Environmental variation drives the decoupling of leaf and root traits within species along an elevation gradient.

BACKGROUND AND AIMS: Plant performance is enhanced by balancing above- and below-ground resource uptake through the intraspecific adjustment of leaf and root traits. It is assumed that these organ adjustments are at least partly coordinated, so that analogous leaf and root traits broadly covary. Understanding the extent of such intraspecific leaf-root trait covariation would strongly contribute to our understanding of how plants match above- and below-ground resource use strategies as their environment changes, but comprehensive studies are lacking. METHODS: We measured analogous leaf and root traits from 11 species, as well as climate, soil and vegetation properties along a 1000-m elevation gradient in the French Alps. We determined how traits varied along the gradient, to what extent this variation was determined by the way different traits respond to environmental cues acting at different spatial scales (i.e. within and between elevations), and whether trait pairs covaried within species. KEY RESULTS: Leaf and root trait patterns strongly diverged: across the 11 species along the gradient, intraspecific leaf trait patterns were largely consistent, whereas root trait patterns were highly idiosyncratic. We also observed that, when compared with leaves, intraspecific variation was greater in root traits, due to the strong effects of the local environment (i.e. at the same elevation), while landscape-level effects (i.e. at different elevations) were minor. Overall, intraspecific trait correlations between analogous leaf and root traits were nearly absent. CONCLUSIONS: Our study suggests that environmental gradients at the landscape level, as well as local heterogeneity in soil properties, are the drivers of a strong decoupling between analogous leaf and root traits within species. This decoupling of plant resource acquisition strategies highlights how plants can exhibit diverse whole-plant acclimation strategies to modify above- and below-ground resource uptake, improving their resilience to environmental change.

Automated surveillance systems for healthcare-associated infections: results from a European survey and experiences from real-life utilization.

BACKGROUND: As most automated surveillance (AS) methods to detect healthcare-associated infections (HAIs) have been developed and implemented in research settings, information about the feasibility of large-scale implementation is scarce. AIM: To describe key aspects of the design of AS systems and implementation in European institutions and hospitals. METHODS: An online survey was distributed via e-mail in February/March 2019 among (i) PRAISE (Providing a Roadmap for Automated Infection Surveillance in Europe) network members; (ii) corresponding authors of peer-reviewed European publications on existing AS systems; and (iii) the mailing list of national infection prevention and control focal points of the European Centre for Disease Prevention and Control. Three AS systems from the survey were selected, based on quintessential features, for in-depth review focusing on implementation in practice. FINDINGS: Through the survey and the review of three selected AS systems, notable differences regarding the methods, algorithms, data sources, and targeted HAIs were identified. The majority of AS systems used a classification algorithm for semi-automated surveillance and targeted HAIs were mostly surgical site infections, urinary tract infections, sepsis, or other bloodstream infections. AS systems yielded a reduction of workload for hospital staff. Principal barriers of implementation were strict data security regulations as well as creating and maintaining an information technology infrastructure. CONCLUSION: AS in Europe is characterized by heterogeneity in methods and surveillance targets. To allow for comparisons and encourage homogenization, future publications on AS systems should provide detailed information on source data, methods, and the state of implementation.

Intravaginal administration of gelatine capsules containing freeze-dried autochthonous lactobacilli: a double-blind, randomised clinical trial of safety.

Vaginal lactobacilli (LAB) in probiotic formulas constitute a promising alternative for microbiome reconstitution and for the prevention and treatment of urogenital infections. A double-blind, randomised clinical trial was conducted to assess the safety of LAB-gelatine capsules vaginally administered to healthy sexually active women. Participants were randomised into three groups: intervention A: Lactobacillus reuteri CRL1324, Lactobacillus gasseri CRL1263 and CRL1307; intervention B: Lactobacillus rhamnosus CRL1332, L. gasseri CRL1256 and CRL1320; and intervention C: placebo. In a survey and clinical evaluation, participants received a blister with 7 capsules to be administered 1 per day. A second sampling and a new survey were conducted 3-10 days after completing application. Colposcopy was performed to assess adverse effects on vaginal-cervical mucosa. Vaginal swabs were taken for Gram staining to determine the Nugent score, and obtainment of viable-cell cultures to quantify cultivable lactic acid bacteria and pathogens. The main outcomes evaluated were overall satisfaction and secondary effects, including discomfort, urogenital infection, inflammatory response or other symptoms. No significant differences were found in Nugent score or in leukocyte numbers in vaginal samples either before or after the three interventions. However, a tendency to decrease in both the Nugent score and in leukocyte numbers was observed after interventions A and B, though not after C. A significant increase in cultivable lactobacilli was determined after LAB interventions. No severe adverse events were detected. LAB-containing capsules were well tolerated by subjects, so they could be proposed as an adequate alternative to restore vaginal lactobacilli in sexually active women.

