Factors Associated with Respiratory Health and Function in Duchenne Muscular Dystrophy: A Systematic Review and Evidence Grading.

BACKGROUND: Despite advances in the medical management of the disease, respiratory involvement remains a significant source of morbidity and mortality in children and adults with Duchenne muscular dystrophy (DMD). OBJECTIVE: The objective of this systematic literature review was to synthesize and grade published evidence of factors associated with respiratory health and function in DMD. METHODS: We searched MEDLINE, Embase, and the Cochrane Library for records of studies published from January 1, 2000 (to ensure relevance to current care practices), up until and including December 31, 2022, reporting evidence of prognostic indicators and predictors of disease progression in DMD. The quality of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. RESULTS: The bibliographic search strategy resulted in the inclusion of 29 articles. In total, evidence of 10 factors associated with respiratory health and function in patients with DMD was identified: glucocorticoid exposure (high- to very low-quality evidence), DMD mutations (low-quality evidence), DMD genetic modifiers (low-quality evidence), other pharmacological interventions (i.e., ataluren, eteplirsen, idebenone, and tamoxifen) (moderate- to very low-quality evidence), body mass index and weight (low-quality evidence), and functional ability (low-quality evidence). CONCLUSIONS: In conclusion, we identified a total of 10 factors associated with respiratory health in function in DMD, encompassing both pharmacological therapies, genetic mutations and modifiers, and patient clinical characteristics. Yet, more research is needed to further delineate sources of respiratory heterogeneity, in particular the genotype-phenotype association and the impact of novel DMD therapies in a real-world setting. Our synthesis and grading should be helpful to inform clinical practice and future research of this heavily burdened patient population.

[Neural networks and clinical efficacy of transcranial brain stimulation in psychiatry]. / Neurale netwerken en klinische effecti­vi­teit van transcraniële hersenstimulatie in de psychiatrie.

BACKGROUND: Non-invasive forms of brain stimulation, including transcranial magnetic stimulation and direct current stimulation, are increasingly being considered by clinicians as a somatic treatment option for psychiatric disorders. AIM: Review article on the history, efficacy transcranial brain stimulation in psychiatric disorders and the role of neural networks for improving clinical efficacy. METHOD: Review of scientific literature. RESULTS: Transcranial magnetic stimulation has been proven effective for the treatment of depression, but treatment efficacy varies widely for other psychiatric disorders. Transcranial direct current stimulation is still at an experimental stage, but results suggest that using weak currents can have positive effects. Neuroscience research provides tools for improving therapeutic outcomes based on neural network approaches. CONCLUSION: Transcranial brain stimulation grafted on network information appears to be a promising approach for enhancing therapeutic outcome in psychiatric disorders.

Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions.

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.

Identifying and optimizing human endometrial gene expression signatures for endometrial dating.

