Design, synthesis and antiplasmodial evaluation of new amide-, carbamate-, and ureido-type harmicines.

Malaria, one of the oldest parasitic diseases, remains a global health threat, and the increasing resistance of the malaria parasite to current antimalarials is forcing the discovery of new, effective drugs. Harmicines, hybrid compounds in which harmine/ß-carboline alkaloids and cinnamic acid derivatives are linked via an amide bond or a triazole ring, represent new antiplasmodial agents. In this work, we used a multiple linear regression technique to build a linear quantitative structure-activity relationship (QSAR) model, based on a group of 40 previously prepared amide-type (AT) harmicines and their antiplasmodial activities against erythrocytic stage of chloroquine-sensitive strain of P. falciparum (Pf3D7). After analysing the QSAR model, new harmicines were designed and synthesized: six amide-type, eleven carbamate-type and two ureido-type harmicines at the N-9 position of the ß-carboline core. Subsequently, we evaluated the antiplasmodial activity of the new harmicines against the erythrocytic and hepatic stages of the Plasmodium life cycle in vitro and their antiproliferative activity against HepG2 cells. UT harmicine (E)-1-(2-(7-methoxy-1-methyl-9H-pyrido[3,4-b]indol-9-yl)ethyl)-3-(3-(3-(trifluoromethyl)phenyl)allyl)urea at the N-9 position of the ß-carboline ring exhibited pronounced antiplasmodial activity against both the erythrocytic and the hepatic stages of the Plasmodium life cycle, accompanied by good selectivity towards Plasmodium.

Upper motor neurons are a target for gene therapy and UCHL1 is necessary and sufficient to improve cellular integrity of diseased upper motor neurons.

There are no effective cures for upper motor neuron (UMN) diseases, such as amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, and hereditary spastic paraplegia. Here, we show UMN loss occurs independent of spinal motor neuron degeneration and that UMNs are indeed effective cellular targets for gene therapy, which offers a potential solution especially for UMN disease patients. UCHL1 (ubiquitin C-terminal hydrolase-L1) is a deubiquitinating enzyme crucial for maintaining free ubiquitin levels. Corticospinal motor neurons (CSMN, a.k.a UMNs in mice) show early, selective, and profound degeneration in Uchl1nm3419 (UCHL1-/-) mice, which lack all UCHL1 function. When UCHL1 activity is ablated only from spinal motor neurons, CSMN remained intact. However, restoring UCHL1 specifically in CSMN of UCHL1-/- mice via directed gene delivery was sufficient to improve CSMN integrity to the healthy control levels. In addition, when UCHL1 gene was delivered selectively to CSMN that are diseased due to misfolded SOD1 toxicity and TDP-43 pathology via AAV-mediated retrograde transduction, the disease causing misfolded SOD1 and mutant human TDP-43 were reduced in hSOD1G93A and prpTDP-43A315T models, respectively. Diseased CSMN retained their neuronal integrity and cytoarchitectural stability in two different mouse models that represent two distinct causes of neurodegeneration in ALS.

Sensory adaptations reshaped intrinsic factors underlying morphological diversification in bats.

BACKGROUND: Morphological evolution may be impacted by both intrinsic (developmental, constructional, physiological) and extrinsic (ecological opportunity and release) factors, but can intrinsic factors be altered by adaptive evolution and, if so, do they constrain or facilitate the subsequent diversification of biological form? Bats underwent deep adaptive divergences in skull shape as they evolved different sensory modes; here we investigate the potential impact of this process on two intrinsic factors that underlie morphological variation across organisms, allometry, and modularity. RESULTS: We use comparative phylogenetic and morphometric approaches to examine patterns of evolutionary allometry and modularity across a 3D geometric morphometric dataset spanning all major bat clades. We show that allometric relationships diverge between echolocators and visually oriented non-echolocators and that the evolution of nasal echolocation reshaped the modularity of the bat cranium. CONCLUSIONS: Shifts in allometry and modularity may have significant consequences on the diversification of anatomical structures, as observed in the bat skull.

Crystalloids and colloids in critical patient resuscitation.