Effect of Milk Fermented with Lactic Acid Bacteria on Diarrheal Incidence, Growth Performance and Microbiological and Blood Profiles of Newborn Dairy Calves.

The effect of the administration of milk fermented with lactic acid bacteria to calves was evaluated. The strains included were: Lactobacillus murinus CRL1695, Lact. mucosae CRL1696, Lact. johnsonii CRL1693, and Lact. salivarius CRL1702, which were selected for their beneficial and functional properties and isolated from healthy calves in the northwestern region of Argentina. The trial was conducted on a dairy farm located in Tucumán (Holando-Argentino calves). A randomized controlled trial was performed in which 56 new-born animals were divided into two groups: the treated group (T) received the fermented milk for 60 days and the control group (C) only milk. The animals were fed a solid diet ad libitum. The treated group was given a daily dose of 1 × 109CFU of the probiotic fermented milk while the control group was fed milk. Body weight and biometrical parameters were recorded between 15 and 60 days of age, and average daily gain was calculated with three samplings per animal throughout the trial. Rectal swabs and fecal and blood samples were also collected. Results showed the efficacy of the probiotic: lower morbidity and mortality of calves (morbidity was 69.20% in animals without the probiotic, and 46.15% in probiotic-treated animals, with P = 0.09; mortality in C was 34.61 and 7.69% in animals fed with ferment milk; P = 0.02).The calves fed with probiotic evidenced an improvement in nutritional parameters, body condition and weight gain (health index P = 0.01; average daily gain P = 0.03).Viable bacterial numbers showed no differences between the two experimental groups. Hematological parameters and serum proteins were not modified by the treatment. The results suggest that the fermented milk containing lactic acid bacteria can be a viable veterinary product for young calves due to its beneficial effects on health and growth.

Reactive Oxygen Species Mediates the Synergistic Activity of Fenretinide Combined with the Microtubule Inhibitor ABT-751 against Multidrug-Resistant Recurrent Neuroblastoma Xenografts.

ABT-751 is a colchicine-binding site microtubule inhibitor. Fenretinide (4-HPR) is a synthetic retinoid. Both agents have shown activity against neuroblastoma in laboratory models and clinical trials. We investigated the antitumor activity of 4-HPR + the microtubule-targeting agents ABT-751, vincristine, paclitaxel, vinorelbine, or colchicine in laboratory models of recurrent neuroblastoma. Drug cytotoxicity was assessed in vitro by a fluorescence-based assay (DIMSCAN) and in subcutaneous xenografts in nu/nu mice. Reactive oxygen species levels (ROS), apoptosis, and mitochondrial depolarization were measured by flow cytometry; cytochrome c release and proapoptotic proteins were measured by immunoblotting. 4-HPR + ABT-751 showed modest additive or synergistic cytotoxicity, mitochondrial membrane depolarization, cytochrome c release, and caspase activation compared with single agents in vitro; synergism was inhibited by antioxidants (ascorbic acid, α-tocopherol). 4-HPR + ABT-751 was highly active against four xenograft models, achieving multiple maintained complete responses. The median event-free survival (days) for xenografts from 4 patients combined was control = 28, 4-HPR = 49, ABT-751 = 77, and 4-HPR + ABT-751 > 150 (P < 0.001). Apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL) was significantly higher in 4-HPR + ABT-751-treated tumors than with single agents (P < 0.01) and was inhibited by ascorbic acid and α-tocopherol (P < 0.01), indicating that ROS from 4-HPR enhanced the activity of ABT-751. 4-HPR also enhanced the activity against neuroblastoma xenografts of vincristine or paclitaxel, but the latter combinations were less active than 4-HPR + ABT-751. Our data support clinical evaluation of 4-HPR combined with ABT-751 in recurrent and refractory neuroblastoma. Mol Cancer Ther; 15(11); 2653-64. ©2016 AACR.

