Quality assurance of radiation therapy after breast-conserving surgery among patients in the BOOG 2013-08 trial.

BACKGROUND AND PURPOSE: In the BOOG 2013-08 trial (NCT02271828), cT1-2N0 breast cancer patients were randomized between breast conserving surgery with or without sentinel lymph node biopsy (SLNB) followed by whole breast radiotherapy (WBRT). While awaiting primary endpoint results (axillary recurrence rate), this study aims to perform a quality assurance analysis on protocol adherence and (incidental) axillary radiation therapy (RT) dose. MATERIALS AND METHODS: Patients were enrolled between 2015 and 2022. Data on prescribed RT and (in 25% of included patients) planning target volumes (PTV) parameters were recorded for axillary levels I-IV and compared between treatment arms. Multivariable linear regression analysis was performed to determine prognostic variables for incidental axillary RT dose. RESULTS: 1,439/1,461 included patients (98.5%) were treated according to protocol and 87 patients (5.9%) received regional RT (SLNB 10.9%, no-SLNB 1.5 %). In 326 patients included in the subgroup analysis, the mean incidental PTV dose at axilla level I was 59.5% of the prescribed breast RT dose. In 5 patients (1.5%) the mean PTV dose at level I was ≥95% of the prescribed breast dose. No statistically or clinically significant differences regarding incidental axillary RT dose were found between treatment arms. Tumour bed boost (yes/no) was associated with a higher incidental mean dose in level I (R2 = 0.035, F(6, 263) = 1.532, p 0.168). CONCLUSION: The results indicate that RT-protocol adherence was high, and that incidental axillary RT dose was low in the BOOG 2013-08 trial. Potential differences between treatmentarms regarding the primary endpoint can thus not be attributed to different axillary radiation doses.

Navigating job and cancer demands during treatment: A qualitative study of ovarian cancer patients.

OBJECTIVE: Our objective was to obtain perspectives from ovarian cancer patients on job demands, cancer demands, and workplace or cancer resources and strategies to manage the cancer-work interface using the cancer-work management conceptual framework. METHODS: We recruited ovarian cancer patients receiving systemic therapy who screened positive for financial distress using Comprehensive Score for Financial Toxicity <26. Interviews were conducted with participants about their costs of care, including employment concerns. Interviews were recorded, transcribed verbatim, and analyzed by three researchers using an inductive thematic analysis. RESULTS: Of 22 participants, the average age was 57 years old, 36% were Black, 68% had income <$40,000, 41% had public insurance, and 68% were being treated for recurrent disease. Job demands included decreased productivity, inability to return to work, and worry about losing a job or employer-based health insurance coverage. Cancer demands included physical and cognitive limitations due to cancer treatment and reliance on caregivers, especially for transportation. Workplace resources/strategies including having a supportive employer, modifying job responsibilities, and utilizing family medical leave. Cancer care resources/strategies included planning appointments ahead of time and utilizing resources, such as disability. CONCLUSIONS: Cancer care teams should consider screening patients for employment concerns; streamline care to minimize the side effects, time, and transportation demands of treatment on patients and caregivers; maximize utilization of available resources; and proactively communicate with employers to accommodate patients and caregivers who want or need to work.

Multi-center bonds as resonance hybrids: A real space perspective.

The concept of distinct bonds within molecules has proven to be successful in rationalizing chemical reactivity. However, bonds are not a well-defined physical concept, but rather vague entities, described by different and often contradicting models. With probability density analysis, which can-in principle-be applied to any wave function, bonds are recovered as spin-coupled positions within most likely electron arrangements in coordinate space. While the wave functions of many systems are dominated by a single electron arrangement that is built from two-center two-electron bonds, some systems require several different arrangements to be well described. In this work, a range of these multi-center bonded molecules are classified and investigated with probability density analysis. The results are compared with valence bond theory calculations and data from collision-induced dissociation experiments.

Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis.

Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments.

Modulating medial prefrontal cortex activity using real-time fMRI neurofeedback: Effects on reality monitoring performance and associated functional connectivity.

