin D3 and vitamin K2 supplements alone or in combination on osteocalcin levels and metabolic parameters in patients with T2DM. METHODS: A double-blind, randomized clinical trial was carried out in 40 patients aged between 30 and 70 years old for 3 months. Clinical and laboratory assessment was carried out at the beginning and at the end of the treatment. The patients were divided into three groups: (a) 1000 IU vitamin D3 + a calcinated magnesium placebo (n = 16), (b) 100 µg of Vitamin K2 + a calcinated magnesium placebo (n = 12), and (c) 1000 IU vitamin D3 + 100 µg vitamin K2 (n = 12). RESULTS: After treatment in the total studied population, a significant decrease in glycemia (p = 0.001), HOMA-IR (Homeostatic model assessment-insulin resistance) (p = 0.040), percentage of pancreatic beta cells (p < 0.001), uOC/cOC index and diastolic blood pressure (p = 0.030) were observed; in vitamin D3 group, differences in serum undercarboxylated osteocalcin (p = 0.026), undercarboxylated to carboxylated osteocalcin index (uOC/cOC) (p = 0.039) glucose (p < 0.001) and  % of functional pancreatic beta cells (p < 0.001) were demonstrated. In vitamin K2 group a significant decrease in glycemia (p = 0.002), HOMA-IR (p = 0.041), percentage of pancreatic beta cells (p = 0.002), and in cOC (p = 0.041) were observed, conversely cOC concentration was found high. Finally, in the vitamins D3 + K2 a significant decrease in glycemia (p = 0.002), percentage of pancreatic beta cells (p = 0.004), and in the uOC/cOC index (p = 0.023) were observed. CONCLUSION: Individual or combined supplementation with vitamins D3 and K2 significantly decreases the glucose levels and  % of functional pancreatic beta cells, while D3 and D3 + K2 treatments also induced a reduction in the uOC/cOC index. Only in the group with vitamin D3 supplementation, it was observed a reduction in undercarboxylated osteocalcin while vitamin K2 increased the carboxylated osteocalcin levels.Trial registration NCT04041492.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

[Treatment of refractory aggressiveness by amygdalotomy and posteromedial hypothalamotomy by radiofrequency]. / Tratamiento de la agresividad refractaria mediante amigdalotomia e hipotalamotomia posteromedial por radiofrecuencia.

INTRODUCTION: Since, under certain circumstances, defensive or attacking behaviours display a pattern of motor dominance, as observed in subjects who participate in contact or fighting sports, aggressive behaviour was considered to have a dominant motor pattern. With the aim of preventing the functional problems reported with bilateral lesion procedures involving both the central nucleus of the amygdala and the posteromedial hypothalamus, the decision was made to combine them; thus, an amygdalotomy of the central nucleus of the amygdala and a posteromedial hypothalamotomy were to be performed simultaneously and unilaterally, on the basis of the motor dominance of the patient determined by means of the Edinburgh test. PATIENTS AND METHODS: This study describes the surgical experience in a series of nine patients diagnosed with refractory neuroaggressive syndrome. As part of the study protocol, a magnetic resonance brain scan was performed to rule out the presence of neoplasms, vascular diseases, infections and degenerative disorders. The degree of aggressiveness was quantified using Yudofsky's Overt Aggression Scale. Additionally, manual dominance was determined by means of the Edinburgh test. RESULTS AND CONCLUSIONS: Good control of aggressiveness was seen immediately. In some cases it was necessary to reduce the antipsychotic or benzodiazepine medication, as it was seen to increase aggressiveness. Only one case required a second surgical intervention. Follow-up was achieved in 100% of the cases at 24 months and 78% at 36 months.