STUDY QUESTION: What are the key considerations for developing an enhanced transcriptomic method for secretory endometrial tissue dating? SUMMARY ANSWER: Multiple gene expression signature combinations can serve as biomarkers for endometrial dating, but their predictive performance is variable and depends on the number and identity of the genes included in the prediction model, the dataset characteristics and the technology employed for measuring gene expression. WHAT IS KNOWN ALREADY: Among the new generation of transcriptomic endometrial dating (TED) tools developed in the last decade, there exists variation in the technology used for measuring gene expression, the gene makeup and the prediction model design. A detailed study, comparing prediction performance across signatures for understanding signature behaviour and discrepancies in gene content between them, is lacking. STUDY DESIGN, SIZE, DURATION: A multicentre prospective study was performed between July 2018 and October 2020 at five different centres from the same group of clinics (Spain). This study recruited 281 patients and finally included in the gene expression analysis 225 Caucasian patients who underwent IVF treatment. After preprocessing and batch effect filtering, gene expression measurements from 217 patients were combined with artificial intelligence algorithms (support vector machine, random forest and k-nearest neighbours) allowing evaluation of different prediction models. In addition, secretory-phase endometrial transcriptomes from gene expression omnibus (GEO) datasets were analysed for 137 women, to study the endometrial dating capacity of genes independently and grouped by signatures. This provided data on the consistency of prediction across different gene expression technologies and datasets. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies were analysed using a targeted TruSeq (Illumina) custom RNA expression panel called the endometrial dating panel (ED panel). This panel included 301 genes previously considered relevant for endometrial dating as well as new genes selected for their anticipated value in detecting the secretory phase. Final samples (n = 217) were divided into a training set for signature discovery and an independent testing set for evaluation of predictive performance of the new signature. In addition, secretory-phase endometrial transcriptomes from GEO were analysed for 137 women to study endometrial dating capacity of genes independently and grouped by signatures. Predictive performance among these signatures was compared according to signature gene set size. MAIN RESULTS AND THE ROLE OF CHANCE: Testing of the ED panel allowed development of a model based on a new signature of 73 genes, which we termed 'TED' and delivers an enhanced tool for the consistent dating of the secretory phase progression, especially during the mid-secretory endometrium (3-8 days after progesterone (P) administration (P + 3-P + 8) in a hormone replacement therapy cycle). This new model showed the best predictive capacity in an independent test set for staging the endometrial tissue in the secretory phase, especially in the expected window of implantation (average of 114.5 ± 7.2 h of progesterone administered; range in our patient population of 82-172 h). Published sets of genes, in current use for endometrial dating and the new TED genes, were evaluated in parallel in whole-transcriptome datasets and in the ED panel dataset. TED signature performance was consistently excellent for all datasets assessed, frequently outperforming previously published sets of genes with a smaller number of genes for dating the endometrium in the secretory phase. Thus, this optimized set exhibited prediction consistency across datasets. LARGE SCALE DATA: The data used in this study is partially available at GEO database. GEO identifiers GSE4888, GSE29981, GSE58144, GSE98386. LIMITATIONS, REASONS FOR CAUTION: Although dating the endometrial biopsy is crucial for investigating endometrial progression and the receptivity process, further studies are needed to confirm whether or not endometrial dating methods in general are clinically useful and to guide the specific use of TED in the clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: Multiple gene signature combinations provide adequate endometrial dating, but their predictive performance depends on the identity of the genes included, the gene expression platform, the algorithms used and dataset characteristics. TED is a next-generation endometrial assessment tool based on gene expression for accurate endometrial progression dating especially during the mid-secretory. STUDY FUNDING/COMPETING INTEREST(S): Research funded by IVI Foundation (1810-FIVI-066-PD). P.D.-G. visiting scientist fellowship at Oxford University (BEFPI/2010/032) and Josefa Maria Sanchez-Reyes' predoctoral fellowship (ACIF/2018/072) were supported by a program from the Generalitat Valenciana funded by the Spanish government. A.D.-P. is supported by the FPU/15/01398 predoctoral fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). D.W. received support from the NIHR Oxford Biomedical Research Centre. The authors do not have any competing interests to declare.

Analysis of body condition indices reveals different ecotypes of the Antillean manatee.

Assessing the body condition of wild animals is necessary to monitor the health of the population and is critical to defining a framework for conservation actions. Body condition indices (BCIs) are a non-invasive and relatively simple means to assess the health of individual animals, useful for addressing a wide variety of ecological, behavioral, and management questions. The Antillean manatee (Trichechus manatus manatus) is an endangered subspecies of the West Indian manatee, facing a wide variety of threats from mostly human-related origins. Our objective was to define specific BCIs for the subspecies that, coupled with additional health, genetic and demographic information, can be valuable to guide management decisions. Biometric measurements of 380 wild Antillean manatees captured in seven different locations within their range of distribution were obtained. From this information, we developed three BCIs (BCI1 = UG/SL, BCI2 = W/SL3, BCI3 = W/(SL*UG2)). Linear models and two-way ANCOVA tests showed significant differences of the BCIs among sexes and locations. Although our three BCIs are suitable for Antillean manatees, BCI1 is more practical as it does not require information about weight, which can be a metric logistically difficult to collect under particular circumstances. BCI1 was significantly different among environments, revealing that the phenotypic plasticity of the subspecies have originated at least two ecotypes-coastal marine and riverine-of Antillean manatees.

