Plasma and milk metabolomics revealed changes in amino acid metabolism in Holstein dairy cows under heat stress.

Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe-, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0-82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa-, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0-64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe-/DCa-, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (-65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D3/Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (-69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se-. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.

Dietary supplementation of vitamin D3 and calcium partially recover the compromised time budget and circadian rhythm of lying behavior in lactating cows under heat stress.

Heat stress (HS) impedes cattle behavior and performance and is an animal comfort and welfare issue. The objective of this study was to characterize the time budget and circadian rhythm of lying behavior in dairy cows during HS and to assess the effect of dietary supplementation of vitamin D3 and Ca. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83 ± 27 d in milk) housed in tiestalls were used in a split-plot design with the concentration of dietary vitamin E and Se as main plots (LESe: 11.1 IU/kg and 0.55 mg/kg, and HESe: 223 IU/kg and 1.8 mg/kg, respectively). Within each plot cows were randomly assigned to (1) HS with low concentrations of vitamin D3 and Ca (HS, 1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) thermoneutral pair-fed (TNPF) with low concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively) in a Latin square design with 14-d periods and 7-d washouts. Lying behavior was measured with HOBO Loggers in 15-min intervals. Overall, cows in HS spent less time lying per day relative to TNPF from d 7 to 14. Daily lying time was positively correlated with milk yield, energy-corrected milk yield, and feed efficiency, and was negatively correlated with rectal temperature, respiratory rate, fecal calprotectin, tumor necrosis factor-α, and C-reactive protein. A treatment by time interaction was observed for lying behavior: the time spent lying was lesser for cows in HS than in TNPF in the early morning (0000-0600 h) and in the night (1800-2400 h). The circadian rhythm of lying behavior was characterized by fitting a cosine function of time into linear mixed model. Daily rhythmicity of lying was detected for cows in TNPF and HS+D3/Ca, whereas only a tendency in HS cows was observed. Cows in TNPF had the highest mesor (the average level of diurnal fluctuations; 34.2 min/h) and amplitude (the distance between the peak and mesor; 17.9 min/h). Both the mesor and amplitude were higher in HS+D3/Ca relative to HS (26.6 vs. 25.2 min/h and 3.91 min/h vs. 2.18 min/h, respectively). The acrophase (time of the peak) of lying time in TNPF, HS, and HS+D3/Ca were 0028, 0152, and 0054 h, respectively. Lastly, a continuous increase in daily lying time in TNPF was observed during the first 4 d of the experimental period in which DMI was gradually restricted, suggesting that intake restrictions may shift feeding behavior and introduce biases in the behavior of animals. In conclusion, lying behavior was compromised in dairy cows under HS, characterizing reduced daily lying time and disrupted circadian rhythms, and the compromised lying behavior can be partially restored by supplementation of vitamin D3 and Ca. Further research may be required for a more suitable model to study behavior of cows under HS.

Fish intake in pregnant women and its impact on maternal-fetal health status.

OBJECTIVE: The objective was to evaluate the consumption of fish in pregnant women and its association with maternal and infant outcomes. MATERIAL AND METHODS: In this observational study carried out at the La Fe University and Polytechnic Hospital in Valencia, 300 pregnant women participated. The participants were divided into 2 groups according to their fish consumption during pregnancy for comparison. The χ2 test or ANOVA test were applied for comparisons for qualitative and quantitative variables respectively. RESULTS: It was observed that 49% of women consumed adequate amounts of fish during pregnancy (2 or 3 weekly servings). Significant differences were observed for iron supplementation (higher in women with inadequate fish consumption), threatened pregnancy loss (higher in women with inadequate fish consumption), infant size (better in women with adequate fish consumption), and arterial O2 pressure (better in women with adequate fish consumption). In regard to the other components of the dietary pattern, no differences were observed but the adequacy of intake for grains and white meat was very poor (less than 5.0%). CONCLUSIONS: Half of the women met the recommendations for fish intake during pregnancy and presented an overall healthier eating pattern but without statistical significance.

Increased dietary vitamin D3 and calcium partially alleviate heat stress symptoms and inflammation in lactating Holstein cows independent of dietary concentrations of vitamin E and selenium.