Neuroimaging studies have found 'reality monitoring', our ability to distinguish internally generated experiences from those derived from the external world, to be associated with activity in the medial prefrontal cortex (mPFC) of the brain. Here we probe the functional underpinning of this ability using real-time fMRI neurofeedback to investigate the involvement of mPFC in recollection of the source of self-generated information. Thirty-nine healthy individuals underwent neurofeedback training in a between groups study receiving either Active feedback derived from the paracingulate region of the mPFC (21 subjects) or Sham feedback based on a similar level of randomised signal (18 subjects). Compared to those in the Sham group, participants receiving Active signal showed increased mPFC activity over the course of three real-time neurofeedback training runs undertaken in a single scanning session. Analysis of resting state functional connectivity associated with changes in reality monitoring accuracy following Active neurofeedback revealed increased connectivity between dorsolateral frontal regions of the fronto-parietal network (FPN) and the mPFC region of the default mode network (DMN), together with reduced connectivity within ventral regions of the FPN itself. However, only a trend effect was observed in the interaction of the recollection of the source of Imagined information compared with recognition memory between participants receiving Active and Sham neurofeedback, pre- and post- scanning. As such, these findings demonstrate that neurofeedback can be used to modulate mPFC activity and increase cooperation between the FPN and DMN, but the effects on reality monitoring performance are less clear.

Patient-reported outcomes of ductoscopy procedures for pathologic nipple discharge.

BACKGROUND: Pathologic nipple discharge (PND) is a common complaint often associated with breast cancer. However, when ultrasound and mammography are negative, the chances of malignancy are lower than 5%. Currently, major duct excision and microdochectomy are often recommended to alleviate symptoms and definitely rule out malignancy, but can cause infections and breastfeeding problems. Ductoscopy is a minimally invasive endoscopy technique that allows visualization of the mammary ducts and may not only obviate surgery but also detect malignancy. The aim of this study was to determine quality of life (QOL) after ductoscopy in patients with PND. MATERIALS AND METHODS: All PND patients referred for ductoscopy between 2014 and 2015 to our hospital were included. Ductoscopy procedures were performed under local anaesthesia in the outpatient clinic. Patients were asked to fill out questionnaires (Breast-Q, EQ-5D-5L and SF-36) on the day of ductoscopy, and after 2 weeks, 3 and 6 months. Additionally, we performed reliability analysis to determine if these questionnaires were suitable for PND patients. RESULTS: Fifty consecutive patients underwent ductoscopy of whom 47 patients participated in this study. One domain of SF-36 (vitality) varied significantly over time. Breast-Q, SF-36 and EQ-5D-5L showed that QOL after ductoscopy for PND was unaffected by ductoscopy. Success of the ductoscopy procedure was a significant predictor for satisfaction with the result domain. CONCLUSION: Ductoscopy is a minimally invasive technique that does not seem to impact QoL of PND patients over time. Breast-Q, SF-36 and EQ-5D-5L seem to be suitable existing QOL tests for PND patients undergoing ductoscopy, whereas SF-36 would require modifications.

Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.

Inherited cutis laxa, or inelastic, sagging skin is a genetic condition of premature and generalised connective tissue ageing, affecting various elastic components of the extracellular matrix. Several cutis laxa syndromes are inborn errors of metabolism and lead to severe neurological symptoms. In a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability we performed exome sequencing to elucidate the underlying genetic defect. We identified the amino acid substitution R275W in phosphatidylinositol 4-kinase type IIα, caused by a homozygous missense mutation in the PI4K2A gene. We used lipidomics, complexome profiling and functional studies to measure phosphatidylinositol 4-phosphate synthesis in the patient and evaluated PI4K2A deficient mice to define a novel metabolic disorder. The R275W residue, located on the surface of the protein, is involved in forming electrostatic interactions with the membrane. The catalytic activity of PI4K2A in patient fibroblasts was severely reduced and lipid mass spectrometry showed that particular acyl-chain pools of PI4P and PI(4,5)P2 were decreased. Phosphoinositide lipids play a major role in intracellular signalling and trafficking and regulate the balance between proliferation and apoptosis. Phosphatidylinositol 4-kinases such as PI4K2A mediate the first step in the main metabolic pathway that generates PI4P, PI(4,5)P2 and PI(3,4,5)P3 . Although neurologic involvement is common, cutis laxa has not been reported previously in metabolic defects affecting signalling. Here we describe a patient with a complex neurological phenotype, premature ageing and a mutation in PI4K2A, illustrating the importance of this enzyme in the generation of inositol lipids with particular acylation characteristics.

De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study.

