Congenital heart defects in offspring of women with Type 2 diabetes - a systematic review.

INTRODUCTION: The risk of congenital heart defects in the offspring of women with Type 2 diabetes is only sparsely described. The aim of this review was to estimate the prevalence of congenital heart defects in offspring of women with Type 2 diabetes in comparison to offspring of women with Type 1 diabetes and to offspring of the background population. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A literature search was performed in the PubMed, Embase and Cochrane databases. Studies were included if they were published from 2007 to 2018, comprised a minimum of 200 offspring of women with Type 2 diabetes and examined the prevalence of congenital heart defects. RESULTS: Five cohort studies with a total of 23,845 offspring of women with Type 2 diabetes were included. The studies were heterogeneous with respect to method of diagnosis and whether terminated pregnancies were included, and a meta-analysis could not be performed. The mean prevalence of congenital heart defects was 44 (range: 26-65) per 1,000 offspring. The mean relative risk was 0.82 (range: 0.53-1.01) compared with offspring of women with Type 1 diabetes, and 3.83 (range: 2.53-5.49) compared with the background population. A positive association was described between the prevalence of congenital heart defects and the maternal glycated haemoglobin level, but not with medical treatment. CONCLUSIONS: The risk of congenital heart defects among offspring of women with Type 2 diabetes was comparable to that of offspring of women with Type 1 diabetes and almost four times higher than in the background population.

Neurostereologic Lesion Volumes and Spreading Depolarizations in Severe Traumatic Brain Injury Patients: A Pilot Study.

BACKGROUND: Spreading depolarizations (SDs) occur in 50-60% of patients after surgical treatment of severe traumatic brain injury (TBI) and are independently associated with unfavorable outcomes. Here we performed a pilot study to examine the relationship between SDs and various types of intracranial lesions, progression of parenchymal damage, and outcomes. METHODS: In a multicenter study, fifty patients (76% male; median age 40) were monitored for SD by continuous electrocorticography (ECoG; median duration 79 h) following surgical treatment of severe TBI. Volumes of hemorrhage and parenchymal damage were estimated using unbiased stereologic assessment of preoperative, postoperative, and post-ECoG serial computed tomography (CT) studies. Neurologic outcomes were assessed at 6 months by the Glasgow Outcome Scale-Extended. RESULTS: Preoperative volumes of subdural and subarachnoid hemorrhage, but not parenchymal damage, were significantly associated with the occurrence of SDs (P's < 0.05). Parenchymal damage increased significantly (median 34 ml [Interquartile range (IQR) - 2, 74]) over 7 (5, 8) days from preoperative to post-ECoG CT studies. Patients with and without SDs did not differ in extent of parenchymal damage increase [47 ml (3, 101) vs. 30 ml (- 2, 50), P = 0.27], but those exhibiting the isoelectric subtype of SDs had greater initial parenchymal damage and greater increases than other patients (P's < 0.05). Patients with temporal clusters of SDs (≥ 3 in 2 h; n = 10 patients), which included those with isoelectric SDs, had worse outcomes than those without clusters (P = 0.03), and parenchymal damage expansion also correlated with worse outcomes (P = 0.01). In multivariate regression with imputation, both clusters and lesion expansion were significant outcome predictors. CONCLUSIONS: These results suggest that subarachnoid and subdural blood are important primary injury factors in provoking SDs and that clustered SDs and parenchymal lesion expansion contribute independently to worse patient outcomes. These results warrant future prospective studies using detailed quantification of TBI lesion types to better understand the relationship between anatomic and physiologic measures of secondary injury.

Early focal brain injury after subarachnoid hemorrhage correlates with spreading depolarizations.

