Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1ß in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis.

The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1ß in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 (p = 0.049) and the IL-18 rs187238 G-carrier genotype (p = 0.042) were associated with severe fibrosis. The IL-18 rs1946518 TT genotype was associated with an increased risk of relapse (p = 0.05), whereas GG was related to better renal outcomes (p = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement (p = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up.

Impact of sediment mobilization on trace elements release in Galician Rías (NW Iberian Peninsula): insights into aquaculture.

In the latest years, the concentration levels of certain metals and metalloids in the sediments of the Galician Rías have shown an increasing trend (e.g., As, Zn, Cu, Pb, Hg). These areas are also characterized by their richness in nutrients and their great aquaculture or mariculture activity, with the presence of more than 3500 mussel rafts in the Rías Baixas. The inner areas of the Galician Rías are subjected to activities that resuspend the sediment such as high levels of maritime traffic and dredging or cleaning operations. It is likely that a transfer of these elements to the water column happens during the resuspension of sediments caused by natural events or anthropogenic activities. In this study, selected samples of surface sediments of the Ría de Pontevedra (NW Spain) were subjected to a procedure of aerobic oxidation to determine the concentration of some elements (Fe, Mn, Cu, Cr, Pb, Hg, and Zn) released from the sediment to the aqueous phase. The experiment was carried out within 5 days. Measurements of pH and total concentration were taken both in water and sediment samples. Furthermore, speciation of trace elements was carried out in the sediment samples. Trace element concentrations were lower in the sediments during aerobic oxidation, being released to the aqueous phase. From an environmental point of view, Cu was the only trace element released in quantities that may be toxic for the organisms in the area. This problem of sediment oxidation related to dredging activities or natural storm conditions should be considered in environmental impact studies and transferred to stakeholders.

Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche.

We have described multipotent progenitor-like cells within the major pancreatic ducts (MPDs) of the human pancreas. They express PDX1, its surrogate surface marker P2RY1, and the bone morphogenetic protein (BMP) receptor 1A (BMPR1A)/activin-like kinase 3 (ALK3), but not carbonic anhydrase II (CAII). Here we report the single-cell RNA sequencing (scRNA-seq) of ALK3bright+-sorted ductal cells, a fraction that harbors BMP-responsive progenitor-like cells. Our analysis unveiled the existence of multiple subpopulations along two major axes, one that encompasses a gradient of ductal cell differentiation stages, and another featuring cells with transitional phenotypes toward acinar tissue. A third potential ducto-endocrine axis is revealed upon integration of the ALK3bright+ dataset with a single-cell whole-pancreas transcriptome. When transplanted into immunodeficient mice, P2RY1+/ALK3bright+ populations (enriched in PDX1+/ALK3+/CAII- cells) differentiate into all pancreatic lineages, including functional ß-cells. This process is accelerated when hosts are treated systemically with an ALK3 agonist. We found PDX1+/ALK3+/CAII- progenitor-like cells in the MPDs of types 1 and 2 diabetes donors, regardless of the duration of the disease. Our findings open the door to the pharmacological activation of progenitor cells in situ.

Fecal pulmonary embolism: a case report and literature review.

Pulmonary embolism (PE) is a common cause of death in hospitalized patients. These emboli are usually related to deep venous thrombosis, but other etiologic factors may be the cause. A 60-year-old male was diagnosed with rectal adenocarcinoma and treated by surgical rectal resection. After surgery, he presented with a decreased level of consciousness and hypoxia with no signs of bleeding. PE was ruled out by pulmonary angiography. Given the hemodynamic instability, contrast-enhanced CT was performed, showing a discrete leak related to the rectal anastomosis, which required urgent surgery. The patient suffered cardiorespiratory arrest prior to surgery, and once resolved, the surgical procedure was limited to disconnecting the intestinal anastomosis, leaving the colon and rectal stumps free in the abdomen and keeping the abdominal cavity open with negative-pressure therapy. The patient suffered from another cardiorespiratory arrest after surgery, with abdominal distension and serous-hemorrhagic material discharge through the negative-pressure device. On a new surgical revision, no bleeding was identified, so the symptoms were attributed to coagulopathy. The patient died and autopsy was performed. The autopsy revealed no surgery-related complications. The lungs were increased in weight and showed a normal macroscopic appearance; in contrast, the histological study revealed multiple and bilateral thrombo-embolisms affecting small distal arteries. Those thrombi were composed of intestinal contents, including vegetal particles, mucinous and biliary material, fibrin, and bacterial structures. Fecal PE is an extremely infrequent event. Isolated cases have been described in association with communications between the digestive tract lumen and the systemic circulation, with a generally fatal prognosis.

