Spanish validation of the short version of the racing and crowded thoughts questionnaire (RCTQ-13).

BACKGROUND: The Racing and Crowded Thoughts Questionnaire (RCTQ-13) is the most widely used specific scale for the measurement of racing thoughts, but there is currently no Spanish version that allow the evaluation in Spanish-speaking patients. The objective of this study is to translate, adapt, and validate the RCTQ-13 in a Colombian population with affective disorders. METHODS: The questionnaire was translated and back-translated, and corrections were implemented following a pilot test to improve comprehensibility. We included patients with Bipolar I Disorder and with Major depressive disorder seen in three centers in the city of Medellín, Colombia. We evaluate structural validity with confirmatory factor analysis, internal consistency, and test-retest reliability. Construct validity was also assessed with the comparison between euthymic, maniac, and depressive episodes and the correlation with worry, rumination, and mania scales. Responsiveness was measured 1 month after the first evaluation. Based on item response theory (IRT), we also estimated item difficulty, discrimination, and fit using a generalized partial credit model. RESULTS: Two hundred fifty subjects were included. Confirmatory factor analysis revealed that the three-factor structure of the scale was appropriate. Internal consistency was adequate for the entire scale (Cronbach's alpha = 0.95, 95% CI: 0.94-0.96) and for each factor. Test-retest reliability was good (intraclass correlation coefficient = 0.82, 95%IC: 0.70-0.88). For construct validity, we observed differences between patients with different types of affective episodes, a moderate positive correlation with the Penn State Worry Scale (r = 0.55) and the Ruminative Response Scale (r = 0.42), and a low negative correlation with the Young Mania Rating Scale (r = - 0.10). Responsiveness was proved to be adequate. Under IRT, the response thresholds for the response options are organized for all items. The infit was adequate for all items and the outfit was acceptable. CONCLUSIONS: The Spanish version of the RCTQ-13 is a reliable, valid, and responsive scale and can be used for the clinical assessment of the construct of racing and crowded thoughts in patients with the spectrum of affective disorders in whom this experience can be expressed with different nuances. Further research is needed to expand the relationship with rumination and worry.

Unraveling Polyphyly in Flourensia (Asteraceae, Heliantheae, Enceliinae) and the Establishment of a New Genus Austroflourensia.

The monophyly of Flourensia was examined for the first time by sequencing the nuclear ITS and plastid psbA- trnH regions in 18 species of the genus, analyzing them along with representatives of the remaining genera of subtribe Enceliinae. Results showed strong evidence for the polyphyly of Flourensia identifying two well-supported groups: Flourensia, a clade from North America including the type F. laurifolia, and another clade, here designed as the new genus Austroflourensia, containing the South American species. Austroflourensia is related to the other four genera composing the subtribe Enceliinae, whereas Flourensia s.s. is sister to all of them. Austroflourensia can be mainly distinguished by having a shrubby or subshrubby habit, capitula always radiate usually arranged in weakly cymose-corymbose capitulescences, phyllaries 2-3-seriate, and disc corollas shortly dentate. This paper proposes twelve new combinations to accommodate species previously described in the genus Flourensia and provides emended descriptions of Flourensia and the new genus Austroflourensia. The illustration of the type of the new genus, a distribution map, and a key to the genera of Enceliinae are also provided.

Block-based spectral image reconstruction for compressive spectral imaging using smoothness on graphs.

A novel reconstruction method for compressive spectral imaging is designed by assuming that the spectral image of interest is sufficiently smooth on a collection of graphs. Since the graphs are not known in advance, we propose to infer them from a panchromatic image using a state-of-the-art graph learning method. Our approach leads to solutions with closed-form that can be found efficiently by solving multiple sparse systems of linear equations in parallel. Extensive simulations and an experimental demonstration show the merits of our method in comparison with traditional methods based on sparsity and total variation and more recent methods based on low-rank minimization and deep-based plug-and-play priors. Our approach may be instrumental in designing efficient methods based on deep neural networks and covariance estimation.

