Applications of psychoneuroimmunology models of toxic stress in prevention and intervention efforts across early development.

Although evidence supporting psychoneuroimmunology (PNI) models of toxic stress have emerged over the past decade, the PNI field has struggled to integrate these important findings into real-world practical applications. There is great potential for these models to reduce the societal burden of childhood adversity by facilitating early detection and prevention with those children and adolescents at greatest risk for stress-related physical and psychological disorders. But further research is needed to validate and scale developmentally appropriate interventions with specific immune and endocrine mechanism-based targets that are developmentally sensitive. The allostatic load and additive PNI models of toxic stress exposure in youth are summarized. These models highlight the importance of integrating a standardized screening of environmental and interpersonal risk factors with stable and scalable cognitive and biological markers of risk. PNI models of toxic stress illustrate the need for intervention delivery as early as possible to prevent negative health outcomes in youth and comprehensive screening efforts would facilitate the deployment of community and family level interventions. This review discusses practical applications of toxic stress models that are currently under investigation, clarifies key obstacles, such as research gaps and scalability, and provides potential solutions, including cross-disciplinary partnerships.

Innate and humoral immune parameters at delivery in colostrum and calves from heifers experimentally infected with Neospora caninum.

Neospora caninum is a leading cause of abortion in cattle worldwide. The study of the immune response against N. caninum is critical to understand its epidemiology, pathogenesis, diagnosis and, ultimately, in preventing and controlling bovine neosporosis. Herein, we determined the gene expression of innate immune components endosomal RNA-sensing TLRs, BMAP28 cathelicidin, TNF-α and IL-10 and characterized the variation in both IgG ratio and avidity at delivery in N. caninum-infected heifers challenged at day 210 of gestation, colostrum and their calves. Increased BMAP28 expression was observed not only in colostrum but also in peripheral blood mononuclear cells (PBMC) and umbilical cord of calves from N. caninum-infected heifers in comparison with mock-infected control group. In addition, statistically significant decrease of TLR7 and IL-10 expression levels were observed in umbilical cord, suggesting an attempt to avoid an exacerbated immune response against the parasite. At delivery, serum and colostrum samples from infected group evidenced specific IgG anti-N. caninum. Infected heifers showed IgG1/IgG2 ratios <1 and high avidity specific IgG. As expected, colostrum samples of these animals exhibited a high IgG1 concentration and elevated avidity values. Three out of four calves from N. caninum-infected heifers had specific IgG with IgG1/IgG2 ratios>1 and lower avidity values before colostrum intake. Interestingly, both IgG1/IgG2 ratios and avidity values increased in seropositive calves after colostrum intake. Overall, this study provides novel information on neonatal immunity in congenitally infected calves, which is essential to understand how the immune pathways could be manipulated or immune components could be employed in order to improve protection against neosporosis.

Milk production responses to altering the dietary ratio of palmitic and oleic acids varies with production level in dairy cows.