Transcriptional changes through menstrual cycle reveal a global transcriptional derepression underlying the molecular mechanism involved in the window of implantation.

The human endometrium is a dynamic tissue that only is receptive to host the embryo during a brief time in the middle secretory phase, called the window of implantation (WOI). Despite its importance, regulation of the menstrual cycle remains incompletely understood. The aim of this study was to characterize the gene cooperation and regulation of menstrual cycle progression, to dissect the molecular complexity underlying acquisition of endometrial receptivity for a successful pregnancy, and to provide the scientific community with detailed gene co-expression information throughout the menstrual cycle on a user-friendly web-tool database. A retrospective gene co-expression analysis was performed based on the endometrial receptivity array (ERarray) gene signature from 523 human endometrial samples collected across the menstrual cycle, including during the WOI. Gene co-expression analysis revealed the WOI as having the significantly smallest proportion of negative correlations for transcriptional profiles associated with successful pregnancies compared to other cycle stages, pointing to a global transcriptional derepression being involved in acquisition of endometrial receptivity. Regulation was greatest during the transition between proliferative and secretory endometrial phases. Further, we prioritized nuclear hormone receptors as major regulators of this derepression and proved that some genes and transcription factors involved in this process were dysregulated in patients with recurrent implantation failure. We also compiled the wealth of gene co-expression data to stimulate hypothesis-driven single-molecule endometrial studies in a user-friendly database: Menstrual Cycle Gene Co-expression Network (www.menstrualcyclegcn.com). This study revealed a global transcriptional repression across the menstrual cycle, which relaxes when the WOI opens for transcriptional profiles associated with successful pregnancies. These findings suggest that a global transcriptional derepression is needed for embryo implantation and early development.

Femtosecond Laser Pulse Driven Caustic Spin Wave Beams.

Controlling the directionality of spin waves is a key ingredient in wave-based computing methods such as magnonics. In this Letter, we demonstrate this particular aspect by using an all-optical pointlike source of continuous spin waves based on frequency comb rapid demagnetization. The emitted spin waves contain a range of k vectors and by detuning the applied magnetic field slightly off the ferromagnetic resonance (FMR), we observe X-shaped caustic spin wave patterns at 70° propagation angles as predicted by theory. When the harmonic of the light source approaches the FMR, the caustic pattern gives way to uniaxial spin wave propagation perpendicular to the in-plane component of the applied field. This field-controlled propagation pattern and directionality of optically emitted short-wavelength spin waves provide additional degrees of freedom when designing magnonic devices.

Consecuencias sociolaborales del confinamiento por la COVID-19 en pacientes con esclerosis múltiple en dos poblaciones muy diferentes / Socio-labor consequences of confinement by COVID-19 in patients with multiple sclerosis in two very different populations