Efficacy and Safety of Anticonvulsants for the Inpatient Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis.

AIM: To examine the efficacy and safety of antiepileptic drugs (AED) for the inpatient treatment of patients with moderate to severe alcohol withdrawal syndrome (AWS). METHODS: We searched in databases and gray literature to include randomized controlled clinical trials in adults that compare the use of AED versus placebo or any other medication. Studies that did not specify severity or were performed on an outpatient basis were excluded. The outcomes were improvement of symptoms, delirium tremens, seizures and adverse events. Two researchers independently selected the references, extracted the data and assessed the risk of bias. A qualitative synthesis was made and, when the heterogeneity was mild or moderate, a meta-analysis was performed. The quality of the evidence obtained was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: In total, 26 studies with 1709 patients were included. No benefit is described in withdrawal syndrome severity measured by scales or in the development of delirium tremens. The only possible meta-analysis showed that there are no differences in the incidence of seizures (risk ratio [RR] = 1.0; confidence interval (CI) 95% 0.76-1.33), even when compared with placebo (RR = 0.95; CI95% 0.57-1.57). There were also no differences in adverse events, although a higher proportion of some mild cases were described with the use of carbamazepine and valproic acid. CONCLUSIONS: The routine use of AED is not suggested in the treatment of patients with moderate or severe AWS unless indicated for comorbidity (weak recommendation against using moderate quality of evidence).

[Deliberative dialogue with Ibero-American universities on interventions in student mental health during the COVID-19 pandemicDiálogo deliberativo com universidades ibero-americanas sobre intervenções em saúde mental dos estudantes na pandemia de COVID-19]. / Diálogo deliberativo con universidades iberoamericanas sobre intervenciones en salud mental estudiantil durante la pandemia de COVID-19.

Objective: To contextualize a synthesis of evidence on interventions in student mental health during the COVID-19 pandemic through a deliberative dialogue with Ibero-American universities. Methods: An evidence synthesis and synchronous dialogues were previously conducted, consisting of subgroup discussions about the design and implementation of mental health interventions. An analysis of dialogic data was conducted, then organized by topic. Results: Fifty-seven representatives of 17 public and private Ibero-American universities participated in the meeting. In terms of the design of interventions, mental health is perceived as neglected, although its profile was raised by the pandemic. Interventions are guided by detection of needs; scientific evidence is rarely used to design them. Importance was given to forming an interdisciplinary team with continuous training in order to design a specific program that also covers families and teaching/administrative staff. In terms of implementation, problems include saturation of services due to high demand and lack of basic resources among students. Regarding the provision of resources, the influence of the broader context, including the institutional context, is undeniable. The dialogues were perceived as an opportunity to build a new set of interventions. Conclusions: These dialogues enriched the description of interventions already described in the literature on student mental health during the COVID-19 pandemic. However, implementing such interventions in the region means addressing previous neglect and a high level of unmet basic needs.

Objetivo: Contextualizar uma síntese de evidências sobre intervenções em saúde mental de estudantes universitários na pandemia de COVID-19, por meio do diálogo deliberativo com universidades ibero-americanas. Métodos: A partir de uma síntese de evidências previamente elaborada, o diálogo síncrono foi conduzido por meio de discussões em subgrupos sobre o planejamento e a implementação de intervenções em saúde mental. Os dados obtidos foram analisados e resumidos por área temática. Resultados: Cinquenta e sete integrantes de 17 universidades ibero-americanas públicas e privadas participaram do encontro. Os participantes indicaram que a saúde mental é negligenciada no planejamento das intervenções, mas ganhou visibilidade na pandemia. As intervenções são direcionadas às necessidades identificadas e raramente planejadas com base em evidências científicas. Disseram considerar importante formar uma equipe interdisciplinar com capacitação contínua para planejar um programa específico que englobe também familiares e o corpo docente e administrativo. Implementar intervenções é complicado porque os serviços estão sobrecarregados devido à grande demanda e à falta de recursos básicos para os estudantes. O contexto macro e institucional claramente influencia a disponibilização de recursos. O diálogo foi visto como uma oportunidade para consolidar um novo conjunto de intervenções. Conclusões: O presente diálogo contribuiu para enriquecer a literatura de intervenções de saúde mental para estudantes universitários na pandemia de COVID-19. Implementar intervenções no nosso contexto requer sanar as falhas por negligência passada e as enormes necessidades básicas não atendidas.