Twelve multiparous Holstein cows (42.2 ± 5.6 kg of milk/d; 83 ± 27 d in milk) were used in a split-plot design testing the effects of mineral and vitamin supplementation on the time course of animal performance, metabolism, and inflammation markers during heat stress. The main plot was the average concentrations of dietary vitamin E and Se (adequate: 11.1 IU/kg of vitamin E and 0.55 mg/kg of Se, and high: 223 IU/kg of vitamin E and 1.8 mg/kg of Se, respectively). Within each plot, cows were randomly assigned to (1) heat stress (HS) with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73%, respectively), (2) HS with high concentrations of vitamin D3 and Ca (HS+D3/Ca; 3,764 IU/kg and 0.97%, respectively), or (3) pair-feeding (PF) in thermoneutrality with adequate concentrations of vitamin D3 and Ca (1,012 IU/kg and 0.73% Ca) in a Latin square design with 14-d periods and 7-d washouts. The highest rectal temperature was recorded at 1700 h for HS (39.4°C; mean of d 1 to 14), being 1.2 and 0.8°C greater than for PF and HS+D3/Ca, respectively. Respiratory rate and water intake were higher in HS (73 breaths/min and 115 L/d, respectively) relative to PF (28 breaths/min and 76 L/d). Heat stress decreased dry matter intake progressively, reaching a nadir on d 5 to 7 (33% reduction) and was not different between treatments. Milk yield decreased progressively in all treatments, but remained greater in PF relative to HS from d 3 to 14 (10%), whereas HS and HS+D3/Ca were not different. Milk fat, protein, and lactose concentrations and yields were lower in HS relative to PF from d 3 to 14, but not different between HS and HS+D3/Ca. Relative to PF, preprandial insulin concentrations were increased in HS, whereas plasma nonesterified fatty acids were decreased on d 7 and 14. Plasma lipopolysaccharide-binding protein concentrations increased in HS cows on d 7 and 14, respectively, relative to PF, whereas they were reduced in HS + D3/Ca on d 14. Plasma C-reactive protein, tumor necrosis factor-α, and fecal calprotectin were increased in HS relative to both PF and HS+D3/Ca on d 7 and 14. Rectal temperature was positively associated with plasma lipopolysaccharide-binding protein (r = 0.72), tumor necrosis factor-α (r = 0.74), C-reactive protein (r = 0.87), and with milk somatic cells (r = 0.75). Plasma 8-hydroxy-2-deoxyguanosine concentrations presented a 3-way interaction, where 8-hydroxy-2-deoxyguanosine was lower in HS than in PF on d 7 and 14, and lower in HS+D3/Ca relative to HS on d 14 in the adequate vitamin E and Se treatment, but no effects were observed in the high vitamin E and Se group. Plasma superoxide dismutase concentrations increased over time, and were higher in HS relative to PF on d 14, whereas HS+D3/Ca was similar to HS. Heat stress markedly reduced milk production and milk components while increasing markers of leaky gut and inflammation. In contrast, vitamin D3 and Ca supplementation reduced hyperthermia (d 7-14), markers of leaky gut, and inflammation independent of dietary concentrations of vitamin E and Se.

3D scaffolds of caprolactone/chitosan/polyvinyl alcohol/hydroxyapatite stabilized by physical bonds seeded with swine dental pulp stem cell for bone tissue engineering.

Bone Regeneration represents a clinical need, related to bone defects such as congenital anomalies, trauma with bone loss, and/or some pathologies such as cysts or tumors This is why a polymeric biomaterial that mimics the osteogenic composition and structure represents a high potential to face this problem. The method of obtaining these materials was first to prepare a stabilized hydrogel by means of physical bonds and then to make use of the lyophilization technique to obtain the 3D porous scaffolds with temperature conditions of -58 °C and pressure of 1 Pa for 16 h. The physicochemical and bioactive properties of the scaffolds were studied. FTIR and TGA results confirm the presence of the initial components in the 3d matrix of the scaffold. The scaffolds exhibited a morphology with pore size and interconnectivity that promote good cell viability. Together, the cell viability and proliferation test, Alamar BlueTM and the differentiation test: alizarin staining, showed the ability of physically stabilized scaffolds to proliferate and differentiate swine dental pulp stem cell (DPSCs) followed by mineralization. Therefore, the Cs-PCL-PVA-HA scaffold stabilized by physical bonds has characteristics that suggest great utility for future complementary in vitro tests and in vivo studies on bone defects. Likewise, this biomaterial was enhanced with the addition of HA, providing a scaffold with osteoconductive properties necessary for good regeneration of bone tissue. Graphical abstract.

