Neurodevelopmental outcomes of very preterm infants born following early foetal growth restriction with absent end-diastolic umbilical flow

This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain.Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors

Sucesión fúngica en la hojarasca de Nothofagus dombeyi

The experiment was performed in two sites of Nahuel Huapi National Park: nearby Lake Gutiérrez and Quetrihué Peninsula. The method used was direct observation on sterilized leaves previously incubated in between leaf-litter on special traps. Leaves were observed in the laboratory monthly during two years, determining tbe presence and relative frequence of fungi sporulating in both urfaces. Data obtained from both sites were used for preparing double entrance tables with taxa grouped according to Mueller-Dombois and Ellenberg (1974) method. As a result six groups of species were disitnguished; GROUP 1 represent the pioneers in the succession on fallen leaves, with Zoellneria eucalypti as dominant. GROUP II is formecl by an enclophytic fungi, Coleophoma cylindrospora and clandosporium. cladosporioides, both considered here primary saprophytes. GROUP III does not show a successional pattern and is composecl by species of diseontinuous appearence originatedin soil: we call these fungí invaders of the leaf-litter. There are Paecilomyces sp. and Acremonium sp. GROUP IV is dominatecl by Trichocladium opacum, which is an aggressive and competitive primarry saprophyte due its complex enzimatic activity. GROUP V is represented mainly by Ascomycetes, accompanied in some cases by a few aeroaquatic fungi. The fonner colonizes the leaves for a long period and can be considered secondary sapro¡phytes. GROUP VI is formed by soil and predator fungí as Monacrosporium gephyropagum and Mucor circinelloides. After 4 years and 10 month apparently the succession did not reach the "climax" state, because only about 70 % of the species found in natural leaf-litter have been detected. There is a certain coherence between SUCCESSIONAL GROUPS and SEASONAL GROUPS, th latter was reported in a previous paper.Se estudia la suces.on ue hongos sobre la hojarasca de Nothofagus dombeyi en dos sitios del Parque Nacional Nahuel Huapí: Lago Gutiérrez y Península Quetrihué (Argentina). El método seguido es el de la observación directa de las hojas esterilizadas incubadas en "trampas" especialmente ubil.:adas entre la hojarasca, las que mensualmente se analizaron en el laboratorio, determinando la presencia y frecuenda relativa (f) de los hongos aparecidos en ambas superficies fo1iares, en cada hoja. Con estos datos se confeccionaron tablas sociológicas de doble entrada, volcándose los relevamientos de taxones en cada sitio y agrupándose según la técnica de Mueller-Dombois y EJlenberg (1974). Como resultado se proponen seis GRUPOS SUCESIONALES. El GRUPO I representa las especies pioneras de la sucesión sobre las hojas caídas en el piso del bosque y su principal componente es Zoell,¡eria. etlcalypti. El GRUPO II está conformado por un hongo endofítico: Coleophoma cylindrospora y por CUIdosporill1n cladoslJOrioides, ambos salJTófitos primarios. El GRUPO III no muestra una neta distribución estacional por su aparición discontinua: está compuesto por hongos del suelo invasores de la hojarasca, como Paecilomyces sp. y Aeremonilllll Sp' El GRUPO IV, cuyo dominante es l'ric1wci(Jclium opaculll ('S un saprófito primario agresivo y competitivo por su variada actividad enzimáliea. El GRUPO V, fomlado básicamente por aswmicetes, col niza la hojarasea por un período largo, a veces están acompañados por hongos aeroacuáticos y pueden considerarse saprófitos secundarios. El GRUPO VI está conformado por hongos de suelo y depredadores, como Monacrosporium. gephyropagum y Mucor circinelloides. Al cabo de 4. años y 8 meses se percibe que la sucesión no ha llegado a su estado "clímax", ya que solamente han apareddo aproximadamente un 70 % de los taxones detectados en la hojarasca natural, empleando el muestreo mensua

