Widespread horse-based mobility arose around 2,200 BCE in Eurasia.

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and widespread integration as a means of transportation remains contentious2-4. Here we assemble a large collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged ~2,200 BCE (Before Common Era), through close kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than ~2,700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly-held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe ~3,000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai ~3,500 BCE, a settlement from Central Asia associated with corrals and a subsistence economy centered on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.

Dissecting the invasion of Galleria mellonella by Yersinia enterocolitica reveals metabolic adaptations and a role of a phage lysis cassette in insect killing.

The human pathogen Yersinia enterocolitica strain W22703 is characterized by its toxicity towards invertebrates that requires the insecticidal toxin complex (Tc) proteins encoded by the pathogenicity island Tc-PAIYe. Molecular and pathophysiological details of insect larvae infection and killing by this pathogen, however, have not been dissected. Here, we applied oral infection of Galleria mellonella (Greater wax moth) larvae to study the colonisation, proliferation, tissue invasion, and killing activity of W22703. We demonstrated that this strain is strongly toxic towards the larvae, in which they proliferate by more than three orders of magnitude within six days post infection. Deletion mutants of the genes tcaA and tccC were atoxic for the insect. W22703 ΔtccC, in contrast to W22703 ΔtcaA, initially proliferated before being eliminated from the host, thus confirming TcaA as membrane-binding Tc subunit and TccC as cell toxin. Time course experiments revealed a Tc-dependent infection process starting with midgut colonisation that is followed by invasion of the hemolymph where the pathogen elicits morphological changes of hemocytes and strongly proliferates. The in vivo transcriptome of strain W22703 shows that the pathogen undergoes a drastic reprogramming of central cell functions and gains access to numerous carbohydrate and amino acid resources within the insect. Strikingly, a mutant lacking a phage-related holin/endolysin (HE) cassette, which is located within Tc-PAIYe, resembled the phenotypes of W22703 ΔtcaA, suggesting that this dual lysis cassette may be an example of a phage-related function that has been adapted for the release of a bacterial toxin.

Tracking population structure and phenology through time using ancient genomes from waterlogged white oak wood.

Whole genome characterizations of crop plants based on ancient DNA have provided unique keys for a better understanding of the evolutionary origins of modern cultivars, the pace and mode of selection underlying their adaptation to new environments and the production of phenotypes of interest. Although forests are among the most biologically rich ecosystems on earth and represent a fundamental resource for human societies, no ancient genome sequences have been generated for trees. This contrasts with the generation of multiple ancient reference genomes for important crops. Here, we sequenced the first ancient tree genomes using two white oak wood remains from Germany dating to the Last Little Ice Age (15th century CE, 7.3× and 4.0×) and one from France dating to the Bronze Age (1700 BCE, 3.4×). We assessed the underlying species and identified one medieval remains as a hybrid between two common oak species (Quercus robur and Q. petraea) and the other two remains as Q. robur. We found that diversity at the global genome level had not changed over time. However, exploratory analyses suggested that a reduction of diversity took place at different time periods. Finally, we determined the timing of leaf unfolding for ancient trees for the first time. The study extends the application of ancient wood beyond the classical proxies of dendroclimatology, dendrochronology, dendroarchaeology and dendroecology, thereby enhancing resolution of inferences on the responses of forest ecosystems to past environmental changes, epidemics and silvicultural practices.

Tailoring the Morphology of Monodisperse Mesoporous Silica Particles Using Different Alkoxysilanes as Silica Precursors.

The hard template method for the preparation of monodisperse mesoporous silica microspheres (MPSMs) has been established in recent years. In this process, in situ-generated silica nanoparticles (SNPs) enter the porous organic template and control the size and pore parameters of the final MPSMs. Here, the sizes of the deposited SNPs are determined by the hydrolysis and condensation rates of different alkoxysilanes in a base catalyzed sol-gel process. Thus, tetramethyl orthosilicate (TMOS), tetraethyl orthosilicate (TEOS), tetrapropyl orthosilicate (TPOS) and tetrabutyl orthosilicate (TBOS) were sol-gel processed in the presence of amino-functionalized poly (glycidyl methacrylate-co-ethylene glycol dimethacrylate) (p(GMA-co-EDMA)) templates. The size of the final MPSMs covers a broad range of 0.5-7.3 µm and a median pore size distribution from 4.0 to 24.9 nm. Moreover, the specific surface area can be adjusted between 271 and 637 m2 g-1. Also, the properties and morphology of the MPSMs differ according to the SNPs. Furthermore, the combination of different alkoxysilanes allows the individual design of the morphology and pore parameters of the silica particles. Selected MPSMs were packed into columns and successfully applied as stationary phases in high-performance liquid chromatography (HPLC) in the separation of various water-soluble vitamins.