We evaluated the effects of altering the dietary ratio of palmitic (C16:0; PA) and oleic (cis-9 C18:1; OA) acids on production responses of cows with a wide range of milk production (32 to 65 kg/d) in a crossover design experiment with a preliminary period. Thirty-two multiparous Holstein cows (144 ± 54 d in milk) were assigned randomly to a treatment sequence. Treatments were diets supplemented with fatty acid (FA) blends (1.5% of diet dry matter) that provided 80% C16:0 + 10% cis-9 C18:1 (PA) and 60% C16:0 + 30% cis-9 C18:1 (PA+OA). The corn silage and alfalfa-based diets contained 20.0% forage neutral detergent fiber (NDF), 28.5% starch, and 17.1% crude protein. Treatment periods were 21 d with the final 5 d used for data and sample collection. Treatment did not affect dry matter intake (DMI), milk yield, energy-corrected milk (ECM), body weight, or body weight change. The PA+OA diet increased total, 16-carbon, and 18-carbon FA digestibility compared with the PA diet. Compared with PA+OA, PA increased fat yield (1.97 vs. 1.91 kg/d) and protein yield (1.61 vs. 1.55 kg/d). The PA diet also increased the yield of de novo (448 vs. 428 g/d) and mixed (749 vs. 669 g/d) milk FA and decreased the yield of preformed FA (605 vs. 627 g/d) compared with PA+OA. Interactions were detected between treatment and preliminary milk yield for DMI, total FA intake, 16-carbon FA intake, ECM, 3.5% fat-corrected milk (linear interaction), and a tendency for milk yield (linear interaction); lower-producing cows (<45 kg/d) had increased DMI and ECM on the PA diet, whereas higher-producing cows (>55 kg/d) had increased DMI and ECM on the PA+OA diet. A linear interaction was detected between treatment and preliminary milk yield for mixed milk FA yield (linear interaction) and a tendency for de novo milk FA yield (linear interaction). Our results demonstrate that feeding a fat supplement containing more cis-9 C18:1 replacing C16:0 increased production responses (DMI, milk yield, and ECM) in higher-producing cows, but decreased production responses in lower-producing cows.

Effects of commercially available palmitic and stearic acid supplements on nutrient digestibility and production responses of lactating dairy cows.

We evaluated the effects of commercially available fatty acid (FA) supplements containing palmitic (C16:0) and stearic acid (C18:0) on nutrient digestibility and production responses of dairy cows. Thirty-six mid-lactation (146 ± 55 d in milk) multiparous Holstein cows were randomly assigned to twelve 3 × 3 balanced truncated Latin squares, with 3 treatments and 2 consecutive 35-d periods, with the final 5 d used for sample and data collection. Treatments were (1) a control diet containing no supplemental FA (CON), (2) a control diet supplemented with a commercially available C16:0 supplement (PA), and (3) a control diet supplemented with a commercially available C16:0 and C18:0 supplement (MIX). Supplements were fed at 1.5% dry matter and replaced soyhulls in CON. The statistical model included the random effect of cow nested within square and the fixed effects of treatment, period, square, and their interactions. Preplanned contrasts were (1) overall effect of FA treatments [CON vs. the average of the FA treatments (FAT); 1/2 (PA + MIX)], and (2) effect of FA supplement (PA vs. MIX). Treatment had no effects on dry matter intake, body weight, or body weight change. Compared with CON, FAT decreased digestibilities of total FA and 18-carbon FA but did not affect dry matter and neutral detergent fiber digestibility. Compared with MIX, PA increased dry matter and neutral detergent fiber digestibilities by 3.6 and 4.8 percentage units, respectively. The PA also increased total FA and 18-carbon FA digestibilities but did not alter 16-carbon FA digestibility compared with MIX. Using a Lucas test, we estimated apparent digestibility coefficients of 0.768 and 0.553 for the PA and MIX supplements, respectively. Compared with CON, FAT increased milk yield and tended to increase energy-corrected milk, but did not affect yield of milk fat or milk protein. The PA increased energy-corrected milk and milk fat yield but had no effect on milk protein yield compared with MIX. Our results indicate that dairy cows producing around 45 kg of milk respond better to a FA supplement enriched in C16:0 compared with a supplement containing both C16:0 and C18:0, which is likely due in part to PA increasing FA and neutral detergent fiber digestibility compared with MIX.

Acetyl-l-carnitine deficiency in patients with major depressive disorder.