[Clinical experience with erenumab during the first year of treatment]. / Experiencia clínica con erenumab durante el primer año de tratamiento.

INTRODUCTION: Erenumab, a calcitonin gene-related peptide antagonist, has been approved for migraine prophylaxis. It represents an alternative for patients with multiple treatment failures, who have a low quality of life and high associated disability. AIM: To analyse the effectiveness and safety of erenumab during the first year of treatment and to assess its impact on quality of life and disability. PATIENTS AND METHODS: It is a longitudinal prospective observational study conducted over 15 months. Patients who met the funding criteria for erenumab were included. Data concerning years of illness, migraine days/month, pain intensity, previous treatments, doses and adverse effects were collected. In addition, quality of life and disability were assessed using the Migraine-Specific Quality Of Life Questionnaire 2.1 and Migraine Disability Assessment Scale, repeated at three and 12 months. RESULTS: Forty-three patients were included, 79.1% female, 95.3% with chronic migraine and with a mean age of 48.2 years. Prior to erenumab they had 20 migraine days/month, a pain intensity of 8.2 and a 30.6% quality of life, and 72.5% had very severe disability. Fifteen patients stopped taking erenumab due to inefficacy and one due to intolerance. Thirteen received erenumab for one year and 14 continued with the treatment. All four effectiveness variables were significantly improved with erenumab by the third month. Fifteen patients (34.9%) had adverse effects, most of which were mild. Constipation was the most frequent. CONCLUSIONS: Erenumab proved effective in most patients for migraine prophylaxis in the first three months, significantly reducing the number of migraine days/month, pain intensity and associated disability. Moreover, it significantly improved their quality of life . It is a safe drug.

TITLE: Experiencia clínica con erenumab durante el primer año de tratamiento.Introducción. El erenumab, un antagonista del péptido relacionado con el gen de la calcitonina, ha sido autorizado para la profilaxis de la migraña. Se presenta como una alternativa para pacientes con múltiples fracasos terapéuticos, los cuales presentan baja calidad de vida y alta discapacidad asociada. Objetivo. Analizar la efectividad y la seguridad del erenumab durante el primer año de tratamiento y evaluar su impacto en la calidad de vida y la discapacidad. Pacientes y métodos. Estudio observacional prospectivo longitudinal realizado durante 15 meses. Se incluyó a los pacientes que cumplían los criterios de financiación del erenumab. Se recogieron años de enfermedad, días de migraña/mes, intensidad del dolor, tratamientos previos, dosis y efectos adversos. Además, se evaluaron la calidad de vida y la discapacidad mediante los cuestionarios Migraine-Specific Quality Of Life Questionnaire 2.1 y Migraine Disability Assessment Scale, que se repitieron a los tres y a los 12 meses. Resultados. Se incluyó a 43 pacientes, el 79,1% mujeres, el 95,3% con migraña crónica y con una edad media de 48,2 años. Previamente al erenumab presentaban 20 días de migraña/mes, intensidad de dolor 8,2, un 30,6% de calidad de vida y el 72,5% tenía discapacidad muy grave. Quince pacientes suspendieron el erenumab por ineficacia y uno por intolerancia. Trece recibieron erenumab durante un año y 14 continuaban en tratamiento. Las cuatro variables de efectividad mejoraron significativamente con el erenumab al tercer mes. Quince pacientes (34,9%) presentaron efectos adversos, en su mayoría leves. El estreñimiento fue el más frecuente. Conclusiones. El erenumab mostró efectividad en la mayoría de los pacientes para profilaxis de migraña en los tres primeros meses, reduciendo significativamente los días de migraña/mes, la intensidad del dolor y la discapacidad asociada. Además, mejoró significativamente la calidad de vida. Es un fármaco seguro.

A Unifying Framework for Understanding Biological Structures and Functions Across Levels of Biological Organization.

The relationship between structure and function is a major constituent of the rules of life. Structures and functions occur across all levels of biological organization. Current efforts to integrate conceptual frameworks and approaches to address new and old questions promise to allow a more holistic and robust understanding of how different biological functions are achieved across levels of biological organization. Here, we provide unifying and generalizable definitions of both structure and function that can be applied across all levels of biological organization. However, we find differences in the nature of structures at the organismal level and below as compared to above the level of the organism. We term these intrinsic and emergent structures, respectively. Intrinsic structures are directly under selection, contributing to the overall performance (fitness) of the individual organism. Emergent structures involve interactions among aggregations of organisms and are not directly under selection. Given this distinction, we argue that while the functions of many intrinsic structures remain unknown, functions of emergent structures are the result of the aggregate of processes of individual organisms. We then provide a detailed and unified framework of the structure-function relationship for intrinsic structures to explore how their unknown functions can be defined. We provide examples of how these scalable definitions applied to intrinsic structures provide a framework to address questions on structure-function relationships that can be approached simultaneously from all subdisciplines of biology. We propose that this will produce a more holistic and robust understanding of how different biological functions are achieved across levels of biological organization.