Activation of ERK2 in basolateral amygdala underlies the promoting influence of stress on fear memory and anxiety: influence of midazolam pretreatment.

Exposure to emotionally arousing experiences elicits a robust and persistent memory and enhances anxiety. The amygdala complex plays a key role in stress-induced emotional processing and in the fear memory formation. It is well known that ERK activation in the amygdala is a prerequisite for fear memory consolidation. Moreover, stress elevates p-ERK2 levels in several areas of the brain stress circuitry. Therefore, given that the ERK1/2 cascade is activated following stress and that the role of this cascade is critical in the formation of fear memory, the present study investigated the potential involvement of p-ERK2 in amygdala subnuclei in the promoting influence of stress on fear memory formation and on anxiety-like behavior. A robust and persistent ERK2 activation was noted in the Basolateral amygdala (BLA), which was evident at 5min after restraint and lasted at least one day after the stressful experience. Midazolam, a short-acting benzodiazepine ligand, administered prior to stress prevented the increase in the p-ERK2 level in the BLA. Pretreatment with intra-BLA infusion of U0126 (MEK inhibitor), but not into the adjacent central nucleus of the amygdala, attenuated the stress-induced promoting influence on fear memory formation. Finally, U0126 intra-BLA infusion prevented the enhancement of anxiety-like behavior in stressed animals. These findings suggest that the selective ERK2 activation in BLA following stress exposure is an important mechanism for the occurrence of the promoting influence of stress on fear memory and on anxiety-like behavior.

Perinatal protein deprivation facilitates accumbal ERK phosphorylation in cocaine-sensitized adult rats.

In previous studies we described that perinatal protein deprivation facilitates the development and expression of behavioral sensitization to cocaine. In this research, we explored whether the increased reactivity observed in deprived (D) versus control (C) rats is also evident during drug-free withdrawal periods. Considering that activation of the extracellular signal-regulated protein kinase (ERK) is suggested to be involved in cocaine-induced behavioral sensitization, we study the effects of perinatal protein deprivation on phosphorylated ERK2 (pERK2) protein levels in the NAc (core and shell) during different drug-free withdrawal periods. To induce behavioral sensitization, C- and D-rats received a daily injection of cocaine (5-10 mg/kg, i.p.) for 7 days and locomotor activity was performed on days 1 and 7. Cocaine-sensitized animals were left drug-free and pERK2 was assessed on withdrawal days (WD) 1, 4, 7 and 21. In the NAc core, cocaine induced ERK signaling pathway activation in a dose-dependent manner, and only D-rats showed a significant increase in pERK2 protein levels with the lowest dose of cocaine (5 mg/kg). Moreover, sensitized C-rats with 10 mg/kg showed an increase in pERK2 levels from WD7 while D-rats showed this activation on WD4, which remained increased on WD7 and 21. In contrast, in the NAc shell, only sensitized D-rats with cocaine 10 mg/kg showed ERK2 activation on WD21. These results suggest that perinatal protein deprivation facilitates the molecular processes involved in neuronal plasticity occurring during withdrawal.

High resolution micro arthrography of hard and soft tissues in a murine model.

