The Fetal Brain Sparing Response to Hypoxia: Physiological Mechanisms

How the fetus withstands an environment of reduced oxygenation during life in the womb has been a vibrant area of research since this field was introduced by Joseph Barcroft, a century ago. Studies spanning five decades have since used the chronically instrumented fetal sheep preparation to investigate the fetal compensatory responses to hypoxia. This defence is contingent on the fetal cardiovascular system, which in late gestation adopts strategies to decrease oxygen consumption and redistribute the cardiac output away from peripheral vascular beds and towards essential circulations, such as those perfusing the brain. The introduction of simultaneous measurement of blood flow in the fetal carotid and femoral circulations by ultrasonic transducers has permitted investigation of the dynamics of the fetal brain sparing response for the first time. Now we know that major components of fetal brain sparing during acute hypoxia are triggered exclusively by a carotid chemoreflex and that they are modified by endocrine agents and the recently discovered vascular oxidant tone. The latter is determined by the interaction between nitric oxide and reactive oxygen species. The fetal brain sparing response matures as the fetus approaches term, in association with the prepartum increase in fetal plasma cortisol and treatment of the preterm fetus with clinically-relevant doses of synthetic steroids mimics this maturation. Despite intense interest into how the fetal brain sparing response may be affected by adverse intrauterine conditions, this area of research has been comparatively scant but it is likely to take centre stage in the near future.Dino Giussani is supported by the British Heart Foundation, The Biotechnology and Biological Sciences Research Council, The Royal Society, The Wellcome Trust, Action Medical Research and the Isaac Newton Trust. I am grateful to past and present members of my group and Professor Abigail Fowden and Dr Caroline Shaw for insightful discussion.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27109

Tort, Social Security, and No-Fault Schemes: Lessons from Real-World Experiments

Background Anthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years. Methods Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old. Results There were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV. Conclusions We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.Funding Agencies|Medical Research Council of Southeast Sweden||Center for Medical Image Science and Visualization (CMIV)||Linkoping University||Futurum||King Gustaf V and Queen Victoria Freemason Foundation||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council Grant|12661|</p

Atrial fibrillation and its association with type 2 diabetes and hypertension in a Swedish community.

Aim: To explore the prevalence of atrial fibrillation in patients with hypertension and type 2 diabetes and to identify possible mechanisms for the development of atrial fibrillation. Methods: A community-based, cross-sectional observational study was conducted in the primary health care in Skara, Sweden, and 1739 subjects (798 men, 941 women) were surveyed. Patients were categorized as those with hypertension only (n = 597); those with both hypertension and type 2 diabetes (n = 171), and those with type 2 diabetes only (n = 147). In the reference population, 824 normotensive subjects without diabetes were identified and used as controls. Participants were examined for cardiovascular risk factors including fasting blood glucose, serum insulin, blood pressure, lipids and anthropometric measures. Resting electrocardiogram (ECG) was recorded and Minnesota-coded. Insulin resistance was measured by the homeostasis model assessment (HOMA). Results: Age-adjusted prevalence of atrial fibrillation was 2% in patients with hypertension only, 6% in patients with both hypertension and type 2 diabetes, 4% in patients with type 2 diabetes only and 2% in controls, respectively. Age and sex adjusted odds ratios (OR) (95% CI) were; hypertension 0.7 (0.30-1.5), combined hypertension and type 2 diabetes 3.3 (1.6-6.7), and type 2 diabetes 2.0 (0.9-4.7). The association with combined hypertension and type 2 diabetes remained significant when adjusted for cardiovascular disease (CVD) risk factors and body mass index (BMI), was attenuated with adjustment for ischemic ECG; 2.4 (1.1-5.0) and lost significance with adjustment for insulin resistance; 1.3 (0.5-3.1). Conclusions: Atrial fibrillation is associated with the combined occurrence of type 2 diabetes and hypertension. Insulin resistance may be a common underlying mechanism

The assessment of renal function in relation to the use of drugs in elderly in nursing homes; a cohort study

Background Renal function decreases with age. Dosage adjustment according to renal function is   indicated for many drugs, in order to avoid adverse reactions of medications and/or   aggravation of renal impairment. There are several ways to assess renal function in   the elderly, but no way is ideal. The aim of the study was to explore renal function   in elderly subjects in nursing homes and the use of pharmaceuticals that may be harmful   to patients with renal impairment. Methods 243 elderly subjects living in nursing homes were included. S-creatinine and s-cystatin   c were analysed. Renal function was estimated using Cockcroft-Gault formula, Modification   of Diet in Renal Disease (MDRD) and cystatin C-estimated glomerular filtration rate   (GFR). Concomitant medication was registered and four groups of renal risk drugs were   identified: metformin, nonsteroidal anti-inflammatory drugs (NSAID), angiotensin-converting   enzyme -inhibitors/angiotensin receptor blockers and digoxin. Descriptive statistics   and the Kappa test for concordance were used. Results Reduced renal function (cystatin C-estimated GFR &lt; 60 ml/min) was seen in 53%. Normal   s-creatinine was seen in 41% of those with renal impairment. Renal risk drugs were   rather rarely prescribed, with exception for ACE-inhibitors. Poor concordance was   seen between the GFR estimates as concluded by other studies. Conclusions The physician has to be observant on renal function when prescribing medications to   the elderly patient and not only rely on s-creatinine level. GFR has to be estimated   before prescribing renal risk drugs, but using different estimates may give divergence   in the results