El confinamiento debido a la pandemia de la COVID-19, realizado a nivel mundial, ha tenido consecuencias casi siempre negativas en los pacientes con esclerosis múltiple (EM). OBJETIVO: Hemos comparado el efecto sociolaboral que el confinamiento ha podido tener en pacientes con EM de dos poblaciones tan diferentes como son España y China. MÉTODO: Se elaboraron unos cuestionarios a lo que respondieron un grupo de pacientes de EM que son revisados en la unidad de EM del hospital Vithas (Fundación DINAC) en Sevilla, y pacientes con EM atendidos en varias provincias de China durante el mes de abril de 2020, con el objetivo de analizar las diferencias y similitudes del efecto sociolaboral entre ambas poblaciones. Para llevar a cabo este análisis se creó una base de datos que se analizó posteriormente. RESULTADOS: La población china tiene una mayor proporción de pacientes más jóvenes y no hay diferencia respecto al género. La mayoría de las variables estudiadas se comportaron de igual forma en los pacientes con EM tanto españoles como chinos. Los pacientes españoles presentaron menos impacto (30,7%) en su situación socioeconómica que los chinos (44%), p < 0,05. No hubo diferencias importantes en el resto de las variables entre las dos poblaciones. Las redes sociales fueron muy utilizadas en la mayoría de los enfermos de ambas poblaciones. CONCLUSIONES: Los pacientes con EM padecen de forma muy similar las consecuencias de la pandemia en su situación sociolaboral y utilizan de forma parecida las redes sociales y el apoyo de la familia. Los pacientes españoles disfrutan de más estabilidad económica, probablemente gracias al apoyo social que reciben

The confinement due to the global COVID-19 pandemic has almost had negative consequences in patients with multiple sclerosis (MS). OBJECTIVE: We wanted to compare the socio-labor effect of confinement in two populations as different as Spain and China, in patients with MS. METHOD: Questionnaires were applied to a group of MS patients who have been reviewed in the MS unit of the Vithas hospital (DINAC Foundation) in Seville, and MS patients attended in various provinces of China during the month of April 2020, with the aim of analyzing the differences and similarities of the socio-labor effect between both populations. To carry out this analysis, a database was created and subsequently analyzed. RESULTS: The Chinese population has a higher proportion of younger patients and there is no difference regarding gender. Most of the variables studied behaved the same way in both Spanish and Chinese MS patients. Spanish patients had less impact (30.7%) on their socio-economic situation than Chinese (44%), P < .05. There were no important differences in the rest of the variables between the two populations. Social networks were widely used in the majority of patients in both populations. CONCLUSIONS: MS patients suffer in a very similar way from the consequences of the pandemic on their socio-labor situation and similarly use social networks and family support. Spanish patients seem to have more economic stability, which may be due to social economic support

Social and professional consequences of COVID-19 lockdown in patients with multiple sclerosis from two very different populations. / Consecuencias sociolaborales del confinamiento por la COVID-19 en pacientes con esclerosis múltiple en dos poblaciones muy diferentes.

The global lockdown measures implemented due to the COVID-19 pandemic have nearly always had negative consequences for patients with multiple sclerosis (MS). OBJECTIVE: We compared the social and professional effects of confinement on patients with MS in 2 very different populations, from Spain and China. METHODS: Questionnaires were administered to a group of patients with MS who consulted at the MS unit of Vithas hospital (DINAC Foundation) in Seville, and patients with MS attended in several provinces of China in April 2020, with the aim of analysing the differences and similarities between populations in the social and professional effects of confinement. To this end, a database was created and subsequently analysed. RESULTS: The Chinese population includes a higher proportion of younger patients and no differences were identified regarding sex. Most of the variables studied behaved in the same way in both patient populations. Spanish patients presented a lesser impact (30.7%) on their socio-economic situation than Chinese patients (44%) (P < .05). There were no significant differences between populations in the remaining variables. Social networks were widely used in the majority of patients from both populations. CONCLUSIONS: The social and professional consequences of the pandemic were very similar in both groups; the use of social networks and family support was also similar. Spanish patients seem to present greater economic stability, perhaps due to the social support they receive.

Brain areas associated with clinical and cognitive insight in psychotic disorders: A systematic review and meta-analysis.

