Then, where do we put our limited resources on the medium and longe-term?; Comments on rehm and colleague’s hypothesis / Entonces, ¿dónde destinamos nuestros limitados recursos a medio y largo plazo?; comentarios sobre la hipótesis de rehm y colaboradores

During the first wave of the pandemic we did not observe in our daily practice either any clear increase of drug treatment demand or a high number nor a high number of COVID-19 infections amongst patients in addiction treatment, according to our data. Interpreting these results, we respond to Jürgen Rehm’s and colleges essay. They proposed two main scenarios with opposite predictions regarding the impact of the current crisis on the level and patterns of alcohol consumption. We felt compelled to imagine not only what would happen if their hypothesis became true but also how this situation will unfold. Again we could forecast two somewhat opposite schemes regarding the resource demands for alcohol dependence patients during the medium and longer term pandemic: the first scenario would favour the reinforcement of specialized drug addiction centres to cope with this supposed increased alcohol consumption; the second scenario supports primary care centres. We conclude that primary care centres should be the first reinforced. (AU)

Durante la primera ola de la pandemia no observamos en nuestra práctica diaria un claro aumento de la demanda de tratamiento ni un elevado número de infecciones por COVID-19 entre pacientes en tratamiento por adicciones, según nuestros datos. Al interpretar estos resultados, respondemos al ensayo de Jürgen Rehm y colaboradores. Ellos Propusieron dos escenarios principales con predicciones opuestas en relación con el impacto de la crisis actual sobre el nivel y los patrones de consumo de alcohol. Nos sentimos obligados a imaginar no solo lo que sucedería si su hipótesis se hiciera realidad, sino también cómo ésta se desarrollaría. Nuevamente podríamos prever dos escenarios que de alguna manera serían opuestos, en relación a la demanda de recursos para los pacientes con dependencia del alcohol durante la pandemia a medio y largo plazo: el primer escenario favorecería el refuerzo de los centros especializados de tratamiento de adicciones para hacer frente a este supuesto aumento del consumo de alcohol; el segundo escenario apoya a los centros de atención primaria. Concluimos que los centros de atención primaria deberían de ser los primeros reforzados. (AU)

[Intensities in the application of robotic technologies in upper extremity rehabilitation after a stroke: a systematic review of randomised controlled clinical trials]. / Intensidades en la aplicación de tecnologías robóticas en la rehabilitación de las extremidades superiores tras un ictus: revisión sistemática de ensayos clínicos controlados aleatorizados.

INTRODUCTION: In the vast majority of cases stroke entails long-term limitations in the use of the upper extremities that are affected. Robotic technologies provide beneficial results in motor rehabilitation, but the optimal levels of intensity are not known. AIMS: To review the scientific literature (over the last 10 years) on robotic therapies (intervention group) compared to conventional therapies (control group) in the chronic phase of stroke, and to study correlations between variables that characterise the interventions and intensity variables. SUBJECTS AND METHODS: A systematic review was conducted of randomised controlled clinical trials in PubMed, Web of Science, Cochrane Library and Google Scholar, with results assessed by the Fugl-Meyer Assessment-Upper Extremity Motor Score (mFMA-UE). The methodological quality was analysed using the Physiotherapy Evidence Database scale (PEDro). RESULTS: Thirteen studies from evidence level I (92%, excellent) were selected. Positive correlations between minutes per week and improvements in mFMA-UE are observed in the control group and in the intervention group, with a higher level of significance for the latter. Negative correlations are observed between the number of months since the lesion and improvements in the control and intervention groups. An exponential regression is included, which illustrates differences between the control group and the intervention group in favour of the latter. A negative correlation is observed between the total duration and the number of minutes per week. CONCLUSION: Significant correlations are observed between intensity (minutes per week) and mFMA-UE, with a higher level of significance in the intervention group.

