Analysis of Microtubule Polymerization During Axon Outgrowth Using Fluorescently Labeled Microtubule Plus-End Tracking Proteins.

The study of microtubules arrangements and dynamics during axon outgrowth and pathfinding has gained scientific interest during the last decade, and numerous technical resources for its visualization and analysis have been implemented. In this chapter, we describe the cell culture protocols of embryonic cortical and retinal neurons, the methods for transfecting them with fluorescent reporters of microtubule polymerization, and the procedures for time-lapse imaging and quantification in order to study microtubule dynamics during axon morphogenesis.

Protecting TiS3 Photoanodes for Water Splitting in Alkaline Media by TiO2 Coatings.

Titanium trisulfide (TiS3) nanoribbons, when coated with titanium dioxide (TiO2), can be used for water splitting in the KOH electrolyte. TiO2 shells can be prepared through thermal annealing to regulate the response of TiS3/TiO2 heterostructures by controlling the oxidation time and growth atmosphere. The thickness and structure of the TiO2 layers significantly influence the photoelectrocatalytic properties of the TiS3/TiO2 photoanodes, with amorphous layers showing better performance than crystalline ones. The oxide layers should be thin enough to transfer photogenerated charge through the electrode-electrolyte interface while protecting TiS3 from KOH corrosion. Finally, the performance of TiS3/TiO2 heterostructures has been improved by coating them with various electrocatalysts, NiSx being the most effective. This research presents new opportunities to create efficient semiconductor heterostructures to be used as photoanodes in corrosive alkaline aqueous solutions.

Sigmoid adenocarcinoma hosted in a giant inguinoscrotal hernia.

Colorectal cancer is the most frequently diagnosed neoplasm in the population worldwide, regardless of sex. Its presentation is variable, from asymptomatic cases that are diagnosed in the population screening programme, to perforation or intestinal obstruction that appear urgently. The location of the neoplasia inside an inguinal hernia, although it is described in the literature, is uncommon and may increase the risk of incarceration or strangulation with the need for urgent surgery. We report a patient who presents adenocarcinoma of the sigmoid colon lodged in a giant inguino-scrotal hernia.

Carpectomía de la fila proximal en procesos degenerativos de la muñeca. Nuestra experiencia a mediano plazo / Proximal row carpectomy in degenerative wrist conditions. Our medium-term experience

Objetivo: Evaluar los resultados clínico-radiográficos a mediano plazo del tratamiento de los procesos degenerativos de la muñeca mediante carpectomía proximal. Materiales y Métodos: Estudio descriptivo retrospectivo de 33 pacientes operados entre 2009 y 2019 en nuestro Centro. Se evaluaron el rango de movilidad, el dolor con la escala analógica visual y la capacidad funcional con el cuestionario QuickDASH. Se realizaron pruebas de valoración biomecánica. Se estudió la incidencia de complicaciones y de una segunda intervención. Se evaluó la progresión radiográfica de la artrosis y su asociación con los malos resultados clínicos. Resultados:El seguimiento medio fue de 10 años. El rango de movilidad medio fue de 77,11° en el arco de flexo-extensión y 36,7° en el radiocubital. El puntaje medio de dolor evolucionó de 7,9 a 2,7 tras la cirugía (p <0,003). El puntaje QuickDASH en el último control fue de 24,3. Se halló una asociación inversa entre el grado de artrosis radiocarpiana preoperatoria y el resultado clínico (p <0,03); sin embargo, no hubo una relación entre la evolución artrósica radiográfica posoperatoria con la mala evolución (p <0,04). Cuatro pacientes necesitaron una segunda intervención mediante artrodesis total de muñeca. Conclusiones: La carpectomía proximal es una opción terapéutica que ofrece resultados satisfactorios a mediano plazo en pacientes con procesos degenerativos de la muñeca, proporciona un adecuado rango de movilidad con una baja tasa de complicaciones. El uso de esta técnica en pacientes con degeneración articular de mayor grado antes de la cirugía puede llevar a un peor resultado clínico. Nivel de Evidencia: IV

