Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Low elementary movement speed is associated with poor motor skill in Turner's syndrome

The article aims to discriminate between 2 features that in principle both may be characteristic of the frequently observed poor motor performance in girls with Turner's syndrome (TS). On the one hand, a reduced movement speed that is independent of variations in spatial accuracy demands and therefore suggests a problem in motor execution. On the other hand, a disproportional slowing down of movement speed under spatial-accuracy demands, indicating a more central problem in motor programming. To assess their motor performance problems, 15 girls with TS (age 9.6-13.0 years) and 14 female controls (age 9.1-13.0 years) were tested using the Movement Assessment Battery for Children (MABC). In additionally, an experimental procedure using a variant of Fitts' graphic aiming task was used to try and disentangle the role of spatial-accuracy demands in different motor task conditions. The results of the MABC reestablish that overall motor performance in girls with TS is poor. The data from the Fitts' task reveal that TS girls move with the same accuracy as their normal peers but show a significantly lower speed independent of task difficulty. We conclude that a problem in motor execution is the main factor determining performance differences between girls with TS and controls.     

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits

The human dopamine D4 receptor (DRD4) is of major interest in molecular studies of schizophrenia and personality traits. We examined the association of schizophrenia and polymorphisms in the upstream region of the DRD4 gene (−768G>A in the negative modulator region; −521C>T, −376C>T, and −291C>T in the cell type-specific promoter region; and −616C>G between the two regions) in 208 schizophrenic patients and 210 normal controls. No significant difference in genotype and allele frequencies was observed between the two groups, indicating that these polymorphisms do not make a major contribution to the pathogenesis of schizophrenia. We also studied the association of polymorphisms in the upstream region and a 48-bp repeat polymorphism in exon III of the DRD4 gene with personality traits in 173 Japanese individuals who completed the temperament and character inventory (TCI). The −768G>A polymorphism was significantly associated with reward dependence (P = 0.044), while no significant association was observed between novelty seeking and polymorphisms in the upstream region or the exon III repeat polymorphism of the DRD4 gene. Received: August 28, 2000 / Accepted: October 25, 2000     

Functional Cluster Analysis of CT Perfusion Maps: A New Tool for Diagnosis of Acute Stroke?

CT perfusion imaging constitutes an important contribution to the early diagnosis of acute stroke. Cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) maps are used to estimate the severity of cerebral damage after acute ischemia. We introduce functional cluster analysis as a new tool to evaluate CT perfusion in order to identify normal brain, ischemic tissue and large vessels. CBF, CBV and TTP maps represent the basis for cluster analysis applying a partitioning (k-means) and density-based (density-based spatial clustering of applications with noise, DBSCAN) paradigm. In patients with transient ischemic attack and stroke, cluster analysis identified brain areas with distinct hemodynamic properties (gray and white matter) and segmented territorial ischemia. CBF, CBV and TTP values of each detected cluster were displayed. Our preliminary results indicate that functional cluster analysis of CT perfusion maps may become a helpful tool for the interpretation of perfusion maps and provide a rapid means for the segmentation of ischemic tissue.     

A novel insertional mutation at exon VII of the myelin proteolipid protein gene in Pelizaeus -- Merzbacher disease

Pelizaeus — Merzbacher disease (PMD) is an X-linked neurologicaldisorder characterized by dysmyelination in the central nervoussystem (CNS). Recently mutations of the myelln proteollpid protein(PLP) gene which encodes both PLP and Its Isoform, DM-20 generatedby alternative spllcing, have been demonstrated In PMD patients.We analyzed the seven exons of the PLP gene of a Japanese boyaffected with PMD by direct sequencing and identified an Insertionevent In exon Vll of the PLP gene. This mutation was also presentIn his carrier mother, but was absent In ninety-five X chromosomesof normal Japanese. The frame-shift mutation leads to the productionof truncated PLP with altered carboxyl terminal amlno acid sequences,resulting In conslderable change of the structure of PLP andDM-20 necessary for functional purposes. This is the first reportof a mutation In exon Vll of the PLP gene associated with PMD.     

Accounting for Intergenerational Cascade Testing in Economic Evaluations of Clinical Genomics: A Scoping Review

ObjectivesClinical genomics is emerging as a diagnostic tool in the identification of blood relatives at risk of developing heritable diseases. Our objective was to identify how genetic cascade screening has been incorporated into health economic evaluations.MethodsA scoping review was conducted to identify how multiple generations of a family were included in economic evaluations of clinical genomic sequencing, how many and which relatives were included, and uptake rates. Databases were searched for full economic evaluations of genetic interventions that screened multiple generations of families and were in English language, and no restrictions were made for disease or publication type. Data were synthesized using a narrative approach.ResultsTwenty-five studies were included covering a range of diseases in various countries. Markov cohort models were mostly used with hypothetical populations and unsupported by clinical evidence. Cascade testing was either the primary intervention or secondary to the index cases. The number and type of relatives were based on assumptions or identified through population or family records, clinical registry data, or clinical literature. Studies included only immediate family members and the uptake of testing ranged between 20% and 100%. All interventions were reported as cost-effective, and a higher number of relatives was a key driver.ConclusionsSeveral economic evaluations have considered the impacts of cascade testing interventions within clinical genomics. Ideally, models supported with high-quality clinical data are needed and, in their absence, transparent and justifiable assumptions of uptake rates and choices about including relatives. Consideration of more appropriate modeling types is required.     

Acupoint stimulation for long COVID: A promising intervention: 穴位刺激治疗长新冠:一种有前景的干预措施

“Long COVID” is a sustained symptom following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to recent statistics, at least 65 million people have long COVID, which poses a long-term threat to human health. The pathogenic mechanisms of coronavirus disease 2019 (COVID-19) are complex and affect multiple organs and systems. Common symptoms include palpitations, breathing difficulties, attention and memory deficits, fatigue, anxiety, and depression. It is difficult to achieve satisfactory treatment effect with a single intervention. Currently, treatment strategies for long COVID are still in the exploratory stage, and there is an urgent need to find appropriate and effective methods for long COVID treatment. Traditional Chinese medicine is effective in treating the various phases of COVID-19. Previous studies have shown that acupoint stimulation therapy is effective in improving palpitations, dyspnea, cognitive impairment, anxiety, depression, and other symptoms in patients. According to previous studies, acupoint stimulation may improve various symptoms related to long COVID. This paper discusses the potential application value of acupoint stimulation in the treatment of long COVID-related symptoms, based on the common sequelae of various systems involved in long COVID, and the effect of acupoint stimulation in the treatment of similar symptoms and diseases in recent years.