TITLE: Tratamiento de la agresividad refractaria mediante amigdalotomia e hipotalamotomia posteromedial por radiofrecuencia.Introduccion. Dado que, en algunas circunstancias, las conductas defensivas o de ataque muestran un patron de dominancia motora, tal como se observa en los sujetos dedicados a los deportes de contacto o de lucha, se considero que la conducta agresiva tiene un patron motor dominante. Con el fin de evitar los problemas funcionales descritos con los procedimientos de lesion bilateral tanto del nucleo central de la amigdala como del hipotalamo posteromedial, se decidio combinarlos; es decir, realizar amigdalotomia del nucleo central de la amigdala e hipotalamotomia posteromedial de manera unilateral y simultanea, basandose en la dominancia motora del paciente mediante la prueba de Edimburgo. Pacientes y metodos. Este estudio muestra la experiencia quirurgica en una serie de nueve pacientes con el diagnostico de sindrome neuroagresivo resistente al tratamiento farmacologico. Dentro del protocolo de estudio, se les realizo resonancia magnetica cerebral para descartar la presencia de neoplasias, enfermedades vasculares, infecciones y trastornos degenerativos. El grado de agresividad se cuantifico mediante la escala global de agresividad de Yudofsky. Adicionalmente, se determino la dominancia manual a traves de la prueba de Edimburgo. Resultados y conclusiones. El buen control de la agresividad se observo de modo inmediato. En algunos casos fue necesario reducir la medicacion de antipsicoticos o benzodiacepinas, ya que aumentaban la agresividad. Solo un caso requirio una segunda cirugia. Se logro seguimiento del 100% de los casos en 24 meses y del 78% en 36 meses.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Avaliação da suplementação antioxidante na dieta para galos de matrizes pesadas em idade avançada sobre parâmetros reprodutivos / Evaluation of antioxidant supplementation in diet for aging broiler breeder roosters on reproductive parameters

Objetivou-se avaliar os efeitos de antioxidantes suplementados às dietas de galos de matrizes pesadas em idade avançada sobre as características reprodutivas. Foram utilizados galos da linhagem Cobb com 47 semanas de idade. Estes foram distribuídos em quatros tratamentos, de acordo com a adição de antioxidante à dieta, sendo: A = grupo controle (sem suplementação antioxidante); B = suplementação de 9ppm de citranaxantina; C = suplementação de 6ppm de cantaxantina e D = 150ppm de vitamina E. Foram avaliadas as características seminais, tais como volume, vigor, motilidade e concentração, a composição de ácidos graxos do sêmen (saturados, insaturados, monoinsaturados, poli-insaturados, ômega 3, ômega 6 e ômega 9) e a correlação entre o peso dos testículos e o peso dos galos. Não foram observados efeitos das substâncias antioxidantes testadas sobre os parâmetros reprodutivos avaliados. Os antioxidantes avaliados não influenciam as respostas reprodutivas de machos reprodutores de matrizes pesadas em idade avançada.(AU)

This study aimed to evaluate the effect of antioxidant supplementation in diets of aging broiler breeder roosters on reproductive characteristics. Cobb roosters were divided into four groups, according to antioxidant addition, where: A = control group (without antioxidant supplementation); B = 9ppm of citranaxanthin; C = 6ppm of canthaxanthin, and D = 150ppm of vitamin E. Seminal characteristics (volume, force, motility and concentration), semen fatty acid composition (saturated, unsaturated, monounsaturated, polyunsaturated, ω3, ω6 and ω9), and the correlation between testis weight with rooster weight were evaluated. No effects of the antioxidants tested were observed. The antioxidants do not influence the reproductive responses of aging male broiler breeder.(AU)

Manejo fisioterapéutico del dolor en personas quemadas en sus tres fases de recuperación. Revisión sistemática / Physical therapy pain management in burned in three stages of recovery. Systematic review