Tolerability of High-Dose Venlafaxine After Switch From Escitalopram in Nonresponding Patients With Major Depressive Disorder.

BACKGROUND: Within a single depressive episode, most patients receive different antidepressants because of an inadequate response to the first-line antidepressant. A commonly used strategy is to switch from a selective serotonin reuptake inhibitor to a selective serotonin-norepinephrine reuptake inhibitor. However, little is known about the tolerability of this switch with consideration of dose and drug concentration in blood. METHODS: After 4 weeks of inadequate response to escitalopram (10-20 mg/d), medication was switched to another 4 weeks of venlafaxine (VF, 150-375 mg/d) in 234 depressed patients. Serum concentrations, depression severity, and adverse drug reactions (ADRs) were assessed weekly. RESULTS: The switch of medication led to an increase of ADRs such as reduced salivation (+11%), orthostatic dizziness (+11%), and sweating (+9.8%). The most frequent ADRs during treatment with VF were reduced salivation (28.6%), sweating (24.6%), and orthostatic dizziness (15.8%). In patients receiving high-dose VF, a significant improvement of depressive symptomatology was observed, and most ADRs decreased during the course of treatment, even in patients above the therapeutic reference range. LIMITATIONS: Patients and physicians were aware of medication, and there was no direct comparison with the herein presented switch of medication. IMPLICATIONS: This study provides important information about the tolerability of a commonly used antidepressant treatment strategy. More detailed information about putative ADRs may help clinicians increase compliance through effective patient education. Because ADRs of VF were associated with the plasma concentration, therapeutic drug monitoring is recommended to guide the therapy and manage problems of tolerability.

Teaching Conflicts of Interest and Shared Decision-Making to Improve Risk Communication: a Randomized Controlled Trial.

BACKGROUND: Risk communication is a core aspect of a physician's work and a fundamental prerequisite for successful shared decision-making. However, many physicians are not able to adequately communicate risks to patients due to a lack of understanding of statistics as well as inadequate management of conflicts of interest (COI). OBJECTIVE: To evaluate the effects of an integrated curriculum encompassing COI and shared decision-making on the participants' risk communication competence, that is, their competence to advise patients on the benefits and harms of diagnostic or therapeutic interventions. DESIGN: A rater-blind randomized controlled trial with a 30 (± 1)-week follow-up conducted from October 2016 to June 2017 at two German academic medical centers. PARTICIPANTS: Sixty-three medical students in their fourth or fifth year. INTERVENTIONS: Participants received either a newly developed 15-h curriculum or a course manual adapted from teaching as usual. MAIN MEASURES: Primary outcome: change in risk communication performance in a video-observed structured clinical examination (VOSCE). KEY RESULTS: Participants were 25.7 years old on average (SD 3.6); 73% (46/63) were female. Increase in risk communication performance was significantly higher in the intervention group with post-intervention Cohen's d of 2.35 (95% confidence interval (CI) 1.62 to 3.01, p < 0.01) and of 1.83 (CI 1.13 to 2.47, p < 0.01) 30 (± 1) weeks later. Secondary outcomes with the exception of frequency of interactions with the pharmaceutical industry also showed relevant improvements in the intervention as compared with the control group (d between 0.91 and 2.04 (p < 0.001)). CONCLUSIONS: Our results show that an integrated curriculum encompassing COI and risk communication leads to a large and sustainable increase in risk communication performance. We interpret the large effect sizes to be a result of the integration of topics that are usually taught separately, leading to a more effective organization of knowledge. TRIAL REGISTRATION: The trial is registered in the International Clinical Trials Registry with the trial number DRKS00010890.