Variación estacional de la micoflora en la hojarasca de Nothofagus DombeyI

Los organismos degradadores, hongos y bacterias, cumplen una función vital en los ecosistemas de bosque, manteniendo el reciclado de la materia. Aquellos actúan sobre los detritos vegetales y animales alimentando un proceso que conduce a la formación de humus y otras sustancias orgánicas y a la liberación de nutrientes que de tal manera quedan disponibles para su utilización por los productores primarios. Como este abastecimiento de nutrientes es un factor limitante, los degradadores controlan indirectamente la productividad del bosque. Además los microorganismos tienden a hacer más perfectos e intrabióticos los ciclos de los nutrientes en los ecosistemas, contribuyendo a evitar la pérdida de sustancias minerales mediante relaciones simbióticas con las raíces de las Cormofitas (micorrizas) y con la retención temporaria de nutrientes en sus talos. Por todo esto, su acción se considera de suma importancia para los sistemas ecológicos a nivel delsuelo, donde la descomposición es el proceso más activo

ROS-Scavenging Enzymes as an Antioxidant Response to High Concentration of Anthracene in the Liverwort <i>Marchantia polymorpha</i> L.

Marchantia polymorpha L. responds to environmental changes using a myriad set of physiological responses, some unique to the lineage related to the lack of a vascular- and root-system. This study investigates the physiological response of M. polymorpha to high doses of anthracene analysing the antioxidant enzymes and their relationship with the photosynthetic processes, as well as their transcriptomic response. We found an anthracene dose-dependent response reducing plant biomass and associated to an alteration of the ultrastructure of a 23.6% of chloroplasts. Despite a reduction in total thallus-chlorophyll of 31.6% of Chl a and 38.4% of Chl b, this was not accompanied by a significant change in the net photosynthesis rate and maximum quantum efficiency (Fv/Fm). However, we found an increase in the activity of main ROS-detoxifying enzymes of 34.09% of peroxidase and 692% of ascorbate peroxidase, supported at transcriptional level with the upregulation of ROS-related detoxifying responses. Finally, we found that M. polymorpha tolerated anthracene-stress under the lowest concentration used and can suffer physiological alterations under higher concentrations tested related to the accumulation of anthracene within plant tissues. Our results show that M. polymorpha under PAH stress condition activated two complementary physiological responses including the activation of antioxidant mechanisms and the accumulation of the pollutant within plant tissues to mitigate the damage to the photosynthetic apparatus

Classical homeopathy in the treatment of cancer patients - a prospective observational study of two independent cohorts

BACKGROUND: Many cancer patients seek homeopathy as a complementary therapy. It has rarely been studied systematically, whether homeopathic care is of benefit for cancer patients. METHODS: We conducted a prospective observational study with cancer patients in two differently treated cohorts: one cohort with patients under complementary homeopathic treatment (HG; n = 259), and one cohort with conventionally treated cancer patients (CG; n = 380). For a direct comparison, matched pairs with patients of the same tumour entity and comparable prognosis were to be formed. Main outcome parameter: change of quality of life (FACT-G, FACIT-Sp) after 3 months. Secondary outcome parameters: change of quality of life (FACT-G, FACIT-Sp) after a year, as well as impairment by fatigue (MFI) and by anxiety and depression (HADS). RESULTS: HG: FACT-G, or FACIT-Sp, respectively improved statistically significantly in the first three months, from 75.6 (SD 14.6) to 81.1 (SD 16.9), or from 32.1 (SD 8.2) to 34.9 (SD 8.32), respectively. After 12 months, a further increase to 84.1 (SD 15.5) or 35.2 (SD 8.6) was found. Fatigue (MFI) decreased; anxiety and depression (HADS) did not change. CG: FACT-G remained constant in the first three months: 75.3 (SD 17.3) at t0, and 76.6 (SD 16.6) at t1. After 12 months, there was a slight increase to 78.9 (SD 18.1). FACIT-Sp scores improved significantly from t0 (31.0 - SD 8.9) to t1 (32.1 - SD 8.9) and declined again after a year (31.6 - SD 9.4). For fatigue, anxiety, and depression, no relevant changes were found. 120 patients of HG and 206 patients of CG met our criteria for matched-pairs selection. Due to large differences between the two patient populations, however, only 11 matched pairs could be formed. This is not sufficient for a comparative study. CONCLUSION: In our prospective study, we observed an improvement of quality of life as well as a tendency of fatigue symptoms to decrease in cancer patients under complementary homeopathic treatment. It would take considerably larger samples to find matched pairs suitable for comparison in order to establish a definite causal relation between these effects and homeopathic treatment