TITLE: Intensidades en la aplicación de tecnologías robóticas en la rehabilitación de las extremidades superiores tras un ictus: revisión sistemática de ensayos clínicos controlados aleatorizados.Introducción. El ictus conlleva limitaciones a largo plazo en el uso de las extremidades superiores afectadas en la gran mayoría de los casos. Las tecnologías robóticas aportan resultados beneficiosos en rehabilitación motora, pero se desconocen los niveles óptimos de intensidad. Objetivos. Revisar la literatura científica (últimos diez años) sobre terapias robóticas (grupo de intervención) en comparación con las terapias convencionales (grupo control) en la fase crónica del ictus y estudiar correlaciones entre las variables que caracterizan a las intervenciones y las variables de intensidad. Sujetos y métodos. Se realizó una revisión sistemática de ensayos clínicos controlados aleatorizados en PubMed, Web of Science, Cochrane Library y Google Scholar, con resultados valorados mediante la Fugl-Meyer Assessment-Upper Extremity Motor Score (mFMA-UE). La calidad metodológica se analizó mediante la escala Physiotherapy Evidence Database (PEDro). Resultados. Se seleccionaron 13 estudios, de nivel de evidencia I (92% excelente). Se observan correlaciones positivas entre los minutos semanales y las mejoras en la mFMA-UE en el grupo control y el grupo de intervención, con mayor nivel de significación para este último. Se observan correlaciones negativas entre el número de meses desde la lesión y las mejoras en el grupo control y en el grupo de intervención. Se incluye una regresión exponencial, que ilustra diferencias entre el grupo control y el grupo de intervención en favor de éste. Se observa una correlación negativa entre la duración total y la cantidad de minutos semanales. Conclusión. Se observan correlaciones significativas entre la intensidad (minutos semanales) y la mFMA-UE, con un mayor nivel de significación en el grupo de intervención.

The role of personality dimensions, depressive symptoms and other psychosocial variables in predicting postpartum suicidal ideation: a cohort study.

Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck's personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01-1.06; and OR, 1.03; 95%CI 1.01-1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11-1.26), personal psychiatric history (OR 2.1; 95%CI 1.33-3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12-3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.

Trastornos relacionados con el gen IRF6: a propósito de un caso de síndrome de pterigium poplíteo / Disorders related to the IRF6 gene: A case of popliteal pterygium syndrome

Los trastornos relacionados con mutaciones del gen IRF6, comprenden desde una afectación casi asintomática con la única presencia de hoyuelos labiales que son la manifestación más sutil del síndrome de van der Woude, hasta manifestaciones congénitas graves que incluyen anomalías faciales, musculoesqueléticas y genitourinarias que corresponden al síndrome de pterigium poplíteo. Pese a que existe cierta relación fenotipo-genotipo entre las mutaciones del gen IRF6, estas tienen una penetrancia incompleta y una expresión variable, inter e intrafamiliar

The disorders related to IRF6 encompass a spectrum from an almost asymptomatic affectation, with the only presence of isolated lip pits, which are a mild presentation of van der Woude syndrome, to the presence in the other extreme, of congenital manifestations that include facial anomalies, musculoskeletal and genitourinary malformations, corresponding to popliteal pterygium syndrome. Although there is a certain phenotype-genotype relationship between mutations of the IRF6 gene, such mutations have incomplete penetrance and variable inter-and intra-familial expression

Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI).

BACKGROUND: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aß) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aß species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. METHODS: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aß40 and Aß42 peptides. The association between Aß40 and Aß42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aß levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aß plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. RESULTS: FBB-PET global SUVR correlated weakly but significantly with Aß42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aß measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aß FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aß measurements (p value for interaction = 0.105). CONCLUSION: Brain and plasma Aß levels are partially correlated in individuals diagnosed with SCD. Aß plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.

FACEHBI: A Prospective Study of Risk Factors, Biomarkers and Cognition in a Cohort of Individuals with Subjective Cognitive Decline. Study Rationale and Research Protocols.