Impact of lifestyle in prostate cancer patients. What should we do?

OBJECTIVE: This review aimed to analyze interventions raised within primary and tertiary prevention concerning the disease's incidence, progression, and recurrence of Prostate Cancer (PCa). Priority was given to the multidisciplinary approach of PCa patients with an emphasis on modifiable risk factors. MATERIALS AND METHODS: We conducted a comprehensive literature review in the following databases: Embase, Central, and Medline. We included the most recent evidence assessing cohort studies, case-control studies, clinical trials, and systematic reviews published in the last five years. We only included studies in adults and in vitro or cell culture studies. The review was limited to English and Spanish articles. RESULTS: Preventive interventions at all levels are the cornerstone of adherence to disease treatment and progression avoidance. The relationship in terms of healthy lifestyles is related to greater survival. The risk of developing cancer is associated to different eating habits, determined by geographic variations, possibly related to different genetic susceptibilities. DISCUSSION: PCa is the second most common cancer in men, representing a leading cause of death among men in Latin America. Prevention strategies and healthy lifestyles are associated with higher survival rates in PCa patients. Also, screening for anxiety and the presence of symptoms related to mood disorders is essential in the patient's follow-up concerning their perception of the condition.

Lifting the Bar: A Relationship-Orienting Intervention Reduces Recidivism Among Children Reentering School From Juvenile Detention.

When children return to school from juvenile detention, they face a severe stigma. We developed a procedure to orient educators and students toward each other as positive relationship partners during this period. In Study 1, through a structured exercise, students reentering school powerfully articulated to an educator of their choosing their prosocial hopes for school as well as challenges they faced. In a preliminary field trial (N = 47), presenting this self-introduction to this educator in a one-page letter via a third-party requesting the educator's help reduced recidivism to juvenile detention through the next semester from 69% to 29%. In Study 2 (preregistered), the letter led experienced teachers (N = 349) to express greater commitment to, anticipate more success for, and feel more love and respect for a student beginning their reentry into school, potentially initiating a better trajectory. The results suggest how relationship-orienting procedures may sideline bias and make school more supportive for students facing stigma.

Molecular mechanisms for understanding the association between TMPRSS2 and beta coronaviruses SARS-CoV-2, SARS-CoV and MERS-CoV infection: scoping review.

The aim of this scoping review was to identify knowledge gaps and to describe the current state of the research on the association between TMPRSS2 and the essential beta coronaviruses (Beta-CoVs) infection and the molecular mechanisms for this association. We searched MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). We included 13 studies. Evidence shows an essential role of TMPRSS2 in Spike protein activation, entry, and spread into host cells. Co-expression of TMPRSS2 with cell surface receptors (ACE2 or DPP4) increased virus entry. This serine protease is involved in the formation of large syncytia between infected cells. TMPRSS2 cleaved the Spike protein of SARS-CoV, SARS-CoV-2, and MERS-CoV, and increased virus propagation. Accumulating evidence suggests that TMPRSS2 is an essential protease for virus replication. We highlighted its critical molecular role in membrane fusion and the impact in viral mRNA replication, then promoting/driving pathogenesis and resistance.

Normal values for respiratory sleep polygraphy in children aged 4 to 9 years at 2,560 m above sea level.