Effects of magnetic seizure therapy on anterograde and retrograde amnesia in treatment-resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT) is the gold standard for treatment-resistant depression (TRD). However, cognitive side effects, mainly anterograde and retrograde amnesia, frequently occur. Magnetic seizure therapy (MST) is tested using more focal seizure induction. However, the suggestion MST may be more beneficial than ECT because it causes fewer amnesia have not yet been comprehensively investigated using common neuropsychological testing specifically for ECT. We aimed to examine whether MST causes anterograde and retrograde amnesia. METHODS: Ten patients with TRD were treated with MST (8.9 [2] treatments) at 100% machine output, a frequency of 100 Hz and 657.4 (62) pulses per train. The short form of the Autobiographical Memory Inventory was administered to test retrograde amnesia. Furthermore, an extended neuropsychological test battery, including verbal and nonverbal recall as well as recognition tasks, was used. RESULTS: We observed changes in retrograde amnesia, although they were not clinically relevant (mean: -0.42 ± 0.14). Furthermore, no anterograde amnesia as well as no effects on global cognitive status, attention, language, and executive functions after MST were measured. CONCLUSIONS: The cognitive safety and efficacy of MST in patients with TRD were indicated. However, the main limitations of the present study were the small sample and as a consequence, the low statistical power to detect changes after treatment. Therefore, our findings require replication in further studies. In addition, a direct comparison between MST and ECT in a larger sample should be performed before MST can be discussed as an alternative treatment approach to ECT in clinical practice.

Higher BDNF plasma levels are associated with a normalization of memory dysfunctions during an antidepressant treatment.

One important symptom of patients with major depressive disorder (MDD) is memory dysfunction. However, little is known about the relationship between memory performance and depression severity, about the course of memory performance during antidepressant treatment as well as about the relationship between memory performance and brain-derived neurotrophic factor (BDNF). Memory function [learning and delayed recall) was assessed in 173 MDD patients (mean age 39.7 ± 11.3 years] treated by a pre-defined treatment algorithm within the early medication change (EMC) study at baseline, days 28 and 56. Depression severity was assessed in weekly intervals, BDNF plasma levels were measured at baseline, days 14 and 56, BDNF exon IV and p11 methylation status at baseline. Linear mixed regression models revealed that the course of depression severity was not associated with the course of learning or delayed recall in the total group. 63 (36%) of the investigated patients showed memory deficits (percent range ≤ 16) at baseline. Of those, 26(41%) patients experienced a normalization of their memory deficits during treatment. Patients with a normalization of their delayed recall performance had significantly higher plasma BDNF levels (p = 0.040) from baseline to day 56 than patients with persistent deficits. Baseline BDNF exon IV promoter and p11 gene methylation status were not associated with memory performance. Our results corroborate a concomitant amelioration of learning and delayed recall dysfunctions with successful antidepressant therapy in a subgroup of patients and support a role of BDNF in the neural mechanisms underlying the normalization of memory dysfunctions in MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96.

Effects of age on depressive symptomatology and response to antidepressant treatment in patients with major depressive disorder aged 18 to 65 years.

BACKGROUND: There is evidence that symptomatology in patients with major depressive disorder (MDD) changes with age. However, studies comparing depressive symptomatology between different age groups during antidepressant therapy are rare. We compared demographic and clinical characteristics in depressed patients of different age groups at baseline and during treatment. METHODS: 889 MDD inpatients were divided into four age groups (18-29, 30-39, 40-49, 50-65 yrs.). Demographic and clinical characteristics including depressive symptomatology (assessed by the Inventory of Depressive Symptoms) were assessed at baseline and weekly during treatment. RESULTS: At baseline, young patients (18-29 years) significantly more often reported cognitive symptoms like irritability, suicidality, negative self-concept and interpersonal sensitivity and more often suffered from drug abuse and comorbid personality disorders. Late middle aged patients (50-65 years) significantly more often suffered from neuro-vegetative symptoms such as reduced general interest, sexual interest and sleep disturbances and more often showed a recurrent MDD and comorbid physical disorders. During therapy, symptoms such as interpersonal sensitivity in young patients and low interest in sex in late middle aged patients persisted until the end of treatment while all other symptoms declined until day 56. LIMITATIONS: The herein presented age differences in depressive symptomatology only hold true for the study medication and are not generalizable to other antidepressants agents. CONCLUSION: There are substantial differences in the clinical presentation of depression between age groups. Whereas many of these differences disappear during treatment, some differences persisted until the end of treatment. These findings my help to more specifically tailor the treatment of depressed patients.