OBJECTIVE: To investigate whether spreading depolarization (SD)-related variables at 2 different time windows (days 1-4 and 5-8) after aneurysmal subarachnoid hemorrhage (aSAH) correlate with the stereologically determined volume of early focal brain injury on the preinterventional CT scan. METHODS: In this observational multicenter study of 54 patients, volumes of unaffected brain tissue, ventricles, cerebellum, aSAH, intracerebral hemorrhage, and focal parenchymal hypodensity were stereologically estimated. Patients were electrocorticographically monitored using subdural electrodes for 81.8 hours (median) (interquartile range: 70.6-90.5) during days 1-4 (n = 54) and for 75.9 (59.5-88.7) hours during days 5-8 (n = 51). Peak total SD-induced depression duration of a recording day (PTDDD) and peak numbers of (1) SDs, (2) isoelectric SDs, and (3) spreading depressions of a recording day were determined following the recommendations of the Co-Operative Studies on Brain Injury Depolarizations. RESULTS: Thirty-three of 37 patients with early focal brain injury (intracerebral hemorrhage and/or hypodensity) in contrast to 7 of 17 without displayed SDs during days 1-4 (sensitivity: 89% [95% confidence interval, CI: 75%-97%], specificity: 59% [CI: 33%-82%], positive predictive value: 83% [CI: 67%-93%], negative predictive value: 71% [CI: 42%-92%], Fisher exact test, p < 0.001). All 4 SD-related variables during days 1-4 significantly correlated with the volume of early focal brain injury (Spearman rank order correlations). A multiple ordinal regression analysis identified the PTDDD as the most important predictor. CONCLUSIONS: Our findings suggest that early focal brain injury after aSAH is associated with early SDs and further support the notion that SDs are a biomarker of focal brain lesions.

The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review.

AIMS/HYPOTHESIS: We assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2) diabetes and investigated if the rate of congenital malformations was similar in women with near-normal glycemic control compared to the background population. We also assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational diabetes with special focus on women with near-normal HbA1c in early pregnancy. MATERIALS AND METHODS: This is a literature review based on an electronic literature search of the databases PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the search terms diabetes, pregnancy, HbA1c or glycemic control and congenital anomaly or congenital anomaly. We included original papers in English published after 1997 with data on congenital malformations and HbA1c in at least 250 women with pregestational diabetes. RESULTS: Nine papers with in total 6225 women with type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in women with type 2 diabetes and for the combined group of women with pregestational diabetes, the relative risk compared to the background population was 3.2. In women with HbA1c < 53 mmol/mol (7.0%) in early pregnancy or HbA1c 53-64 mmol/mol (7.0-8.0%) the prevalence of congenital malformations was 4.3 and 3.7%, respectively, with a relative risk of 2.2 and 1.9, respectively. CONCLUSIONS: In pregnant women with pregestational diabetes the prevalence of congenital abnormalities was threefold higher in women with pregestational diabetes compared to the background population. However, HbA1c below 53 mmol/mol (7.0%) in early pregnancy was also associated with a two times increased risk of congenital malformations compared to the background population.

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Quantitative relationships in delphinid neocortex.

Possessing large brains and complex behavioral patterns, cetaceans are believed to be highly intelligent. Their brains, which are the largest in the Animal Kingdom and have enormous gyrification compared with terrestrial mammals, have long been of scientific interest. Few studies, however, report total number of brain cells in cetaceans, and even fewer have used unbiased counting methods. In this study, using stereological methods, we estimated the total number of cells in the neocortex of the long-finned pilot whale (Globicephala melas) brain. For the first time, we show that a species of dolphin has more neocortical neurons than any mammal studied to date including humans. These cell numbers are compared across various mammals with different brain sizes, and the function of possessing many neurons is discussed. We found that the long-finned pilot whale neocortex has approximately 37.2 × 10(9) neurons, which is almost twice as many as humans, and 127 × 10(9) glial cells. Thus, the absolute number of neurons in the human neocortex is not correlated with the superior cognitive abilities of humans (at least compared to cetaceans) as has previously been hypothesized. However, as neuron density in long-finned pilot whales is lower than that in humans, their higher cell number appears to be due to their larger brain. Accordingly, our findings make an important contribution to the ongoing debate over quantitative relationships in the mammalian brain.

Comparison of quantitative estimation of intracerebral hemorrhage and infarct volumes after thromboembolism in an embolic stroke model.

BACKGROUND: Strokes have both ischemic and hemorrhagic components, but most studies of experimental stroke only address the ischemic component. This is likely because investigations of hemorrhagic transformation are hindered by the lack of methods based on unbiased principles for volume estimation. AIMS: We evaluated different methods for estimating the volume of infarcts, hemorrhages, after embolic middle cerebral artery occlusion with or without thrombolysis. METHODS: An experimental thromboembolytic rat model was used in this study. The rats underwent surgery and were placed in two groups. Group 1 was treated with saline, and group 2 was treated with 20 mg/kg recombinant tissue plasminogen activator to promote intracerebral hemorrhages. Stereology, semiautomated computer estimation, and manual erythrocyte counting were used to test the precision and efficiency of determining the size of the infarct and intracerebral hemorrhage. RESULTS: No differences were observed in the infarct volume or amount of bleeding when comparing the three methods of volume estimation. Although semiautomated computer estimation and manual erythrocyte counting provided similar results as the stereological measurements, the stereological method was the most efficient and advantageous. CONCLUSIONS: We found that stereology was the superior method for quantification of hemorrhagic volume, especially for rodent petechial bleeding, which is otherwise difficult to measure. Our results suggest the possibility of measuring both the ischemic and the hemorrhagic components of stroke, two parameters that may be differentially regulated when therapeutic regimens are tested.

Application of stereological methods to estimate post-mortem brain surface area using 3T MRI.

The Cavalieri and Vertical Sections methods of design based stereology were applied in combination with 3 tesla (i.e. 3T) Magnetic Resonance Imaging (MRI) to estimate cortical and subcortical volume, area of the pial surface, area of the grey-white matter boundary, and thickness of the cerebral cortex. The material comprises eight human cadaveric cerebri which had been separated into sixteen cerebral hemisphere specimens prior to embedding in agar gel. The results from MRI were compared with corresponding 'gold standard' values subsequently obtained by application of the same methodology using physical sectioning of the specimens. 95% agreement intervals revealed poor agreement between MR imaging and physical sectioning, specially for pial surface and thickness, as well as cerebral cortex and subcortex volumes. On average, pial surface area was estimated to be almost half the extent using MRI compared to physical sectioning (i.e. 45%, p<0.05) and the average thickness of the cerebral cortex was calculated to be much greater (by 60.9%) on the MR images compared to the physical sections (3.7mm versus 2.3mm, p<0.001). The main cause of the discrepancies is that the resolution of the MR images is not sufficient to always allow reliable depiction of the cerebral sulci on 2D image sections. Accurate application of manual stereological methods for measuring the cortical surface area thus requires higher resolution MR imaging than is typically applied at 3T.

[Abscess in the spleen in a 28 year-old, previously healthy man]. / Miltabsces hos en 28-årig, tidligere rask mand.

A 28 year-old, previously healthy man was hospitalised with acute abdominal pain and a high fever. During six months the patient had suffered from severe pain in his left shoulder, left part of the thorax and over time also in the upper part of the abdomen. When hospitalised he showed biochemical signs of infection and a computer tomography of the abdomen revealed an 11 cm abscess in the spleen. Non-haemolytic streptococci were found after aspiration. Initially the abscess was treated with antibiotics and ultrasound-guided drainage. Due to lack of curative effect of drainage splenectomy was finally performed.

[Tracing exposed flight passengers after discovery of pulmonary tuberculosis]. / Smitteopsporing efter fund af lungetuberkulose hos flyrejsende.

During international air travel individuals stay in a closed environment which might lead to a risk of transmission of respiratory infectious diseases such as tuberculosis carried by infectious travellers. Tracing exposed passengers requires international cooperation and assistance from relevant authorities. We describe an investigation among fellow passengers to a traveller with sputum positive pulmonary tuberculosis.

Trouble-shooting deployment and recovery options for various stationary passive acoustic monitoring devices in both shallow- and deep-water applications.

Deployment of any type of measuring device into the ocean, whether to shallow or deeper depths, is accompanied by the hope that this equipment and associated data will be recovered. The ocean is harsh on gear. Salt water corrodes. Currents, tides, surge, storms, and winds collaborate to increase the severity of the conditions that monitoring devices will endure. All ocean-related research has encountered the situations described in this paper. In collating the details of various deployment and recovery scenarios related to stationary passive acoustic monitoring use in the ocean, it is the intent of this paper to share trouble-shooting successes and failures to guide future work with this gear to monitor marine mammal, fish, and ambient (biologic and anthropogenic) sounds in the ocean-in both coastal and open waters.

A neurological comparative study of the harp seal (Pagophilus groenlandicus) and harbor porpoise (Phocoena phocoena) brain.