BACKGROUND: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. OBJECTIVES: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). DESIGN: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. SETTING: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. PARTICIPANTS: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. MEASUREMENTS: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. RESULTS: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. CONCLUSIONS: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

Adipose tissue and serum CCDC80 in obesity and its association with related metabolic disease.

Coiled-coil domain-containing 80 (CCDC80) is an adipocyte-secreted protein that modulates glucose homeostasis in response to diet-induced obesity in mice. The objective of this study is to analyze the link between human CCDC80 and obesity. CCDC80 protein expression was assessed in paired visceral (VAT) and subcutaneous (SAT) adipose tissue from 10 subjects (BMI range 22.4-38.8 kg/m2). Circulating CCDC80 levels were quantified in serum samples from two independent cross-sectional cohorts comprising 33 lean and 15 obese (cohort 1) and 32 morbid obese (cohort 2) male subjects. Insulin sensitivity, insulin secretion and blood neutrophil count were quantified in serum samples from both cohorts. Additionally, circulating free IGF-1 levels and oral glucose tolerance tests (OGTT) were assessed in cohort 1 whereas C-reactive protein levels and degree of atherosclerosis and hepatic steatosis were studied in cohort 2. In lean subjects, total CCDC80 protein content assessed by immunoblotting was lower in VAT than in SAT. In obese patients, CCDC80 was increased in VAT (P<0.05), but equivalent in SAT compared with lean counterparts. In cohort 1, serum CCDC80 correlated negatively with the acute insulin response to glucose and IGF1 levels, and positively with blood neutrophil count, independently of BMI, but not with insulin sensitivity. In cohort 2, serum CCDC80 was positively linked to the inflammatory biomarker C-reactive protein (r=0.46; P=0.009), atherosclerosis (carotid intima-media thickness, r=0.62; P<0.001) and hepatic steatosis (ANOVA P=0.025). Overall, these results suggest for the first time that CCDC80 may be a component of the obesity-altered secretome in VAT and could act as an adipokine whose circulant levels are linked to glucose tolerance derangements and related to inflammation-associated chronic complications.

Coping strategies and postpartum depressive symptoms: A structural equation modelling approach.

BACKGROUND: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks. METHODS: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression. RESULTS: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism. CONCLUSIONS: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies.

Behavioral scales used in severe and moderate traumatic brain injury.

UNLABELLED: Neurobehavioral disorders are common consequences of traumatic brain injury (TBI) that should be objectively assessed in this population. The use of scales allows us to unify terms both in clinical practice and investigative work; it also constitutes a useful guide in clinical interviews and makes it possible to see outcome changes in patients with or without intervention. The aim of this study is to review the most frequently neurobehavioral scales used to measure the non-cognitive disorders of conduct in TBI patients. METHOD: A systematic and descriptive literature review was done in Medline, without time limit, which focused on scales applied to behavioral disorders in moderate and severe TBI patients. RESULTS: Ninety articles were selected for the final review and thirty-seven different scales were identified. Seven of these instruments represent sixty-five percent of all behavioral scales applied in the studies collected and were selected for the present review. There are scales that are more general and include a wide range of neurobehavioral symptoms, like the Neurobehavioral Rating Scale and the Neuropsychiatric Inventory. On the opposite, there are questionnaires that focus on specific symptoms like aggressiveness, agitation and apathy such as the Agitated Behavior Scale or the Apathy Evaluation Scale. The forms for caregiver or staff were the most prevalent in our review. The most representative behavioral scales applied to moderate and severe TBI patients were analyzed using clinical useful, covered domains, item descriptions, administration procedures and psychometric properties.

Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.

The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.

Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st Century

The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis. Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs (AU)

Las reacciones de hipersensibilidad a medicamentos han aumentado en los últimos 10 años debido a la exposición prolongada por parte de los pacientes a mejores medicamentos diana con más potencial alergénico, incluyendo los anticuerpos monoclonales. Estas reacciones impiden que los pacientes puedan ser tratados con medicamentos de primera línea disminuyendo la calidad y expectancia de vida. El uso de pre medicaciones para evitar estas reacciones, incluyendo los anti-histamínicos, los bloqueantes de leukotrienos y los esteroides son capaces de proteger a pacientes con reacciones moderadas pero no protegen contra reacciones anafilácticas. En cambio la desensibilización a medicamentos es capaz de proteger contra la anafilaxia al mismo tiempo que provee a los pacientes con la medicina más adecuada para su tratamiento. Aunque los mecanismos de la desensibilización no están totalmente esclarecidos existen modelos celulares in vitro y modelos de roedores in vivo basados en la desensibilización IgE de mastocitos que han permitido establecer las bases y principios de la desensibilización y proveer protocolos in vivo para proteger a los pacientes altamente sensibilizados de reacciones de hipersensibilidad y anafilácticas. Esta revisión intenta proveer información acerca de los avances en los mecanismos de desensibilización, los principios y la práctica de las desensibilizaciones, los diferentes protocolos con los datos de eficacia y seguridad basadas en evidencia. Las desensibilizaciones a medicamentos solo pueden ser proveídas por alergólogos, enfermeras entrenadas y expertos farmacéuticos/as puesto que son tratamientos de alto riesgo en los cuales pacientes altamente sensibilizados son expuestos a las medicinas a las cuales están sensibilizados, con el consecuente riesgo de reacción de hipersensibilidad severa o fatal (AU)

Plasma PTX3 protein levels inversely correlate with insulin secretion and obesity, whereas visceral adipose tissue PTX3 gene expression is increased in obesity.

Plasma acutephase protein pentraxin 3 (PTX3) concentration is dysregulated in human obesity and metabolic syndrome. Here, we explore its relationship with insulin secretion and sensitivity, obesity markers, and adipose tissue PTX3 gene expression. Plasma PTX3 protein levels were analyzed in a cohort composed of 27 lean [body mass index (BMI) ≤ 25 kg/m(2)] and 48 overweight (BMI 25-30 kg/m(2)) men (cohort 1). In this cohort, plasma PTX3 was negatively correlated with fasting triglyceride levels and insulin secretion after intravenous and oral glucose administration. Plasma PTX3 protein and PTX3 gene expression in visceral (VAT) and subcutaneous (SAT) whole adipose tissue and adipocyte and stromovascular fractions were analyzed in cohort 2, which was composed of 19 lean, 28 overweight, and 15 obese subjects (BMI >30 kg/m(2)). An inverse association with body weight and waist/hip ratio was observed in cohort 2. In VAT depots, PTX3 mRNA levels were higher in subjects with BMI >25 kg/m(2) than in lean subjects, positively correlated with IL-1ß mRNA levels, and higher in the adipocyte than stromovascular fraction. Human preadipocyte SGBS cell line was used to study PTX3 production in response to factors that obesity entails. In SGBS adipocytes, PTX3 gene expression was enhanced by IL-1ß and TNFα but not IL-6 or insulin. In conclusion, the negative correlation between PTX3 and glucose-stimulated insulin secretion suggests a role for PTX3 in metabolic control. PTX3 gene expression is upregulated in VAT depots in obesity, despite lower plasma PTX3 protein, and by some proinflammatory cytokines in cultured adipocytes.

Dynamics of sperm DNA fragmentation in patients carrying structurally rearranged chromosomes.

This investigation was conducted to assess the baseline level of sperm DNA fragmentation (SDF) in a cohort of patients presenting chromosomal rearrangements (nine reciprocal translocations and two inversions). In a separate experiment, a dynamic analysis to calculate the rate of SDF (rSDF), after a varying period of sperm storage (0 h, 1 h, 4 h, 8 h and 24 h) at 37 °C, was performed. Results were compared with eight fertile donors. Different experimental approaches to assess SDF, such as terminal transferase dUTP nick-end labelling (TUNEL), sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCDt), were used. No differences for the baseline level of SDF were found. Carriers of reorganized genomes showed statistically higher levels of SDF than did control donors (p = 0.025 for TUNEL; p = 0.022 for SCSA; p = 0.014 for SCDt). However, 54.5% (6/11) of the patients presented values similar to those of control donors. There was no significant difference in rSDF (p = 0.34). Nevertheless, the results suggest that a high variability for SDF and rSDF exists in these patients. Routine analysis of SDF and rSDF should be considered in patients presenting rearranged genomes to determine fertility status for assisted reproductive techniques (ART) purposes.

