A complex relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin.

We investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule ß-arrestin-2 (ß-Arr2) is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and survival of adult-born granule cells are absent in the ß-Arr2 knockout (KO) mice. To our surprise, fluoxetine induced a dramatic upregulation of the number of doublecortin (DCX)-expressing cells in the ß-Arr2 KO mice, indicating that this marker can be increased even though AHN is not. We discovered two other conditions where a complex relationship occurs between the number of DCX-expressing cells compared to levels of AHN: a chronic antidepressant model where DCX is upregulated and an inflammation model where DCX is downregulated. We concluded that assessing the number of DCX-expressing cells alone to quantify levels of AHN can be complex and that caution should be applied when label retention techniques are unavailable.

Omphalines A-E: ent-Rosane-Type Diterpenoids from the Madagascar Endemic Plant, Omphalea oppositifolia.

From the less polar fraction of the MeOH extract of the leaves and twigs of Omphalea oppositifolia, five new ent-rosane-type diterpenoids, named omphalines A-E (1-5), were isolated together with one known compound, 7-keto-ent-kaurane-16ß,17-diol (6), by a combination of various kinds of chromatography. The structure of omphaline A (1) was elucidated to be 19-nor-ent-rosane-4,15-diene-2ß,6α-diol-3-one. Omphalines B (2), C (3), D (4), and E (5) possessed two double bonds at 5- and 15-positions, and hydroxy functional groups at 3ß-, 2α,3α-, 2α,3ß-, and 2α,19-positions, respectively. The absolute configuration of 1 was determined by the comparison of the experimental electronic circular dichroism (ECD) spectrum and calculated ECD spectra.

Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial.

IMPORTANCE: Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects. OBJECTIVE: To test whether selepressin improves outcome in septic shock. DESIGN, SETTING, AND PARTICIPANTS: An adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 µg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018. INTERVENTIONS: Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters. MAIN OUTCOMES AND MEASURES: Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy-free days, and ICU-free days. RESULTS: Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, -1.3 to 2.4]; P = .30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, -6.5% to 8.8%]; P = .77; kidney replacement therapy-free days: 18.5 vs 18.2; difference, 0.3 [95% CI, -2.1 to 2.6]; P = .85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, -1.2 to 2.2]; P = .41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%). CONCLUSIONS AND RELEVANCE: Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02508649.

Differentiating between underwater construction noise of monopile and jacket foundations for offshore windmills: a case study from the Belgian part of the North Sea.

Steel monopiles, jackets requiring four steel pinpiles, and gravity-based foundations were applied in offshore wind farms in the Belgian part of the North Sea. This paper compares the underwater noise generated during the piling activities of steel monopiles at the Belwind wind farm (Blighbank) with that of jacket pinpiles at the C-Power project (Thorntonbank). Underwater noise was measured at various distances from the pile driving location. The underwater noise was quantified by its zero to peak sound pressure level (L(z-p)), unweighted sound exposure level (SEL), cumulative SEL, and 1/3 octave spectra. No significant differences in L(z-p) could be demonstrated (monopile L(z-p): 179-194 dB re 1 µPa, jacket L(z-p): 172-189 dB re 1 µPa). SEL showed no statistical difference between monopile and jacket and varied between 145 and 168 dB re 1 µPa(2)s. Furthermore, near identical spectra were measured for both types of piling. Piling of the jacket pinpiles took, however, about 2.5 times the time of the monopile. When standardised to megawatt installed per foundation both types of piling scored near equally. As an illustration, the radius of major behavioural disturbance (L(p-p) = 155 dB re 1 µPa) in the harbour porpoise Phocoena phocoena was estimated by a model at 16 km for monopiles and at 8 km for jacket.

Hybridization increases genetic diversity in Schistosoma haematobium populations infecting humans in Cameroon.