Fluid resuscitation is essential for the survival of critically ill patients in shock, regardless of the origin of shock. A number of crystalloids and colloids (synthetic and natural) are currently available, and there is strong controversy regarding which type of fluid should be administered and the potential adverse effects associated with the use of these products, especially the development of renal failure requiring renal replacement therapy. Recently, several clinical trials and metaanalyses have suggested the use of hydroxyethyl starch (130/0.4) to be associated with an increased risk of death and kidney failure, and data have been obtained showing clinical benefit with the use of crystalloids that contain a lesser concentration of sodium and chlorine than normal saline. This new information has increased uncertainty among clinicians regarding which type of fluid should be used. We therefore have conducted a review of the literature with a view to developing practical recommendations on the use of fluids in the resuscitation phase in critically ill adults.

Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids.

UNLABELLED: The role of sclerostin on bone metabolism and its relation to sex steroids in patients with prostate cancer (PC) is not well known. We found that sclerostin levels are significantly increased in PC patients, particularly in those with androgen deprivation therapy (ADT), and there is an inverse relationship between sclerostin levels and testosterone. INTRODUCTION: Recent studies have evaluated sclerostin levels in bone diseases as osteoporosis. However, there are few data in PC patients, particularly in patients with hypogonadism related to ADT. The aim of the present study was to compare serum sclerostin levels in ADT/non-ADT-treated PC patients and healthy controls and to evaluate their relationship with sex steroids and bone metabolism. METHODS: We performed a cross-sectional study involving 81 subjects: 25 ADT-treated PC patients, 34 PC patients without ADT treatment, and 22 healthy controls. We measured serum sclerostin levels, bone turnover markers, bone mineral density (BMD) in all individuals, and sex steroids levels in PC patients. RESULTS: Serum sclerostin levels were significantly higher in PC patients compared to those in control subjects. ADT-treated patients had significantly higher sclerostin levels than PC patients without ADT treatment: ADT 64.52 ± 27.21 pmol/L, non-ADT 48.24 ± 15.93 pmol/L, healthy controls 38.48 ± 9.19 pmol/L, p < 0.05. In PC patients, we found a negative relationship between serum sclerostin levels and androgens after age adjustment (total testosterone: r = -0.309, p = 0.029; bioavailable testosterone: r = -0.280, p = 0.049; free testosterone: r = -0.299, p = 0.035). We did not observe any relationship between sclerostin levels and bone turnover markers or BMD in any group. CONCLUSIONS: Circulating sclerostin levels are significantly increased in patients with PC and particularly in those receiving ADT. The inverse relationship between serum sclerostin and testosterone in these patients suggests that androgens are key regulators of bone metabolism in this population.

Effects of Habitat and Fruit Scent on the Interactions between Short-tailed Fruit Bats and Piper Plants.

Piper is a mega-diverse genus of pioneer plants that contributes to the maintenance and regeneration of tropical forests. In the Neotropics, Carollia bats use olfaction to forage for Piper fruit and are a main disperser of Piper seeds via consumption and subsequent defecation during flight. In return, Piper fruits provide essential nutrients for Carollia year-round. There is evidence that the types and diversity of Piper frugivores are influenced by the primary habitat type of different Piper species (forest and gap), with forest Piper depending more on bats for seed dispersal; however, this pattern has not been tested broadly. We aimed to characterize and compare the interactions between Carollia and Piper across forested and gap habitats, and further investigate whether differences in fruit traits relevant to bat foraging (i.e., scent) could underlie differences in Carollia-Piper interactions. We collected nightly acoustic ultrasonic recordings and 24 h camera trap data in La Selva, Costa Rica across 12 species of Piper (six forest, six gap) and integrated this information with data on Carollia diet and Piper fruit scent. Merging biomonitoring modalities allowed us to characterize ecological interactions in a hierarchical manner: from general activity and presence of bats, to visitations and inspections of plants, to acquisition and consumption of fruits. We found significant differences in Carollia-Piper interactions between forested and gap habitats; however, the type of biomonitoring modality (camera trap, acoustics, diet) influenced our ability to detect these differences. Forest Piper were exclusively visited by bats, whereas gap Piper had a more diverse suite of frugivores; the annual diet of Carollia, however, is dominated by gap Piper since these plants produce fruit year-round. We found evidence that fruit scent composition significantly differs between forest and gap Piper, which highlights the possibility that bats could be using chemical cues to differentially forage for gap vs. forest Piper. By integrating studies of Piper fruit scent, plant visitation patterns, and Carollia diet composition, we paint a clearer picture of the ecological interactions between Piper and Carollia, and plant-animal mutualisms more generally.