Sperm DNA integrity and meiotic behavior assessment in an infertile male carrier of a 9qh+++ polymorphism.

Although several reports on male infertility suggest a relationship between chromosome 9 polymorphisms and infertility, the effects on the phenotype have not been extensively reported. In this study, an infertile patient was found to carry a 9qh+++ chromosome. The flow cytometric TUNEL assay and SCD test have been applied to characterize sperm DNA integrity. In order to assess its meiotic behaviour, synapsis, recombination, and aneuploidy, analyses have been also performed. Sperm DNA fragmentation (SDF) was 77.81% and 87% for the TUNEL and SCD tests, respectively. Ninety-two percent of pachytene cells analyzed showed meiotic abnormalities. The mean number of MLH1 foci per pachytene in the control group was higher (49) than the mean found in the 9qh+++ patient (38) (P < .0001). In spermatozoa, significant increases of disomy rates were observed for chromosome 18 and for the sex chromosomes (P < .0001). These disturbances could be present in other male carriers of a less marked 9qh+.

Adaptive behaviour in Angelman syndrome: its profile and relationship to age.

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder usually caused by an anomaly in the maternally inherited chromosome 15. The main features are severe intellectual disability, speech impairment, ataxia, epilepsy, sleep disorder and a behavioural phenotype that reportedly includes happy disposition, attraction to/fascination with water and hypermotoric behaviour. METHOD: We studied the level of adaptive behaviour and the adaptive behavioural profile in the areas of 'motor skills', 'language and communication', 'personal life skills' and 'community life skills' in a group of 25 individuals with genetically confirmed AS, to determine whether there is a specific adaptive behaviour profile. RESULTS AND CONCLUSIONS: None of the individuals, whatever their chronological age, had reached a developmental age of 3 years. A specific adaptive behaviour profile was found, with 'personal life skills' emerging as relative strengths and 'social and communication skills' as weaknesses.

Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia.

Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders. Schizophrenia is a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654 schizophrenic patients and 604 controls for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39 Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability to schizophrenia (odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated with schizophrenia, as well as for common CNVs that may act as susceptibility factors by disturbing glutathione metabolism.

Mood changes after delivery: role of the serotonin transporter gene.

BACKGROUND: Polymorphic variations in the serotonin transporter gene (5-HTT) moderate the depressogenic effects of tryptophan depletion. After childbirth there is a sharp reduction in brain tryptophan availability, thus polymorphic variations in 5-HTT may play a similar role in the post-partum period. AIMS: To study the role of 5-HTT polymorphic variations in mood changes after delivery. METHOD: One thousand, eight hundred and four depression-free Spanish women were studied post-partum. We evaluated depressive symptoms at 2-3 days, 8 weeks and 32 weeks post-partum. We used diagnostic interview to confirm major depression for all probable cases. Based on two polymorphisms of 5-HTT (5-HTTLPR and STin2 VNTR), three genotype combinations were created to reflect different levels of 5-HTT expression. RESULTS: One hundred and seventy-three women (12.7%) experienced major depression during the 32-week post-partum period. Depressive symptoms were associated with the high-expression 5-HTT genotypes in a dose-response fashion at 8 weeks post-partum, but not at 32 weeks. CONCLUSIONS: High-expression 5-HTT genotypes may render women more vulnerable to depressive symptoms after childbirth.