BACKGROUND: Hybrids between Schistosoma haematobium (Sh) and S. bovis (Sb) have been found in several African countries as well as in Europe. Since the consequences of this hybridization are still unknown, this study aims to verify the presence of such hybrids in Cameroonian humans, to describe the structure of S. haematobium populations on a large geographic scale, and to examine the impact of these hybrids on genetic diversity and structure of these populations. METHODS: From January to April 2019, urine from infected children was collected in ten geographically distinct populations. Miracidia were collected from eggs in this urine. To detect the presence of hybrids among these miracidia we genotyped both Cox1 (RD-PCR) and ITS2 gene (PCR-RFLP). Population genetic diversity and structure was assessed by genotyping each miracidium with a panel of 14 microsatellite markers. Gene diversity was measured using both heterozygosity and allelic richness indexes, and genetic structure was analyzed using paired Fst, PCA and Bayesian approaches. RESULTS: Of the 1327 miracidia studied, 88.7% were identified as pure genotypes of S. haematobium (Sh_Sh/Sh) while the remaining 11.3% were hybrids (7.0% with Sh_Sh/Sb, 3.7% with Sb_Sb/Sh and 0.4% with Sb_Sh/Sb). No miracidium has been identified as a pure genotype of S. bovis. Allelic richness ranged from 5.55 (Loum population) to 7.73 (Matta-Barrage) and differed significantly between populations. Mean heterozygosity ranged from 53.7% (Loum) to 59% (Matta Barrage) with no significant difference. The overall genetic differentiation inferred either by a principal component analysis or by the Bayesian approach shows a partial structure. Southern populations (Loum and Matta Barrage) were clearly separated from other localities but genetic differentiation between northern localities was limited, certainly due to the geographic proximity between these sites. CONCLUSIONS: Hybrids between S. haematobium and S. bovis were identified in 11.3% of miracidia that hatched from eggs present in the urine of Cameroonian schoolchildren. The percentages of these hybrids are correlated with the genetic diversity of the parasite, indicating that hybridization increases genetic diversity in our sampling sites. Hybridization is therefore a major biological process that shapes the genetic diversity of S. haematobium.

Nasal-type T-cell lymphoma referred as fungal rhinosinusitis: Case report.

NKTCL is a rare and destructive midline tumor that can be easily misdiagnosed as other more common inflammatory processes. The differential diagnosis of NKTCL should always be kept in mind for any lesion of the paranasal sinuses with atypical presentation and nonresponsive to conventional treatments.

Choledochus angulation by T-tube. / Angulación de colédoco por sonda en T.

BACKGROUND: The presence of bile stasis is a frequent mechanism for presenting choledocholithiasis and recurrence of this one. The bile duct angulation, also known as "elbow sign," could be a risk factor for reducing the flow of bile and forming stones and it has been reported as a consequence secondary to the use of T-tube. The recurrence of choledocholithiasis without the use of T-tube in the bile duct is minimal, whereas in those with T-tube is four times higher in bile duct exploration surgeries. We present a case report of a patient who underwent T-tube laparoscopic bile duct exploration surgery, who had a bile duct angulation and residual choledocholithiasis as a complication. CASE REPORT: 34-yeard-old female, who presented acute cholecystitis and underwent cholecystectomy. In this operation it was detected choledocholithiasis, which is why it was carried out a T-tube bile duct exploration surgery for acute cholecystitis, without solving the choledocholithiasis condition. Afterwards, she had three endoscopic retrograde cholangiopancreatography procedures, requiring endoscopic hemoclip. Four months later, she was referred to a third-level hospital for definitive treatment with unsolved choledocholithiasis. CONCLUSIONS: The bile duct angulation by T-tube is unusual and it favors bile duct dilatation, stasis of bile pigments and new stones formation. We consider that the best surgical option is the biliary bypass.