Obstructive sleep apnea syndrome affects 1%-4% of all children worldwide. Currently, diagnosis of obstructive sleep apnea is based on sea-level guidelines, without taking into account the altitude at which the populations live. It has been shown that at 3,200 m of altitude there is an increase in obstructive events in healthy children aged 7 to 16 years; on the other hand, it is known that SpO2 dispersion between individuals becomes wider as altitude increases, a phenomenon that is more marked during sleep. About 17 million Colombians live in regions between 2,500 m and 2,700 m, as do significant populations in other Latin American countries. This research aimed to characterize respiratory polygraphy sleep parameters in healthy, non-snoring children aged 4-9 years living at 2,560 m. We carried out home respiratory polygraphy in 32 children with a mean age of 6.2 years (range 4-9 years). The average recorded sleep time was 7.8 h, the median apnea-hypopnea index was 9.2/h, the obstructive apnea-hypopnea index had a median of 8.8/h (p5 4.2 to p95 17.9) and central apnea a median of 0.4/h. The median SpO2 was 93% (p5 90.5 to p95 94) and transcutaneous CO2 had a median of 39.4 mmHg (p531.7 to p95 42.3). The median oxygen desaturation index ≥ 3% was 11.2 and median oxygen desaturation index ≥ 4% was 3.9. Normal measurements for respiratory polygraphy obtained at sea level do not apply to children at altitude. If such guidelines are used, obstructive sleep apnea will be over-diagnosed, resulting in unnecessary adenotonsillectomies, among other interventions.

Immunonutrition hope? Oral nutritional supplement on cancer treatment.

OBJECTIVES: To determine the efficacy and safety of antitumoral nutritional supplement (Oncoxin® ), and to describe its mechanism of action. METHODS: Scoping review according to the recommendations of the Joanna Briggs Institute included patients older than 18 years who have any kind of tumour and receive Oncoxin® as a supplement regarding the efficacy in terms of antitumoral properties, quality of life and survival, safety in terms of adverse events, and the mechanism of action. With no limit for language or setting, MEDLINE (Pubmed), EMBASE (Scopus), LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception to May 2021. FINDINGS: A promising increment of survival and quality of life in terms of Karnofsky and EORTC scales. Regarding the mechanism of action, studies suggest that it modifies inflammatory mediators' expression, as evidenced by the reduction of COX-2, IL-1ß, IL-6, TNF-α, IL-1ß, IL-12 and IFN-γ. Besides, it promotes an arrest in the progression of cells from G1 into S, along with an increase in p27 and a decrease in cyclin D1 and pRb. It decreases the levels of pro-inflammatory cytokines, it can also decrease cytokines with antitumor activity such as IFN-γ, which should be further explored in larger trials and the long term. INTERPRETATIONS AND IMPLICATIONS: Current literature shows promising complementary effects of oral supplements to the standard treatment of cancer patients in diverse scenarios. It might help patients to deal with toxicities and adverse effects related to cancer treatment and improve their nutritional or clinical profiles.

Outpatient Physical Therapy for Functional Neurological Disorder: A Preliminary Feasibility and Naturalistic Outcome Study in a U.S. Cohort.

OBJECTIVE: Despite promising research and consensus recommendations on the important therapeutic role of physical therapy for motor functional neurological disorder (FND), little is known about the feasibility and potential efficacy of implementing physical therapy for this population in a U.S.-based outpatient program. Given health care system differences internationally, this is an important gap in the literature. METHODS: In this retrospective cohort study, the authors investigated the relationship between treatment adherence and clinical outcome in a hospital-based outpatient physical therapy clinical program. Medical records of 50 consecutive patients with motor FND referred from an FND clinical program were reviewed. The physical therapy intervention included a 1-hour initial assessment and the development of individualized treatment plans guided by published consensus recommendations. Statistical analyses included nonparametric, univariate screening tests followed by multivariate regression analyses. RESULTS: In univariate analyses, there was a statistically significant positive correlation between the number of sessions attended and clinical improvement. This relationship held when adjusting for demographic variables, concurrent psychogenic nonepileptic seizures, and other major neurological comorbidities. In a post hoc analysis of the subset of individuals with available gait speed data, posttreatment 10-meter gait speed times improved compared with baseline measurements. Baseline neuropsychiatric factors did not correlate with clinical improvement. CONCLUSIONS: This preliminary, retrospective cohort study demonstrated that treatment adherence to a U.S.-based outpatient physical therapy program was associated with clinical improvement. Prospective observational and randomized controlled trials are needed to further optimize physical therapy for patients with functional motor symptoms in the outpatient setting.