Objective: Examining the medium-term clinical and radiological outcomes of proximal carpectomy for treating degenerative wrist conditions. Materials and Methods:Retrospective study of 33 patients who underwent proximal carpectomy between 2009 and 2019. Outcomes were assessed through range of motion measurements, pain evaluation using the Visual Analog Scale (VAS), and functional capacity using the Quick-DASH questionnaire. Biomechanical tests were performed and the rate of complications and reoperations was analyzed. Radiological progression of osteoarthritis and its impact on clinical outcomes were examined. Results: The mean range of motion was 77.11º (range 51­80º) in flexion-extension and 36.7º (range 29­42º) in radioulnar deviation. VAS scores improved significantly from 7.9 (range 7­9) to 2.7 (range 0­7) post-surgery (p<0.003). The Quick-DASH score at the final follow-up was 24.3 (range 11­45). We observed an inverse relationship between preoperative radiocarpal osteoarthritis severity and clinical outcomes (p<0.03), but no link between postoperative osteoarthritis progression and poor outcomes (p<0.04). Four patients (12.12%) required reoperation with total wrist arthrodesis. Conclusions:Proximal carpectomy demonstrates satisfactory medium-term outcomes for degenerative wrist conditions, offering good range of motion and a low complication rate. However, patients with more severe preoperative joint degeneration may lead to poorer clinical outcomes. Level of Evidence: IV

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder.

Application of the REAL-score prognostic index in decision making in rectal cancer surgery.

BACKGROUND: Colorectal anastomosis leak (AL) is the most feared complication of rectal cancer surgery (1-19%) as it increases morbidity and mortality and worsens oncological outcomes in terms of local recurrence and survival. The publication of the REAL-score index makes it possible to predict the risk of AL and compare the expected results with those obtained. METHOD: Observational, descriptive, longitudinal and retrospective study of patients operated on for rectal cancer at the Miguel Servet University Hospital, in Zaragoza, Spain, in 2019. Statistical analysis of morbidity and mortality outcome variables and the REAL-score index using ROC curves. RESULTS: Of 80 patients operated on for rectal cancer, colorectal anastomosis was performed in 52 and temporary ileostomy in 11 (21.2%). Morbidity was high (38.4%), but severe only in 7.7% (Clavien-Dindo IIIb), with no deaths. There were four dehiscences: one type B and three type C. A direct relationship between high risk of AL and the practice of temporary stoma is observed when the cut-off point of the REAL-score exceeds 14.74%. CONCLUSIONS: REAL-score can help in decision-making in rectal cancer surgery. Above a cut-off point, the risk of AL would imply a selective ileostomy.

ANTECEDENTES: La dehiscencia de la anastomosis colorrectal (DA) es la complicación más temida de la cirugía del cáncer de recto (1-19%), pues incrementa la morbimortalidad y empeora los resultados oncológicos en términos de recidiva local y supervivencia. La publicación del índice REAL-score permite predecir el riesgo de DA y comparar los resultados esperados con los obtenidos. MÉTODO: Estudio observacional, descriptivo, longitudinal y retrospectivo, de pacientes intervenidos de cáncer de recto en el Hospital Universitario Miguel Servet, en Zaragoza, España, en 2019. Análisis estadístico de variables resultado de morbimortalidad y del índice REAL-score mediante curvas ROC. RESULTADOS: De 80 pacientes intervenidos de cáncer de recto, se realizó anastomosis colorrectal en 52 e ileostomía temporal en 11 (21.2%). La morbilidad fue alta (38.4%), pero grave solo en el 7.7% (Clavien-Dindo IIIb), sin ningún fallecimiento. Hubo cuatro dehiscencias: una de tipo B y tres de tipo C. Se observa una relación directa entre alto riesgo de DA y la práctica de estoma temporal cuando el punto de corte del REAL-score supera el 14.74%. CONCLUSIONES: El REAL-score puede ayudar en la toma de decisiones en la cirugía del cáncer de recto. Por encima de un punto de corte, el riesgo de DA implicaría ileostomía selectiva.

Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice.