INTRODUCCIÓN: La presencia de estasis biliar es un mecanismo frecuente para presentar coledocolitiasis y su recurrencia. La angulación del conducto biliar, también llamada «signo del codo¼, puede ser un factor de riesgo para disminuir el flujo biliar y propiciar la formación de litos, y ha sido reportada como una complicación del uso de sonda en T. La posibilidad de recurrencia de la coledocolitiasis sin colocación de sonda en T en una exploración quirúrgica de vía biliar es mínima, y en aquellas con sonda es cuatro veces mayor. Se presenta el caso de una paciente operada de exploración de la vía biliar con colocación de sonda en T que presentó como complicación una angulación de la vía biliar y coledocolitiasis residual. CASO CLÍNICO: Mujer de 34 años con colecistitis crónica litiásica agudizada que fue sometida a colecistectomía. En la intervención se notó la presencia de coledocolitiasis, por lo que se hizo una exploración de vía biliar y se colocó una sonda en T, sin resolver el cuadro de coledocolitiasis. Posteriormente se hicieron tres colangiopancreatografías retrógradas endoscópicas que fueron fallidas, lo cual ameritó la colocación de hemoclip por sangrado. Cuatro meses después, la paciente fue referida a tercer nivel con diagnóstico de coledocolitiasis no resuelta para tratamiento definitivo. CONCLUSIONES: La angulación de la vía biliar por sonda en T es poco frecuente y favorece la dilatación del conducto biliar común, la estasis de pigmentos biliares y la formación de litos. Consideramos que la mejor opción quirúrgica es la derivación biliodigestiva.

The cell wall and secretory proteome of a tobacco cell line synthesising secondary wall.

The utility of plant secondary cell wall biomass for industrial and biofuel purposes depends upon improving cellulose amount, availability and extractability. The possibility of engineering such biomass requires much more knowledge of the genes and proteins involved in the synthesis, modification and assembly of cellulose, lignin and xylans. Proteomic data are essential to aid gene annotation and understanding of polymer biosynthesis. Comparative proteomes were determined for secondary walls of stem xylem and transgenic xylogenic cells of tobacco and detected peroxidase, cellulase, chitinase, pectinesterase and a number of defence/cell death related proteins, but not marker proteins of primary walls such as xyloglucan endotransglycosidase and expansins. Only the corresponding detergent soluble proteome of secretory microsomes from the xylogenic cultured cells, subjected to ion-exchange chromatography, could be determined accurately since, xylem-specific membrane yields were of poor quality from stem tissue. Among the 109 proteins analysed, many of the protein markers of the ER such as BiP, HSP70, calreticulin and calnexin were identified, together with some of the biosynthetic enzymes and associated polypeptides involved in polymer synthesis. However 53% of these endomembrane proteins failed identification despite the use of two different MS methods, leaving considerable possibilities for future identification of novel proteins involved in secondary wall polymer synthesis once full genomic data are available.

Evolution and current status of research in phenolic compounds.

Phenolic compounds are ubiquitous in plants which collectively synthesize several thousand different chemical structures characterized by hydroxylated aromatic ring(s). These compounds play several important functions in plants. They represent a striking example of metabolic plasticity enabling plants to adapt to changing biotic and abiotic environments and provide to plant products colour, taste, technological properties and putative health promoting benefits. Phenolic compounds represent the most studied phytochemicals and have been widely exploited as model systems in different areas of plant research. Initial studies in the field concerned the analytical characterization of a wide range of structures and of relevant enzymes with PAL being one of the most studied plant enzymes. This research is still active due to the complexity of the structures and the biosynthetic pathways As an example, the nature and functions of enzymes involved in lignin synthesis have been revisited several times, even in recent years. More recently, molecular biology and genomics have provided additional understanding of the mechanisms underlying the synthesis of these compounds with special emphasis on the regulation of gene expression by environmental factors. The extensive characterization of genes encoding the different enzymatic steps of flavonoid synthesis and cytochrome P450 genes have been among the most recent advances in this area. Metabolic engineering of lignins and flavonoids has been deeply investigated. Significant positive results have been obtained in both areas but the negative European opinion towards genetically modified organisms has considerably hampered potential applications. From a more basic point of view, global approaches (such as transcript and metabolite profiling) have investigated the repercussions of these engineered modulations of specific phenolics synthesis on other branches of plant metabolism. These studies have revealed a substantial and sometimes unexpected network of regulatory interactions. In the present time, the societal demand and an increasing interest for practical applications has stimulated a wide range of biological and epidemiological studies aiming at characterizing the health promoting properties of specific phenolic compounds with antioxidant activities towards cancer, cardiovascular and neurodegenerative diseases or for use in antiaging or cosmetic products. Increased emphasis on sustainable development should stimulate innovative investigations on phenolic synthesis for improving plant biomass and for a better control of plant and animal health.

