Meta-analysis of overnight closed-loop randomized studies in children and adults with type 1 diabetes: the Cambridge cohort

Aim

We reviewed the safety and efficacy of overnight closed-loop insulin delivery compared with conventional continuous subcutaneous insulin infusion (CSII) in two distinct age groups with type 1 diabetes mellitus (T1DM), young people aged 5 to 18 years and adults, combining data of previously published randomized studies.

Methods

We evaluated four randomized crossover studies in 17 children and adolescents [13.4 ± 3.6 years; mean ± standard deviation (SD)] and 24 adults (37.5 ± 9.1 years) on 45 closed-loop (intervention) and 45 CSII (control) visits. Each subject attended for two overnight study visits, using either closed-loop or conventional pump therapy, in random order. In each age group, studies were designed to mimic realistic likely scenarios. In the children and adolescent studies, closed loop was used following a standard evening meal and following 40 min of moderate-intensity exercise. In the adult studies, closed loop was commenced following a 60 g carbohydrate meal or a 100 g carbohydrate meal accompanied by alcohol. The primary outcome measure was time for which plasma glucose was within target range (3.91–8.0 mmol/liter).

Results

Overnight closed loop increased the time in target plasma glucose in both young (from 40% to 60%, p = .002) and adults (from 50% to 76%, p < .001) compared with conventional CSII. Combined analysis showed an increase from 43% to 71% with closed loop (p < .001). Additionally, closed loop reduced the time spent below 3.91 mmol/liter and above 8.0 mmol/liter, from 4.1% to 2.1% (p = .01) and 33% to 20% (p = .03), respectively. Glycemic variability, as measured by the SD of plasma glucose, was lower during closed loop compared with CSII (1.5 versus 2.1 mmol/liter, p = .007).

Conclusions

Overnight closed loop may improve glycemic control and reduce nocturnal hypoglycemia in both young people and adults with T1DM.     

The cytoskeleton in papillomavirus infection

Cytoskeleton defines the shape and structural organization of the cell. Its elements participate in cell motility, intracellular transport and chromosome movement during mitosis. Papillomaviruses (PV) are strictly epitheliotropic and induce self-limiting benign tumors of skin and mucosa, which may progress to malignancy. Like many other viruses, PV use the host cytoskeletal components for several steps during their life cycle. Prior to internalization, PV particles are transported along filopodia to the cell body. Following internalization, retrograde transport along microtubules via the dynein motor protein complex is observed. In addition, viral minichromosomes depend on the host cell machinery for partitioning of viral genomes during mitosis, which may be affected by oncoproteins E6 and E7 of high-risk human PV types. This mini-review summarizes recent advances in our understanding of papillomavirus' interactions with the host cell cytoskeletal elements.     

Complement activation by carbon nanotubes

Carbon nanotube interaction with an important part of the innate immune system, complement, needs to be taken into account when envisaging their use in biomedical applications. Carbon nanotubes (CNTs) and other synthetic materials are recognized by various components of the complement system in human or mammalian blood and also collectins in the lungs. Modification of the surface chemistry of CNTs alters their interactions with complement proteins and collectins. Functionalizations of CNTs which have been tested so far do not completely prevent complement activation or plasma protein binding. The interaction of the functionalized CNTs with the complement system proteins in blood may influence the adhesion of CNTs to phagocytic cells and red blood cells. Excessive activation of complement can have a harmful effect on human tissues and therefore significantly limit CNT applications in biomedicine.     

Internal motion of the vagina after hysterectomy for gynaecological cancer

Background and purpose

The purpose of this study was to investigate position changes of the vagina after hysterectomy for early stage cervical or endometrial cancer and their impact on CTV-PTV margins. We also studied their correlation with surrounding organ filling.

Materials and methods

Fifteen patients underwent T2-weighted MR scans before and weekly during the course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were derived from the boundaries of the CTVs in the main directions and correlated with changes in the volumes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage.

Results

The vaginal CTVs change their position in the pelvis during time with a maximum in anterior-posterior direction. The 95% confidence level was 2.3 cm into the anterior or posterior direction, 1.8 cm to left or right and 1.5 cm towards the cranial. With a homogenous 1.5 cm CTV-PTV margin ?5% inadequately covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin of 1.0 cm. Concerning the impact of organ filling on vaginal position changes we found the only significant correlation with rectal volume and shift of the vagina towards anterior-posterior.

Conclusion

To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins should be generated with the largest size in the anterior-posterior direction. The position shifts were only weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the bladder.     