Chronic cerebral hypoperfusion due to carotid artery stenosis is a major cause of vascular cognitive impairment and dementia (VCID). Bilateral carotid artery stenosis (BCAS) in rodents is a well-established model of VCID where most studies have focused on white matter pathology and subsequent cognitive deficit. Therefore, our aim was to study the implication of adult hippocampal neurogenesis in hypoperfusion-induced VCID in mice, and its relationship with cognitive hippocampal deficits. Mice were subjected to BCAS; 1 and 3 months later, hippocampal memory and neurogenesis/cell death were assessed, respectively, by the novel object location (NOL) and spontaneous alternation performance (SAP) tests and by immunohistology. Hypoperfusion was assessed by arterial spin labeling-magnetic resonance imaging (ASL-MRI). Hypoperfused mice displayed spatial memory deficits with decreased NOL recognition index. Along with the cognitive deficit, a reduced number of newborn neurons and their aberrant morphology indicated a remarkable impairment of the hippocampal neurogenesis. Both increased cell death in the subgranular zone (SGZ) and reduced neuroblast proliferation rate may account for newborn neurons number reduction. Our data demonstrate quantitative and qualitative impairment of adult hippocampal neurogenesis disturbances associated with cerebral hypoperfusion-cognitive deficits in mice. These findings pave the way for novel diagnostic and therapeutic targets for VCID.

MoS2 Photoelectrodes for Hydrogen Production: Tuning the S-Vacancy Content in Highly Homogeneous Ultrathin Nanocrystals.

Tuning the electrocatalytic properties of MoS2 layers can be achieved through different paths, such as reducing their thickness, creating edges in the MoS2 flakes, and introducing S-vacancies. We combine these three approaches by growing MoS2 electrodes by using a special salt-assisted chemical vapor deposition (CVD) method. This procedure allows the growth of ultrathin MoS2 nanocrystals (1-3 layers thick and a few nanometers wide), as evidenced by atomic force microscopy and scanning tunneling microscopy. This morphology of the MoS2 layers at the nanoscale induces some specific features in the Raman and photoluminescence spectra compared to exfoliated or microcrystalline MoS2 layers. Moreover, the S-vacancy content in the layers can be tuned during CVD growth by using Ar/H2 mixtures as a carrier gas. Detailed optical microtransmittance and microreflectance spectroscopies, micro-Raman, and X-ray photoelectron spectroscopy measurements with sub-millimeter spatial resolution show that the obtained samples present an excellent homogeneity over areas in the cm2 range. The electrochemical and photoelectrochemical properties of these MoS2 layers were investigated using electrodes with relatively large areas (0.8 cm2). The prepared MoS2 cathodes show outstanding Faradaic efficiencies as well as long-term stability in acidic solutions. In addition, we demonstrate that there is an optimal number of S-vacancies to improve the electrochemical and photoelectrochemical performances of MoS2.

Paper-based broadband flexible photodetectors with van der Waals materials.

Layered metal chalcogenide materials are exceptionally appealing in optoelectronic devices thanks to their extraordinary optical properties. Recently, their application as flexible and wearable photodetectors have received a lot of attention. Herein, broadband and high-performance paper-based PDs were established in a very facile and inexpensive method by rubbing molybdenum disulfide and titanium trisulfide crystals on papers. Transferred layers were characterized by SEM, EDX mapping, and Raman analyses, and their optoelectronic properties were evaluated in a wavelength range of 405-810 nm. Although the highest and lowest photoresponsivities were respectively measured for TiS3 (1.50 mA/W) and MoS2 (1.13 µA/W) PDs, the TiS3-MoS2 heterostructure not only had a significant photoresponsivity but also showed the highest on/off ratio (1.82) and fast response time (0.96 s) compared with two other PDs. This advantage is due to the band offset formation at the heterojunction, which efficiently separates the photogenerated electron-hole pairs within the heterostructure. Numerical simulation of the introduced PDs also confirmed the superiority of TiS3-MoS2 heterostructure over the other two PDs and exhibited a good agreement with the experimental results. Finally, MoS2 PD demonstrated very high flexibility under applied strain, but TiS3 based PDs suffered from its fragility and experience a remarkable drain current reduction at strain larger than ± 0.33%. However, at lower strains, all PDs displayed acceptable performances.

Cell-specific RNA purification to study translatomes of mouse central nervous system.