Piper es un género megadiverso de plantas pioneras que contribuyen al mantenimiento y regeneración de los bosques tropicales. En el Neotrópico, los murciélagos de género Carollia utilizan el sentido del olfato para encontrar frutos de Piper y son los principales dispersores de estas plantas a través del consumo de los frutos y posterior defecación de las semillas durante el vuelo. A cambio, los frutos de Piper proporcionan nutrientes esenciales para Carollia durante todo el año. Existe evidencia de que los tipos y la diversidad de frugívoros que consumen Piper están influenciados por el tipo de hábitat primario (bosques y claros) de las diferentes especies, y que los Piper de bosque dependen más de los murciélagos para la dispersión de semillas. Sin embargo, este patrón no ha sido corroborado ampliamente. Nuestro objetivo fue caracterizar y comparar las interacciones entre Carollia y Piper en hábitats boscosos y en claros, e investigar más a fondo si las diferencias en los rasgos de las frutas relevantes para la búsqueda de frutos por los murciélagos (es decir, el olor) podrían explicar las diferencias en las interacciones entre Carollia y Piper. Para ello, compilamos grabaciones acústicas ultrasónicas durante la noche y videos con cámaras trampa por 24 horas/día en La Selva, Costa Rica, para 12 especies de Piper (6 de bosque, 6 de claros) e integramos esa información con datos sobre la dieta de Carollia y el aroma de los frutos de Piper. Esta combinación de modalidades de biomonitoreo nos permitió caracterizar las interacciones ecológicas de manera jerárquica: desde la actividad general y la presencia de murciélagos, sus visitas e inspecciones de las plantas, hasta la adquisición y consumo de frutos. Encontramos diferencias significativas entre hábitats boscosos y claros en las interacciones de Carollia y Piper;sin embargo, el tipo de modalidad de biomonitoreo (cámara trampa, acústica, dieta) influyó en nuestra capacidad de detectar estas diferencias. Los Piper de bosque fueron visitados exclusivamente por murciélagos, mientras que los Piper de claros tuvieron un grupo más diverso de frugívoros. La dieta anual de Carollia, sin embargo, está dominada por Piper de claros, ya que estas plantas producen frutos durante todo el año. Encontramos evidencia de que la composición del aroma de los frutos difiere significativamente entre los Piper de bosque y de claros, lo que resalta la posibilidad que los murciélagos puedan estar usando señales químicas para forrajear diferencialmente por Piper de estas dos categorías. La integración de estudios del aroma de los frutos de Piper, patrones de visita a las plantas y composición de la dieta de Carollia nos permitió generar una imagen más clara sobre las interacciones ecológicas entre Piper y Carollia y de los mutualismos planta-animal en general.

Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

Putting the puzzle together: the relationship between floral characters and pollinator morphology determines pollination mode in the fig-fig wasp mutualism.

The diversification of angiosperms has largely been attributed to adaptive radiation of their pollination and mating systems, which are relevant drivers of the macroevolution processes. The fig (Ficus, Moraceae) and fig wasp (Agaonidae, Hymenoptera) interaction is an example of obligate mutualism. Passive and active pollination modes have been associated with morphological traits in both partners. However, more information is required to assess the relationship between floral traits and pollination modes, particularly in Neotropical Ficus species. This study evaluates the morphological traits of figs and fig wasps regarding pollination modes in species belonging to Neotropical Ficus sections (three species each of Americanae and Pharmacosycea). Pollination mode was identified by floral morphology, anther/ovule ratio, and specialized structures fig wasps use for pollen transport (pollen pocket and coxal combs). Fig species in sect. Americanae are actively pollinated because pistillate flowers form a synstigma, present anther/ovule ratios <0.11, and their pollinator Pegoscapus fig wasps have pollen pockets and coxal combs. In contrast, species in sect. Pharmacosycea have free pistillate flowers, with anther/ovule ratios >0.27; they are pollinated by Tetrapus wasps, which lack specialized structures to carry pollen. Each species of Ficus was associated with a single morphospecies of fig wasp. The results support previous contributions that consider reciprocal morphological traits between fig species and their pollinating wasps as evidence of a close co-evolutionary history.