Systematic review of the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion for the treatment of refractory chronic cluster headache.

INTRODUCTION: This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic cluster headache. DEVELOPMENT: Various medical databases were used to perform a systematic review of the scientific literature. The search for articles continued until 31 October 2016, and included clinical trials, systematic reviews and/or meta-analyses, health technology assessment reports, and clinical practice guidelines that included measurements of efficiency/effectiveness or adverse effects associated with the treatment. The review excluded cohort studies, case-control studies, case series, literature reviews, letters to the editor, opinion pieces, editorials, and studies that had been duplicated or outdated by later publications from the same institution. Regarding effectiveness, we found that SPG stimulation had positive results for pain relief, attack frequency, medication use, and patients' quality of life. In the results regarding safety, we found a significant number of adverse events in the first 30 days following the intervention. Removal of the device was necessary in some patients. Little follow-up data, and no long-term data, is available. CONCLUSIONS: These results are promising, despite the limited evidence available. We consider it essential for research to continue into the safety and efficacy of SPG stimulation for patients with refractory chronic cluster headache. In cases where this intervention may be indicated, treatment should be closely monitored.

Robotic-assisted, laparoscopic, and open incisional hernia repair: early outcomes from the Prospective Hernia Study.

PURPOSE: To provide a comparative analysis of short-term outcomes after open, laparoscopic, and robotic-assisted (RAS) ventral incisional hernia (VIH) repairs that include subject-reported pain medication usage and hernia-related quality of life (QOL). METHODS: Subjects were ≥ 18 years old and underwent elective open, laparoscopic or RAS VIH repair without myofascial release. Perioperative clinical outcomes through 30 days were analyzed as were prescription pain medication use and subject-reported responses to the HerQLes Abdominal QOL questionnaire. Observed differences in baseline characteristics were controlled using a weighted propensity score analysis to obviate potential selection bias (inverse probability of treatment weighting, IPTW). A p value < 0.05 was considered statistically significant. RESULTS: Three hundred and seventy-one subjects (RAS, n = 159; open, n = 130; laparoscopic, n = 82) were enrolled in the study across 17 medical institutions within the United States. Operative times were significantly different between the RAS and laparoscopic groups (126.2 vs 57.2, respectively; p < 0.001). Mean length of stay was comparable for RAS vs laparoscopic (1.4 ± 1.0 vs 1.4 ± 1.1, respectively; p = 0.623) and differed for the RAS vs open groups (1.4 ± 1.0 vs 2.0 ± 1.9, respectively; p < 0.001). Conversion rates differed between RAS and laparoscopic groups (0.6% vs 4.9%; p = 0.004). The number of subjects reporting the need to take prescription pain medication through the 2-4 weeks visit differed between RAS vs open (65.2% vs 79.8%; p < 0.001) and RAS vs laparoscopic (65.2% vs 78.75%; p < 0.001). For those taking prescription pain medication, the mean number of pills taken was comparable for RAS vs open (23.3 vs 20.4; p = 0.079) and RAS vs laparoscopic (23.3 vs 23.3; p = 0.786). Times to return to normal activities and to work, complication rates and HerQLes QOL scores were comparable for the RAS vs open and RAS vs laparoscopic groups. The reoperation rate within 30 days post-procedure was comparable for RAS vs laparoscopic (0.6% vs 0%; p = 0.296) and differed for RAS vs open (0.6% vs 3.1%; p = 0.038). CONCLUSIONS: Short-term outcomes indicate that open, laparoscopic, and robotic-assisted approaches are effective surgical approaches to VIH repair; however, each repair technique may demonstrate advantages in terms of clinical outcomes. Observed differences in the RAS vs laparoscopic comparison are longer operative time and lower conversion rate in the RAS group. Observed differences in the RAS vs open comparison are shorter LOS and lower reoperation rate through 30 days in the RAS group. The operative time in the RAS vs open comparison is similar. The number of subjects requiring the use of prescription pain medication favored the RAS group in both comparisons; however, among subjects reporting a need for pain medication, there was no difference in the number of prescription pain medication pills taken. While the study adds to the body of evidence evaluating the open, laparoscopic, and RAS approaches, future controlled studies are needed to better understand pain and QOL outcomes related to incisional hernia repair. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02715622.