The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-l-carnitine (LAC) is critical for hippocampal function and several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased and signal abnormal hippocampal glutamatergic function and dendritic plasticity. LAC supplementation induces rapid and lasting antidepressant-like effects via epigenetic mechanisms of histone acetylation. This mechanistic model led us to evaluate LAC levels in humans. We found that LAC levels, and not those of free carnitine, were decreased in patients with MDD compared with age- and sex-matched healthy controls in two independent study centers. Secondary exploratory analyses showed that the degree of LAC deficiency reflected both the severity and age of onset of MDD. Moreover, these analyses showed that the decrease in LAC was larger in patients with a history of treatment-resistant depression (TRD), among whom childhood trauma and, specifically, a history of emotional neglect and being female, predicted the decreased LAC. These findings suggest that LAC may serve as a candidate biomarker to help diagnose a clinical endophenotype of MDD characterized by decreased LAC, greater severity, and earlier onset as well as a history of childhood trauma in patients with TRD. Together with studies in rodents, these translational findings support further exploration of LAC as a therapeutic target that may help to define individualized treatments in biologically based depression subtype consistent with the spirit of precision medicine.

Neonicotinoid pesticide limits improvement in buzz pollination by bumblebees.

Neonicotinoid pesticides have been linked to global declines of beneficial insects such as bumblebees. Exposure to trace levels of these chemicals causes sub-lethal effects, such as reduced learning and foraging efficiency. Complex behaviours may be particularly vulnerable to the neurotoxic effects of neonicotinoids. Such behaviours may include buzz pollination (sonication), in which pollinators, usually bees, use innate and learned behaviours to generate high-frequency vibrations to release pollen from flowers with specialised anther morphologies. This study assesses the effect of field-realistic, chronic exposure to the widely-used neonicotinoid thiamethoxam on the development of sonication buzz characteristics over time, as well as the collection of pollen from buzz-pollinated flowers. We found that the pollen collection of exposed bees improved less with increasing experience than that of unexposed bees, with exposed bees collecting between 47% and 56% less pollen by the end of 10 trials. We also found evidence of two distinct strategies for maximising pollen collection: (1) extensions to the duration of individual buzzes and (2) extensions of the overall time spent buzzing. We find new complexities in buzz pollination, and conclude that the impacts of field-realistic exposure to a neonicotinoid pesticide may seriously compromise this important ecosystem service.

Impact of Chiropractic Manipulation on Bone and Skeletal Muscle of Ovariectomized Rats.

Evidence suggests that chiropractic manipulation might exert positive effects in osteoporotic patients. The aim of this study was to evaluate the effects of chiropractic manipulation on bone structure and skeletal muscle in rats with bone loss caused by ovariectomy (OVX). The 6-month old Sprague-Dawley rats at 10 weeks following OVX or sham operation (Sh) did not suffer chiropractic manipulation (NM group) or were submitted to true chiropractic manipulation using the chiropractic adjusting instrument Activator V® three times/week for 6 weeks as follows: Force 1 setting was applied onto the tibial tubercle of the rat right hind limb (TM group), whereas the corresponding left hind limb received a false manipulation (FM group) consisting of ActivatorV® firing in the air and slightly touching the tibial tubercle. Bone mineral density (BMD) and bone mineral content (BMC) were determined in long bones and L3-L4 vertebrae in all rats. Femora and tibia were analyzed by µCT. Mechano growth factor (MGF) was detected in long bones and soleus, quadriceps and tibial muscles by immunohistochemistry and Western blot. The decrease of BMD and BMC as well as trabecular bone impairment in the long bones of OVX rats vs Sh controls was partially reversed in the TM group versus FM or NM rats. This bone improvement by chiropractic manipulation was associated with an increased MGF expression in the quadriceps and the anterior tibial muscle in OVX rats. These findings support the notion that chiropractic manipulation can ameliorate osteoporotic bone at least partly by targeting skeletal muscle.

Antibacterial effect of roselle extracts (Hibiscus sabadariffa), sodium hypochlorite and acetic acid against multidrug-resistant Salmonella strains isolated from tomatoes.

UNLABELLED: Antibiotic-resistant Salmonella strains were isolated from saladette and red round type tomatoes, and an analysis done of the antibacterial activity of roselle calyx extracts against any of the identified strains. One hundred saladette tomato samples and 100 red round tomato samples were collected from public markets. Each sample consisted of four whole tomatoes. Salmonella was isolated from the samples by conventional culture procedure. Susceptibility to 16 antibiotics was tested for the isolated Salmonella strains by standard test. The antibacterial effect of four roselle calyx extracts (water, methanol, acetone and ethyl acetate), sodium hypochlorite and acetic acid against antibiotic-resistant Salmonella isolates was evaluated on contaminated tomatoes. Twenty-four Salmonella strains were isolated from 12% of each tomato type. Identified Salmonella serotypes were Typhimurium and Typhi. All isolated strains exhibited resistance to at least three antibiotics and some to as many as 12. Over contaminated tomatoes, the roselle calyx extracts produced a greater reduction (2-2·6 log) in antibiotic-resistant Salmonella strain concentration than sodium hypochlorite and acetic acid. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of multidrug-resistant Salmonella in vegetables is a significant public health concern. Multidrug-resistant Salmonella strains were isolated from raw tomatoes purchased in public markets in Mexico and challenged with roselle Hibiscus sabdariffa calyx extracts, sodium hypochlorite and acetic acid. On tomatoes, the extracts caused a greater reduction in the concentration of antibiotic-resistant Salmonella strains than sodium hypochlorite and acetic acid. Roselle calyx extracts are a potentially useful addition to disinfection procedures of raw tomatoes in the field, processing plants, restaurants and homes.

Endometriosis rectosigmoidea infiltrante profunda. Claves para su diagnóstico / Deep infiltrating rectosigmoid endometriosis. Diagnostic keys

No disponible

Ultrasound-assisted extraction of stilbenoids from grape stems.

A new method for fast determination of stilbenoids from grape stems was developed. Ultrasound-assisted extraction was applied prior to chromatographic determination of stilbenoids in the extracts, and the stability of stilbenoids under extraction conditions was checked. A fractional experimental design was developed to analyze the influence on the extraction process of seven different extraction variables: temperature, ultrasound amplitude, ultrasonic cycle duration, ultrasonic probe type, time, sample-solvent ratio, and solvent (mixtures of ethanol and water). The most important variables for the recovery of major stilbenoids were studied and the final conditions optimized. With this new method, the main stilbenoids found in grape stems can be extracted in 15 min, using 75 °C as the extraction temperature and 80% ethanol as the extraction solvent, and no cleaning step with organic solvent is needed. The optimized method allowed for the analysis of stilbenoid content from 22 grape stem samples, many of them analyzed for the first time.

Electroestimulación del suelo pélvico en mujeres con incontinencia urinaria y/o síndrome de vejiga hiperactiva: una revisión sistemática / Pelvic Floor Electrostimulation in Women With Urinary Incontinence and/or Overactive Bladder Syndrome: A Systematic Review

Contexto: La electroestimulación (EE) es una de las técnicas empleadas en el tratamiento conservador de la incontinencia urinaria (IU) y/o síndrome de vejiga hiperactiva (SVH). Sin embargo, existe controversia en la literatura científica acerca de su eficacia como monoterapia. Objetivo: Evaluar la evidencia científica sobre la EE del suelo pélvico en mujeres con IU y/o SVH. Adquisición de evidencia: Se realizó una revisión sistemática de ensayos clínicos en las bases de datos PubMed, Cochrane, PEDro, Elsevier (Doyma) y EnFisPo (1980-2011). Se evaluó la calidad de los estudios y se extrajo la información de los que reunieron los criterios de inclusión establecidos. Síntesis de evidencia: Un total de 27 ensayos clínicos han sido incluidos en la revisión: 13 ensayos controlados aleatorizados, 11 ensayos aleatorizados no controlados y 3 ensayos no aleatorizados. Conclusión: La mayor parte de los ensayos clínicos concluyen que la EE es eficaz en el tratamiento de la IU y el SVH en mujeres. Sin embargo, son necesarios más estudios de buena calidad metodológica para obtener un mayor nivel de evidencia científica y conocer cuál es la modalidad, tipo y parámetros de corriente óptimas para cada tipo de IU y el SVH (AU)

Context: Electrostimulation (ES) is one of the techniques employed in conservative treatment of urinary incontinence (UI) and/or overactive bladder syndrome (OAB). Nevertheless, there is controversy in the scientific literature regarding its effectiveness as monotherapy. Objective: To evaluate the scientific evidence on ES of the pelvic floor in women with UI and with/without OAB. Evidence acquisition: A systematic review of clinical trials was carried out in the following databases: PubMed, Cochrane, PEDro, Elsevier (Doyma) and EnFisPo (1980-2011). Quality of study registries was evaluated and information was obtained from those that presented the inclusion criteria established in the review. Evidence synthesis: The 27 clinical trials were included in the review: 13 randomized controlled trials, 11 randomized non-controlled trials and 3 non-randomized trials. Conclusion: Most of the clinical trials conclude that ES is effective in the treatment of UI and OAB in women. However, better methodological quality studies are needed to obtain a higher level of scientific evidence and to know the optimal current modality, type and parameters for each type of UI and OAB (AU)

Influence of drug encapsulation within mixed micelles on the excited state dynamics and accessibility to ionic quenchers.

Photophysical techniques, specifically time-resolved fluorescence and laser flash photolysis, have proven to be noninvasive, straightforward, and valuable tools to demonstrate how drug encapsulation into biomimetic mixed micelles (MM) influences the dynamics of excited states and their accessibility to ionic quenchers. This concept has been illustrated by choosing a set of currently administered drugs containing a common naphthalene chromophore, namely, (S)-naproxen and its methyl ester, (R)-cinacalcet and (S)-propranolol. A remarkable increase of their triplet lifetimes is noticed when experiments are performed in MM, indicating efficient entrapment of the drugs in these supramolecular entities. Furthermore, a decrease of 1 order of magnitude in the quenching rate constant of the singlet and triplet excited states (by iodide or nitrite, respectively) is observed upon encapsulation into MM. This approach can in principle be extended to other microenvironments capable of incorporating photoactive compounds.

Mating system in Mexican populations of the annual herb Solanum rostratum Dunal (Solanaceae).

Traditionally, annual colonising species are expected to have high rates of self-fertilisation, although recent theoretical and empirical studies have shown that cross-fertilisation can be selected for under heterogeneous pollination environments. Solanum rostratum is a self-compatible annual herb that colonises disturbed habitats. Despite the lack of physiological mechanisms to prevent self-fertilisation, pollen transfer between individuals is expected to be favoured because of its complex floral morphology. In previous studies of S. rostratum it has been shown that anther dimorphism within flowers results in precise pollen placement on the pollinator's body, and the presence of mirror-image floral morphs within plants promotes outcrossing in experimental arrays. However, the mating system of natural populations of S. rostratum has never been assessed, and thus whether it is predominantly selfing or outcrossing remains unknown. We hypothesise that floral and inflorescence morphology of S. rostratum should facilitate cross-fertilisation, making it a predominantly outcrossing despite its lack of a self-incompatibility system. To test this hypothesis, we estimated outcrossing rates by genotyping 700 individuals at 13 microsatellite loci, sampled from four populations across a 690-km transect in the species' native range. We found that populations had mean outcrossing rates of 0.70 ± 0.03, with multiple sires contributing to paternity of each progeny array (average effective number of sires = 8.97 ± 0.57). This indicates that natural populations S. rostratum have relatively high levels of outcrossing, probably facilitated by its floral and inflorescence morphology. We speculate that partial selfing in this species may be an unavoidable consequence of displaying multiple flowers at the same time (geitonogamy), as well as the result of self-pollen transfer by illegitimate visitors.

Recent trends in the pharmacological activity of isoprenyl phenolics.

A number of prenylated phenols, mainly flavonoids, have been identified as active constituents of medicinal plants. Due to their beneficial effects on human health, this class of compounds has received a great deal of attention, not only from the pharmaceutical industry, but also from other areas of applied sciences, including the food, brewing, and cosmetics industries. The addition of prenyl residues through the activity of isoprenyltransferases, the key biosynthetic enzymes for these plant metabolites, endows flavonoids with a variety of biological activities, mostly due to improved interaction with membranes and proteins. The role of prenylated flavonoids in plants correlates with their activities as antioxidant or anti-infectious agents. In connection with these effects, these compounds have been evaluated for multiple potential uses, e.g. as antibacterial, antiprotozoal, antifungal, anti-inflammatory, antitumor, estrogenic, antidiabetic, or antithrombotic agents, among others. The present review, in principle focused on phenolic derivatives containing a non-cyclized isoprenyl chain, discusses the most relevant pharmacological reports for the period 2005-2012.

Pelvic floor electrostimulation in women with urinary incontinence and/or overactive bladder syndrome: a systematic review.

CONTEXT: Electrostimulation (ES) is one of the techniques employed in conservative treatment of urinary incontinence (UI) and/or overactive bladder syndrome (OAB). Nevertheless, there is controversy in the scientific literature regarding its effectiveness as monotherapy. OBJECTIVE: To evaluate the scientific evidence on ES of the pelvic floor in women with UI and with/without OAB. EVIDENCE ACQUISITION: A systematic review of clinical trials was carried out in the following databases: PubMed, Cochrane, PEDro, Elsevier (Doyma) and EnFisPo (1980-2011). Quality of study registries was evaluated and information was obtained from those that presented the inclusion criteria established in the review. EVIDENCE SYNTHESIS: The 27 clinical trials were included in the review: 13 randomized controlled trials, 11 randomized non-controlled trials and 3 non-randomized trials. CONCLUSION: Most of the clinical trials conclude that ES is effective in the treatment of UI and OAB in women. However, better methodological quality studies are needed to obtain a higher level of scientific evidence and to know the optimal current modality, type and parameters for each type of UI and OAB.

Long-term evaluation of phrenic nerve pacing for respiratory failure due to high cervical spinal cord injury.

OBJECTIVES: Phrenic nerve pacing is a method of respiratory support that can replace mechanical ventilation in high-level cervical spinal cord injury patients with diaphragmatic paralysis. Our objective was to evaluate survival and long-term quality of life in patients with external respiratory support by PNP vs volumetric respirator in patients with severe respiratory insufficiency due to a high-level spinal cord injury. DESIGN: This is a retrospective review study of a prospectively collected database for evaluate the survival and a questionnaire for quality of life has been collected face-to-face or by telephone at present. PATIENTS: Cervical SCI patients with permanent respiratory support (PNP or MV). METHODS: Long-term evaluation of a cohort of PNP-supported patients. We performed a comparison between these patients and volumetric respirator-supported patients. For survival analysis, we used the Kaplan-Meier method and Cox proportional hazards model. The health-related quality of life was assessed with SF-36 questionnaire, a general HRQL evaluation. RESULTS: One hundred twenty six patients on permanent respiratory support were evaluated during the study period. Of these, 38 were on PNP and 88 were mechanically ventilated. Paced patients were younger and had a longer survival, but in a multivariate analysis adjusted for age using a multiple logistic correlation we found that length of survival was greater for PNP patients. In terms of HRQL, the PNP-supported patients showed better results in terms of social functioning. CONCLUSIONS: PNP is a stable and effective method of long-term respiratory support in this type of patients (SCI patients dependent on external respiratory support). In these patients it improves the length of survival and some social issues by quality of life when compared with patients under MV.

n-3 Fatty acid supplementation in burned paediatric patients.