Alternative techniques in cochlear implant surgery: Subtotal petrosectomy.

OBJECTIVES: To report and analyze three cases of subtotal petrosectomy (SP) in cochlear implant surgery at our institution, and establish the indications, surgical technique and complications encountered. MATERIALS AND METHOD: A retrospective descriptive study is proposed, analyzing a series of three clinical cases of subtotal petrosectomy as surgical technique for cochlear implant surgery at San Ignacio University Hospital (Bogotá, Colombia) from year 2004 to 2019. RESULTS: A total of three cases of subtotal petrosectomy as surgical technique in cochlear implant candidates were analyzed. The indications were the presence of a wide mastoid cavity after canal wall down mastoidectomy, extrusion of the electrode into the external auditory canal with a wide mastoid cavity and erosion of the posterior wall of the ear canal, and the presence of cholesteatoma in a cophotic ear with previous surgery. The ear canal was defunctionalized in all three cases; in two of them with obliteration of the Eustachian tube and in none of the cases the mastoid was obliterated. There was a single complication associated with the procedure corresponding to a small retention cholesteatoma in the skin of the obliterated duct sac, that didn't required surgical intervention. CONCLUSION: Subtotal petrosectomy is a surgical alternative for cochlear implant surgery in patients with chronic ear pathology, wide cavities or cochlear implant extrusion, not associated to significant complications.

The Effects of Positive Psychological Interventions on Medical Patients' Anxiety: A Meta-analysis.

OBJECTIVE: Positive psychology interventions, which involve systematic completion of activities designed to promote well-being, are being increasingly studied in medically ill patients. However, the extent to which these interventions ameliorate patient anxiety remains unclear. Therefore, the aim of the study was to conduct a meta-analysis to determine the efficacy of positive psychology interventions in reducing anxiety in medical patients. METHODS: Electronic databases Medline, PsycINFO, SciELO, Cochrane (Central), and ClinicalTrials.gov were searched from inception to June 18, 2018, to identify studies of positive psychology interventions that included a validated measure of anxiety as an outcome measure. RESULTS: The search generated a total of 1024 studies. Twelve randomized controlled trials (n = 1131) delivered to medical patients were included in the review, and a further 11 nonrandomized trials (n = 300) were included in a secondary analysis. Positive psychology interventions were effective at reducing patient anxiety relative to a control with a small to medium effect size (g = -0.34, 95% confidence interval = -0.50 to -0.18), and results were maintained at a mean of 8-week follow-up (g = -0.31, 95% confidence interval = -0.54 to -0.08). Clinician-led interventions seemed to be more effective than self-administered interventions, and longer interventions were more effective than shorter interventions. Secondary analysis of nonrandomized trials also found that positive psychology interventions are associated with reduced anxiety. CONCLUSIONS: Positive psychology interventions seem to be effective at reducing medical patient anxiety. Future research is needed to determine optimal intervention characteristics, including dose and intervention content, that maximize the observed treatment effects.

Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder.

OBJECTIVE: Some individuals with functional neurological disorder (FND) exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. Given that the multimodal integration network (insula, dorsal cingulate, temporoparietal junction (TPJ)) is implicated in convergent sensorimotor, affective and interoceptive processing, we hypothesised that patients with FND would exhibit altered motor and amygdalar resting-state propagation to this network. Patient-reported symptom severity and clinical outcome were also hypothesised to map onto multimodal integration areas. METHODS: Between-group differences in primary motor and amygdalar nuclei (laterobasal, centromedial) were examined using graph-theory stepwise functional connectivity (SFC) in 30 patients with motor FND compared with 30 healthy controls. Within-group analyses correlated functional propagation profiles with symptom severity and prospectively collected 6-month outcomes as measured by the Screening for Somatoform Symptoms Conversion Disorder subscale and Patient Health Questionnaire-15 composite score. Findings were clusterwise corrected for multiple comparisons. RESULTS: Compared with controls, patients with FND exhibited increased SFC from motor regions to the bilateral posterior insula, TPJ, middle cingulate cortex and putamen. From the right laterobasal amygdala, the FND cohort showed enhanced connectivity to the left anterior insula, periaqueductal grey and hypothalamus among other areas. In within-group analyses, symptom severity correlated with enhanced SFC from the left anterior insula to the right anterior insula and TPJ; increased SFC from the left centromedial amygdala to the right anterior insula correlated with clinical improvement. Within-group associations held controlling for depression, anxiety and antidepressant use. CONCLUSIONS: These neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.