Relevance of the Salvage Pathway to N-Hexanoylsphingosine Metabolic Downregulation in Human Neurotumor Cells: Implications for Apoptosis

N-Hexanoylsphingosine (C6-Cer) is currently being evaluated as an antineoplastic agent, after preclinical studies showing its property to reduce tumor growth. Herein it is reported that the cytotoxic effect of C6-Cer, as observed in CHP-100 neurotumor cells, impinges on its continuous uptake from the culture medium, ensuring maintainance of elevated steady-state intracellular levels, in the face of the rapid metabolic removal. C6-Cer metabolism not only does occur by direct glucosylation but is also relevantly driven by utilization via the sphingosine salvage pathway, leading to accumulation of natural ceramide that, in CHP-100 cells, has been demonstrated to lack apoptotic properties. Upon inhibition of glucosylceramide synthase by D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, previously shown to enhance C6-Cer cytotoxic activity, short-chain ceramide metabolism was partly redirected to the salvage pathway, likely attenuating the chemosensitizing effect of the above-mentioned compound. Elucidation of the metabolic machinery driving C6-Cer recycling via the salvage pathway might thus be relevant for optimization of its therapeutic utilization

Brefeldin A Limits N-Hexanoylsphingosine-Induced Accumulation of Natural Ceramide via the Salvage Pathway by Enhancing Glucosylation

Cells actively metabolize exogenously administered N-hexanoylsphingosine (C6-Cer) to natural (i.e. long-chain) ceramide (LC-Cer) via the sphingosine (Sph) salvage pathway, namely via C6-Cer deacylation and Sph reacylation with a long-chain fatty acid. Based on the observation that the mycotoxin brefeldin A (BFA), a Golgi complex disassembler, impairs C6-Cer-evoked LC-Cer accumulation, it has been hypothesized that the integrity of the above-mentioned organelle might be necessary for C6-Cer processing via the salvage pathway and that BFA might block the phenomenon at the step short-chain ceramide deacylation. The present study shows that BFA indeed attenuates C6-Cer-evoked LC-Cer accumulation in human neurotumor CHP-100 cells: evidence is however provided that the phenomenon is not due to impaired synthesis of LC-Cer, but to its enhanced conversion to glucosylceramide. The possibility is discussed that this outcome might be a consequence of the BFA well-established property to induce the merging of the cis-Golgi region with endoplasmic reticulum, namely the compartments in which glucosylceramide synthase and ceramide synthases have been reported to reside

Differential chemosensitizing effect of two glucosylceramide synthase inhibitors in hepatoma cells

It has been proposed that ceramide mediates anthracyclin-induced apoptosis and that drug resistance may arise due to upregulated removal of this active lipid through glucosylation. We report that HepG2 hepatoma cells displayed only a modest apoptotic response to doxorubicin treatment, accompanied by a substantial elevation of ceramide levels only at toxic drug concentrations. D,L-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1-propanol (PDMP) and D,L-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP), used at concentrations causing a 90% inhibition of ceramide glucosylation, enhanced doxorubicin-elicited ceramide elevation, but only PDMP potentiated apoptosis. Exogenously administered ceramide had only a marginal apoptotic effect on HepG2 cells; moreover, even in this case, apoptosis was propagated by PDMP but not by PPPP. PDMP moderately inhibited P-glycoprotein activity only at the highest concentration tested, but its chemosensitizing effect was still outstanding at lower concentrations, at which P-gp inhibition was no longer observed. These results demonstrate that the chemosensitizing effect of PDMP is, at least partly, independent from its activity as a glucosylceramide synthase inhibitor. Moreover, P-glycoprotein inhibition is not central to the phenomenon. (C) 2001 Academic Press