Does nasal echolocation influence the modularity of the mammal skull?

In vertebrates, changes in cranial modularity can evolve rapidly in response to selection. However, mammals have apparently maintained their pattern of cranial integration throughout their evolutionary history and across tremendous morphological and ecological diversity. Here, we use phylogenetic, geometric morphometric and comparative analyses to test the hypothesis that the modularity of the mammalian skull has been remodelled in rhinolophid bats due to the novel and critical function of the nasal cavity in echolocation. We predicted that nasal echolocation has resulted in the evolution of a third cranial module, the 'nasal dome', in addition to the braincase and rostrum modules, which are conserved across mammals. We also test for similarities in the evolution of skull shape in relation to habitat across rhinolophids. We find that, despite broad variation in the shape of the nasal dome, the integration of the rhinolophid skull is highly consistent with conserved patterns of modularity found in other mammals. Across their broad geographical distribution, cranial shape in rhinolophids follows two major divisions that could reflect adaptations to dietary and environmental differences in African versus South Asian distributions. Our results highlight the potential of a relatively simple modular template to generate broad morphological and functional variation in mammals.

3D Printing and Surgical Simulation for Management of Large and Giant Congenital Melanocytic Nevi.

Tissue expansion with subsequent adjacent tissue transfer is often the preferred and sometimes the only option for reconstruction of large and giant congenital melanocytic nevi. Successful reconstruction with maximal efficiency and optimal aesthetic outcome requires careful planning of the tissue transfer, which itself requires careful selection of the tissue expander size and positioning. Unfortunately, there is little opportunity to gain experience in these skills due to the rarity of this condition. In situations where there is a rare condition that requires a complex technical procedure with much interoperative decision-making, surgical experience can be supplemented with the use of surgical simulation. In this article, we report on the use of three-dimensional patient imaging, three-dimensional printing, and surgical simulation for planning the reconstruction of large and giant congenital melanocytic nevi. We describe how this technology allows us to simulate multiple different approaches to expander placement and adjacent tissue transfer. We also describe how these simulations can be used to create cutting guides to guide final incision design and reduce intraoperative decision-making. Finally, we discuss how these models can be used to educate patients and families about the process and outcomes of nevus excision and reconstruction.

Size And Locomotor Ecology Have Differing Effects on the External and Internal Morphologies of Squirrel (Rodentia: Sciuridae) Limb Bones.

Mammals exhibit a diverse range of limb morphologies that are associated with different locomotor ecologies and structural mechanics. Much remains to be investigated, however, about the combined effects of locomotor modes and scaling on the external shape and structural properties of limb bones. Here, we used squirrels (Sciuridae) as a model clade to examine the effects of locomotor mode and scaling on the external shape and structure of the two major limb bones, the humerus and femur. We quantified humeral and femoral morphologies using 3D geometric morphometrics and bone structure analyses on a sample of 76 squirrel species across their four major ecotypes. We then used phylogenetic generalized linear models to test how locomotor ecology, size, and their interaction influenced morphological traits. We found that size and locomotor mode exhibit different relationships with the external shape and structure of the limb bones, and that these relationships differ between the humerus and femur. External shapes of the humerus and, to a lesser extent, the femur are best explained by locomotor ecology rather than by size, whereas structures of both bones are best explained by interactions between locomotor ecology and scaling. Interestingly, the statistical relationships between limb morphologies and ecotype were lost when accounting for phylogenetic relationships among species under Brownian motion. That assuming Brownian motion confounded these relationships is not surprising considering squirrel ecotypes are phylogenetically clustered; our results suggest that humeral and femoral variation partitioned early between clades and their ecomorphologies were maintained to the present. Overall, our results show how mechanical constraints, locomotor ecology, and evolutionary history may enact different pressures on the shape and structure of limb bones in mammals.