Fearful Attachment Linked to Childhood Abuse, Alexithymia, and Depression in Motor Functional Neurological Disorders.

Insecure attachment is a predisposing risk factor for the development of functional neurological disorder (FND). There is limited research investigating connections between attachment styles, other predisposing vulnerabilities, and symptom severity in patients with motor FND. By using a within-group design with prospective data collection, the authors performed univariate tests followed by multivariate linear regressions to investigate neuropsychiatric factors associated with four attachment styles (secure, fearful, preoccupied, and dismissing) among 56 patients with motor FND (mean age=40.2 years [SD=13.0]; women, N=41; men, N=15). In univariate analyses, fearful attachment style was associated with self-reported adverse life event burden, alexithymia, dissociation, depression, anxiety, impaired stress coping skills, functional neurologic symptom severity, and marital status. In a multivariate stepwise linear regression analysis, childhood abuse, alexithymia, depression, and not being married independently predicted fearful attachment. In a post hoc analysis, childhood sexual and emotional abuse were each independently associated with fearful attachment tendencies. There were no independent predictors of secure, preoccupied, or dismissing attachment styles in this study population. Future studies with larger cohorts are needed to investigate nuanced relationships among predisposing vulnerabilities for the development of FND, as well as potential links between risk factors, functional neurologic symptom severity, and clinical outcomes.

Secure Attachment and Depression Predict 6-Month Outcome in Motor Functional Neurological Disorders: A Prospective Pilot Study.

BACKGROUND: The relationships between baseline neuropsychiatric factors and clinical outcome in patients with functional neurological disorder (FND)/conversion disorder remain poorly understood. OBJECTIVE: This prospective, naturalistic pilot study investigated links between predisposing vulnerabilities (risk factors) and clinical outcome in patients with motor FND engaged in usual care within a subspecialty FND clinic. METHODS: Thirty-four patients with motor FND were enrolled and completed baseline and 6-month follow-up psychometric questionnaires. Univariate screening tests followed by multivariate linear regression analyses were used to investigate neuropsychiatric predictors of 6-month clinical outcome in patients with motor FND. RESULTS: In univariate analyses, baseline secure attachment traits and depression as measured by the Relationship Scales Questionnaire and Beck Depression Inventory-II positively correlated with improved Patient Health Questionnaire-15 scores. In a multivariate linear regression analysis adjusting for the interval time between baseline and follow-up data collection, baseline secure attachment and depression scores independently predicted improvements in Patient Health Questionnaire-15 scores. In additional analyses, patients with a diagnosis of psychogenic nonepileptic seizures compared to individuals with other motor FND subtypes showed a trend toward worse 6-month physical health outcomes as measured by the Short Form Health Survey-36. CONCLUSION: Future large-scale, multi-site longitudinal studies are needed to comprehensively investigate neuropsychiatric predictors of clinical outcome in patients with motor FND, including functional weakness, functional movement disorders, and psychogenic nonepileptic seizures.

A Cross Talk between Neuronal Urokinase-type Plasminogen Activator (uPA) and Astrocytic uPA Receptor (uPAR) Promotes Astrocytic Activation and Synaptic Recovery in the Ischemic Brain.