OBJECTIVE: Recent developments on high resolution micro computed tomography (µCT) allow imaging of soft tissues in small animal joints. Nevertheless, µCT images cannot distinguish soft tissues from synovial fluid due to their similar mass density, limiting the 3D assessment of soft tissues volume and thickness. This study aimed to evaluate a lead chromate contrast agent for µCΤ arthrography of rat knee joints ex vivo. DESIGN: Intact tibiofemoral rat joints were injected with the contrast agent at different concentrations and imaged using a µCT at 2.7 µm isotropic voxel size. Cartilage thickness was measured using an automated procedure, validated against histological measurements, and analyzed as a function of µCT image resolution. Changes in hard and soft tissues were also analyzed in tibiofemoral joints 4 weeks after surgical destabilization of the medial meniscus (DMM). RESULTS: The contrast agent diffused well throughout the whole knee cavity without penetrating the tissues, therefore providing high contrast at the boundaries between soft tissues and synovial fluid space. Thickness analysis of cartilage demonstrated a high similarity between histology and µ-arthrography approaches (R(2) = 0.90). Four weeks after surgical DMM, the development of osteophytes (Oph) and cartilage ulcerations was recognizable with µCT, as well as a slight increase in trabecular bone porosity, and decrease in trabecular thickness. CONCLUSIONS: A lead chromate-based contrast agent allowed discriminating the synovial fluid from soft tissues of intact knee joints, and thus made possible both qualitative and quantitative assessment of hard and soft tissues in both intact and DMM tibiofemoral joints using high resolution µCT.

Microcalcifications increase coronary vulnerable plaque rupture potential: a patient-based micro-CT fluid-structure interaction study.

Asymptomatic vulnerable plaques (VP) in coronary arteries accounts for significant level of morbidity. Their main risk is associated with their rupture which may prompt fatal heart attacks and strokes. The role of microcalcifications (micro-Ca), embedded in the VP fibrous cap, in the plaque rupture mechanics has been recently established. However, their diminutive size offers a major challenge for studying the VP rupture biomechanics on a patient specific basis. In this study, a highly detailed model was reconstructed from a post-mortem coronary specimen of a patient with observed VP, using high resolution micro-CT which captured the microcalcifications embedded in the fibrous cap. Fluid-structure interaction (FSI) simulations were conducted in the reconstructed model to examine the combined effects of micro-Ca, flow phase lag and plaque material properties on plaque burden and vulnerability. This dynamic fibrous cap stress mapping elucidates the contribution of micro-Ca and flow phase lag VP vulnerability independently. Micro-Ca embedded in the fibrous cap produced increased stresses predicted by previously published analytical model, and corroborated our previous studies. The 'micro-CT to FSI' methodology may offer better diagnostic tools for clinicians, while reducing morbidity and mortality rates for patients with vulnerable plaques and ameliorating the ensuing healthcare costs.

Activity of irinotecan and temozolomide in the presence of O6-methylguanine-DNA methyltransferase inhibition in neuroblastoma pre-clinical models.

BACKGROUND: The combination of temozolomide (TMZ) and irinotecan is a regimen used in neuroblastoma patients with recurrent disease. O(6)-methylguanine-DNA methyltransferase (MGMT) may have a function in resistance to TMZ. Using neuroblastoma pre-clinical models, we determined whether the inhibition of MGMT by O(6)-benzylguanine (O6-BG) could enhance the anti-tumour activity of TMZ and irinotecan. METHODS: The cytotoxicity of TMZ and irinotecan, either alone or in combination, was measured in five neuroblastoma cell lines in the presence or absence of O6-BG with a fluorescence-based cell viability assay (DIMSCAN). Anti-tumour activity was measured in three neuroblastoma xenograft models. RESULTS: MGMT mRNA and protein were expressed in 9 out of 10 examined cell lines. Pretreatment of cells with 25 µM O6-BG decreased MGMT protein expression and enhanced The TMZ cytotoxicity by up to 0.3-1.4 logs in four out of five tested cell lines. TMZ (25 mg kg(-1) per day for 5 days every 3 weeks for four cycles) did not significantly improve mice survival, whereas the same schedule of irinotecan (7.5 mg kg(-1) per day) significantly improved survival (P<0.0001) in all three xenograft models. Combining O6-BG and/or TMZ with irinotecan further enhanced survival. CONCLUSION: Our in vitro and in vivo findings suggest that irinotecan drives the activity of irinotecan and TMZ in recurrent neuroblastoma. Inhibitors of MGMT warrant further investigation for enhancing the activity of regimens that include TMZ.