The cetacean brain is well studied. However, few comparisons have been done with other marine mammals. In this study, we compared the harp seal (Pagophilus groenlandicus) and the harbor porpoise brain (Phocoena phocoena). Stereological methods were applied to compare three areas of interest: the entire neocortex and two subdivisions of the neocortex, the auditory and visual cortices. The total number of neurons and glial cells in the three regions was estimated. The main results showed that the harbor porpoise have an estimated 14.9 × 10(9) neocortical neurons and 34.8 × 10(9) neocortical glial cells, whereas the harp seal have 6.1 × 10(9) neocortical neurons and 17.5 × 10(9) neocortical glial cells. The harbor porpoise have significantly more neurons and glial cells in the auditory cortex than in the visual cortex, whereas the pattern was opposite for the harp seal. These results are the first to provide estimates of the number of neurons and glial cells in the neocortex of the harp seal and harbor porpoise brain and offer new data to the comparative field of mammalian brain evolution.

Age and Parkinson's disease-related neuronal death in the substantia nigra pars compacta.

During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder of this system, Parkinson's disease, is characterized by a selective, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. This review includes studies quantifying age and Parkinson's-related changes of the substantia nigra, with emphasis on stereological studies performed in the substantia nigra pars compacta.

Validation of in vitro probabilistic tractography.

Diffusion weighted imaging (DWI) and tractography allow the non-invasive study of anatomical brain connectivity. However, a gold standard for validating tractography of complex connections is lacking. Using the porcine brain as a highly gyrated brain model, we quantitatively and qualitatively assessed the anatomical validity and reproducibility of in vitro multi-fiber probabilistic tractography against two invasive tracers: the histochemically detectable biotinylated dextran amine and manganese enhanced magnetic resonance imaging. Post mortem DWI was used to ensure that most of the sources known to degrade the anatomical accuracy of in vivo DWI did not influence the tracking results. We demonstrate that probabilistic tractography reliably detected specific pathways. Moreover, the applied model allowed identification of the limitations that are likely to appear in many of the current tractography methods. Nevertheless, we conclude that DWI tractography can be a precise tool in studying anatomical brain connectivity.

Total neocortical cell number in the mysticete brain.

The cetacean brain has long been of scientific interest, not only because of its large size - the largest in the animal kingdom - but also because of its high gyrification. It shows several adaptations to the aquatic environment, especially in the cortical arrangements of functional areas. To study structural aspects of the mysticete brain we estimated neocortical features in the common minke whale using stereological methods. The neocortex was surprisingly thick, equal to that in humans. The total neocortical neuron number was 12.8 x 10(9), and the total neocortical glia number 98.2 x 10(9). Total cell numbers in the auditory and visual cortex were also estimated, and showed that the auditory cortex contained more cells than the visual cortex. In this small sample, no sexual dimorphism was seen within the neocortex of the common minke whale. Our aim was to estimate the total cell number, cortical volume and cell density in the entire mysticete neocortex and compare the total cell number in the auditory cortex with that of the visual cortex using stereological methods. Here, we used the common minke whale as a model of all mysticetes. We wanted to compare these neocortical features to those of other mammals to forward understanding of the evolution of the mammalian brain.

Can the Glycemic Index (GI) be used as a tool in the prevention and management of Type 2 diabetes?

The large increase in type 2 diabetes (T2DM), the considerable lifetime risk of diabetes and the loss of lifetime call for concerted action to prevent T2DM and its complications. Since diabetes is characterized by abnormal glucose metabolism, the question arises of whether a high intake of carbohydrates that are rapidly absorbed as glucose may increase the risk and worsen the course of T2DM. To quantify the impact of carbohydrates on blood glucose the glycemic index (GI) and the glycemic load (GL) have been applied. The GI of a food is a method of ranking carbohydrate rich foods according to their glycemic responses. GI is defined as the incremental area under the blood glucose curve of 50g carbohydrate of a test food expressed as a percentage of the area of the response to an equivalent amount of a reference food (glucose or white bread). In relation to GI/GL and prevention of T2DM there is insufficient information from observational studies to determine whether a positive association exists or not. Only randomized controlled clinical intervention studies will be able to provide the final answer. From meta-analyses of randomised controlled clinical trials comparing low and high GI diets in the treatment of diabetes it has been found that low GI diets improve the glycemic control. Labeling of foods with GI would be helpful for persons with diabetes, but the usefulness for healthy subjects remains to be clarified. At present it seems premature to introduce GI labeling for the entire population.