In the past years, ample interest in brain abnormalities related to clinical and cognitive insight in psychosis has contributed several neuroimaging studies to the literature. In the current study, published findings on the neural substrates of clinical and cognitive insight in psychosis are integrated by performing a systematic review and meta-analysis. Coordinate-based meta-analyses were performed with the parametric coordinate-based meta-analysis approach, non-coordinate based meta-analyses were conducted with the metafor package in R. Papers that could not be included in the meta-analyses were systematically reviewed. Thirty-seven studies were retrieved, of which 21 studies were included in meta-analyses. Poorer clinical insight was related to smaller whole brain gray and white matter volume and gray matter volume of the frontal gyri. Cognitive insight was predominantly positively associated with structure and function of the hippocampus and ventrolateral prefrontal cortex. Impaired clinical insight is not associated with abnormalities of isolated brain regions, but with spatially diffuse global and frontal abnormalities suggesting it might rely on a range of cognitive and self-evaluative processes. Cognitive insight is associated with specific areas and appears to rely more on retrieving and integrating self-related information.

Decreased functional connectivity of the insula within the salience network as an indicator for prospective insufficient response to antidepressants.

Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received ≥ two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with ≥ two antidepressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the ≥2 antidepressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response.

[Consensus statement on the application of rTMS in depression in the Netherlands and Belgium]. / Consensusverklaring voor de toepassing van rTMS bij depressie in Nederland en België.

BACKGROUND: Since 2017, repetitive transcranial magnetic stimulation (rTMS) has become eligible for reimbursement for the treatment of therapy-resistant depression in the Dutch healthcare system.
AIM: To initiate a guideline in the Netherlands and Belgium for the safe and effective application of rTMS for the treatment of depression.
METHOD: Based on literature review, existing guidelines and consensus among Dutch rTMS experts, recommendations were developed regarding the implementation of rTMS as a treatment of depression. All available evidence was weighed and discussed among all co-authors and recommendations were reached by consensus among the group.
RESULTS: rTMS targeting the dorsolateral prefrontal cortex (DLPFC) should be seen as a first choice in the treatment of depression using high-frequency rTMS (left) or, as an alternative, low-frequency rTMS (right). Stimulation protocols should use more than 1000 pulses per session for an average of 20-30 sessions, offered in 2-5 sessions per week. Contraindications for rTMS include epilepsy, intracranial presence of (magnetisable) metals, pacemaker and cochlear implant.
CONCLUSION: rTMS, performed by competent professionals is an effective and safe treatment for depression.

Measuring empathy in schizophrenia: The Empathic Accuracy Task and its correlation with other empathy measures.

INTRODUCTION: Empathy is an interpersonal process impaired in schizophrenia. Past studies have mainly used questionnaires or performance-based tasks with static cues to measure cognitive and affective empathy. We used the Empathic Accuracy Task (EAT) designed to capture dynamic aspects of empathy by using videoclips in which perceivers continuously judge emotionally charged stories. We compared individuals with schizophrenia with a healthy comparison group and assessed correlations among EAT and three other commonly used empathy measures. METHOD: Patients (n = 92) and a healthy comparison group (n = 42) matched for age, gender and education completed the EAT, the Interpersonal Reactivity Index, Questionnaire of Cognitive and Affective Empathy and Faux Pas. Differences between groups were analyzed and correlations were calculated between empathy measurement instruments. RESULTS: The groups differed in EAT performance, with the comparison group outperforming patients. A moderating effect was found for emotional expressivity of the target: while both patients and the comparison group scored low when judging targets with low expressivity, the comparison group performed better than patients with more expressive targets. Though there were also group differences on the empathy questionnaires, EAT performance did not correlate with questionnaire scores. CONCLUSIONS: Individuals with schizophrenia benefit less from the emotional expressivity of other people than the comparison group, which contributes to their impaired empathic accuracy. The lack of correlation between the EAT and the questionnaires suggests a distinction between self-report empathy and actual empathy performance. To explore empathic difficulties in real life, it is important to use instruments that take the interpersonal perspective into account.

Auditory hallucinations, top-down processing and language perception: a general population study.

BACKGROUND: Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated. METHODS: We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems. RESULTS: A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not. CONCLUSIONS: The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.

Lateral parietal cortex in the generation of behavior: Implications for apathy.