EspañolLos mamíferos exhiben una amplia gama de morfologías de las extremidades, las cuales están asociadas con diferentes ecologías de locomoción y mecánicas estructurales. Sin embargo, aún queda mucho por investigar sobre cómo los tipos de locomoción y el tamaño corporal han afectado conjuntamente la forma externa y las propiedades estructurales de los huesos de las extremidades. En este estudio, usamos al clado de las ardillas (Sciuridae) como un modelo para examinar los efectos del tipo de locomoción y el tamaño en la forma externa y la estructura de los dos huesos principales de las extremidades, el húmero y el fémur. Utilizando morfometría geométrica en 3D y análisis de estructura ósea, cuantificamos la morfología humeral y femoral en una muestra de 76 especies de ardillas que abarcan sus cuatro ecotipos principales. Posteriormente, usamos modelos filogenéticos generalizados lineales para investigar cómo la ecología locomotora, el tamaño, y la interacción entre estos factores influencian los rasgos morfológicos. Encontramos que el tamaño y el tipo de locomoción exhiben diferentes relaciones con la forma externa y la estructura de los huesos de las extremidades, y que estas relaciones difieren entre el húmero y el fémur. La variación de la forma externa del húmero y, en menor medida, del fémur está más relacionada con la ecología locomotora que con el tamaño. Por otro lado, las diferencias en la estructura de ambos huesos se explican mejor por una combinación de efectos de la ecología locomotora y el tamaño. Curiosamente, las relaciones estadísticas entre la morfología de las extremidades y el ecotipo se pierden al incorporar las relaciones filogenéticas entre las especies bajo un modelo de movimiento browniano. El hecho de que asumir un modelo de movimiento browniano modifique estas relaciones no es sorprendente, considerando que los ecotipos de ardillas están agrupados filogenéticamente. Nuestros resultados además sugieren que la variación en morfología humeral y femoral se dividieron tempranamente entre clados y estas ecomorfologías se mantuvieron hasta el presente.En general, nuestros resultados demuestran cómo las restricciones mecánicas, la ecología locomotora y la historia evolutiva pueden ejercer diferentes presiones sobre la forma y la estructura de los huesos de las extremidades en los mamíferos.

Utility of a buccal swab point-of-care test for the IFNL4 genotype in the era of direct acting antivirals for hepatitis C virus.

BACKGROUND: The CC genotype of the IFNL4 gene is known to be associated with increased Hepatitis C (HCV) cure rates with interferon-based therapy and may contribute to cure with direct acting antivirals. The Genedrive® IFNL4 is a CE marked Point of Care (PoC) molecular diagnostic test, designed for in vitro diagnostic use to provide rapid, real-time detection of IFNL4 genotype status for SNP rs12979860. METHODS: 120 Participants were consented to a substudy comparing IFNL4 genotyping results from a buccal swab analysed on the Genedrive® platform with results generated using the Affymetix UK Biobank array considered to be the gold standard. RESULTS: Buccal swabs were taken from 120 participants for PoC IFNL4 testing and a whole blood sample for genetic sequencing. Whole blood genotyping vs. buccal swab PoC testing identified 40 (33%), 65 (54%), and 15 (13%) had CC, CT and TT IFNL4 genotype respectively. The Buccal swab PoC identified 38 (32%) CC, 64 (53%) CT and 18 (15%) TT IFNL4 genotype respectively. The sensitivity and specificity of the buccal swab test to detect CC vs non-CC was 90% (95% CI 76-97%) and 98% (95% CI 91-100%) respectively. CONCLUSIONS: The buccal swab test was better at correctly identifying non-CC genotypes than CC genotypes. The high specificity of the Genedrive® assay prevents CT/TT genotypes being mistaken for CC, and could avoid patients being identified as potentially 'good responders' to interferon-based therapy.