Predictors of the effectiveness of an early medication change strategy in patients with major depressive disorder.

BACKGROUND: Patients with Major Depressive Disorder (MDD) who are non-improvers after two weeks of antidepressant treatment have a high risk of treatment failure. Recently, we did not find differences in outcomes in non-improvers randomized to an early medication change (EMC) strategy compared to treatment as usual (TAU). This secondary analysis investigated possible predictors of higher remission rates in the EMC strategy. METHODS: Of 192 non-improvers (i.e. decrease of ≤20% on the HAMD-17 depression scale) after a two-week treatment with escitalopram, n = 97 were randomized to EMC (immediate switch to high doses of venlafaxine XR) and n = 95 to TAU (continued escitalopram until day 28 with non-responders switched to venlafaxine XR). We first analyzed patient characteristics, psychopathological features and subtypes of MDD by logistic regression analyses as possible predictors of remission rates. In a second investigation, we analyzed the predictors, which showed a significant association in the first analysis before Bonferroni-Holm correction by chi-squared tests separated for treatment groups. All analyses were corrected by Bonferroni-Holm method. RESULTS: The first analyses yielded no statistically significant results after correction for multiple testing. In the second analyses, however, patients with prior medication at study entry showed higher remission rates in EMC than in TAU (24.2% versus 8.6%, p = 0.017; Bonferroni-Holm corrected significance level: p = 0.025.). Furthermore, patients with a recurrent course of MDD benefited less from treatment as usual (p = 0.009; Bonferroni-Holm corrected significance level: p = 0.025). Age, sex, age of onset, psychiatric or somatic comorbidities, and other subtypes of MDD did not predict remission rates. CONCLUSIONS: Although in our first analysis we found statistically non-significant results, the second analysis showed significant differences in remission rates between patients with or without previous medication and in patients with recurrent MDD or the first depressive episode. It would therefore be valuable to examine in larger and prospective studies whether remission rates can be increased by quick escalation of treatment in certain subgroups of patients. Promising subgroups to be tested are patients who were previously medicated, and who show a recurrent course of MDD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00974155 . Registered at the 10th of September 2009. Retrospectively registered.

Clinical Predictors of Response to Magnetic Seizure Therapy in Depression: A Preliminary Report.

OBJECTIVES: Magnetic seizure therapy (MST) is a novel convulsive brain stimulation method in clinical testing, which is used as an alternative for electroconvulsive therapy in patients with treatment-resistant depression (TRD). Preliminary studies have suggested that MST leads to fewer cognitive adverse effects than electroconvulsive therapy but has similar efficacy. However, the clinical predictors of response to MST have not been evaluated yet. This study aimed to investigate whether these predictors can be identified in patients with TRD. METHODS: Thirty-eight patients with TRD were included. As clinical predictors for treatment response, we used the diagnosis, sex, age, family history, and severity of depression, as well as the melancholic, psychotic, anxiety, and atypical depression symptoms. A response was defined as an improvement higher than 50% on the 28-item Hamilton Rating Scale for Depression. The binary logistic regression, stepwise linear regression, and effect sizes were calculated. RESULTS: We found that 68.4% of the patients responded to MST. The responders had significantly fewer previous depressive episodes, less severe depression, and fewer melancholic (anhedonia) and anxiety symptoms than the nonresponders. In addition, responders were more likely to have a positive family history of depression than nonresponders. In particular, the number of previous episodes and a family history of depression were significant predictors of the response to MST. CONCLUSIONS: We demonstrate that the chronicity, severity, and family history of depression, as well as the presence of melancholic and anxiety symptoms, can serve as clinical predictors of the response to MST. Further research with a larger sample size will be required to verify these preliminary findings.

Photorhabdus luminescens lectin A (PllA): A new probe for detecting α-galactoside-terminating glycoconjugates.