Modification of hemicellulose content by antisense down-regulation of UDP-glucuronate decarboxylase in tobacco and its consequences for cellulose extractability.

Extractability and recovery of cellulose from cell walls influences many industrial processes and also the utilisation of biomass for energy purposes. The utility of genetic manipulation of lignin has proven potential for optimising such processes and is also advantageous for the environment. Hemicelluloses, particularly secondary wall xylans, also influence the extractability of cellulose. UDP-glucuronate decarboxylase produces UDP-xylose, the precursor for xylans and the effect of its down-regulation on cell wall structure and cellulose extractability in transgenic tobacco has been investigated. Since there are a number of potential UDP-glucuronate decarboxylase genes, a 490bp sequence of high similarity between members of the family, was chosen for general alteration of the expression of the gene family. Sense and antisense transgenic lines were analysed for enzyme activity using a modified and optimised electrophoretic assay, for enzyme levels by western blotting and for secondary cell wall composition. Some of the down-regulated antisense plants showed high glucose to xylose ratios in xylem walls due to less xylose-containing polymers, while arabinose and uronic acid contents, which could also have been affected by any change in UDP-xylose provision, were unchanged. The overall morphology and stem lignin content of the modified lines remained little changed compared with wild-type. However, there were some changes in vascular organisation and reduction of xylans in the secondary walls was confirmed by immunocytochemistry. Pulping analysis showed a decreased pulp yield and a higher Kappa number in some lines compared with controls, indicating that they were less delignified, although the level of residual alkali was reduced. Such traits probably indicate that lignin was less available for removal in a reduced background of xylans. However, the viscosity was higher in most antisense lines, meaning that the cellulose was less broken-down during the pulping process. This is one of the first studies of a directed manipulation of hemicellulose content on cellulose extractability and shows both positive and negative outcomes.

Introduction of sense constructs of cinnamate 4-hydroxylase (CYP73A24) in transgenic tomato plants shows opposite effects on flux into stem lignin and fruit flavonoids.

Understanding regulation of phenolic metabolism underpins attempts to engineer plants for diverse properties such as increased levels of antioxidant flavonoids for dietary improvements or reduction of lignin for improvements to fibre resources for industrial use. Previous attempts to alter phenolic metabolism at the level of the second enzyme of the pathway, cinnamate 4-hydroxylase have employed antisense expression of heterologous sequences in tobacco. The present study describes the consequences of homologous sense expression of tomato CYP73A24 on the lignin content of stems and the flavonoid content of fruits. An extensive number of lines were produced and displayed four developmental variants besides a normal phenotype. These aberrant phenotypes were classified as dwarf plants, plants with distorted (curly) leaves, plants with long internodes and plants with thickened waxy leaves. Nevertheless, some of the lines showed the desired increase in the level of rutin and naringenin in fruit in a normal phenotype background. However this could not be correlated directly to increased levels of PAL and C4H expression as other lines showed less accumulation, although all lines tested showed increases in leaf chlorogenic acid which is typical of Solanaceous plants when engineered in the phenylpropanoid pathway. Almost all transgenic lines analysed showed a considerable reduction in stem lignin and in the lines that were specifically examined, this was correlated with partial sense suppression of C4H. Although not the primary purpose of the study, these reductions in lignin were amongst the greatest seen in plants modified for lignin by manipulation of structural genes. The lignin showed higher syringyl to coniferyl monomeric content contrary to that previously seen in tobacco engineered for downregulation of cinnamate 4-hydroxylase. These outcomes are consistent with placing CYP73A24 more in the lignin pathway and having a role in flux control, while more complex regulatory processes are likely to be involved in flavonoid and chlorogenic acid accumulation.

Continuity of primary care and emergency department utilization among elderly people.

BACKGROUND: People aged 65 years or more represent a growing group of emergency department users. We investigated whether characteristics of primary care (accessibility and continuity) are associated with emergency department use by elderly people in both urban and rural areas. METHODS: We conducted a cross-sectional study using information for a random sample of 95,173 people aged 65 years or more drawn from provincial administrative databases in Quebec for 2000 and 2001. We obtained data on the patients' age, sex, comorbidity, rate of emergency department use (number of days on which a visit was made to an emergency department per 1000 days at risk [i.e., alive and not in hospital] during the 2-year study period), use of hospital and ambulatory physician services, residence (urban v. rural), socioeconomic status, access (physician: population ratio, presence of primary physician) and continuity of primary care. RESULTS: After adjusting for age, sex and comorbidity, we found that an increased rate of emergency department use was associated with lack of a primary physician (adjusted rate ratio [RR] 1.45, 95% confidence interval [CI] 1.41-1.49) and low or medium (v. high) levels of continuity of care with a primary physician (adjusted RR 1.46, 95% CI 1.44-1.48, and 1.27, 95% CI 1.25-1.29, respectively). Other significant predictors of increased use of emergency department services were residence in a rural area, low socioeconomic status and residence in a region with a higher physician:population ratio. Among the patients who had a primary physician, continuity of care had a stronger protective effect in urban than in rural areas. INTERPRETATION: Having a primary physician and greater continuity of care with this physician are factors associated with decreased emergency department use by elderly people, particularly those living in urban areas.

Addressing suicidal ideations through the realization of meaningful personal goals.

A personal goal intervention program was offered to early retirees aged 50 to 65 years with the objective of increasing their subjective well-being. The program was aimed at helping the participants set, plan, pursue, and realize their personal goals. A subsample of 21 participants with suicidal ideas was identified from a larger sample (N = 354) of retirees living in the community who took part in the study to evaluate the program. The experimental (n = 10) and control (n = 11) groups were compared on their answers to 16 goal and psychological well-being questionnaires. By the end of the program, the experimental group had improved significantly more than the control group on hope, goal realization process, serenity, flexibility, and positive attitude toward retirement. The levels of depression and psychological distress significantly decreased. These gains were maintained 6 months later. The positive results obtained from this study could lead to an innovative way to help people with suicidal ideations.

[Mental health through management of personal projects: an intervention with young retired people]. / La santé mentale par la gestion des projets personnels: une intervention auprès de jeunes retraités.

A personal goal-based intervention was offered to retired people aged 50 to 65 years with the objective of increasing their subjective well-being and their mental health. More specifically, the program presented here was aimed to promote the setting, planning, and realization of personal projects through a learning process based on a cognitive approach. At the end of the program, the experimental group (n = 117) had improved significantly more than the control group (n = 177) on all the goal and subjective well-being indicators, and this gain was maintained six months later. Some ideas to make the program more effective are discussed.

Super-drained distally based neurofasciocutaneous sural flap: a case series and review of literature.

OBJECTIVE: The distally based neurofasciocutaneous sural flap is central to the armamentarium for the reconstruction of leg's distal third, ankle, and hindfoot. Despite the use of adapted techniques aimed at increasing the flap's reliability, venous congestion remains a frequently encountered problem. We present a venous super-drainage technique used by the senior author to reduce venous congestion and improve flap reliability when harvesting larger flaps. METHODS: A retrospective chart review, from January 2002 to October 2008, at 2 tertiary care centers, was conducted on all cases of inferior limb reconstruction with reverse sural flaps on defects greater than 10 × 5 cm. In addition, a literature review was carried out to examine the average sural flap surface area and reported complications published from 1992 to 2012. We then compared our results with those published in the literature. RESULTS: A total of 15 flaps were identified. Mean flap dimensions were 14 × 8.5 cm (mean area = 115.27 cm(2); 95% confidence interval, 99.28-131.26). None of the flaps developed complications (arterial or venous insufficiency, partial/complete necrosis). The average flap surface area in the literature is 55.08 cm(2), with a 22% rate of total complications. We harvested significantly larger flaps (P < .001) with a significantly lower total complication rate (P < .05) when compared with that reported in the literature. CONCLUSION: Anastomosing the proximal end of the lesser saphenous vein with a vein at the defect site improves venous outflow, effectively reducing the incidence of venous congestion, increases the potential flap size, and improves reliability.