[Adherence to biological therapies in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. (Study ADhER-1)]. / Adherencia terapéutica a fármacos biológicos en pacientes con artritis reumatoide, artritis psoriásica y espondilitis anquilosante. (Estudio ADhER-1).

BACKGROUND: To quantify adherence to biological disease-modifying anti-rheumatic drugs (DMARD) and to determine the factors that can predict adherence in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis in daily clinical practice. METHODS: An observational, descriptive, cross-sectional and single-center study was carried out. Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who were in treatment with subcutaneous biological DMARD were included. Variables related to socioeconomic status, disease, biological therapy and safety were recorded. Adherence was calculated by using medication possession ratio, Compliance Questionnaire on Rheumatology and Morisky Medication Adherence Scale Questionnaire. RESULTS: One hundred twelve patients and 6 different biological DMARDs were included. Mean age was 56.8±13.2 years and 52.7% were women. The percentage of adherent patients was 59.3% in rheumatoid arthritis, 62.5% in psoriatic arthritis and 76.2% in ankylosing spondylitis. Lesser adherence was associated with the administration of the drug by a family member and/or caregiver (odds ratio: 9.6; 95% confidence interval: 1.5-61.8 (p <.05)). There were no differences between adherent and non-adherent patients in terms of the biological DMARD used. CONCLUSIONS: There are no differences in adherence to biological therapies among patients with chronic inflammatory arthropathies. Adherence correlates negatively with administration of biological DMARD by a family member and / or caregiver.

Role of low-level quinolone resistance in generating tolerance in Escherichia coli under therapeutic concentrations of ciprofloxacin.

BACKGROUND: Tolerance (including persistence) and resistance result in increased survival under antibiotic pressure. OBJECTIVES: We evaluated the interplay between resistance and tolerance to ciprofloxacin under therapeutic and killing conditions to determine the contribution of low-level quinolone resistance (LLQR) mechanisms to tolerance. We also determined how the interaction between resistance (LLQR phenotypes) and tolerance was modified under SOS response suppression. METHODS: Twelve isogenic Escherichia coli strains harbouring quinolone resistance mechanisms combined with SOS response deficiency and six clinical E. coli isolates (LLQR or non-LLQR) were evaluated. Survival (tolerance or persistence) assays were used to measure surviving bacteria after a short period (up to 4 h) of bactericidal antibiotic treatment under therapeutic and killing concentrations of ciprofloxacin [1 mg/L, EUCAST/CLSI breakpoint for resistance; and 2.5 mg/L, peak serum concentration (Cmax) of this drug]. RESULTS: QRDR substitutions (S83L in GyrA alone or combined with S80R in ParC) significantly increased the fraction of tolerant bacteria (2-4 log10 cfu/mL) after exposure to ciprofloxacin at clinically relevant concentrations. The impact on tolerant bacteria due to SOS response suppression (including persistence mediated by the tisB gene) was reversed by LLQR mechanisms at therapeutic concentrations. Furthermore, no reduction in the fraction of tolerant bacteria due to SOS response suppression was observed when S83L in GyrA plus S80R in ParC were combined. CONCLUSIONS: Tolerance and quinolone resistance mutations interact synergistically, giving LLQR mechanisms an additional role in allowing bacterial survival and evasion of therapeutic antimicrobial conditions by a combination of the two strategies. At clinically relevant concentrations, LLQR mechanisms reverse further impact of SOS response suppression in reducing bacterial tolerance.

Use of barley straw as a support for the production of conidiospores of Trichoderma harzianum.

In this work was to evaluate the conidiospores production of Trichoderma harzianum using barley straw as substrate. Four growth conditions were used; washed and unwashed barley straw and washed and unwashed barley straw supplemented with mineral salts. The highest spore production was observed when washed barley straw supplemented with mineral salts with 1.56 × 1010 conidiospores/gram of dry matter (gdm) at 216 h of cultivation was used. The effect of substrate moisture on spore production was studied, three initial moisture levels of the substrate were tested and it was observed that a humidity of 80 % of the substrate improves the production of conidiospores reaching a concentration of 2.35 × 1010 conidiospores/gdm at 136 h. Finally, conidiospores viability was evaluated for 12 months by keeping them on the conidia and substrate, and viability of 71 % of the conidiospores was observed, so this maintenance method is an excellent means of conserving the conidiospores viability.