PURPOSE: An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST). METHODS: Patients with cT1-4N0-3 breast cancer treated with NST (2006-2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients. RESULTS: A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00-1.02), year of diagnosis (OR 0.47, CI 0.44-0.50), HER2-positive disease (OR 0.62, CI 0.52-0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06-1.65, T3 vs. T1 OR 2.04, CI 1.58-2.63, T4 vs. T1 OR 6.37, CI 4.26-9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28-2.12) were correlated with performing ALND in cN+ patients. CONCLUSIONS: ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Gas phase dynamics, conformational transitions and spectroscopy of charged saccharides: the oxocarbenium ion, protonated anhydrogalactose and protonated methyl galactopyranoside.

Protonated intermediates are postulated to be involved in the rate determining step of many sugar reactions. This paper presents a study of protonated sugar species, isolated in the gas phase, using a combination of infrared multiple photon dissociation (IRMPD) spectroscopy, classical ab initio molecular dynamics (AIMD) and quantum mechanical vibrational self-consistent field (VSCF) calculations. It provides a likely identification of the reactive intermediate oxocarbenium ion structure in a d-galactosyl system as well as the saccharide pyrolysis product anhydrogalactose (that suggests oxocarbenium ion stabilization), along with the spectrum of the protonated parent species: methyl d-galactopyranoside-H+. Its vibrational fingerprint indicates intramolecular proton sharing. Classical AIMD simulations for galactosyl oxocarbenium ions, conducted in the temperature range ∼300-350 K (using B3LYP potentials on-the-fly) reveal efficient transitions on the picosecond timescale. Multiple conformers are likely to exist under the experimental conditions and along with static VSCF calculations, they have facilitated the identification of the individual structural motifs of the galactosyl oxocarbenium ion and protonated anhydrogalactose ion conformers that contribute to the observed experimental spectra. These results demonstrate the power of experimental IRMPD spectroscopy combined with dynamics simulations and with computational spectroscopy at the anharmonic level to unravel conformer structures of protonated saccharides, and to provide information on their lifetimes.

Working memory moderates the association between condom use intentions and behavior among moderate-to-heavy drinking men who have sex with men.

Men who have sex with men (MSM) are a high-risk population for HIV infection and this risk is increased for those who consume alcohol. Condomless anal intercourse (CAI) is the central transmission risk factor for this population. This study examined whether individual differences in working memory moderated the association between intentions to use condoms and the frequency of CAI among MSM who engaged in anal intercourse over a subsequent 6-week period. Moderate- and heavy-drinking MSM (n = 207) completed questionnaires regarding alcohol use and condom use intentions and an operation span task to assess working memory at baseline. Participants then completed 6 weeks of morning surveys via a mobile phone app to assess anal intercourse frequency with and without condoms. Negative binomial regression analyses showed that the association between intentions to use condoms and episodes of CAI during the monitoring period was moderated by working memory such that intentions predicted CAI for those high in working memory but not those low in working memory. These results support the view that self-reported intentions may be less-likely to translate into health behaviors among those with poorer executive functioning skills.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology.

The development of new therapies to slow down or halt the progression of Parkinson's disease is a health care priority. A key pathological feature is the presence of alpha-synuclein aggregates, and there is increasing evidence that alpha-synuclein propagation plays a central role in disease progression. Consequently, the downregulation of alpha-synuclein is a potential therapeutic target. As a chronic disease, the ideal treatment will be minimally invasive and effective in the long-term. Knockdown of gene expression has clear potential, and siRNAs specific to alpha-synuclein have been designed; however, the efficacy of siRNA treatment is limited by its short-term efficacy. To combat this, we designed shRNA minicircles (shRNA-MCs), with the potential for prolonged effectiveness, and used RVG-exosomes as the vehicle for specific delivery into the brain. We optimized this system using transgenic mice expressing GFP and demonstrated its ability to downregulate GFP protein expression in the brain for up to 6 weeks. RVG-exosomes were used to deliver anti-alpha-synuclein shRNA-MC therapy to the alpha-synuclein preformed-fibril-induced model of parkinsonism. This therapy decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons, and improved the clinical symptoms. Our results confirm the therapeutic potential of shRNA-MCs delivered by RVG-exosomes for long-term treatment of neurodegenerative diseases.

Barriers to front propagation in laminar, three-dimensional fluid flows.

We present experiments on one-way barriers that block reaction fronts in a fully three-dimensional (3D) fluid flow. Fluorescent Belousov-Zhabotinsky reaction fronts are imaged with laser-scanning in a laminar, overlapping vortex flow. The barriers are analyzed with a 3D extension to burning invariant manifold (BIM) theory that was previously applied to two-dimensional advection-reaction-diffusion processes. We discover tube and sheet barriers that guide the front evolution. The experimentally determined barriers are explained by BIMs calculated from a model of the flow.