Cerebellar alterations in cannabis users: A systematic review.

Cannabis is the most used illicit substance in the world. As many countries are moving towards decriminalization, it is crucial to determine whether and how cannabis use affects human brain and behavior. The role of the cerebellum in cognition, emotion, learning, and addiction is increasingly recognized. Because of its high density in CB1 receptors, it is expected to be highly affected by cannabis use. The aim of this systematic review is to investigate how cannabis use affects cerebellar structure and function, as well as cerebellar-dependent behavioral tasks. Three databases were searched for peer-reviewed literature published until March 2018. We included studies that focused on cannabis effects on cerebellar structure, function, or cerebellar-dependent behavioral tasks. A total of 348 unique records were screened, and 40 studies were included in the qualitative synthesis. The most consistent findings include (1) increases in cerebellar gray matter volume after chronic cannabis use, (2) alteration of cerebellar resting state activity after acute or chronic use, and (3) deficits in memory, decision making, and associative learning. Age of onset and higher exposure to cannabis use were frequently associated with increased cannabis-induced alterations. Chronic cannabis use is associated with alterations in cerebellar structure and function, as well as with deficits in behavioral paradigms that involve the cerebellum (eg, eyeblink conditioning, memory, and decision making). Future studies should consider tobacco as confounding factor and use standardized methods for assessing cannabis use. Paradigms exploring the functional activity of the cerebellum may prove useful as monitoring tools of cannabis-induced impairment.

Generation of induced pluripotent stem cells from ADHD patients who do or do not respond to Methylphenidate treatment.

As a neurodevelopmental multifactorial disorder whose prevalence has been increasing worldwide, attention-deficit hyperactivity disorder (ADHD) is considered a public health concern. Methylphenidate (MPH) is the drug of choice for ADHD; however, not all patients respond fully to this treatment. Therefore, exploring the underlying molecular mechanisms involved in ADHD and potential novel therapeutic targets is crucial. Here, we generated induced pluripotent stem cells (iPSCs) from Peripheral Blood Mononuclear Cells (PBMCs) retrieved from four ADHD patients (two MPH responders and two non-responders) using Sendai virus. These lines might be helpful for the in vitro investigation of ADHD pathophysiology in a patient-specific manner.

[Yellow nail syndrome. A case report with postmortem study]. / Síndrome de las uñas amarillas. Presentación de un caso con estudio autópsico.

Yellow nail syndrome is a rare disease of unknown aetiology. Patients with YNS have a characteristic yellowish-coloured nails, pulmonary alterations and primary lymphedema. To the best of our knowledge, only a few reports of autopsy findings in these patients have been published. Its aetiology possibly involves a primary malformation of larger lymph vessels. We describe autopsy findings not previously associated with yellow nail syndrome, such as expansion of mediastinal lymph-nodes and splenic sinusoids. The present autopsy reveals hitherto unreported findings associated with YNS, such as alterations in splenic sinusoids and mediastinal lymph-node sinuses.

THSD7A-positive membranous nephropathy after kidney transplantation: A case report.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome after kidney transplantation (KT); however, scarce is known regarding post-KT thrombospondin type-1 domain-containing 7A (THSD7A)-positive MN. Herein, we report on a 72-year-old woman with end-stage kidney disease due to chronic interstitial nephritis (1996). In February 2020, she received a second deceased-donor KT, achieving optimal kidney function but presenting early post-KT proteinuria, reaching up to 1800mg/24h six months after transplantation, controlled with renin-angiotensin-aldosterone system (RAAS) blockade. In July 2021, a kidney allograft biopsy revealed features consistent with MN. Immunohistochemical stains showed diffuse and granular THSD7A and C4d deposition in glomerular capillary walls and negative PLA2R and IgG4 staining. No anti-THSD7A antibodies were detected in the serum. The pre-implantation biopsy showed no MN-associated lesions and negative THSD7A staining. Secondary triggers such as malignancy were discarded. The present report illustrates a THSD7A-positive MN in a KT recipient. Despite lacking native kidney biopsy and early presentation, a recurrent MN seemed unprovable due to documented native kidney disease and a long time span between native kidney disease and MN diagnosis. We, therefore, presumed primary de novo disease. Two years after KT, kidney function remains stable, and the patient has reached complete remission of proteinuria.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Concordance of p16INK4a and E6*I mRNA among HPV-DNA-Positive Oropharyngeal, Laryngeal, and Oral Cavity Carcinomas from the ICO International Study.

Background: Tests or test algorithms for diagnosing HPV-driven oral cavity and laryngeal head and neck carcinomas (HNC) have not been yet validated, and the differences among oral cavity and laryngeal sites have not been comprehensively evaluated. We aimed to assess the utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC) and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16INK4a immunohistochemistry, taking E6*I mRNA detection as the reference standard. Methods: Formalin-fixed paraffin-embedded OCC, OPC, and LC carcinomas were collected from pathology archives in 29 countries. All samples were subjected to histopathological evaluation, DNA quality control, and HPV-DNA detection. All HPV-DNA-positive samples (including 78 OCC, 257 OPC, and 51 LC out of 3680 HNC with valid HPV-DNA results) were also tested for p16INK4a immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16INK4a: (a) >25%, (b) >50%, and (c) ≥70%. The concordance of p16INK4a and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was assessed. Results: A total of 78 OCC, 257 OPC, and 51 LC were HPV-DNA-positive and further tested for p16INK4a and E6*I mRNA. The percentage of concordance between p16INK4a (cutoff ≥ 70%) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was 79.5% (95% CI 69.9−89.1%), 82.1% (95% CI 77.2−87.0%), and 56.9% (95% CI 42.3−71.4%), respectively. A p16INK4a cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16INK4a cutoffs, the percentage of discordant cases was higher for HPV16- than HPV-non16-positive cases. Conclusions: The diagnostic algorithm of HPV-DNA testing followed by p16INK4a immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16INK4a expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. Our study provides new insights into the use HPV-DNA, p16INK4a, and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16INK4a cutoffs to be used. More studies are warranted to clarify the role of p16INK4a and HPV status in both OPC and non-OPC HNC.

Factors driving sediment compositional change in the distal area of the Ria de Vigo (NW Spain): oceanographic processes vs. paleopollution.

We analyze potential Late Holocene metal contamination along a sediment core collected in the distal zone of Ria de Vigo (North Spain). Statistical treatment of the dataset based on a multiproxy approach enabled us to identify and disentangle factors influencing the depositional processes and the preservation of the records of this activity in the area over the last ≈3000 years BP. Some layers of the analyzed core have significant enrichment in Cu and a moderate enrichment in Ag, Mo, As, Sb, S, Zn, Ni, Sn, Cd, Cr, Co, Pb, and Li. The enrichment of these elements in some layers of this core may be related to mining activities that have taken place since classical times in the region. Successive phases of pollution were identified along the core KSGX24 related to the Late Bronze Age (≈3000-2450 years BP), Iron Age (≈2450-1850 years BP), Roman times (≈1850-1550 years BP), Middle Ages (≈1250-500 years BP), and industrial and modern (≈250-0 years BP) anthropic activities. The protection of the Cies Islands, the erosive and transport capacity of the rivers in the region, oscillations of the oceanographic and climatic regime, atmospheric contamination, and diagenetic sedimentary processes might have contributed to the accumulation and preservation of this record in the distal region of the Ria de Vigo. The studied core shows that the industrial and preindustrial anthropic impacts caused an environmental liability and contributed to the presence of moderate to heavy pollution of various metals in surface and subsurface sediment layers in the distal sector of the Ria de Vigo, which could be a hazard to biota.

Role of Human Papillomavirus Infection in Head and Neck Cancer in Italy: The HPV-AHEAD Study.

Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000-2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16INK4a staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16INK4a double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.

Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers.

CPT-11, also known as irinotecan, is a prodrug that is approved for the treatment of advanced colorectal cancer. The active metabolite of CPT-11, SN38 (7-ethyl-10-hydroxy-camptothecin), has 100- to 1000-fold more potent cytotoxic activity in tissue cell culture compared with CPT-11. However, parental administration of SN38 is not possible because of its inherently poor water solubility. It is reported here that a multiarm poly(ethylene glycol) (PEG) backbone linked to four SN38 molecules (PEG-SN38) has been successfully prepared with high drug loading and significantly improved water solubility (400- to 1000-fold increase). Three different protecting strategies have been developed in order to selectively acylate the 20-OH of SN38 to preserve its E-ring in the lactone form (the active form of SN38 with cytotoxic activities) while PEG is still attached. One chemical process has been optimized to make a large quantity of the PEG-SN38 conjugate with a high yield that can be readily adapted for scale-up production. The PEG-SN38 conjugates have shown excellent in vitro anticancer activity, with potency similar to that of native SN38, in a panel of cancer cell lines. The PEG-SN38 conjugates also have demonstrated superior anticancer activity in the MX-1 xenograft mice model compared with CPT-11. Among the four conjugates, PEG-Gly-(20)-SN38 (23) has been selected as the lead candidate for further preclinical development.

Sedimentation rates and trace metal input history in intertidal sediments from San Simón Bay (Ría de Vigo, NW Spain) derived from 210Pb and 137Cs chronology.

(210)Pb and (137)Cs dating methods, accompanied by a high-resolution geochemical study, were applied to intertidal sediments containing both fine and coarse-grained particles and also, anthropogenic Pb in order to establish sedimentation rates and historical trends in heavy metal input. Sedimentation rates were established according to the "Constant Flux:Constant Sedimentation" (CF:CS) (210)Pb dating model, which was preferred rather than the "Constant Rate of Supply-Minimum Variance" (CRS-MV) model. Variations in sediment grain-size were accounted for by application of several normalization procedures. Al was selected for grain-size correction. Corrected sedimentation rates obtained from (210)Pb dating were corroborated through a second independent radionuclide tracer and by comparison of peak trace metal inputs into the environment with peaks in the sediment. The Chernobyl maximum was identified in the normalized (137)Cs activity profile. Sedimentation rates of 6.2+/-1.2 mm y(-1) and 3.1+/-0.5 mm y(-1) for the upper (two muddy layers) and 6.0+/-2.0 mm y(-1) for the lower (sandy) intertidal mud flat deposits of San Simón Bay were determined. According to the established chronology, human-induced environmental changes were detected in total metal concentrations (Cu, Pb, Zn) and in sediment grain-size and composition.

Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD): A Review.

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in the pediatric population. The clinical management of ADHD is currently limited by a lack of reliable diagnostic biomarkers and inadequate therapy for a minority of patients who do not respond to standard pharmacotherapy. There is optimism that noninvasive brain stimulation may help to address these limitations. Transcranial magnetic stimulation and transcranial direct current stimulation are 2 methods of noninvasive brain stimulation that modulate cortical excitability and brain network activity. Transcranial magnetic stimulation can be used diagnostically to probe cortical neurophysiology, whereas daily use of repetitive transcranial magnetic stimulation or transcranial direct current stimulation can induce long-lasting and potentially therapeutic changes in targeted networks. In this review, we highlight research showing the potential diagnostic and therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in pediatric ADHD. We also discuss the safety and ethics of using these tools in the pediatric population.

Trichoderma genes in plants for stress tolerance- status and prospects.

Many filamentous fungi from the genus Trichoderma are well known for their anti-microbial properties. Certain genes from Trichoderma spp. have been identified and transferred to plants for improving biotic and abiotic stress tolerance, as well for applications in bioremediation. Several Trichoderma genomes have been sequenced and many are in the pipeline, facilitating high throughput gene analysis and increasing the availability of candidate transgenes. This, coupled with improved plant transformation systems, is expected to usher in a new era in plant biotechnology where several genes from these antagonistic fungi can be transferred into plants to achieve enhanced stress tolerance, bioremediation activity, herbicide tolerance, and reduction of phytotoxins. In this review, we illustrate the major achievements made by transforming plants with Trichoderma genes as well as their possible mode of action. Moreover, examples of efficient application of genetically modified plants as biofactories to produce active Trichoderma enzymes are indicated.

The influence of weather and climate on the reliability of magnetic properties of tree leaves as proxies for air pollution monitoring.

Monthly monitoring of magnetic properties of Platanus hispanica tree leaves was used to assess atmospheric pollution in Madrid (Spain) and its suburban town of Pozuelo de Alarcón. Magnetic susceptibility, isothermal remanent magnetisation and metal concentrations were analysed to study the sources of atmospheric pollutants and their spatial and temporal evolution. In addition to urban dust, our results indicated that lithogenic dust and incorporation of trace metals in the leaf tissue also control the magnetic susceptibility of tree leaves. Global comparisons with cities of different climatic regimes suggest that air humidity is the key factor controlling the relative influence of pollutants, lithogenic dust and biological effects on the magnetic properties of tree leaves. Interaction of the atmosphere and tree leaves depends not only on local meteorology but also on climate. Climate, especially air humidity, and meteorology need to be considered when interpreting the magnetic properties of tree leaves as an atmospheric pollution tool.

Assessment of the health quality of Ria de Aveiro (Portugal): heavy metals and benthic foraminifera.