A reduction in goal-directed behavior, or apathy, occurs in neurological and psychiatric disorders, though its neural substrates remain unclear. Deficits in circuits connecting the prefrontal cortex to subcortical regions are considered to underlie apathy. Although apathy is empirically associated with widespread changes in these regions, studies across disorders also link apathy with the lateral parietal cortex. Such variety in regional involvement is consistent with the established role of prefrontal and subcortical regions in models of goal-directed behavior, and with the suggestion of subtypes of apathy. However, these models do not provide a basis for the involvement of the lateral parietal cortex with apathy. Here, we review the association between lateral parietal cortex dysfunction and apathy across disorders and analyze the putative cognitive functions that may link this region with goal-directed behavior. We suggest that neural processes in the angular and supramarginal gyri of the inferior parietal lobule may provide an interface enabling the transformation of internal goals to external actions through intentional initiation of action interrelated with mechanisms of primary sensorimotor transformation. Consequently, we propose that impairment in this process of embedding intended action in a 'body schema' facilitating adequate recruitment of an effector system, is the likely mechanism underlying the association between the lateral parietal cortex and apathy. Considering the evidence, we propose a revised neurocognitive model of apathy where deficient internal initiation of behavior mediated by the inferior parietal lobule may be sufficient, though not necessary, to reduce goal-directed behavior, and may constitute a volitional subtype of apathy.

Social cognitive group treatment for impaired insight in psychosis: A multicenter randomized controlled trial.

PURPOSE: The majority of people with schizophrenia has impaired insight, which is related to a poorer outcome. In this study, we evaluate a new psychosocial intervention 'REFLEX' aimed at improving insight in people with schizophrenia. REFLEX focuses on targeting stigma-sensitivity, perspective taking and self-reflection in people with schizophrenia and low insight. Primary objective is to improve insight and subsequently to improve functional outcome and symptoms. METHOD: A total of 121 people diagnosed with schizophrenia according to DSM IV criteria with impaired insight was included in 2012-2015 from seven sites in a multicenter randomized controlled trial. REFLEX was compared to an active control condition consisting of group-wise simplified cognitive remediation training. Primary outcome of the study were the preconditions of insight: internalized stigma, self-reflection, mental flexibility and perspective taking. Clinical insight and cognitive insight were secondary outcomes. RESULTS: Although perspective taking, self-reflection, mental flexibility and stigma sensitivity remained unchanged after the intervention, results showed a significant improvement of clinical insight in both conditions directly after treatment (SAI-E Rater, p < .001, PANSS G12, p < .005) and at follow-up (SAI-E Rater, p < .01, SAI-E interview, p < .001, PANSS G12, p < .0001). Improvement of clinical insight directly after treatment was larger in the REFLEX condition (SAI-E Rater, p < .05). Other outcomes (self-esteem, quality of life and depression) remained unchanged. CONCLUSION: Though insight improved in both conditions, REFLEX was not superior to simplified drill-and-practice cognitive remediation training. Nevertheless, this study indicates that structured interventions can significantly improve insight. Further research on the underlying mechanisms of both conditions is needed, as insight is unlikely to improve spontaneously in chronic patients.

Metacognitive reflection and insight therapy (MERIT) for patients with schizophrenia.

BACKGROUND: Impaired metacognition is associated with difficulties in the daily functioning of people with psychosis. Metacognition can be divided into four domains: Self-Reflection, Understanding the Other's Mind, Decentration, and Mastery. This study investigated whether Metacognitive Reflection and Insight Therapy (MERIT) can be used to improve metacognition. METHODS: This study is a randomized controlled trial. Patients in the active condition (n = 35) received forty MERIT sessions, the control group (n = 35) received treatment as usual. Multilevel intention-to-treat and completers analyses were performed for metacognition and secondary outcomes (psychotic symptomatology, cognitive insight, Theory of Mind, empathy, depression, self-stigma, quality of life, social functioning, and work readiness). RESULTS: Eighteen out of 35 participants finished treatment, half the drop-out stemmed from therapist attrition (N = 5) or before the first session (N = 4). Intention-to-treat analysis demonstrated that in both groups metacognition improved between pre- and post-measurements, with no significant differences between the groups. Patients who received MERIT continued to improve, while the control group returned to baseline, leading to significant differences at follow-up. Completers analysis (18/35) showed improvements on the Metacognition Assessment Scale (MAS-A) scales Self Reflectivity and metacognitive Mastery at follow-up. No effects were found on secondary outcomes. CONCLUSIONS: On average, participants in the MERIT group were, based on MAS-A scores, at follow-up more likely to recognize their thoughts as changeable rather than as facts. MERIT might be useful for patients whose self-reflection is too limited to benefit from other therapies. Given how no changes were found in secondary measures, further research is needed. Limitations and suggestions for future research are discussed.