Variación de dosis de radioyodo en pacientes con cáncer diferenciado de tiroides post implementación de guías ATA 2015 / Variation of radioiodine dose in patients with differentiated thyroid cancer after implementation of the ATA 2015 guidelines

Introducción: El cáncer diferenciado de tiroides (CDT), es actualmente la neoplasia endocrina más frecuente. Su tratamiento estándar es la resolución quirúrgica, asociado a ablación con radioyodo (RI) según la clasificación propuesta por la American Thyroid Association (ATA). Las indicaciones y dosis de este último, han ido variando en los últimos años según avanzan las investigaciones en este ámbito. Objetivo: En el siguiente estudio se compararon las dosis de RI utilizadas previo y posterior a la implementación de las últimas guías de la ATA. Materiales y métodos: Estudio retrospectivo observacional de 70 pacientes con diagnóstico de CDT del Hospital Clínico de la Universidad de Chile entre 2012 y 2017. Se agruparon los pacientes en dos cohortes, los operados entre los años 2012-2015 y los 2016-2017 clasificándolos según riesgo ATA, TNM y riesgo de recurrencia. Se consignaron las dosis de RI utilizadas y se compararon entre las cohortes. Análisis estadístico: Mann Whithney. Resultados: Al comparar la dosis de RI entre ambas cohortes, según TNM y riesgo ATA, se obtuvo los siguientes resultados: los pacientes T1b de la cohorte 2012-2015 presentaron dosis de RI significativamente mayores que los de la cohorte 2016-2017; también se evidenció que en pacientes N0 hubo una diferencia estadísticamente significativa, mostrando una tendencia a disminuir la dosis de RI; además, en los pacientes de la cohorte 2012-2015 con riesgo ATA intermedio, se obtuvo que las dosis de RI fueron significativamente mayores que las utilizadas en la cohorte 2016-2017. Conclusión: Se concluye que las variaciones de las dosis de RI utilizadas en pacientes con CDT en un hospital universitario van acorde a las recomendaciones internacionales actuales, particularmente la publicación de la guía ATA 2015, aplicándose radioablación con menor dosis de RI. Dado este cambio, se ha evidenciado igualdad de efectos con dosis menores de RI y consecuentemente menos efectos adversos.

Introduction: Differentiated thyroid cancer (CDT) is currently the most frequent endocrine neoplasia. Its standard of care is surgical treatment, associated with radioiodine ablation (IR) according to the classification proposed by the American Thyroid Association (ATA). The indications and doses of the latter have changed in recent years as research in this area advances. Objective: In the following study, the doses of IR used before and after the implementation of the latest ATA guidelines were compared. Materials and methods: Retrospective observational study of 70 patients with a diagnosis of CDT from the Clinical Hospital of the University of Chile between 2012 and 2017. Patients were grouped into two cohorts, those surgically intervened between the years 2012-2015 and 2016-2017, classifying them according to ATA risk, TNM and recurrence risk. The IR doses used were reported and compared between the cohorts. Statistical analysis: Mann Whithney. Results: When comparing the IR dose between both cohorts, according to TNM and ATA risk, the following results were obtained: T1b patients in the 2012-2015 cohort had significantly higher IR doses than those in the 2016-2017 cohort; It was also evidenced that N0 patients showed a statistically significant tendency to decrease the IR dose; In addition, the 2012-2015 cohort with intermediate ATA risk, revealed IR doses significantly higher than those used in the 2016-2017 cohort. Conclusion: It is concluded that the variations in IR doses, used in patients with CDT in a university hospital, are in accordance with current international recommendations, particularly the publication of the ATA 2015 guidelines, applying radioablation with a lower dose of IR. Given this change, equality of effects has been evidenced with lower doses of IR and consequently fewer adverse effects.

[Glutamate, hypothalamus-hypophysis-adrenal axis and clinical manifestations in multiple sclerosis]. / Glutamato, eje hipotalamo-hipofiso-adrenal y manifestaciones clinicas en la esclerosis multiple.

