心内补片左室重建术治疗心肌梗塞后巨大室壁瘤五例

我们行心内补片左室重建术治疗心肌梗塞后左心室巨大室壁瘤５例。巨大室壁瘤多有严重临床症状，左室功能进行性减退。我们采用的方法系不强调室壁瘤切除，而在于解剖上更生理性地重建左心室，恢复左心室的几何形状及各层次心室肌的正常收缩方向。该方法适用于室壁瘤内口明显扩大、瘤体严重钙化或同时有室间隔受累者。术后早期效果非常满意，心功能均明显改善。本文还介绍了手术方法及术中可能出现情况的处理。     

Adenovirus hepatitis in an immunosuppressed adult patient.

The role of adenovirus as an etiologic agent of hepatic damage has been controversial. A fatal case of adenovirus infection with fulminant hepatitis in a young immunosuppressed adult patient is presented. Intranuclear inclusions were confined to the liver. Electron microscopy revealed crystalline arrays of virions within hepatocytes. This is apparently the first reported case of adenovirus hepatitis occurring in an adult. Adenovirus hepatitis represents another hazard for the immunosuppressed patient.     

Improving aerosol distributions below clouds by assimilating satellite-retrieved cloud droplet number

Limitations in current capabilities to constrain aerosols adversely impact atmospheric simulations. Typically, aerosol burdens within models are constrained employing satellite aerosol optical properties, which are not available under cloudy conditions. Here we set the first steps to overcome the long-standing limitation that aerosols cannot be constrained using satellite remote sensing under cloudy conditions. We introduce a unique data assimilation method that uses cloud droplet number (N(d)) retrievals to improve predicted below-cloud aerosol mass and number concentrations. The assimilation, which uses an adjoint aerosol activation parameterization, improves agreement with independent N(d) observations and with in situ aerosol measurements below shallow cumulus clouds. The impacts of a single assimilation on aerosol and cloud forecasts extend beyond 24 h. Unlike previous methods, this technique can directly improve predictions of near-surface fine mode aerosols responsible for human health impacts and low-cloud radiative forcing. Better constrained aerosol distributions will help improve health effects studies, atmospheric emissions estimates, and air-quality, weather, and climate predictions.     

Tutorial on maximum inspiratory and expiratory mouth pressures in individuals with idiopathic Parkinson disease (IPD) and the preliminary results of an expiratory muscle strength training program

Respiratory symptoms are recognized as sequelae of motor dysfunction in idiopathic Parkinson's disease (IPD) and these symptoms have the potential to cause problems with swallow, cough, voice and speech. Specifically, maneuvers that require rapid activation and coordination of upper airway and chest wall musculature become progressively impaired as motor dysfunction progresses during the natural course of the disease. This study reports on the maximum inspiratory and expiratory pressures produced by 28 participants (average age 64) diagnosed with moderate to severe IPD (average stage 2.5 with a range of 2.0-3.0). All measures were collected during the "medication on" state. Outcomes of a specific respiratory muscle strength training technique for improving maximum expiratory pressure are reported for three of the patients in this study. Techniques that focus on strengthening the respiratory muscles in patients with IPD (other than with low load breathing exercises), have not been previously reported. The results of this pilot study demonstrate that respiratory muscle weakness may be an important factor in the respiratory complications in IPD and that respiratory muscle strength training has the potential to improve expiratory muscle strength for this population. This improvement has the potential to positively impact high forced respiratory activities, such as forced breathing maneuvers, swallow, cough and speech functions that require greater magnitude and duration of expiration.     

Genetic defects of human brain development

This review focuses on malformations of the central nervous system that have a genetic etiology. One can view each malformation as giving us unique details on a map entitled "how to make a human brain." The gene(s) that cause each malformation are being identified, allowing discovery of their specific role in neurodevelopment, and defining a "road" on the map. The malformation is then the developmental consequence of "taking a wrong turn." Assimilation of complementary data from other species with human malformation phenotype and genotype is revealing just how wonderful and complex the neurodevelopment map is. Here we highlight recent research on brain malformations and how this is illuminating the map of normal human brain formation.     

Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer's disease

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles in brain MRI scans, providing an efficient approach to monitor degenerative disease in clinical studies and drug trials. First, we used a set of parameterized surfaces to represent the ventricles in four subjects' manually labeled brain MRI scans (atlases). We fluidly registered each atlas and mesh model to MRIs from 17 Alzheimer's disease (AD) patients and 13 age- and gender-matched healthy elderly control subjects, and 18 asymptomatic ApoE4-carriers and 18 age- and gender-matched non-carriers. We examined genotyped healthy subjects with the goal of detecting subtle effects of a gene that confers heightened risk for Alzheimer's disease. We averaged the meshes extracted for each 3D MR data set, and combined the automated segmentations with a radial mapping approach to localize ventricular shape differences in patients. Validation experiments comparing automated and expert manual segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease- and gene-related alterations improved, as the number of atlases, N, was increased from 1 to 9. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases. We formulated a statistical stopping criterion to determine the optimal number of atlases to use. Healthy ApoE4-carriers and those with AD showed local ventricular abnormalities. This high-throughput method for morphometric studies further motivates the combination of genetic and neuroimaging strategies in predicting AD progression and treatment response.     

The repair of gamma-radiation-induced DNA damage is inhibited by microcystin-LR, the PP1 and PP2A phosphatase inhibitor

The genotoxic activity of microcystin-LR (MC-LR) is a matter of debate. MC-LR is known to be a phosphatase inhibitor and it may be expected that it is involved in the regulation of the activity of DNA-dependent protein kinase (DNA-PK), the key enzyme involved in the repair of radiation-induced DNA damage. We studied the effect of MC-LR on the repair capacity of radiation-induced DNA damage in human lymphocytes and human glioblastoma cell lines MO59J and MO59K. A dose of 0.5 microg/ml of MC-LR was chosen because it induced very little early apoptosis which gives no false positive results in the comet assay. Human lymphocytes in G0-phase of the cell cycle were pre-treated with MC-LR for 3 h and irradiated with 2 Gy of gamma radiation. The kinetics of DNA repair was assessed by the comet assay. In addition the frequencies of chromosomal aberrations were analysed. The pre-treatment with MC-LR inhibited the repair of radiation-induced damage and lead to enhanced frequencies of chromosomal aberrations including dicentric chromosomes. The results of a split-dose experiment, where cells were exposed to two 1.5 Gy doses of radiation separated by 3 h with or without MC-LR, confirmed that the toxin increased the frequency of dicentric chromosomes. We also determined the effect of MC-LR and ionizing radiation on the frequency of gamma-H2AX foci. The pre-treatment with MC-LR resulted in reduced numbers of gamma-H2AX foci in irradiated cells. In order to elucidate the impact of MC-LR on DNA-PK we examined the kinetics of DNA repair in human glioblastoma MO59J and MO59K cells. Both cell lines were exposed to 10 Gy of X-rays and DNA repair was analysed by the comet assay. A strong inhibitory effect was observed in the MO59K but not in the MO59J cells. These results indicate that DNA-PK might be involved in DNA repair inhibition by MC-LR.     

De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities,developmental delay,intellectual disability and dysmorphic features

Gross deletions involving the MEIS2 gene have been described in a small number of patients with overlapping phenotypes of atrial or ventricular septal defects, cleft palate, and variable developmental delays and intellectual disability. Non‐specific dysmorphic features were noted in some patients, including broad forehead with high anterior hairline, arched eyebrows, thin or tented upper lip, and short philtrum. Recently, a patient with a de novo single amino acid deletion, c.998_1000delGAA (p.Arg333del), and a patient with a de novo nonsense variant, (c.611C>G, p.Ser204*), were reported with a similar, but apparently more severe phenotypes. Clinical whole exome sequencing (WES) performed at our clinical molecular diagnostic laboratory identified four additional patients with predicted damaging de novo MEIS2 missense variants. Our patients’ features closely resembled those previously reported in patients with gross deletions, but also included some less commonly reported features, such as autism spectrum disorder, hearing loss, and short stature, as well as features that may be unique to nucleotide‐level variants, such as hypotonia, failure to thrive, gastrointestinal, skeletal, limb, and skin abnormalities. All of the observed missense variants, Pro302Leu, Gln322Leu, Arg331Lys, and Val335Ala, are located in the functionally important MEIS2 homeodomain. Pro302Leu is found in the region between helix 1 and helix 2, while the other three are located in the DNA‐binding helix 3. To our knowledge, these are the first described de novo missense variants in MEIS2, expanding the known mutation spectrum of the newly recognized human disorder caused by aberrations in this gene.     

Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions

For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in ‘healthy’ non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h ² ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h ² (vh ²) as an indicator of connectivity dynamics. We observe significant positive IMCC for h ² and vh ², for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h ² and vh ² were found to be differently modified as a function of different epileptic processes: compared to NIZ, \(h_{\text{BOLD}}^{2}\) was higher in IZ1, but lower in IZ2, while \(h_{\text{icEEG}}^{2}\) showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal \(h_{\text{BOLD}}^{2}\) and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.     

Reciprocal peer teaching: students teaching students in the gross anatomy laboratory

Three common instructional strategies used to teach gross anatomy are lecture, discovery or inquiry-based learning, and cooperative learning. One form of cooperative learning, called reciprocal peer teaching (RPT), illustrates circumstances where students alternate roles as teacher and student. By assuming the responsibility of teaching their peers, students not only improve their understanding of course content, but also develop communication skills, teamwork, leadership, confidence and respect for peers that are vital to developing professionalism early in their medical careers. Traditionally in our Anatomy department, students dissect the entire body using a standard dissection manual. More non-traditionally, however, we have increased cooperative learning in the dissection laboratory by involving students in a series of supplementary RPT activities. During these exercises, 10% of the class practiced their demonstration with course instructors until the students felt prepared to demonstrate the exercise to their classmates. We designed one peer demonstration emphasizing three to six teaching objectives for most of the 40 dissection units. This resulted in a compendium of peer demonstrations for implementation throughout the course. The multitude of diverse exercises permitted each student many opportunities to teach their peers. A debriefing questionnaire was administered at the end of the course demonstrating that 100% of students agreed the RPT experience increased their understanding of the topics they taught and 97% agreed it increased their retention of information they taught to their peers. In addition, 92% agreed that RPT improved their communication skills, which can be applied beyond anatomy to their careers as future physicians.