Cell-specific RNA sequencing has revolutionized the study of cell biology. Here, we present a protocol to assess cell-specific translatomes of genetically targeted cell types. We focus on astrocytes and describe RNA purification using RiboTag tools. Unlike single-cell RNA sequencing, this approach allows high sequencing depth to detect low expression genes, and the exploration of RNAs translated in subcellular compartments. Furthermore, it avoids underestimation of transcripts from cells susceptible to cell isolation procedures. The protocol can be applied to a variety of cell types. For complete details on the use and execution of this protocol, please refer to Chai et al. (2017), Díaz-Castro et al. (2021), Díaz-Castro et al. (2019), Srinivasan et al. (2016), and Yu et al. (2018).

Borocarbonitride Layers on Titanium Dioxide Nanoribbons for Efficient Photoelectrocatalytic Water Splitting.

Heterostructures formed by ultrathin borocarbonitride (BCN) layers grown on TiO2 nanoribbons were investigated as photoanodes for photoelectrochemical water splitting. TiO2 nanoribbons were obtained by thermal oxidation of TiS3 samples. Then, BCN layers were successfully grown by plasma enhanced chemical vapour deposition. The structure and the chemical composition of the starting TiS3, the TiO2 nanoribbons and the TiO2-BCN heterostructures were investigated by Raman spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Diffuse reflectance measurements showed a change in the gap from 0.94 eV (TiS3) to 3.3 eV (TiO2) after the thermal annealing of the starting material. Morphological characterizations, such as scanning electron microscopy and optical microscopy, show that the morphology of the samples was not affected by the change in the structure and composition. The obtained TiO2-BCN heterostructures were measured in a photoelectrochemical cell, showing an enhanced density of current under dark conditions and higher photocurrents when compared with TiO2. Finally, using electrochemical impedance spectroscopy, the flat band potential was determined to be equal in both TiO2 and TiO2-BCN samples, whereas the product of the dielectric constant and the density of donors was higher for TiO2-BCN.

The impact of learning opportunities on the development of learning and decision-making: an experiment with passerine birds.

Developmental context has been shown to influence learning abilities later in life, namely through experiments with nutritional and/or environmental constraints (i.e. lack of enrichment). However, little is known about the extent to which opportunities for learning affect the development of animal cognition, even though such opportunities are known to influence human cognitive development. We exposed young zebra finches (Taenopygia guttata) (n = 26) to one of three experimental conditions, i.e. an environment where (i) colour cues reliably predicted the presence of food (associative learning), (ii) a combination of two-colour cues reliably predicted the presence of food (conditional learning), or (iii) colour cues were non-informative (control). After conducting two different discrimination tasks, our results showed that experience with predictive cues can cause increased choice accuracy and decision-making speed. Our first learning task showed that individuals in the associative learning treatment outperformed the control treatment, while task 2 showed that individuals in the conditional learning treatment had shorter latencies when making choices compared with the control treatment. We found no support for a speed-accuracy trade-off. This dataset provides a rare longitudinal and experimental examination of the effect of predictive versus non-predictive cues during development on the cognition of adult animals. This article is part of the theme issue 'Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals'.

Tunable Photodetectors via In Situ Thermal Conversion of TiS3 to TiO2.

In two-dimensional materials research, oxidation is usually considered as a common source for the degradation of electronic and optoelectronic devices or even device failure. However, in some cases a controlled oxidation can open the possibility to widely tune the band structure of 2D materials. In particular, we demonstrate the controlled oxidation of titanium trisulfide (TiS3), a layered semicon-ductor that has attracted much attention recently thanks to its quasi-1D electronic and optoelectron-ic properties and its direct bandgap of 1.1 eV. Heating TiS3 in air above 300 °C gradually converts it into TiO2, a semiconductor with a wide bandgap of 3.2 eV with applications in photo-electrochemistry and catalysis. In this work, we investigate the controlled thermal oxidation of indi-vidual TiS3 nanoribbons and its influence on the optoelectronic properties of TiS3-based photodetec-tors. We observe a step-wise change in the cut-off wavelength from its pristine value ~1000 nm to 450 nm after subjecting the TiS3 devices to subsequent thermal treatment cycles. Ab-initio and many-body calculations confirm an increase in the bandgap of titanium oxysulfide (TiO2-xSx) when in-creasing the amount of oxygen and reducing the amount of sulfur.