TITLE: Glutamato, eje hipotalamo-hipofiso-adrenal y manifestaciones clinicas en la esclerosis multiple.

Flavonol glycosides in Dyssodia tagetiflora and its temporal variation, chemoprotective and ameliorating activities.

Dyssodia tagetiflora is known as 'Tzaracata' and 'flor de muerto'. Recently, D. tagetiflora has been reported to have antioxidant activities in its polar extracts as well as insecticidal activities. Hyperoside (1), avicularin (2) and avicularin acetate (3) have been isolated previously. However, the temporary variation in glycoside flavonoids biosynthesis, as well as antibacterial and chemoprotective activities, have not been reported. The amount of 1, 2 and 3 in the different collections was characterized by HPLC-MS. Two new C-glycosides were characterized, quercetin-4'-methyl ether 6-C glucoside (A1) and quercetin-4'-methyl ether 8-C glucoside (A2), as well as [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]3,4,5-trihydroxyoxane-2,6-dicarboxylate (A3). This is the first report of the presence of C-C flavonoid glycosides compounds in the genus Dyssodia. Hyperoside was the majority compound at all collections. The methanolic extracts of August 2016 and October 2017 were active against Micrococcus luteus and Bacillus subtillis. The methanolic extract has chemoprotective effects because, when applied topically in SKH-1 mice, it decreases the severity of epidermal damage induced by acute exposure to ultraviolet radiation. In addition, cutaneous photocarcinogenesis was decreased in mice treated with the extract. The methanolic extract of D. tagetiflora has chemoprotective properties by decreasing the damage caused by acute and chronic exposure to UV in mice.

Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model.

BACKGROUND: Paclitaxel has been used frequently for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC are associated with high rates of morbidity being anastomotic dehiscence one of the most frequent. The objective of this study is to quantify the effect of Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model. METHODS: After left colon resection and anastomosis, animals were randomized into four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four, animals' peritoneal cavities were examined macroscopically, colon anastomosis burst pressures measured and specimens analyzed histologically. RESULTS: Thirty-nine animals were randomized and 36 were included in the analysis. H group presented the highest burst pressure 105.11 ± 22.9 mmHg, which was 27% higher than C (77.89 ± 27.6 mmHg). On the other hand, HP presented the lowest burst pressure 64 ± 26 mmHg, 16% lower than C group and 39% lower than H, being this latter difference statistically significant (p = 0.004). There were no significant differences regarding weight loss, adhesion scores, perianastomotic abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis, and collagen among groups). CONCLUSION: Strength of colonic anastomosis was improved by isolated hyperthermia and negatively affected by Paclitaxel-based HIPEC.

[A brief history of marijuana in the western world]. / Breve historia sobre la marihuana en Occidente.

Marijuana is a substance with a long and controversial history. At different times in its history, which goes back over 5,000 years, this plant has been used for different purposes, ranging from recreational and leisure to its use in the treatment of several diseases or to offer relief in processes that entail a certain type of malaise, and including its consideration as a means of relaxation and meditation. Although it was supposed that the roots of marijuana lay in Central America, it is now known that this is but an urban legend with little credibility and that its origins can be found recorded in Chinese medical references dating back to the year 2737 BC. Although this plant was not originally from Central America, it has aroused interest around the world, and above all in Mexico. It is in this country where the use of cannabis has gone from applications in textiles and medicine to its free sale, the bans on its use due to political and social pressures, its tolerance and, recently, its decriminalisation for recreational and medicinal use. Unfortunately there are few references on the history of this plant in Mexico, and thus we have considered it interesting to present some data about the generalities of marijuana, a brief history in the world, the development of decriminalisation in North America, its medicinal uses and its course through Mexico to the present day.

TITLE: Breve historia sobre la marihuana en Occidente.La marihuana es una sustancia con una extensa y controvertida historia. A lo largo del tiempo, esta planta, y desde hace mas de 5.000 años, ha sido utilizada para diferentes fines, que van desde el uso ludico y recreativo, pasando por un medio de relajacion y meditacion, hasta su uso en el tratamiento de varias enfermedades o el alivio de procesos vinculados a cierto tipo de malestares. Aunque se supuso que la marihuana tenia su origen en Mesoamerica, ahora se sabe que es solo una leyenda urbana de poca credibilidad y que sus origenes los podemos registrar en referencias medicas chinas datadas alrededor del año 2737 a. de C. Si bien esta planta no tiene un origen mesoamericano, si ha generado interes en el mundo, y sobre todo en Mexico. Es en este pais donde el uso del cannabis ha ido desde intereses textiles y medicinales hasta el consumo ludico, pasando por su venta libre, la prohibicion por presiones politicas y sociales, su tolerancia y, recientemente, su despenalizacion para uso ludico y medicinal. Desgraciadamente existen pocas referencias de la historia de esta planta en Mexico, por lo que ha sido de nuestro interes presentar algunos datos sobre las generalidades de la marihuana, una breve historia en el mundo, el desarrollo de la despenalizacion en Norteamerica, sus usos medicinales y su paso por Mexico hasta nuestros dias.