[rTMS for treatment resistant depression - proposal for a treatment protocol]. / Repetitieve transcraniële magnetische stimulatie bij therapieresistente depressie; voorstel voor een behandelprotocol.

BACKGROUND: At present, the use of repetitive transcranial magnetic stimulation (rtms) for treatment-resistant depression is sufficiently substantiated to be applied in clinical practice. In the Netherlands, it will be reimbursed when offered in combination with cognitive behavior therapy.
AIM: Proposal for a clinical treatment protocol for rtms in The Netherlands.
METHOD: A study of the literature and a critical appraisal of available international guidelines for rtms.
RESULTS: rtms is a safe treatment for patients suffering from a moderate to severe depressive disorder that is relatively treatment-resistant. The duration of the effect is still unknown. It is advised to stimulate the left dorsolateral prefrontal cortex using an intensity of 120% of the resting motor threshold, with a frequency of 10 Hz and using 3000 pulses per session during a total of 20-30 sessions.
CONCLUSION: The proposed treatment protocol is favored based on the available evidence when rtms is used as a treatment aimed to acutely decrease the severity of depressive symptoms. It is further proposed to systematically collect technical and outcome data on treatment with rtms to further improve treatment with rtms in clinical practice.

Multiple sclerosis prevalence in Salta City, Argentina.

INTRODUCTION: Multiple Sclerosis (MS) is one of the leading causes of disability in young adults. Its prevalence varies according to different countries. In Argentina there is a wide heterogeneity regarding data published in different areas of the country. Prevalence established in most studies is 17 cases per 100,000 inhabitants; however, most of the available data comes from studies that took place in Buenos Aires. There is little or no information from other provinces, especially from Northwest of Argentina (NOA), where there are no studies of the disease prevalence. The aim of this study is to investigate MS prevalence, phenotypes and epidemiological characteristics in Salta, Argentina, in order to contribute to the current knowledge of MS epidemiology and distribution in our country. METHODS: A descriptive, observational, transversal study was carried out in the capital city of Salta. Researchers from all public and private hospitals with a Neurology Department have participated. Private researchers who are well known leaders in demyelinating diseases in the city provided valuable information. Patients who did not have medical control for the past two years as well as patients whose last address was not registered in Salta were excluded. RESULTS: 120 registries were obtained from the four hospitals that participated and from the 12 private researchers. Ten patients were excluded due to overlapping data. The population of the area based on 2010 census was 535,310, so we estimated an MS prevalence 23.8 cases per 100,000 inhabitants (95% CI 20.1-27.4), 24.1 cases per 100,000 inhabitants in female population (95% CI 21.2-28.6) and 18.2 cases per 100,000 inhabitants (95% CI 15.2-21.1) in male population. In our analysis, 64 (58.2%) were female and the average age was 42.1 years. 81.8% are recurrent remitting forms, 16.4% secondary progressive and 1.8% primary progressive. CONCLUSION: This is the first study that provides epidemiological data on the prevalence and clinical forms of MS in Salta City as well as in the entire Northwest Region of Argentina(NOA). We estimate a prevalence of 23.8 cases per 100,000 inhabitants, which establishes a moderate risk area for MS.