Lectins play important roles in infections by pathogenic bacteria, for example, in host colonization, persistence, and biofilm formation. The Gram-negative entomopathogenic bacterium Photorhabdus luminescens symbiotically lives in insect-infecting Heterorhabditis nematodes and kills the insect host upon invasion by the nematode. The P. luminescens genome harbors the gene plu2096, coding for a novel lectin that we named PllA. We analyzed the binding properties of purified PllA with a glycan array and a binding assay in solution. Both assays revealed a strict specificity of PllA for α-galactoside-terminating glycoconjugates. The crystal structures of apo PllA and complexes with three different ligands revealed the molecular basis for the strict specificity of this lectin. Furthermore, we found that a 90° twist in subunit orientation leads to a peculiar quaternary structure compared with that of its ortholog LecA from Pseudomonas aeruginosa We also investigated the utility of PllA as a probe for detecting α-galactosides. The α-Gal epitope is present on wild-type pig cells and is the main reason for hyperacute organ rejection in pig to primate xenotransplantation. We noted that PllA specifically recognizes this epitope on the glycan array and demonstrated that PllA can be used as a fluorescent probe to detect this epitope on primary porcine cells in vitro In summary, our biochemical and structural analyses of the P. luminescens lectin PllA have disclosed the structural basis for PllA's high specificity for α-galactoside-containing ligands, and we show that PllA can be used to visualize the α-Gal epitope on porcine tissues.

Glycomimetic, Orally Bioavailable LecB Inhibitors Block Biofilm Formation of Pseudomonas aeruginosa.

The opportunistic Gram-negative bacterium Pseudomonas aeruginosa is a leading pathogen for infections of immuno-compromised patients and those suffering from cystic fibrosis. Its ability to switch from planktonic life to aggregates, forming the so-called biofilms, is a front-line mechanism of antimicrobial resistance. The bacterial carbohydrate-binding protein LecB is an integral component and necessary for biofilm formation. Here, we report a new class of drug-like low molecular weight inhibitors of the lectin LecB with nanomolar affinities and excellent receptor binding kinetics and thermodynamics. This class of glycomimetic inhibitors efficiently blocked biofilm formation of P. aeruginosa in vitro while the natural monovalent carbohydrate ligands failed. Furthermore, excellent selectivity and pharmacokinetic properties were achieved. Notably, two compounds showed good oral bioavailability, and high compound concentrations in plasma and urine were achieved in vivo.

High-Throughput DNA sequencing of ancient wood.

Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high-throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long-term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human-induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro-evolutionary response of trees to climate change and human forest management.

Depression and cognitive deficits as long-term consequences of thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening microangiopathy with a tendency of relapse characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, and spontaneous von Willebrand factor-induced platelet clumping leading to microthrombi. The brain is frequently affected by microthrombi leading to neurologic abnormalities of varying severity. STUDY DESIGN AND METHODS: The aim of this observational cohort study was to investigate the prevalence of depression and cognitive deficits in 104 patients having survived acute TTP. TTP survivors were repeatedly assessed by means of different standardized questionnaires to evaluate depression (IDS-SR) and mental performance (FLei). We received answers of 104 individual TTP patients and 55 of them participated in both surveys. RESULTS: Seventy-one of the 104 responding TTP patients (68%) suffered from depression and the severity of depression was similar in both surveys performed 1 year apart. Furthermore, TTP patients had considerably lower cognitive performance than controls. There was no correlation between prevalence of depression and cognitive deficits and the number and the severity of acute episodes. Impairment of mental performance correlated with the severity of depression (rs  = 0.779). CONCLUSION: The prevalence of depression and cognitive deficits was significantly higher in TTP patients. Cognitive impairment seemed to be a consequence of depression, almost independently of number and severity of TTP episodes.

Guideline adherence of antidepressant treatment in outpatients with major depressive disorder: a naturalistic study.