Cytomorphology and sonographic features of ectopic thymic tissue diagnosed in paediatric FNA biopsies.

INTRODUCTION: Ectopic thymic tissue can arise as an asymptomatic neck mass, which may be detected on imaging studies. The aim of this study was to determine the incidence of ectopic thymic tissue in paediatric FNAs and to the correlate clinical, radiological and cytomorphological findings. METHODS: FNAs in children with neck and mediastinal lesions performed between January 2012 and July 2016 were reviewed for cases of ectopic thymus. These were then evaluated and correlated with the cytology findings. RESULTS: Of 739 FNAs, 13 (1.8%) cases from 11 patients showed ectopic thymic tissue. The targeted lesions were in the thyroid (n = 7), submandibular region (n = 1), superior mediastinum (n = 1) and paratracheal region (n = 1). The most common indication was for microcalcifications concerning for papillary thyroid carcinoma on ultrasound (n = 6). Imaging findings included fusiform lesions with linear and punctuate bright echoes. The cytology evaluation showed small lymphocytes with discohesive epithelioid cells in most cases, and proteinaceous fluid in the cystic case. There were rare macrophages and Hassall's corpuscles. Flow cytometry and/or immunostains were performed in all cases, supporting thymic origin. CONCLUSION: Ectopic thymic tissue is rarely present as a neck mass or thyroid nodule on FNA biopsy. The ultrasound imaging findings reveal a well-defined fusiform lesion with punctate bright echoes that could be misinterpreted as papillary thyroid carcinoma. The aspirates show a small lymphoid population, immunophenotypically compatible with thymic T-cells, in addition to scattered epithelial cells. Therefore, knowledge of the typical ultrasonographic and cytopathological features can help make a definitive diagnosis and avoid more invasive procedures in paediatric patients.

Spanish version validation of the Marihuana Motives Measure in a drug-consuming adolescent sample. / Propiedades psicométricas de la versión española del Marihuana Motives Measure en población adolescente consumidora.

INTRODUCTION: Cannabis is the illicit drug mostly widely consumed by adolescents in Spain. The understanding of consumption motives is an important factor for intervention. In Spain, there are no available instruments for their evaluation, hence, the goal of this paper is to study the psychometric properties of the Marihuana Motives Measure (MMM) in a sample of adolescent consumers. MATERIAL AND METHOD: Firstly, translation and back-translation was performed. A total of 228 adolescent consumers of cannabis were evaluated. Factorial analysis was conducted, and the reliability of the total scores and of each scale of the questionnaire was studied through Cronbach's alpha. Test-retest reliability was analyzed through interclass correlations. Validity evidence of the MMM was examined through correlations between current cannabis use, subjective consumption effects measured with the Addiction Research Center Inventory (ARCI), and personality measured with the Millon Adolescent Clinical Inventory (MACI). RESULTS: High reliability was observed in total score of the MMM (Cronbach α = .86), and high and moderate reliability for each of the five factors obtained in the factorial analysis of the MMM, Social = .82, Enhancement = .72, Coping = .83, Expansion = .74, and Conformity = .64. Significant correlations were also observed between cannabis consumption motives and subjective effects, and between consumption motives and personality. CONCLUSION: The Spanish version of the MMM shows a similar factorial structure as the one obtained by the original author, and its measures are reliable and valid for the study of cannabis consumption motives in adolescent consumer population.

Introducción: El cannabis es la sustancia ilegal que más consumen los adolescentes españoles. Entender los motivos de consumo es un factor importante para la intervención. Actualmente no existe en España un instrumento para su evaluación. El objetivo del presente trabajo es estudiar las propiedades psicométricas de la versión española del cuestionario Marihuana Motives Measure (MMM) en una población de adolescentes consumidores. Material y Métodos: Se llevó a cabo una traducción y retrotraducción del MMM. Un total de 228 adolescentes consumidores de cánnabis fueron evaluados. Se realizó un análisis factorial y se estudió la fiabilidad de la puntuación total y de cada una de las escalas del cuestionario a partir del Alfa de Cronbach. El estudio de la evidencia de validez del MMM se realizó mediante el examen de las correlaciones entre el uso actual de cánnabis, los efectos subjetivos del consumo través del cuestionario ARCI (Addiction Research Center Inventory) y la personalidad, mediante el cuestionario MACI (Millon Adolescent Clinical Inventory). Resultados: Se observó una alta fiabilidad de la puntuación total del MMM (Alfa de Cronbach= 0,86) y entre alta y moderada para cada uno de los cinco factores obtenidos al realizar el análisis factorial del MMM, Social = 0,82; Enhancement = 0,72; Coping = 0,83; Expansion = 0,74; Conformity = 0,64. Además, se observaron correlaciones significativas tanto entre motivos de consumo de cannabis y efectos subjetivos, así como entre motivos de consumo y personalidad. Conclusiones: La versión española del MMM muestra una estructura factorial similar a la obtenida por el autor original y sus medidas resultan fiables y válidas para el estudio de los motivos de consumo de cánnabis en población adolescente consumidora.