Retinal Thickness Changes Over Time in a Murine AD Model APP NL-F/NL-F.

Background: Alzheimer's disease (AD) may present retinal changes before brain pathology, suggesting the retina as an accessible biomarker of AD. The present work is a diachronic study using spectral domain optical coherence tomography (SD-OCT) to determine the total retinal thickness and retinal nerve fiber layer (RNFL) thickness in an APPNL-F/NL-F mouse model of AD at 6, 9, 12, 15, 17, and 20 months old compared to wild type (WT) animals. Methods: Total retinal thickness and RNFL thickness were determined. The mean total retinal thickness was analyzed following the Early Treatment Diabetic Retinopathy Study sectors. RNFL was measured in six sectors of axonal ring scans around the optic nerve. Results: In the APPNL-F/NL-F group compared to WT animals, the total retinal thickness changes observed were the following: (i) At 6-months-old, a significant thinning in the outer temporal sector was observed; (ii) at 15-months-old a significant thinning in the inner temporal and in the inner and outer inferior retinal sectors was noticed; (iii) at 17-months-old, a significant thickening in the inferior and nasal sectors was found in both inner and outer rings; and (iv) at 20-months-old, a significant thinning in the inner ring of nasal, temporal, and inferior retina and in the outer ring of superior and temporal retina was seen. In RNFL thickness, there was significant thinning in the global analysis and in nasal and inner-temporal sectors at 6 months old. Thinning was also found in the supero-temporal and nasal sectors and global value at 20 months old. Conclusions: In the APPNL-F/NL-F AD model, the retinal thickness showed thinning, possibly produced by neurodegeneration alternating with thickening caused by deposits and neuroinflammation in some areas of the retina. These changes over time are similar to those observed in the human retina and could be a biomarker for AD. The APPNL-F/NL-F AD model may help us better understand the different retinal changes during the progression of AD.

Pharmacological Modulation of Neutrophil Extracellular Traps Reverses Thrombotic Stroke tPA (Tissue-Type Plasminogen Activator) Resistance.

Background and Purpose- Recanalization of the occluded artery is a primary goal in stroke treatment. Unfortunately, endovascular treatment is not always available, and tPA (tissue-type plasminogen activator) therapy is limited by its narrow therapeutic window; importantly, the rate of early arterial recanalization after tPA administration is low, especially for platelet-rich thrombi. The mechanisms for this tPA resistance are not well known. Since neutrophil extracellular traps (NETs) have been implicated in this setting, our aim was to study whether NET pharmacological modulation can reverse tPA resistance and the role of TLR4 (Toll-like receptor 4), previously related to NET formation, in thrombosis. Methods- To this goal, we have used a mouse photothrombotic stroke model, which produces a fibrin-free thrombus composed primarily of aggregated platelets and thrombi obtained from human stroke patients. Results- Our results demonstrate that (1) administration of DNase-I, which promotes NETs lysis, but not of tPA, recanalizes the occluded vessel improving photothrombotic stroke outcome; (2) a preventive treatment with Cl-amidine, impeding NET formation, completely precludes thrombotic occlusion; (3) platelet TLR4 mediates NET formation after photothrombotic stroke; and (4) ex vivo fresh platelet-rich thrombi from ischemic stroke patients are effectively lysed by DNase-I. Conclusions- Hence, our data open new avenues for recanalization of platelet-rich thrombi after stroke, especially to overcome tPA resistance.

Lack of the aryl hydrocarbon receptor accelerates aging in mice.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild-type and AhR-null mice along aging to study the relationship between this receptor and age-associated inflammation, termed as "inflammaging," both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels. The absence of AhR also promotes the appearance of brain aging anatomic features, such as the loss of the white matter integrity. In addition, AhR-/- mice present an earlier spatial memory impairment and an enhanced astrogliosis in the hippocampus when compared with their age-matched AhR+/+ controls. Importantly, we have found that AhR protein levels decrease with age in this brain structure, strongly suggesting a link between AhR and aging.-Bravo-Ferrer, I., Cuartero, M. I., Medina, V., Ahedo-Quero, D., Peña-Martínez, C., Pérez-Ruíz, A., Fernández-Valle, M. E., Hernández-Sánchez, C., Fernández-Salguero, P. M., Lizasoain, I., Moro, M. A. Lack of the aryl hydrocarbon receptor accelerates aging in mice.

Validation of a population pharmacokinetic model of adalimumab in a cohort of patients with inflammatory bowel disease.

BACKGROUND: therapeutic monitoring of anti-TNF drugs and anti-drug antibody levels are useful for clinical decision-making, via the rationalization and optimization of the use of anti-TNF treatments. The objective of the present study was to validate the model of Ternant et al., in a cohort of patients with inflammatory bowel diseases (IBD). This model was originally established for patients with rheumatoid arthritis and was used in this study to optimize the adalimumab (ADA) dose and predict ADA trough levels (ATL). METHODS: this study used concentration data points from 30 IBD patients who received ADA treatment between 2014 and 2015. A goodness-of-fit of the model was determined by evaluating the relationship between the observed ATL values and population model-predicted values (PRED) or individual model-predicted values (IPRED). RESULTS: a total of 51 ADA concentration points were analyzed. The bias of the model was 2.39 (95% CI, 1.63-3.15) for PRED and 0.63 (95% CI, 0.23-1.03) for IPRED. The precision was 3.57 (95% CI, 2.90-4.13) and 1.53 (95% CI, 1.22-1.80), respectively. CONCLUSIONS: therapeutic drug monitoring involving ATL may allow the optimization of the treatment of IBD patients. The validation results of the phamacokinectic (PK) model for ADA in IBD patients are inadequate. However, additional studies will strengthen the bias and precision of the model.

Unconventional Approaches to Hydrogen Sorption Reactions: Non-Thermal and Non-Straightforward Thermally Driven Methods.

In the last decades, a broad family of hydrides have attracted attention as prospective hydrogen storage materials of very high gravimetric and volumetric capacity, fast H2 -sorption kinetics, environmental friendliness and economical affordability. However, constraints due to their high activation energies of the different H2 -sorption steps and the Gibbs energy of their reaction with H2 has led to the need of high thermal energy to drive H2 uptake and release. High heat leads to significant degradation effects (recrystallization, phase segregation, nanoparticles agglomeration…) of the hydrides. In this context, this short review aims to summarize alternative non-thermal methods and non-straightforward thermally driven methods to overcome the previous constraints. The phenomenology lying behind these methods, i. e. tribological activation, sonication, and electromagnetic radiation, and the effect of these processes on hydrogen sorption properties of hydrides are described. These non-usual approaches could boost the capability of the next generation of solid-hydride materials for hydrogen conversion in energy sector, in mobile devices and as hydrogen reservoirs.

Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice.

Poststroke cognitive impairment is considered one of the main complications during the chronic phase of ischemic stroke. In the adult brain, the hippocampus regulates both encoding and retrieval of new information through adult neurogenesis. Nevertheless, the lack of predictive models and studies based on the forgetting processes hinders the understanding of memory alterations after stroke. Our aim was to explore whether poststroke neurogenesis participates in the development of long-term memory impairment. Here, we show a hippocampal neurogenesis burst that persisted 1 month after stroke and that correlated with an impaired contextual and spatial memory performance. Furthermore, we demonstrate that the enhancement of hippocampal neurogenesis after stroke by physical activity or memantine treatment weakened existing memories. More importantly, stroke-induced newborn neurons promoted an aberrant hippocampal circuitry remodeling with differential features at ipsi- and contralesional levels. Strikingly, inhibition of stroke-induced hippocampal neurogenesis by temozolomide treatment or using a genetic approach (Nestin-CreERT2/NSE-DTA mice) impeded the forgetting of old memories. These results suggest that hippocampal neurogenesis modulation could be considered as a potential approach for treatment of poststroke cognitive impairment.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease.

AIM: To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. METHODS: In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. RESULTS: Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. CONCLUSIONS: Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.