AIM: To determine the effect of dietary supplementation with n-3 fatty acids (FA) in paediatric burned patients who had less than 20% of total body surface affected. METHODS: Burned patients were randomly assigned into two groups, one of them received a supplement of n-3 FA during 5 weeks; the other group was considered as not n-3 supplemented burned group. A third group of no burned patients was selected as control. Blood samples were collected at admission and in burned groups at the final of the study. Plasma and erythrocyte phospholipid FA composition and some biochemical parameters related to the clinical evolution: total plasma proteins and C3 and C4 complement proteins were determined. RESULTS: In the early post-burn patients, there is an increase in saturated and monounsaturated FAs in plasma phospholipids, and a decrease in polyunsaturated FAs compared with control. These alterations are in favour of proinflammatory response to burn injury. In n-3 FA supplemented group, these changes were further reverted, and a favourable response in the amount of total plasma proteins and in C3 and C4 proteins of the complement system was demonstrated. CONCLUSION: Dietary n-3 FA supplementation might be beneficial for patients suffering thermal injury.

[Therapeutic use and profile of toxicity of the FOLFOX4 regimen]. / Uso terapéutico y perfil de toxicidad del esquema FOLFOX4.

INTRODUCTION: Since the publication of the MOSAIC test results in 2004, the FOLFOX4 regimen has been established as an adjuvant treatment which is recommended in stage III colorectal cancer. The aim of this study is to assess the use of this regimen in our field and to describe its toxicity. METHODS: Descriptive study of treatments with FOLFOX4 prescribed between April 2005 and March 2007. The data was obtained from the Farhos Oncología programme and clinical records. The following data was collected: age, gender, diagnosis, stage of the illness (TNM classification) and adverse reactions, expressing severity according to Common Toxicity Criteria 2.0. RESULTS: The FOLFOX4 regimen was prescribed for 39 patients (24 men and 15 women) with an average age of 59. The diagnoses were: 28 colon cancer (4 stage II, 17 stage III, and 7 stage IV), 10 rectal cancer (1 stage II, 4 stage III, and 5 stage IV) and 1 stage IV gastric cancer. The most frequent adverse reactions were peripheral neuropathy (82 %), neutropenia (56.4 %) and diarrhoea (53.9 %.) When the study was completed, 9 patients continued active treatment with the regimen (average 6.8 cycles.) Of the 30 remaining patients only 16 people completed the 12 planned cycles. 14 patients stopped their treatment (an average of 8.1 cycles) due to toxicity in 10 cases, clinical progression in 3 cases and one patient died. Of the total 368 cycles administered, 68 suffered administration delays and 22 had the dosage reduced. CONCLUSION: The use of the FOLFOX4 regimen has been adjusted to uses with some solid scientific evidence, but its toxicity has limited its use and has made administering the planned dosage levels difficult.

Morphological variation in the flowers of Jacaratia mexicana A. DC. (Caricaceae), a subdioecious tree.

The Caricaceae is a small family of tropical trees and herbs in which most species are dioecious. In the present study, we extend our previous work on dioecy in the Caricaceae, characterising the morphological variation in sexual expression in flowers of the dioecious tree Jacaratia mexicana. We found that, in J. mexicana, female plants produce only pistillate flowers, while male plants are sexually variable and can bear three different types of flowers: staminate, pistillate and perfect. To characterise the distinct types of flowers, we measured 26 morphological variables. Our results indicate that: (i) pistillate flowers from male trees carry healthy-looking ovules and are morphologically similar, although smaller than, pistillate flowers on female plants; (ii) staminate flowers have a rudimentary, non-functional pistil and are the only flowers capable of producing nectar; and (iii) perfect flowers produce healthy-looking ovules and pollen, but have smaller ovaries than pistillate flowers and fewer anthers than staminate flowers, and do not produce nectar. The restriction of sexual variation to male trees is consistent with the evolutionary path of dioecy from hermaphrodite ancestors through the initial invasion of male-sterile plants and a subsequent gradual reduction in female fertility in cosexual individuals (gynodioecy pathway), but further work is needed to confirm this hypothesis.