Introducción: Los equipos interprofesionales especialistas en el abordaje de personas con quemaduras deben tener presente la fisioterapia como una de las primeras opciones terapéuticas en el tratamiento del dolor, ya que es clave importante en el manejo del dolor, puesto que contribuye a disminuir la tasa de complicaciones, atenuar la respuesta al estrés por quemadura y por la estancia hospitalaria, y su manejo facilita la ejecución de otras técnicas terapéuticas que permitan el abordaje sin generar el trauma que implica la coexistencia del dolor y favorecer la calidad de vida de las personas afectadas. Objetivo: Realizar una revisión sistemática para el manejo fisioterapéutico del dolor de la persona quemada en sus tres fases de recuperación. Metodología: Revisión sistemática de la literatura para la identificación de la mejor evidencia disponible en torno a los estudios realizados hasta la fecha, que demuestren evidencia científica sobre la efectividad del manejo fisioterapéutico del dolor en personas quemadas para reducir el impacto que genera en el proceso de recuperación funcional. Resultados: Se encontró disminución del dolor con el uso de realidad virtual para variables, como cambios en la percepción del dolor durante el cambio de vendajes de -1,81 %, cambios en el tiempo invertido en pensar en el dolor durante el cambio de vendajes -19,47 % y cambios en el rango de movimiento de 1 %. Conclusiones: La escasa evidencia existente sugiere que los procedimientos para la disminución del dolor en personas quemadas, en especial las terapias de distracción, el uso de la realidad virtual, el masaje y la terapia de distracción mandibular, son las más utilizadas, las cuales generan disminución en la percepción y calificación del dolor y disminución del tiempo invertido en pensar en éste; sin embargo, los resultados deben observarse con precaución debido al alto riesgo de sesgos de selección y detección y al tamaño de la muestra pequeña en casi todos los estudios (AU)

Introduction: Interprofessional teams specialists in dealing with people with burns must be present as one of the first therapeutic options pain management therefore; Physiotherapy is important in pain management key, since it helps to reduce the rate of complications, reduce the stress response and burn hospital stance and management facilitates the implementation of other therapeutic techniques that allow the approach without generating the trauma of the coexistence of pain and enhance the quality of life of those affected. Aim: To conduct a systematic review for the physiotherapy management of pain of the person burned in three stages of recovery. Methodology: systematic review of literatura to identify the best available evidence regarding the studies to date that demonstrate scientific evidence on the effectiveness of physiotherapy management of pain in people burned to reduce the impact generated in the process functional recovery. Outcome: pain reduction was found with the use of virtual reality as cambios variables in the perception of pain during dressing changes of -1.81 %, changes in invested in thinking about the pain during dressing changes while -19.47 % and changes in the movement range of 1 %. Conclusions: The limited evidence suggests that procedures for reducing pain in people burned in special therapies distraction, the use of virtual reality, massage therapy and mandibular distraction are the most used which generate decreased perception and pain rating and reduced invested in thinking about this time, however, the results should be viewed with caution because of the high risk of selection bias and detection and the small sample size in most studies (AU)

Quantitative analysis of hindlimbs locomotion kinematics in spinalized rats treated with Tamoxifen plus treadmill exercise.

Locomotion recovery after a spinal cord injury (SCI) includes axon regeneration, myelin preservation and increased plasticity in propriospinal and descending spinal circuitries. The combined effects of tamoxifen and exercise after a SCI were analyzed in this study to determine whether the combination of both treatments induces the best outcome in locomotion recovery. In this study, the penetrating injury was provoked by a sharp projectile that penetrates through right dorsal and ventral portions of the T13-L1 spinal segments, affecting propriospinal and descending/ascending tracts. Intraperitoneal application of Tamoxifen and a treadmill exercise protocol, as rehabilitation therapies, separately or combined, were used. To evaluate the functional recovery, angular patterns of the hip, knee and ankle joints as well as the leg pendulum-like movement (PLM) were measured during the unrestricted gait of treated and untreated (UT) animals, previously and after the traumatic injury (15 and 30days post-injury (dpi)). A pattern (curve) comparison analysis was made by using a locally designed Matlab script that determines the Frechet dissimilarity. The SCI magnitude was assessed by qualitative and quantitative histological analysis of the injury site 30days after SCI. Our results showed that all treated groups had an improvement in hindlimbs kinematics compared to the UT group, which showed a poor gait locomotion recovery throughout the rehabilitation period. The group with the combined treatment (tamoxifen+exercise (TE)) presented the best outcome. In conclusion, tamoxifen and treadmill exercise treatments are complementary therapies for the functional recovery of gait locomotion in hemi-spinalized rats.

UPLIFT study - understanding potential long-term impacts on function with tiotropium - and sub-analyses. Bibliographic resume of the obtained results.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a respiratory problem with the highest prevalence and strongest socio-economic impact in the world and whose morbimortality keeps increasing. Treating this disease is a challenge in the field of pneumology since the market now offers a wide range of bronchodilators. Tiotropium bromide, a long-acting anticholinergic bronchodilator, is a drug used to deal with this pathology. AREAS COVERED: The UPLIFT study was a 4-year (2004-2008) clinical multi-center trial in which tiotropium bromide was compared with a placebo. We present a bibliographic resume covering the multiple sub-analyses published since the end of the clinical trial, between 2009-2015. These sub-analyses analyzed the results obtained in UPLIFT in parallel, provided additional data about safety profiles, exacerbations, hospitalization and mortality rates, and lung function, among others. Expert Commentary: Tiotropium bromide is a significant advance for the maintenance treatment of patients with COPD. The favorable results obtained leave the door open to the possibility of improving the natural history of COPD and confirmed tiotropium bromide as the gold standard drug as monotherapy for treatment of COPD.

Inulin as a novel biocompatible coating: evaluation of surface affinities toward CaHPO4, α-Fe2O3, ZnO, CaHPO4@ZnO and α-Fe2O3@ZnO nanoparticles.

The introduction of biocompatible coatings onto nanoparticle surfaces can be synthetically challenging. In this work, calcium phosphate (brushite, CaHPO4⋅2H2O), iron oxide (hematite, α-Fe2O3), zinc oxide (ZnO), and CaHPO4@ZnO and α-Fe2O3@ZnO nanoparticles were synthesized and treated with the biocompatible, biodegradable, polysaccharide inulin {(2R,3S,4S,5R)-2-[[(2R,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxymethyl]-5-(hydroxymethyl)oxolane-2,3,4-triol} under mild conditions. The products were fully characterized by Fourier transforms infrared (FTIR) spectroscopy, energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), differential thermogravimetric/differential thermal analysis (TGA/DTA), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD). Surface interactions among hematite and brushite with inulin are weak, but coating the nanoparticle surface with ZnO increased the affinity toward the polysaccharide. Inulin adsorption on the nanoparticle surface was confirmed by thermal and spectroscopic analyses. The nanoparticles had diameters ranging from 50 to 80nm, with nearly spherical morphology. The nanoparticles sizes, stability and solubility in water could make them useful as components for enriched foods.

A Sativex(®) -like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis.

BACKGROUND AND PURPOSE: Sativex(®) is an oromucosal spray, containing equivalent amounts of Δ(9) -tetrahydrocannabinol (Δ(9) -THC) and cannabidiol (CBD)-botanical drug substance (BDS), which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS). In this study, we investigated whether Sativex may also serve as a disease-modifying agent in the Theiler's murine encephalomyelitis virus-induced demyelinating disease model of MS. EXPERIMENTAL APPROACH: A Sativex-like combination of phytocannabinoids and each phytocannabinoid alone were administered to mice once they had established MS-like symptoms. Motor activity and the putative targets of these cannabinoids were assessed to evaluate therapeutic efficacy. The accumulation of chondroitin sulfate proteoglycans (CSPGs) and astrogliosis were assessed in the spinal cord and the effect of Sativex on CSPGs production was evaluated in astrocyte cultures. KEY RESULTS: Sativex improved motor activity - reduced CNS infiltrates, microglial activity, axonal damage - and restored myelin morphology. Similarly, we found weaker vascular cell adhesion molecule-1 staining and IL-1ß gene expression but an up-regulation of arginase-1. The astrogliosis and accumulation of CSPGs in the spinal cord in vehicle-infected animals were decreased by Sativex, as was the synthesis and release of CSPGs by astrocytes in culture. We found that CBD-BDS alone alleviated motor deterioration to a similar extent as Sativex, acting through PPARγ receptors whereas Δ(9) -THC-BDS produced weaker effects, acting through CB2 and primarily CB1 receptors. CONCLUSIONS AND IMPLICATIONS: The data support the therapeutic potential of Sativex to slow MS progression and its relevance in CNS repair.

The type of fat ingested at breakfast influences the plasma lipid profile of postmenopausal women.

To assess whether the type of fat ingested at breakfast can modify the plasma lipid profile and other cardiovascular risk variables in postmenopausal women at risk of cardiovascular disease, a longitudinal, randomized, and crossover study was carried out with postmenopausal women at risk of CVD. They were randomly assigned to eat each type of breakfast during one month: 6 study periods (breakfast with the same composition plus butter/margarine/virgin olive oil) separated by two washout periods. On the first and last days of each study period, weight, arterial blood pressure, heart rate, and body mass index were recorded in fasting conditions and a blood sample was collected to measure plasma lipid profile. When comparing final values to baseline values, we only found out statistically significant differences on plasma lipid profiles. Butter-based breakfast increased total cholesterol and HDL, while margarine-based breakfast decreased total cholesterol and LDL and increased HDL. After the olive oil-based breakfast intake, a tendency towards a decrease of total cholesterol and LDL levels and an increase of HDL levels was observed. No statistically significant differences were observed in triglycerides levels, BMI, and arterial pressure in any breakfast type. The margarine-based breakfast was the only one which significantly increased the percentage of volunteers with optimal lipid profiles. The polyunsaturated fat at breakfast has improved the plasma lipid profile in the analyzed sample population, suggesting that PUFA-based breakfast can be advisable in women at risk of CVD.

[Nutritional advice to help reduce the cardiovascular risk. Update of the Swiss Federal Office of Public Health's recommendations on fat consumption]. / Comment diminuer son risque cardiovasculaire avec l'alimentation? Rôle des graisses consommées.

The Swiss Federal Office of Public Health's (FOPH) updated its recommendations on fat consumption in 2013. The report recommends that maximum 10% of the daily caloric intake should come from saturated fatty acids, and the total fat intake should account for 20-35%. There is no limitation to dietary cholesterol consumption. Recent studies have shown that replacing consumption of saturated fatty acids by unsaturated fatty acids is more beneficial in terms of cardiovascular prevention than a low fat diet. The purpose of this article is to review the FOPH recommendations on dietary fat as well as the current evidence about their cardiovascular benefit, and to provide a translation of these scientific recommendations into clinical advice.

Influence of light presence and biomass concentration on nutrient kinetic removal from urban wastewater by Scenedesmus obliquus.

This work was aimed at studying the effect of light-darkness and high-low biomass concentrations in the feasibility of removing nitrogen and phosphorus from urban treated wastewater by the microalga Scenedesmus obliquus. Laboratory experiments were conducted in batch, where microalgae were cultured under different initial biomass concentrations (150 and 1500mgSSl(-1)) and light conditions (dark or illuminated). Nutrient uptake was more dependent on internal nutrient content of the biomass than on light presence or biomass concentration. When a maximum nitrogen or phosphorus content in the biomass was reached (around 8% and 2%, respectively), the removal of that nutrient was almost stopped. Biomass concentration affected more than light presence on the nutrient removal rate, increasing significantly with its increase. Light was only required to remove nutrients when the maximum nutrient storage capacity of the cells was reached and further growth was therefore needed. Residence times to maintain a stable biomass concentration, avoiding the washout of the reactor, were much higher than those needed to remove the nutrients from the wastewater. This ability to remove nutrients in the absence of light could lead to new configurations of reactors aimed to wastewater treatment.

Hernioplastia inguinal ambulatoria con anestesia local y sedación: análisis de 1.840 pacientes tras 6 años de seguimiento / Inguinal hernia repair in day surgery setting: a 6 years review in 1840 patients

Introducción: Estudio para evaluar a largo plazo la aplicación y los beneficios del tratamiento de la hernia inguinal con la prótesis de prolene hernia system (PHS), con anestesia local y sedación y en programa de cirugía mayor ambulatoria. Pacientes y métodos: En el periodo 1997-2005 fueron tratados 2.138 pacientes con hernia inguinal en la unidad de cirugía mayor ambulatoria. Todos fueron anestesiados con anestesia local, una mezcla en 20 ml de suero fisiológico de 10 ml de lidocaína al 5 % y 10 ml de bupivacaína con adrenalina. Asimismo, todos fueron sedados con midazolan (0,5-2 mg) y propofol (0,5 ml/kg). Las hernioplastias se realizaron según la técnica de Gilbert y no se empleó quimiprofilaxis de forma rutinaria. El dolor postoperatorio fue valorado según una escala analógica visual. El dolor leve y moderado fue tratado con analgésicos antiinflamatorios no esteroideos o paracetamol. El tiempo medio de los pacientes para el alta en la unidad fue de 6 horas. Se realizaron controles postoperatorios a los 30 días, 3 meses y 6 años por teléfono y siempre que fuese necesario. Resultados: Del total de pacientes intervenidos, en 1.840 casos (86,1 %) se realizó un seguimiento y fueron controlados a los 6 años. Todos habían sido intervenidos en circuito sin ingreso, 147 (7,98 %) mujeres y 1.693 (92,02 %) hombres, y no presentaron eventos adversos en el periodo postoperatorio. La edad media fue de 56 (18-82 años). La clasificación de Gilbert fue I: 15 (0,81 %), II: 49 (2,66 %), III: 736 (40 %), IV: 939 (51,03 %) y V: 101 (5,48 %). En el 91,95 % eran hernias primarias y recidivadas el 8,04 %. La revisión a los 6 años mostró curación en 1.824 pacientes (99,13 %), curación con alguna secuela en 6 pacientes (0,32 %) y recidivas herniarias en 10 pacientes (0,54 %). Conclusiones: El estudio presentado demuestra a largo plazo que la técnica de PHS realizada bajo anestesia local y sedación consciente en un programa de cirugía sin ingreso es un procedimiento efectivo con muy escaso número de recidivas (AU)

Aim: The study is conducted to evaluate long time the feasibility and benefits of inguinal hernia repair with prolene hernia system (PHS) mesh using local anaesthesia with sedation as a day surgery procedure. Patients and methods: 2138 patients with inguinal hernia were attended in the day surgery setting from 1997 to 2005. Patients were sedated with midazolam (0.5-2 mg) and propofol (0.5 ml/kg). Local anaesthesia (20 ml saline solution, 10 ml lidocaine (5 %) and 10 ml bupivacaine with adrenaline. Hernioplasties were performed according to Gilbert technique. No routine chemoprophylaxis. Postoperative pain was assessed using analogical visual scale pain. Mild and moderate postoperative pain was managed with simple analgesics or NSAID or paracetamol. Patients were discharged at 6 hours. Postoperative controls: 30 days, 3 months and 6 years by phone, and always was necessary. Results: 1840 (86,1 %) were controlled 6 years. They were operated as day cases, 147 women (7,98 %) and 1693 men (92,02 %). Mean age was 56 (18-82 years). Gilbert’s classification: I-15 (0.81 %), II-49 (2.66 %), III-736 (40 %), IV-939 (51.03 %) and V-101 (5.48 %). Primary hernias were 1692 (91.95 %) and recurrent 148 (8.04 %). The review at 6 years showed healing in 1824 patients (99.13 %), cure with a sequel in 6 patients (0.32 %) and hernia recurrences in 10 patients (0.54 %). Conclusion: The study presented demonstrates the long term PHS technique performed under local anesthesia and conscious sedation in a program of outpatient surgery is an effective procedure with very low number of relapses (AU)

A rat knockout model implicates TRPC4 in visceral pain sensation.