Utilidad de las baterías neuropsicológicas estandarizadas en sujetos adultos con síndrome de Down y demencia / The Usefulness of standard neuropsychological testing for adults with Down syndrome and dementia

(SD) tienen un riesgo aumentado de desarrollar la enfermedad de Alzheimer (EA). Puesto que en el SD se parte de un nivel intelectual menor que en la población general, a veces resulta difícil objetivar si existe o no, en el envejecimiento, una reducción de sus capacidades para cumplir los criterios diagnósticos de EA. El «Mini-MentalState Examination» (MMSE) y el «Severe ImpairmentBattery» (SIB) son pruebas cognitivas estandarizadas ampliamente utilizadas para detectar demencia en la población general. Escasos estudios han utilizado el MMSE y la SIB en sujetos con SD con sospecha de demencia. El objetivo del presente estudio consistió en analizar la utilidad del MMSE y la SIB en la valoración de las funciones cognitivas de sujetos con SD. Método: Se administró el MMSE y la SIB a 45 sujetos con SD (16 con EA y 29 sin demencia) y el cuestionario «Dementia Questionnaire for Mentally Retarded Persons» (DMR) a sus cuidadores. Resultados: Los sujetos con SD y demencia mostraron una mayor alteración que los sujetos con SD sin demencia en la DMR-social y DMR-total, pero no se hallaron diferencias significativas entre ambos grupos en el rendimiento de la SIB, MMSE ni DMR-cognitivo. Las puntuaciones en la SIB correlacionaron significativamente con las del MMSE, DMR-total, DMR-cognitivo y DMR-social. El rendimiento en el MMSE correlacionó significativamente con el del DMR-total, DMR-cognitivo y SIB. Conclusiones: El MMSE y la SIB son herramientas útiles para el seguimiento de las funciones cognitivas en sujetos con SD y deterioro cognitivo o demencia (AU)

Background: Subjects with Down syndrome (DS) have an increased risk of Alzheimer’s disease (AD). As intellectual ability is lower in DS subjects than among the general population, it is difficult to determine whether cognition has deteriorated with age to the point of fulfilling AD diagnostic criteria. The Mini-Mental State Examination (MMSE) and the Severe Impairment Battery (SIB) are standard cognitive tests widely used to assess dementia in the general population. There are few studies using the MMSE and the SIB on subjects with DS where dementia is suspected. The aim of the present study was to analyse the appropriateness of the SIB and the MMSE in the cognitive assessment of aging subjects with DS. Methods: The SIB and the MMSE were administered to 45 subjects with DS (16 with Alzheimer’s disease and 29 without dementia), and the DMR questionnaire was given to their caregivers. Results: DS subjects with dementia had higher impairment levels than DS subjects without dementia in their social and total DMR scores, but no significant differences were found between the two groups in the SIB and MMSE scores or in cognitive DMR performance. Overall, SIB scores correlated significantly with MMSE results, total DMR, cognitive DMR, and social DMR. MMSE performance correlated significantly with total and cognitive DMR scores as well as SIB score. Conclusion: The SIB and the MMSE are useful assessment tools in monitoring cognitive function among subjects with DS and cognitive loss or dementia (AU)

Fine mapping of a de novo interstitial 10q22-q23 duplication in a patient with congenital heart disease and microcephaly.

In this study we report a female patient with an interstitial duplication of a region (10q22-q23) which is rarely reported in the literature. We fine mapped the aberration with array CGH, which revealed an 18.6-Mb duplication, covering 89 annotated genes, at 10q22.2-q23.33. There were no other deletions or duplications elsewhere in the genome. The main clinical features of the patient are microcephaly and congenital heart disease, which are likely to be caused by dosage effect of one or several genes in the duplicated region. Similar phenotypes have been found in other patients with 10q11-q22 duplications and in two out of three patients with 10q22-q25 duplications. However, most of the duplication cases were investigated only by conventional chromosome analyses, and fine mapping of these and other duplications of 10q22-q23 are warranted for genotype-phenotype comparisons.