Supplementation of DHA-Gold pre and/or postnatally to goat kids modifies in vitro methane production and rumen morphology until 6 mo old.

This study aimed to investigate the effect of pre and/or postnatal supplementation of a dry whole cell algae (DHA-Gold) to goat kids, on in vitro methane (CH4) production, animal growth, and rumen morphology at the age of 6 mo. Furthermore, the in vitro retreatment effect of DHA-Gold was evaluated. Twenty pregnant Saanen goats giving birth to 2 male kids were used. Half of these does were supplemented (D+) with 18.2 g/d of DHA-Gold in the last 3 wk of pregnancy, whereas the other half was not (D-). After kidding, one goat kid per doe in both groups was supplemented daily with 0.28 g/kg of body weight of DHA-Gold (k+) until 12 wk, whereas the other goat kids were untreated (k-). This resulted in 4 experimental groups D+k+, D+k-, D-k+, and D-k-. In vitro incubations were performed at the ages of 4 wk, 11 wk, and 6 mo. At the age of 6 mo, goat kids were euthanized and additional incubations were performed supplementing 4 doses of DHA-Gold (0, 0.4, 0.8, and 1.6 mg/mL). Additionally, rumen tissue of the atrium ruminis, ventral rumen, and dorsal blind sac were collected to assess rumen morphology. Rumen inocula of 4-wk-old goat kids supplemented D+ showed lower (P < 0.05) in vitro CH4 production, however, this was mainly due to a reduction in the overall fermentation, while CH4 expressed relatively to total volatile fatty acids (VFA) was higher when goat kids were treated D+ or k+. The detrimental D+ effect on VFA production diminished at 11 wk old but remained a tendency (0.05 < P < 0.1). As for 4 wk D+ as well as k+ supplementation of DHA-Gold stimulated rather than inhibited in vitro CH4 production expressed relative to total VFA. Supplementation of DHA-Gold either D+ or k+ decreased density, width, and surface area of the ruminal papillae. However, no effect on animal growth was observed. Moreover, detrimental effects of D+ or k+ treatment on VFA production or stimulation of relative CH4 production were no longer observed at 6 mo old. Nevertheless, direct exposure of DHA-Gold to 6-mo-old inoculum linearly (P < 0.05) decreased CH4 and VFA production, which tended (P = 0.06) to be greater when using D-rumen inoculum. Accordingly, neither D+ nor k+ DHA-Gold supplementation showed potential for reduction of rumen methanogenesis. Furthermore, this early life intervention could represent some risk for impaired rumen papillae development, which, however, did not impair animal performance.

Effects of Fiber Purified Extract of Carob Fruit on Fat Digestion and Postprandial Lipemia in Healthy Rats.

Increased postprandial lipemia is a cardiovascular disease (CVD) risk factor. Carob fruit extract (CFE) contains condensed tannins, and their intake has been inversely related to CVD. The objective was to evaluate the in vitro pancreatic lipase activity in the presence of CFE and the in vivo effect of CFE on postprandial lipemia of healthy Wistar rats in acute and subchronic digestibility studies and to relate it with changes in fat digestion and absorption. CFE significantly reduced pancreatic lipase activity. A peak delay and a dose-dependent decrease in plasma triglyceride and cholesterol areas under the curve were observed, effects that increased after the subchronic treatment. The levels of nondigested, nonabsorbed triglycerides of the remaining intestinal lumen fat were significantly higher in the maximum dose of CFE administrated versus the control ( P < 0.05). This study demonstrates for the first time the hypolipemic properties of CFE from the first administration, modifying postprandial lipemia by reducing the extents of fat digestion and absorption.

Dermatitis de contacto alérgica aerotransportada por aceite de neem / Airborne Allergic Contact Dermatitis Caused by Neem Oil

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