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): nutritional assessment]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: valoración del estado nutricional.

Current parameters to assess nutritional status in critically-ill patients are useful to evaluate nutritional status prior to admission to the intensive care unit. However, these parameters are of little utility once the patient's nutritional status has been altered by the acute process and its treatment. Changes in water distribution affect anthropometric variables and biochemical biomarkers, which in turn are affected by synthesis and degradation processes. Increased plasma levels of prealbumin and retinol -proteins with a short half-life- can indicate adequate response to nutritional support, while reduced levels of these proteins indicate further metabolic stress. The parameters used in functional assessment, such as those employed to assess muscular or immune function, are often altered by drugs or the presence of infection or polyneuropathy. However, some parameters can be used to monitor metabolic response and refeeding or can aid prognostic evaluation.

TICACOS international: A multi-center, randomized, prospective controlled study comparing tight calorie control versus Liberal calorie administration study.

Since the first TICACOS study, 3 additional studies have been published comparing a medical nutrition therapy guided by indirect calorimetry to a regimen prescribed on the basis of predictive equations. A recent guidelines document included a meta-analysis including these 4 papers and found a trend for improvement (OR 0.98-1.48) in favor of medical nutrition therapy guided by indirect calorimetry in terms of survival. The aim of our study was to perform a multicenter prospective, randomized, controlled non blinded study in critically patients to assess the added value for measuring daily resting energy expenditure as a guide for nutritional support. The primary objective was to decrease infectious rate of these critically ill patients. MATERIAL AND METHODS: This phase III, multi-center, randomized, controlled non blinded study was planned to include 580 newly-admitted, adult ventilated ICU patients that were planned to stay more than 48 h in the ICU departments. The nutritional support was aimed to meet 80-100% of energy requirement measured by indirect calorimetry. The calorie needs were determined by IC in the Study group and by an equation (20-25 kcal/kg ideal body weight/day) in the Control Group. The ICU staff was trained to strive to supply 80-100% of a patient's energy requirements through artificial nutrition, preferably enteral feeding. Primary endpoint was infection rate and secondary endpoints included other morbidities and mortality during ICU, at 90 and 180 days. Comparison between the study and the control group was performed using T test for equality of means (independent samples test). Correlations were performed using the Pearson correlation test. A p level of 0.05 or below was considered as significant. Cross tabs procedure used Chi-square test for testing differences in complication rates, length of stay and length of ventilation. Correlations between energy balances and complications was also be tested using one way analysis as well as ANOVA analysis between groups and within groups. Kaplan Meir curves assessed the proportion of surviving patients in the 2 groups. RESULTS: Seven centers with a calorimeter available participated to the study. Due to slow inclusion rate, the study was stopped after 6 years and after inclusion of 417 patients only. From the 417 intended to treat patients, 339 followed the protocol. There was no differences between control and study groups in terms of age, sex BMI, SOFA (7.1 ± 3.1 vs 7.4 ± 3.3) and APACHE II scores (22.4 ± 7.9 vs 22.2 ± 7.4). The rate of infection (40 vs 31), including pneumonia rate, need for surgery, dialysis requirement, length of ventilation, ICU length of stay, and hospital length of stay were not different between groups. Mortality (30 in the control vs 21 in the study group) was not significantly different between groups. The decreased mortality observed in the study group when added to previous studies may have a positive effect on the meta-analysis previously published. CONCLUSION: Tight Calorie Control guided by indirect calorimetry decreased the rate of infection and mortality but not significantly. This may be explained by the not relatively small sample size. There results together with the previous 4 prospective randomized studies, may improve the results of the meta-analysis exploring the effects of IC guided nutrition on mortality.

Predicting bite force in mammals: two-dimensional versus three-dimensional lever models.