Little is known about guideline adherence of naturalistic antidepressant drug therapy in outpatients with major depressive disorder (MDD). The aim of the study was to analyze guideline adherence, especially regarding treatment length, treatment evaluation and medication change strategies. We investigated 889 patients with MDD who had been admitted for inpatient treatment and were enrolled in the early medication change trial (ClinicalTrials.gov NCT00974155). We investigated all patients at screening visit regarding previous outpatient drug treatment in the index episode, which was assessed by structured interviews. Demographic variables were obtained from patients and patients' records. 51.0% of the patients had received previous drug treatment in the index episode, 56.6% were females, and their mean age was 40.0 years. In the 153 patients who were pharmacologically treated at least 8 weeks, medication was not changed in 129 (84.3%) patients. Patients who had a medication change in their index episode (n = 24, 15.7%) waited 71.1 weeks (±110.4) for their treatment optimization. Only 5 of those 153 patients (3.3%) had a dose increase, whereas 132 patients (86.3%) had no dose adaption at all. Antidepressant blood levels were measured in 46 patients (30.1%). We conclude that a large proportion of patients with MDD is not treated in adherence to treatment guidelines recommending treatment evaluation (e.g. therapeutic drug monitoring) and treatment change after 4 to 8 weeks in non-responders. Earlier treatment optimization may prevent long-term suffering of patients and may avoid inpatient treatment.

Intrastrand triplex DNA repeats in bacteria: a source of genomic instability.

Repetitive nucleic acid sequences are often prone to form secondary structures distinct from B-DNA. Prominent examples of such structures are DNA triplexes. We observed that certain intrastrand triplex motifs are highly conserved and abundant in prokaryotic genomes. A systematic search of 5246 different prokaryotic plasmids and genomes for intrastrand triplex motifs was conducted and the results summarized in the ITxF database available online at http://bioinformatics.uni-konstanz.de/utils/ITxF/. Next we investigated biophysical and biochemical properties of a particular G/C-rich triplex motif (TM) that occurs in many copies in more than 260 bacterial genomes by CD and nuclear magnetic resonance spectroscopy as well as in vivo footprinting techniques. A characterization of putative properties and functions of these unusually frequent nucleic acid motifs demonstrated that the occurrence of the TM is associated with a high degree of genomic instability. TM-containing genomic loci are significantly more rearranged among closely related Escherichia coli strains compared to control sites. In addition, we found very high frequencies of TM motifs in certain Enterobacteria and Cyanobacteria that were previously described as genetically highly diverse. In conclusion we link intrastrand triplex motifs with the induction of genomic instability. We speculate that the observed instability might be an adaptive feature of these genomes that creates variation for natural selection to act upon.

Covalent Lectin Inhibition and Application in Bacterial Biofilm Imaging.

Biofilm formation by pathogenic bacteria is a hallmark of chronic infections. In many cases, lectins play key roles in establishing biofilms. The pathogen Pseudomonas aeruginosa often exhibiting various drug resistances employs its lectins LecA and LecB as virulence factors and biofilm building blocks. Therefore, inhibition of the function of these proteins is thought to have potential in developing "pathoblockers" preventing biofilm formation and virulence. A covalent lectin inhibitor specific to a carbohydrate binding site is described for the first time. Its application in the LecA-specific in vitro imaging of biofilms formed by P. aeruginosa is also reported.

A meta-analysis of cognitive functions in children and adolescents with major depressive disorder.

The cumulative prevalence rates of major depressive disorders (MDD) in children and adolescents averages 9.5 %. The majority of adults with MDD suffer from significant cognitive deficits, but the available neuropsychological data on the cognitive performance of children and adolescents with MDD yielded mixed results. Meta-analytic methods were used to assess the severity of cognitive deficits in children and adolescents with MDD as compared to healthy children and adolescents. We identified 17 studies comparing the intelligence, executive functions, verbal memory and attention of 447 patients with DSM-IV MDD and 1,347 healthy children and adolescents. Children and adolescents with MDD performed 0.194-0.772 (p < 0.001) standard mean differences worse than healthy control subjects in neuropsychological test procedures. The most pronounced deficits of children and adolescents with MDD were seen in inhibition capacity (STD = 0.772; p = 0.002), phonemic verbal fluency (STD = 0.756; p = 0.0001), sustained attention (STD = 0.522; p = 0.000), verbal memory (STD = 0.516; p = 0.0009) and planning (STD = 0.513; p = 0.014). We revealed cognitive deficits of children and adolescents with MDD in various cognitive domains. Long-term studies should investigate how the cognitive deficits of depressed youth affect their academic and social functioning, and whether age, comorbidity and depression severity play a role in this process.