Acute and chronic pain resulting from injury, surgery, or disease afflicts >100 million Americans each year, having a severe impact on mood, mental health, and quality of life. The lack of structural and functional information for most ion channels, many of which play key roles in the detection and transmission of noxious stimuli, means that there remain unidentified therapeutic targets for pain management. This study focuses on the transient receptor potential canonical subfamily 4 (TRPC4) ion channel, which is involved in the tissue-specific and stimulus-dependent regulation of intracellular Ca²âº signaling. Rats with a transposon-mediated TRPC4-knockout mutation displayed tolerance to visceral pain induced by colonic mustard oil (MO) exposure, but not somatic or neuropathic pain stimuli. Moreover, wild-type rats treated with a selective TRPC4 antagonist (ML-204) prior to MO exposure mimicked the behavioral responses observed in TRPC4-knockout rats. Significantly, ML-204 inhibited visceral pain-related behavior in a dose-dependent manner without noticeable adverse effects. These data provide evidence that TRPC4 is required for detection and/or transmission of colonic MO visceral pain sensation. In the future, inhibitors of TRPC4 signaling may provide a highly promising path for the development of first-in-class therapeutics for this visceral pain, which may have fewer side effects and less addictive potential than opioid derivatives.

Effectiveness of Tai-Chi for decreasing acute pain in fibromyalgia patients.

Tai-Chi has shown benefits in physical and psychological outcomes in diverse populations. We aimed to determine the changes elicited by a Tai-Chi program (12 and 24 weeks) in acute pain (before vs. after session) in fibromyalgia patients. We also assessed the cumulative changes in pain brought about by a Tai-Chi program. Thirty-six patients (29 women) with fibromyalgia participated in a low-moderate intensity Tai-Chi program for 12 weeks (3 sessions/week). Twenty-eight patients (27 women) continued the program for an additional 12 weeks (i. e., 24 weeks). We assessed pain by means of a Visual Analogue Scale (VAS) before and after each single session (i. e., 72 sessions). We observed significant immediate changes (P-values from 0.037 to 0.0001) with an approximately 12% mean decrease of acute pain in the comparison of VAS-values before and after each session (72 sessions in total), with the exception of 4 sessions. We observed significant changes in cumulative pain pre-session (95% CI=-0.019; -0.014; P<0.001) and cumulative pain post-session (95% CI=-0.021; -0.015; P<0.001) along the 24-week intervention only. In conclusion, a low-moderate intensity Tai-Chi program for 12 weeks (3 times/week) decreased levels of acute pain in fibromyalgia patients. A longer period is necessary (e. g. 24 weeks) for observing cumulative changes in pain.

Photobiotreatment model (PhBT): a kinetic model for microalgae biomass growth and nutrient removal in wastewater.

This article proposes a kinetic model for wastewater photobiotreatment with microalgae (the PhBT model). The PhBT model for nutrient uptake, coupled with the Verhulst growth model, is a simple and useful tool to describe batch experiments of nutrient removal by microalgae. The model has been validated with experiments of Chlorella vulgaris (C. vulgaris) grown in wastewater and different synthetic media. The model provided information about nitrogen and phosphorus limitation and their luxury uptake during the test. Productivity observed in synthetic medium (0.17 g SS L(-1) d(-1)) was similar to that obtained in nutrient enriched wastewater (0.15 g SS L(-1) d(-1)). Biomass productivity of this alga in wastewater and the efficient nutrient removal suggested that C. vulgaris could be cultured in wastewater for biomass production while nutrients are reduced from this stream.