Bite force is a measure of whole-organism performance that is often used to investigate the relationships between performance, morphology and fitness. When in vivo measurements of bite force are unavailable, researchers often turn to lever models to predict bite forces. This study demonstrates that bite force predictions based on two-dimensional (2-D) lever models can be improved by including three-dimensional (3-D) geometry and realistic physiological cross-sectional areas derived from dissections. Widely used, the 2-D method does a reasonable job of predicting bite force. However, it does so by over predicting physiological cross-sectional areas for the masseter and pterygoid muscles and under predicting physiological cross-sectional areas for the temporalis muscle. We found that lever models that include the three dimensional structure of the skull and mandible and physiological cross-sectional areas calculated from dissected muscles provide the best predictions of bite force. Models that accurately represent the biting mechanics strengthen our understanding of which variables are functionally relevant and how they are relevant to feeding performance.

A Fruitful Endeavor: Scent Cues and Echolocation Behavior Used by Carollia castanea to Find Fruit.

Frugivores have evolved sensory and behavioral adaptations that allow them to find ripe fruit effectively, but the relative importance of different senses in varying foraging scenarios is still poorly understood. Within Neotropical ecosystems, short-tailed fruit bats (Carollia: Phyllostomidae) are abundant nocturnal frugivores that rely primarily on Piper fruits as a food resource. Previous research has demonstrated that Carollia employs olfaction and echolocation to locate Piper fruit, but it is unknown how their sensory use and foraging decisions are influenced by the complex diversity of chemical cues that fruiting plants produce. Using free-ranging C. castanea and their preferred food, Piper sancti-felicis, we conducted behavioral experiments to test two main hypotheses: (1) foraging decisions in C. castanea are primarily driven by ripe fruit scent and secondarily by vegetation scent, and (2) C. castanea re-weights their sensory inputs to account for available environmental cues, with bats relying more heavily on echolocation in the absence of adequate scent cues. Our results suggest that C. castanea requires olfactory information and relies almost exclusively on ripe fruit scent to make foraging attempts. Piper sancti-felicis ripe fruit scent is chemically distinct from vegetation scent; it is dominated by 2-heptanol, which is absent from vegetation scent, and has a greater abundance of ß-caryophyllene, ß-ocimene, γ-elemene, and α-cubebene. Although variation in echolocation call parameters was independent of scent cue presence, bats emitted longer and more frequent echolocation calls in trials where fruit scent was absent. Altogether, these results highlight the adaptations and plasticity of the sensory system in neotropical fruit bats.

Los frugívoros han evolucionado adaptaciones sensoriales y conductuales que les permiten encontrar frutos maduros de manera efectiva, pero aún existe una falta de conocimiento sobre la importancia relativa de los diferentes sentidos que los frugívoros utilizan en diferentes escenarios de forrajeo. Dentro de los ecosistemas neotropicales, los murciélagos de cola corta (Carollia: Phyllostomidae) son frugívoros nocturnos abundantes que dependen principalmente de los frutos de Piper como recurso alimentario. Previamente se ha demostrado que Carollia emplea el olfato y la ecolocalización para encontrar frutos de Piper, pero se desconoce cómo su uso sensorial y decisiones de forrajeo están influenciados por la compleja diversidad de señales químicas producidas por las plantas. En este trabajo, utilizamos C. castanea y su especie de frutos preferida, Piper sancti-felicis, para llevar a cabo experimentos conductuales y probar dos hipótesis principales: (1) las decisiones de forrajeo de C. castanea son incitadas principalmente por el aroma del fruto maduro y, en segundo lugar, por el aroma de la vegetación, y (2) C. castanea modula el uso de sus sentidos de acuerdo a las señales ambientales disponibles y utiliza la ecolocalización en mayor grado en ausencia de señales olfativas adecuadas. Nuestros resultados sugieren que C. castanea requiere información olfativa y se basa casi exclusivamente en el aroma del fruto maduro para hacer intentos de forrajeo. El aroma del fruto maduro de P. sancti-felicis es químicamente distinto al aroma de su vegetación; está dominado por 2-heptanol, el cual está ausente del aroma de la vegetación, y tiene una mayor abundancia de ß-cariofileno, ß-ocimeno, γ-elemeno, y α-cubibeno. Aunque encontramos que la variación en los parámetros de llamadas de ecolocalización es independiente de la presencia de diferentes señales aromáticas, los murciélagos emitieron llamadas de ecolocalización más largas y frecuentes en los experimentos donde el aroma de fruto estaba ausente. Conjuntamente, estos resultados destacan las adaptaciones y plasticidad del sistema sensorial de los murciélagos frugívoros neotropicales.