Placa eritematosa facial persistente en una paciente anciana / Persistent erythematous facial plaque in an elderly patient

No disponible

Bioactive oleanolic acid saponins and other constituents from the roots of Viguiera decurrens.

The bisdesmoside oleanolic acid saponin, 3-0-(methyl-beta-D-glucuronopyranosiduronoate)-28-0-beta-D-glucopyranosyl-oleanolate along with nine known compounds (two diterpenic acids, one chromene, three triterpenes, one steroidal glycoside, and two monodesmoside oleanolic acid saponins), were obtained from Viguiera decurrens roots. The chemical structure of the bisdesmoside oleanolic saponin was determined by chemical and NMR spectral evidence. A mixture of monodesmoside saponins displayed cytotoxic activity against P388 and COLON cell lines (ED50= 2.3 and 3.6 microg/ml, respectively). Two of the known compounds showed insecticidal activity against the Mexican bean beetle larvae (Epilachna varivestis).

Dealing with diversity: recruiting churches and women for a randomized trial of mammography promotion.

There is little documentation about the recruitment process for church-based health education programs. In this study, the authors recruit African American, Latino, and white churches and women members (age 50 to 80) for a randomized church-based trial of mammography promotion in Los Angeles County. Efforts to enhance recruitment began 10 months before churches were invited to participate and included a variety of community-based strategies. Subsequently, 45 churches were recruited over a 5-month period through group pastor breakfast meetings and church-specific follow-up. In close collaboration with the 45 churches, the authors administered church-based surveys over 6 months and identified 1,967 age-eligible women who agreed to be contacted by the program team. It was found that an extended resource intensive period of relationship-building and community-based activities were necessary to conduct church-based programs effectively, particularly among older and ethnically diverse urban populations.

Evolución del sector femoropoplíteo tras cirugía proximal / Evolution of infrainguinal disease after inflow procedures

Objetivos: Estudio descriptivo de las características clínicas, arteriográficas y hemodinámicas del sector femoropoplíteo de un grupo de pacientes operados del sector aortoiliaco por patología oclusiva y ver la evolución natural del sector infrainguinal durante 5 años de seguimiento desde la cirugía proximal. Métodos: Se seleccionaron 103 pacientes operados del sector proximal entre 1991-1994. Mediante una revisión retrospectiva, se siguió cada uno de estos pacientes, desde el momento de la cirugía proximal, así como en sus revisiones posteriores durante 5 años. Los 103 pacientes fueron clasificados en dos grupos,: GRUPO A, que supone el 31 por ciento, sólo con patología proximal, y el GRUPO B, el 69 por ciento, con patología simultánea de ambos sectores. Se define un subgrupo R con aquellos pacientes de ambos grupos que precisaron cirugía infrainguinal a lo largo de esos 5 años. En el GRUPO B la edad media era superior, existía mayor prevalencia de diabetes y los pacientes se encontraban en estadios clínicos más avanzados. Tanto en el GRUPO A, como en el GRUPO B, la cirugía proximal predominante fue el bypass aortobifemoral, existiendo una permeabilidad a los 5 años superior en el grupo A. En el GRUPO B, simultáneamente a la cirugía proximal, se realizaron más técnicas quirúrgicas asociadas entre las que se incluyen: la endarterectomía femoral, la ampliación de la anastomosis plastiando la profunda, etc. Resultados: La tasa de reintervenciones infrainguinales posteriores fue del 5 por ciento para el GRUPO A y del 36 por ciento para el GRUPO B. La mayor parte de los pacientes que precisaron reintervenciones posteriores presentaban afectación más extensa de la arteria femoral profunda y de ejes distales. Conclusiones: La cirugía infrainguinal se practicó mayoritariamente en aquellos enfermos con patología oclusiva o estenótica del sector femoropoplíteo en el momento de la cirugía proximal (es decir, grupo B). La afectación de ejes distales y de la arteria femoral profunda son las principales variables relacionadas con la probabilidad de cirugía infrainguinal simultánea y en dos tiempos (AU)

Financial aspects of haemophilia care in Puerto Rico and other Latin American countries.