This work analyses the distribution of heavy metals in the sediments of Ria de Aveiro (Portugal) assessed by total digestion and sequential chemical extraction of the sediments. The influence of environmental parameters on the living benthic foraminiferal assemblages was studied. The most polluted parts in the Ria de Aveiro are areas where the residence time is high and cohesive sediments are deposited. Organic matter, which is an excellent scavenger for a number of metals, is in general more abundant in the finer deposits of this lagoon, which act as sinks of anthropogenic pollutants. This condition is observed in Aveiro canals and Murtosa channel where sediments with the highest concentrations of Zn, Pb, Cu, and Cr are found. The sediments of Murtosa channel are also enriched in As, Co and Hg. In Aveiro canals the enrichment of heavy metals is mostly related to the past industrial production at their margins (ceramic and metallurgy), whereas in Murtosa channel with effluent discharges of the Chemical Complex of Estarreja. Foraminiferal density and diversity reach higher values near the lagoon mouth under higher marine influence and decline in general under very low-oxygen conditions. Some species seems to be indifferent to the increasing of TOC (e.g. Haynesina germanica and Ammonia tepida) and some have an opportunistic behaviour in areas with very depressed levels of oxygen (e.g. A. tepida and Quinqueloculina seminulum) whereas other species can better tolerate sulphide/reducing conditions (e.g. H. germanica, Bolivina ordinaria, Buliminella elegantissima, Bulimina elongata/gibba and Nonionella stella) a widespread condition in this lagoon. Foraminiferal density and some species are negatively correlated with concentrations of heavy metals. A most sensitive group of species to higher concentrations of heavy metals is identified (such as B. ordinaria, B. pseudoplicata and B. elongata/gibba) and another one of more tolerant species (such as H. germanica A. tepida and Q. seminulum). Foraminifera are more tolerate higher available concentrations (AC) of Zn in any phase than higher AC of Cu adsorbed do clay minerals (F1) and associated with Fe and Mn oxides (F2) and of Pb in F2; the phase F2, probably the most mobile phase, and even phase F1 seems to be more toxic than the increasing of metals in organic matter (F3).

Transcriptomic response of Arabidopsis thaliana after 24 h incubation with the biocontrol fungus Trichoderma harzianum.

Trichoderma harzianum is a fungus used as biocontrol agent using its antagonistic abilities against phytopathogenic fungi, although it has also direct effects on plants, increasing or accelerating their growth and resistance to diseases and the tolerance to abiotic stresses. We analyzed Arabidopsis thaliana gene expression changes after 24 h of incubation in the presence of T. harzianum T34 using the Affymetrix GeneChip Arabidopsis ATH1. Because this microarray contains more than 22,500 probe sets representing approximately 24,000 genes, we were able to construct a global picture of the molecular physiology of the plant at 24 h of T. harzianum-Arabidopsis interaction. We identified several differentially expressed genes that are involved in plant responses to stress, regulation of transcription, signal transduction or plant metabolism. Our data support the hypothesis that salicylic acid- and jasmonic acid-related genes were down-regulated in A. thaliana after 24 h of incubation in the presence of T. harzianum T34, while several genes related to abiotic stress responses were up-regulated. These systemic changes elicited by T. harzianum in Arabidopsis are discussed.

A pilot study: differential effects of methylphenidate-OROS on working memory and attention functions in children with attention-deficit/hyperactivity disorder with and without behavioural comorbidities.

To examine the effects of methylphenidate-OROS (MPH-OROS) on working memory (WM) and attention functions in children with attention-deficit hyperactivity disorder (ADHD), and to investigate whether there is a differential effect in ADHD children with (ADHD+) and without (ADHD-) behavioural comorbidities. Participants included a clinic referred sample of 12 stimulant naïve school-aged children with a diagnosis of combined ADHD according to the DSM-IV criteria (6 ADHD+, 6 ADHD-), and 11 healthy children. A neuropsychological protocol was applied at three different moments: before treatment, after one those of MPH-OROS, and after one month of MPH-OROS daily treatment. The protocol was simultaneously administered to the control group. Initial differences in attention parameters between naïve children with ADHD and the control group disappeared after the first dose of MPH-OROS. For WM, one month of daily treatment was necessary to achieve this pattern of results. Both ADHD groups (ADHD+ and ADHD-) showed these differences, but there was a greater improvement in (ADHD-). MPH-OROS had an immediate effect on attention deficits, but long-term treatment was needed to improve WM to the level of healthy subjects. The presence of comorbid behavioural conditions determined a less robust response in neuropsychological performance to stimulant treatment.