Connecting behaviour and performance: the evolution of biting behaviour and bite performance in bats.

Variation in behaviour, performance and ecology are traditionally associated with variation in morphology. A neglected part of this ecomorphological paradigm is the interaction between behaviour and performance, the ability to carry out tasks that impact fitness. Here we investigate the relationship between biting behaviour and performance (bite force) among 20 species of ecologically diverse bats. We studied the patterns of evolution of plasticity in biting behaviour and bite force, and reconstructed ancestral states for behaviour and its plasticity. Both behavioural and performance plasticity exhibited accelerating evolution over time, and periods of rapid evolution coincided with major dietary shifts from insect-feeding to plant-feeding. We found a significant, positive correlation between behavioural plasticity and bite force. Bats modulated their performance by changing their biting behaviour to maximize bite force when feeding on hard foods. The ancestor of phyllostomids was likely a generalist characterized by high behavioural plasticity, a condition that also evolved in specialized frugivores and potentially contributed to their diversification.

Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study.

The purpose of this paper is to determine the incidence of fungal colonization and infection in non-neutropenic critically ill patients and to identify factors favoring infection by Candida spp. A total of 1,655 consecutive patients (>18 years of age) admitted for > or = 7 days to 73 medical-surgical Spanish intensive care units (ICUs) participated in an observational prospective cohort study. Surveillance samples were obtained once a week. One or more fungi were isolated in different samples in 59.2% of patients, 94.2% of which were Candida spp. There were 864 (52.2%) patients with Candida spp. colonization and 92 (5.5%) with proven Candida infection. In the logistic regression analysis risk factors independently associated with Candida spp. infection were sepsis (odds ratio [OR] = 8.29, 95% confidence interval [CI] 5.07-13.6), multifocal colonization (OR = 3.49, 95% CI 1.74-7.00), surgery (OR = 2.04, 95% CI 1.27-3.30), and the use of total parenteral nutrition (OR = 4.37, 95% CI 2.16-8.33). Patients with Candida spp. infection showed significantly higher in-hospital and intra-ICU mortality rates than those colonized or non-colonized non-infected (P < 0.001). Fungal colonization, mainly due to Candida spp., was documented in nearly 60% of non-neutropenic critically ill patients admitted to the ICU for more than 7 days. Proven candidal infection was diagnosed in 5.5% of cases. Risk factors independently associated with Candida spp. infection were sepsis, multifocal colonization, surgery, and the use of total parenteral nutrition.

[Assessment of nutritional interventions and hygiene and health habits in a cohort of primary school students]. / Evaluación de dos intervenciones nutricionales y de hábitos de higiene y salud en una cohorte de alumnos de enseñanza primaria.

OBJECTIVE: To quantify by means of the so-called "Healthy lifestyle pyramid" and after two educational interventions, the changes in food intake, daily activities, and hygiene and health habits in the short and long terms in a cohort of healthy children. MATERIALS AND METHOD: prospective longitudinal study with baseline assessment of dietary and lifestyle habits, and two assessments after two educational interventions. RESULTS: 52 children participated, mean age 7.9 years, 15.4% of them being obese. There was a statistically significant reduction in whole milk intake in both the short and long term. There was a significant decrease in the short term in the intake of processed cold meat and an increase in fruit intake. There was a significant reduction in sweets intake in the short term. There was a statistically significant change in hand washing in the short and long terms, as well as in beach bathing after eating. There also was a significant change in achieving an appropriate posture and not bathing too far away, both in the long run. Finally, there was a significant change in the short term in not using inappropriate sports playing fields. The frequency at which they practise sports in the long term was significantly increased as well as the number of weekly sports, in the short term. CONCLUSIONS: After two educational interventions, the children did significant modifications of their health habits in the short term or the long term, which contributes to modify the risk factors for disease in the adulthood.