Patient advisors for victims of traumatic amputation: a critical intervention / Le patient-ressource chez les victimes d'amputation traumatique

Patient advisors for victims of traumatic amputation: a critical intervention. Since 2014, the Centre of Expertise in Reimplantation and Microsurgical Revascularization at the University of Montreal (CEVARMU) has been recruiting on an ad hoc basis former patients, who have completed the rehabilitation process, to accompany and support new patients at the Centre during their care process. Considered full-fledged partners of the care team, these patient advisors are invited to meet with patients who are hospitalized or in the rehabilitation process to not only share their experience but also ensure that the treatment plans proposed to the patients are well understood and meet their needs. Around forty interventions have been conducted by five patient advisors, helping to strengthen the credibility of professional interventions, break down patients' isolation, and give new meaning to the work of health professionals.

Le patient-ressource chez les victimes d'amputation traumatique. Depuis 2014, le Centre d'expertise en réimplantation ou revascularisation microchirurgicale d'urgence (CEVARMU) fait appel, sur une base ponctuelle, à d'anciens patients ayant terminé leur processus de réadaptation afin d'accompagner et de soutenir les patients nouvellement arrivés au centre dans leur propre processus de soins. Considérés comme des partenaires à part entière de l'équipe, ces patients-ressources sont invités à venir rencontrer, sur une base bénévole, les patients hospitalisés ou qui sont en processus de réadaptation afin de témoigner de leur expérience mais aussi de s'assurer que les plans de traitement proposés aux patients soient bien compris par ces derniers et qu'ils répondent à leurs besoins. Une quarantaine d'interventions ont été réalisées par cinq patientsressources et ont permis de renforcer la crédibilité des interventions des professionnels, de briser l'isolement des patients et de redonner du sens au travail des professionnels.

The polymorphism of the genes/enzymes involved in the last two reductive steps of monolignol synthesis: what is the functional significance?

The polymorphism of genes and enzymes involved in the last two steps of monolignol synthesis is examined in the light of recent data coming from genomic studies and mutant/transformant analyses. The two catalytic activities considered--cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD)--are encoded by small multigene families. While some degree of diversification can be noted at the sequence level, it is often difficult to use this information to assign substrate specificities to each member of a gene family. Expression profiles, however, suggest for both CAD and CCR the existence of two sub-families: one devoted to developmental lignification, and the other involved in the synthesis of defence-related compounds.

Vortioxetine for the treatment of major depressive disorder.

Vortioxetine (Brintellix(®), 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a multimodal antidepressant targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin (5-HT) transporter (5-HTT). Vortioxetine administration induces antidepressant- and anxiolytic-like effects, and can enhance cognitive performance in rodents. Several clinical trials have reported the efficiency and a satisfactory tolerability of vortioxetine treatment in depressed patients. Remarkably, vortioxetine has a specific positive impact on cognitive symptoms in depressed patients. Overall, vortioxetine is an efficacious antidepressant drug for the treatment of patients with a major depressive episode and has a unique mechanism of action offering a new therapeutic option.

Modeling treatment-resistant depression.

Depression is a polygenic and highly complex psychiatric disorder that is currently a major burden on society. Depression is highly heterogeneous in presentation and frequently exhibits high comorbidity with other psychiatric and somatic disorders. Commonly used treatments, such as selective serotonin reuptake inhibitors (SSRIs), are not ideal since only a subset of patients achieve remission. In addition, the reason why some individuals respond to SSRIs while others don't are unknown. Here we begin to ask what the basis of treatment resistance is, and propose new strategies to model this phenomenon in animals. We focus specifically on animal models that offer the appropriate framework to study treatment resistance with face, construct and predictive validity.