Propiedades psicométricas de la versión española del Marihuana Motives Measure en población adolescente consumidora / Spanish version validation of the Marihuana Motives Measure in a drug-consuming adolescent sample

Introducción: El cannabis es la sustancia ilegal que más consumen los adolescentes españoles. Entender los motivos de consumo es un factor importante para la intervención. Actualmente no existe en España un instrumento para su evaluación. El objetivo del presente trabajo es estudiar las propiedades psicométricas de la versión española del cuestionario Marihuana Motives Measure (MMM) en una población de adolescentes consumidores. Material y Métodos: Se llevó a cabo una traducción y retrotraducción del MMM. Un total de 228 adolescentes consumidores de cánnabis fueron evaluados. Se realizó un análisis factorial y se estudió la fiabilidad de la puntuación total y de cada una de las escalas del cuestionario a partir del Alfa de Cronbach. El estudio de la evidencia de validez del MMM se realizó mediante el examen de las correlaciones entre el uso actual de cánnabis, los efectos subjetivos del consumo través del cuestionario ARCI (Addiction Research Center Inventory) y la personalidad, mediante el cuestionario MACI (Millon Adolescent Clinical Inventory). Resultados: Se observó una alta fiabilidad de la puntuación total del MMM (Alfa de Cronbach= 0,86) y entre alta y moderada para cada uno de los cinco factores obtenidos al realizar el análisis factorial del MMM, Social = 0,82; Enhancement = 0,72; Coping = 0,83; Expansion = 0,74; Conformity = 0,64. Además, se observaron correlaciones significativas tanto entre motivos de consumo de cannabis y efectos subjetivos, así como entre motivos de consumo y personalidad. Conclusiones: La versión española del MMM muestra una estructura factorial similar a la obtenida por el autor original y sus medidas resultan fiables y válidas para el estudio de los motivos de consumo de cánnabis en población adolescente consumidora

Introduction: Cannabis is the illicit drug mostly widely consumed by adolescents in Spain. The understanding of consumption motives is an important factor for intervention. In Spain, there are no available instruments for their evaluation, hence, the goal of this paper is to study the psychometric properties of the Marihuana Motives Measure (MMM) in a sample of adolescent consumers. Material and Method: Firstly, translation and back-translation was performed. A total of 228 adolescent consumers of cannabis were evaluated. Factorial analysis was conducted, and the reliability of the total scores and of each scale of the questionnaire was studied through Cronbach’s alpha. Test-retest reliability was analyzed through interclass correlations. Validity evidence of the MMM was examined through correlations between current cannabis use, subjective consumption effects measured with the Addiction Research Center Inventory (ARCI), and personality measured with the Millon Adolescent Clinical Inventory (MACI). Results: High reliability was observed in total score of the MMM (Cronbach alfa = .86), and high and moderate reliability for each of the five factors obtained in the factorial analysis of the MMM, Social = .82, Enhancement = .72, Coping = .83, Expansion = .74, and Conformity = .64. Significant correlations were also observed between cannabis consumption motives and subjective effects, and between consumption motives and personality. Conclusion: The Spanish version of the MMM shows a similar factorial structure as the one obtained by the original author, and its measures are reliable and valid for the study of cannabis consumption motives in adolescent consumer population

A specific nanobody prevents amyloidogenesis of D76N ß2-microglobulin in vitro and modifies its tissue distribution in vivo.

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of ß2-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type ß2-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The ß2-microglobulin -binding nanobody, Nb24, more potently inhibits D76N ß2-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In ß2-microglobulin knock out mice, the D76N ß2-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type ß2-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis.