Ring Chromosome 7 Presenting with Intrauterine Growth Restriction and Multiple Anomalies

SummaryObjectiveRing chromosome 7 is a very rare chromosomal anomaly that may have a grave prognosis. Nevertheless, the clinical features associated with ring chromosome 7 are highly variable. Here, we report a case with ring chromosome 7 and the perinatal findings.Case ReportA 32-year-old, gravida 1, para 0, woman was referred to our hospital because of intrauterine growth restriction (IUGR) and oligohydramnios at 35 weeks of gestation. Prenatal ultrasound revealed a severe IUGR fetus presenting with multicystic kidney, hydronephrosis and oligohydramnios. At parturition, the birth weight of this male infant was 1,720 g, and a battery of anomalies were also noted, including imperforate anus, hypospadia, micropenis, right cryptorchidism, severe IUGR, multiple nevi on the forehead, shoulder and left thigh, brain atrophy, right multicystic kidney, and left mild hydronephrosis. Cytogenetic study from cord blood revealed a ring chromosome 7.ConclusionRing chromosome 7 is extremely rare and our case might be the 15th and youngest case in the medical literature. Our case had multicystic kidney and imperforate anus, which have not been reported previously. Prenatal diagnosis of ring chromosome 7 is very difficult. When fetuses present with severe IUGR, oligohydramnios and multicystic kidney, chromosomal aberrations should be kept in mind, and perinatal cytogenetic workup is warranted

Hospital admissions for respiratory system diseases in adults with intellectual disabilities in Southeast London:a register-based cohort study

BACKGROUND: Intellectual disability (ID) carries a high impact on need for care, health status and premature mortality. Respiratory system diseases contribute a major part of mortality among people with ID, but remain underinvestigated as consequent morbidities. METHODS: Anonymised electronic mental health records from the South London and Maudsley Trust (SLaM) were linked to national acute medical care data. Using retrospective cohort and matched case–control study designs, adults with ID receiving SLaM care between 1 January 2008 and 31 March 2013 were identified and compared with local catchment residents for respiratory system disease admissions. Standardised admission ratios (SARs) were first calculated, followed by a comparison of duration of hospitalisation with respiratory system disease between people with ID and age-matched and gender-matched random counterparts modelled using linear regression. Finally, the risk of readmission for respiratory system disease was analysed using the Cox models. RESULTS: For the 3138 adults with ID identified in SLaM, the SAR for respiratory system disease admissions was 4.02 (95% CI 3.79 to 4.26). Compared with adults without ID, duration of hospitalisation was significantly longer by 2.34 days (95% CI 0.03 to 4.64) and respiratory system disease readmission was significantly elevated (HR=1.35; 95% CI 1.17 to 1.56) after confounding adjustment. CONCLUSIONS: Respiratory system disease admissions in adults with ID are more frequent, of longer duration and have a higher likelihood of recurring. Development and evaluation of potential interventions to the preventable causes of respiratory diseases should be prioritised

Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials

Shallow Subsurface Structure in the Hualien Basin and Relevance to the Damage Pattern and Fault Rupture during the 2018 Hualien Earthquake

The 2018 M[w] 6.4 Hualien earthquake generated a large peak-to-peak velocity of over 2  m/s, with a period of 3 s at the south end of the Milun fault, which resulted in the collapse of five buildings. To investigate the shallow subsurface soil structure and evaluate possible effects on the ground motion and building damage, we performed microtremor measurements in the Hualien basin. Based on the velocity structure jointly inverted from both Rayleigh-wave dispersion curves and microtremor horizontal-to-vertical spectral ratio data, we found that the shallow subsurface structure generally deepens from west to east. Close to the Milun fault, the structure becomes shallower, which is consistent with faulting during the 2018 earthquake and the long-term tectonic displacement. There is no significant variation for the site conditions in the north–south direction that can explain the large peak ground velocity in the south. As a result of the dense measurements in the heavily damaged area, where three high-rise buildings totally collapsed, these locations have the average S-wave velocity of the upper 30 m (AVs₃₀) values and are relatively high compared to the more distant area from the Meilun River. This is somewhat unusual, because lower AVs₃₀ values indicating softer ground conditions are expected close to the river. We did not find any characteristic subsurface soil structure that may contribute to the building collapses. The large 3 s pulse was probably generated by source effects, rather than subsurface soil amplification

Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia

Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, “Chen Pi.” Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4H/PDE4L) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation

The 2005 Ilan earthquake doublet and seismic crisis in northeastern Taiwan: evidence for dyke intrusion associated with on-land propagation of the Okinawa Trough

Northern Taiwan underwent mountain building in the early stage of the Taiwan orogeny but is currently subjected to post-collisional crustal extension. It may be related to gravitational collapse or to the rifting of the Okinawa Trough, which lies offshore northeastern Taiwan. The Ilan Plain, northeastern Taiwan, which is bounded by the normal fault systems and filled up with thick Pliocene–Pleistocene sedimentary sequences, formed under such an extension environment. Over there on 2005 March 5 two earthquakes with about the same magnitude (M_L = 5.9) occurred within 68 s and produced intense aftershocks activity according to the records of Central Weather Bureau Seismic Network of Taiwan. We relocated the earthquake sequence by the three-dimension earthquake location algorithm with the newly published 3-D Vp and Vp/Vs velocity model, and determined the first-polarity focal mechanisms of the earthquake doublet. One major cluster of aftershocks which trends E–W and dips steeply to the south can be identified and picked up as a potential fault plane. The focal mechanisms of the two main shocks are both classified as normal type by first-polarity but strike-slip by centroid moment tensor inversion; however two methods both yield consistent E–W strike. Static coseismic deformation was additionally determined from Global Positioning System (GPS) daily solutions at a set of continuous GPS stations and from strong-motion seismographs. These data show NW–SE extension at high angle to the fault plane, which cannot be explained from a simple strike-slip double-couple mechanism. On the other hand, the small vertical displacements and steep fault plane cannot be explained from a simple normal event as well. We present from elastic dislocation modelling that the geodetic data are best explained by significant component of tensile source with centimetre-scale of opening on a 15-km-long fault extending from 1 to 13 km depth. We therefore interpret the crisis as the result of dyke intrusion at the very tip of the Okinawa Trough, which is reasonably driven by backarc spreading

Spin State Disproportionation in Insulating Ferromagnetic LaCoO3 Epitaxial Thin Films

The origin of insulating ferromagnetism in epitaxial LaCoO3 films under tensile strain remains elusive despite extensive research efforts have been devoted. Surprisingly, the spin state of its Co ions, the main parameter of its ferromagnetism, is still to be determined. Here, we have systematically investigated the spin state in epitaxial LaCoO3 thin films to clarify the mechanism of strain induced ferromagnetism using element-specific x-ray absorption spectroscopy and dichroism. Combining with the configuration interaction cluster calculations, we unambiguously demonstrate that Co3+ in LaCoO3 films under compressive strain (on LaAlO3 substrate) are practically a low spin state, whereas Co3+ in LaCoO3 films under tensile strain (on SrTiO3 substrate) have mixed high spin and low spin states with a ratio close to 1:3. From the identification of this spin state ratio, we infer that the dark strips observed by high-resolution scanning transmission electron microscopy indicate the position of Co3+ high spin state, i.e., an observation of a spin state disproportionation in tensile-strained LaCoO3 films. This consequently explains the nature of ferromagnetism in LaCoO3 films

Neurological Complications in Young Infants With Acute Bacterial Meningitis

We aimed to evaluate the occurrence, treatment, and outcomes of neurological complications after bacterial meningitis in young infants. A case series study from a retrospective cohort from two tertiary-level medical centers in Taiwan between 2007 and 2016 was conducted. Eighty-five young infants aged < 90 days with bacterial meningitis were identified. 25 (29.4%) were born at preterm. Group B Streptococcus (GBS) and Escherichia coli caused 74.1% of identified cases. Despite the majority (90.6%) initially received microbiologically appropriate antibiotics, 65 (76.5%) had experienced at least one neurological complication identified at a median of 6 days (range: 1–173) after onset of bacterial meningitis. The most common neurological complication was seizure (58.8%), followed by subdural effusion (47.1%), ventriculomegaly (41.2%), subdural empyema (21.2%), hydrocephalus (18.8%), ventriculitis (15.3%), periventricular leukomalacia (11.8%), and encephalomalacia (10.6%). Nine patients (10.6%) died (including 4 had critical discharge on request) and 29/76 (38.2%) of the survivors had major neurological sequelae at discharge. Nighteen (22.4%) received surgical intervention due to these complications. After multivariate logistic regression, initial seizure (adjusted odds ratio [aOR]: 4.76, 95% confidence interval [CI]: 1.7–13.0, P = 0.002) and septic shock (aOR: 6.04; 95% CI: 1.35–27.0, P = 0.019) were independent predictors for final unfavorable outcomes.Conclusions: Neurological complications and sequelae are common in young infants after bacterial meningitis. Patients presented with early seizure or septic shock can be an early predictor of final unfavorable outcomes and require close monitoring. Further research regarding how to improve clinical management and outcomes is warranted