Urokinase-type plasminogen activator (uPA) is a serine proteinase that, upon binding to its receptor (uPAR), catalyzes the conversion of plasminogen into plasmin on the cell surface. Our previous studies indicate that uPA and uPAR expression increase in the ischemic brain during the recovery phase from an acute ischemic injury and that uPA binding to uPAR promotes neurological recovery after an acute ischemic stroke. Here, we used male mice genetically deficient on either uPA (uPA-/-) or uPAR (uPAR-/-) or with a four-amino acid substitution into the growth factor domain of uPA that abrogates its binding to uPAR (PlatGFDhu/GFDhu) to investigate the mechanism whereby uPA promotes neurorepair in the ischemic brain. We found that neurons release uPA and astrocytes recruit uPAR to their plasma membrane during the recovery phase from a hypoxic injury and that binding of neuronal uPA to astrocytic uPAR induces astrocytic activation by a mechanism that does not require plasmin generation, but instead is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2)-regulated phosphorylation of the signal transducer and activator of transcription 3 (STAT3). We report that uPA/uPAR binding is necessary and sufficient to induce astrocytic activation in the ischemic brain and that astrocytes activated by neuronal uPA promote synaptic recovery in neurons that have suffered an acute hypoxic injury via a mechanism mediated by astrocytic thrombospondin-1 (TSP1) and synaptic low-density lipoprotein receptor-related protein-1 (LRP1). In summary, we show that uPA/uPAR-induced astrocytic activation mediates a cross talk between astrocytes and injured neurons that promotes synaptic recovery in the ischemic brain.SIGNIFICANCE STATEMENT To date, there is no therapeutic strategy to promote synaptic recovery in the injured brain. Here, we show that neurons release urokinase-type plasminogen activator (uPA) and astrocytes recruit the uPA receptor (uPAR) to their plasma membrane during the recovery phase from a hypoxic injury. We found that binding of neuronal uPA to astrocytic uPAR promotes astrocytic activation and that astrocytes activated by uPA-uPAR binding promote synaptic recovery in neurons that have suffered a hypoxic injury by a mechanism that does not require plasmin generation, but instead is mediated by ERK1/2-regulated STAT3 phosphorylation, astrocytic thrombospondin-1 (TSP1) and synaptic low-density lipoprotein receptor-related protein-1 (LRP1). Our work unveils a new biological function for uPA-uPAR as mediator of a neuron-astrocyte cross talk that promotes synaptic recovery in the ischemic brain.

Haralick textural features on T2 -weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer.

PURPOSE: To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. MATERIALS AND METHODS: In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T2 -weighted sequences (T2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. RESULTS: Three T2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T2 -w contrast, T2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. CONCLUSION: T2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:103-117.

Stratifying the potential local transmission of Zika in municipalities of Antioquia, Colombia.

OBJECTIVE: To stratify and understand the potential transmission processes of Zika virus in Colombia, in order to effectively address the efforts on surveillance and disease control. METHODS: We compare R0 of Zika for municipalities based on data from the regional surveillance system of Antioquia, Colombia. The basic reproduction number (R0 ) and its 95% confidence intervals were estimated from an SIR model with implicit vector dynamics, in terms of recovered individuals in each time unit, using an approximate solution. These parameters were estimated fitting the solution of the model to the daily cumulative frequency of each Zika case according to symptoms onset date relative to the index case reported to the local surveillance system. RESULTS: R0 was estimated for 20 municipalities with a median of 30 000 inhabitants, all located less than 2200 m above sea level. The reported cases ranged from 17 to 347 between these municipalities within 4 months (January to April of 2016). The results suggest that 15 municipalities had a high transmission potential (R0  > 1), whereas in five municipality transmissions were potentially not sustaining (R0  < 1), although the upper bound of the confidence interval of the R0 for 3 of these 5 was greater than one, indicating the possibility of an outbreak later on. CONCLUSION: The study identified high-risk municipalities (R0  > 1) and provide a technique to optimise surveillance and control of Zika. Health authorities should promote the collection, analysis, modelling and sharing of anonymous data onto individual cases to estimate R0 .