The present cost of optimal care in haemophilia is very high. The paradigm of comprehensive care approach, including the essential elements of continuous integrated multidisciplinary health services and the provision of home care with early use of antihaemophilic products requires abundant economic resources that usually are not readily available in nonaffluent countries. A cost-effective comprehensive paediatric haemophilia programme has been operating in Puerto Rico during the last 15 years that provides quality care to over 90% of paediatric haemophiliacs, and is financed mainly by the local government health system. Efforts are also being made to provide and/or coordinate health care to all adult haemophilic patients through the Puerto Rico Pediatric Hemophilia Treatment Center. Information on the haemophilia care available in Latin American countries is scanty. The data available indicate that with a few exceptions, haemophilia care in this vast region is suboptimal. Apparently, early diagnosis is not common, there is lack of accessibility of services in most countries, comprehensive care is not the rule, safe high-purity AHF concentrates are used infrequently, and home care is used rarely. The main antihaemophilic products used are fresh frozen plasma and cryoprecipitate due to the high cost of modern antihaemophilic factor concentrates. The average per capita income of the main Latin American countries is about one-quarter of that of the USA and Canada. The existing economic situation of most Latin American countries would make it very difficult for them to purchase modern antihaemophilic products regularly and provide quality comprehensive care to their haemophilia patients, unless they make special efforts and get some type of external help. As a result of this study recommendations are made to improve the quality and accessibility of services to haemophilia patients in Latin America and other nonaffluent countries.

Urinary assays for desmosine and hydroxylysylpyridinoline in the detection of cirrhosis.

BACKGROUND/AIMS: Non-invasive markers of liver fibrosis have great potential for both the diagnosis and therapy of liver disease and cirrhosis. The aim of this study was to evaluate the potential of urinary amino acids desmosine (DES) and isodesmosine (IDES) derived from the breakdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) derived from fibrillar collagen in diagnosing chronic liver disease. METHODS: We studied 48 patients with chronic liver disease who had varying degrees of liver fibrosis, graded 0-6 using a modified Knodell score, and 20 control subjects without liver disease. Urinary DES (microg/g creatinine) and HP (nmol/mmol creatinine) were measured by an isotope dilution, high performance liquid chromatography method. For liver disease patients, aminoterminal propeptide of type III procollagen (PIIINP) and alanine aminotransferase were determined. The urine and serum markers were correlated to degree of fibrosis and inflammation on liver biopsies. Differences between groups were analyzed by ANOVA and multiple linear regression was applied to determine independence of variables. Sensitivity, specificity and receiver operating curves were derived for each marker. RESULTS: In the 17 patients with liver fibrosis score of 5-6, mean urinary DES, IDES, HP and LP were all significantly greater than in the control group (p<0.05). Urinary DES and IDES correlated best with fibrosis score, r=0.61 for both markers. The correlation coefficient between serum PIIINP and fibrosis score was 0.47. Urinary DES and HP each had an overall diagnostic accuracy of 77% for fibrosis. Combining markers improved accuracy to over 80%. No correlation was seen between the urinary markers and inflammation scores. CONCLUSIONS: Urinary DES and HP are potentially useful clinical markers for liver fibrosis, especially when used in combination or in association with PIIINP.

Hemostatic abnormalities associated with monoclonal gammopathies.

To confirm and expand previous observations about the association of monoclonal gammopathies with hemostatic defects, a prospective evaluation was made in 42 patients with lymphoplasmacytic disorders. The incidence of bleeding complications was low, despite the diversity of abnormal hemostatic tests observed in these patients. Patients with myeloma frequently had abnormal coagulation tests, including thrombin time (64%), fibrin degradation products (32%), platelet aggregation tests with different agonist (30% to 55%), and bleeding time (22%). The lack of platelet response to ristocetin and normal ristocetin cofactor activity in four patients with myeloma may suggest a Bernard-Soulier-type defect. Serum viscosity was negatively correlated with platelet aggregation with collagen, ristocetin, and adenosine diphosphate. In patients with immunoglobulin myeloma, there was a positive correlation between an increased viscosity and a prolonged thrombin time. This study demonstrates the wide variety of coagulation abnormalities in lymphoplasmacytic disorders, usually without significant clinical implications.