Evaluation of CSF-Chlamydia pneumoniae,CSF-tau,and CSF-Abeta42 in Alzheimer’s disease and vascular dementia

The potential role of microbiological factors such as Chlamydia pneumoniae (ChP) in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD) and vascular dementia (VD), has been suggested, but the correctness of this hypothesis still needs to be tested. In this study the appearance of ChP in the cerebrospinal fluid (CSF) of 57 AD and 21 VD patients and in 47 controls (CG) as well as the influence of ChP on the levels of tau protein and Abeta42 were investigated. The frequency of ChP occurrence in the AD patient group (43.9%) was significantly higher (p < 0.001) than in the control group (10.6%). In the case of VD patients, 9.5% of this group was positive for ChP. The presence of ChP DNA in the CSF of patients with AD significantly increases the occurrence of this disease (odds ratio = 7.21). Cerebrospinal fluid Abeta42 levels were significantly lower in patients with AD than in the CG (p < 0.001). Cerebrospinal tau protein was significantly higher in AD vs. CG (p = 0.007). However, no relationships between the presence of the bacterium in CSF and the level of either tau or Abeta42 protein were observed. In conclusion, we may suspect that testing for the presence of ChP in CSF, along with the tau and Abeta42 markers, may be used in the clinic diagnosis of AD.     

Temporally graded activation of neocortical regions in response to memories of different ages

The temporally graded memory impairment seen in many neurobehavioral disorders implies different neuroanatomical pathways and/or cognitive mechanisms involved in storage and retrieval of memories of different ages. A dynamic interaction between medial-temporal and neocortical brain regions has been proposed to account for memory's greater permanence with time. Despite considerable debate concerning its time-dependent role in memory retrieval, medial-temporal lobe activity has been well studied. However, the relative participation of neocortical regions in recent and remote memory retrieval has received much less attention. Using functional magnetic resonance imaging, we demonstrate robust, temporally graded signal differences in posterior cingulate, right middle frontal, right fusiform, and left middle temporal regions in healthy older adults during famous name identification from two disparate time epochs. Importantly, no neocortical regions demonstrated greater response to older than to recent stimuli. Our results suggest a possible role of these neocortical regions in temporally dating items in memory and in establishing and maintaining memory traces throughout the lifespan. Theoretical implications of these findings for the two dominant models of remote memory functioning (Consolidation Theory and Multiple Trace Theory) are discussed.     

Sensory learning-induced enhancement of inhibitory synaptic transmission in the barrel cortex of the mouse

In adult mice, repetitive pairing of stimulation of mystacial vibrissae with an electrical shock to the tail induces expansion of the cortical representation of stimulated vibrissae accompanied by elevation of the GABAergic markers. Here, we show that this associative learning paradigm results in a selective increase in the frequency of spontaneous inhibitory postsynaptic currents in layer IV excitatory neurons located within the barrel representing stimulated vibrissae, evident 24 h after the end of training. The mean amplitude of spontaneous inhibitory postsynaptic potentials recorded from excitatory neurons was unchanged. Recordings from layer IV excitatory and fast spiking neurons showed that the training induced changes neither in the mean frequency nor it the mean amplitude of spontaneous excitatory postsynaptic currents. On the other hand, the mean amplitude of field potentials evoked by the stimulation of layer VI and recorded in layer IV was significantly reduced. These data indicate that aversive training results in a selective and long-lasting enhancement of GABAergic transmission within the cortical representation of stimulated vibrissae, which may result in a decrease in layer VI-evoked field responses.     

Giant cell ependymoma: a case report

Ependymomas account for 3-9% of all neuroepithelial tumors. A peculiar variant of ependymoma known as "giant cell ependymoma" ("GCE") is especially rarely reported, it may pose some difficulties for the diagnosing neuropathologist. Here we present a case of a giant cell ependymoma occuring in a 17-year-old patient with the history of 2-year recurrent headaches and a 1-month history of vision impairment. CT scanning demonstrated a mass in the left occipital lobe, arising from the occipital horn of the lateral ventricle. Histological, immunohistochemical and electron microscopic findings were consistent with high-grade ependymoma. Especially striking was the presence of bizzare pleomorphic giant cells which predominated in the tumor tissue. As a result the diagnosis of GCE was established. This type of neoplasm necessitates, at least in theory, differentiation with anaplastic oligodendroglioma, clear cell ependymoma, pleomorphic xanthoastrocytoma, giant cell glioblastoma, and subependymal giant cell astrocytoma. To date giant cell ependymomas (GCEs) were reported in seven cases in the literature. To the best of our knowledge this is the 8th case in the literature. In spite of apparently "worrisome" histology GCE seems to be a neoplasm with a relatively good prognosis.