Совершенствование практической подготовки студентов на кафедре инфекционных болезней

ОБРАЗОВАНИЕ МЕДИЦИНСКОЕВУЗЫМЕДИЦИНСКИЕ УЧЕБНЫЕ ЗАВЕДЕНИЯПРАКТИЧЕСКАЯ ПОДГОТОВКАКАФЕДРА ИНФЕКЦИОННЫХ БОЛЕЗНЕЙСТУДЕНТЫ МЕДИЦИНСКИХ УЧЕБНЫХ ЗАВЕДЕНИ

Ectopic fat is associated with cardiac remodeling—A comprehensive assessment of regional fat depots in type 2 diabetes using multi-parametric MRI

BackgroundDifferent regional depots of fat have distinct metabolic properties and may relate differently to adverse cardiac remodeling. We sought to quantify regional depots of body fat and to investigate their relationship to cardiac structure and function in Type 2 Diabetes (T2D) and controls.MethodsFrom the SCAPIS cohort in Linköping, Sweden, we recruited 92 subjects (35% female, mean age 59.5 ± 4.6 years): 46 with T2D and 46 matched controls. In addition to the core SCAPIS data collection, participants underwent a comprehensive magnetic resonance imaging examination at 1.5 T for assessment of left ventricular (LV) structure and function (end-diastolic volume, mass, concentricity, ejection fraction), as well as regional body composition (liver proton density fat fraction, visceral adipose tissue, abdominal subcutaneous adipose tissue, thigh muscle fat infiltration, fat tissue-free thigh muscle volume and epicardial adipose tissue).ResultsCompared to the control group, the T2D group had increased: visceral adipose tissue volume index (P &lt; 0.001), liver fat percentage (P &lt; 0.001), thigh muscle fat infiltration percentage (P = 0.02), LV concentricity (P &lt; 0.001) and LV E/e'-ratio (P &lt; 0.001). In a multiple linear regression analysis, a negative association between liver fat percentage and LV mass (St Beta −0.23, P &lt; 0.05) as well as LV end-diastolic volume (St Beta −0.27, P &lt; 0.05) was found. Epicardial adipose tissue volume and abdominal subcutaneous adipose tissue volume index were the only parameters of fat associated with LV diastolic dysfunction (E/e'-ratio) (St Beta 0.24, P &lt; 0.05; St Beta 0.34, P &lt; 0.01, respectively). In a multivariate logistic regression analysis, only visceral adipose tissue volume index was significantly associated with T2D, with an odds ratio for T2D of 3.01 (95% CI 1.28–7.05, P &lt; 0.05) per L/m2 increase in visceral adipose tissue volume.ConclusionsEctopic fat is predominantly associated with cardiac remodeling, independently of type 2 diabetes. Intriguingly, liver fat appears to be related to LV structure independently of VAT, while epicardial fat is linked to impaired LV diastolic function. Visceral fat is associated with T2D independently of liver fat and abdominal subcutaneous adipose tissue

The influence of social phobia in first episode of psychosis and attentional processing and the ability to use theory of mind

Chapter One: Literature Review This chapter reviews the research surrounding the prevalence of comorbid social phobia in people diagnosed with schizophrenia. It then critically evaluates the eight studies that have specifically explored the relationships, if any, between social phobia and psychotic symptoms. The review surmises that the research findings are inconsistent, which seem to be attributable to methodological differences between all the studies in terms of participant selection, chronicity of psychotic symptoms and lack of consistent measures. Chapter Two: Research Report This study investigates attentional processing, the influence of social phobia and the ability to use Theory of Mind (ToM: the ability to infer other people's mental states and behaviour) in people diagnosed with their first episode of psychosis, when compared to healthy matched controls. The results showed that the first episode group attended towards negative evaluation, somatic sensations, physical threat, but not social situation word groups. Social phobia was highly prevalent in the first episode of psychosis cohort (37%) and this anxiety disorder was unrelated to psychotic symptoms. ToM processing was impaired in the first episode group. ToM was not related to social phobia symptoms, but was related to social functioning. Chapter Three: Critical Appraisal This section presents an overview of the experiences and personal reflections of the work that constitutes this thesis and includes the main personal learning points.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The importance of comorbidity in analysing patient costs in Swedish primary care

BACKGROUND: The objective was to explore the usefulness of the morbidity risk adjustment system Adjusted Clinical Groups(® )(ACG), in comparison with age and gender, in explaining and estimating patient costs on an individual level in Swedish primary health care. Data were retrieved from two primary health care centres in southeastern Sweden. METHODS: A cross-sectional observational study. Data from electronic patient registers from the two centres were retrieved for 2001 and 2002, and patients were grouped into ACGs, expressing the individual combination of diagnoses and thus the comorbidity. Costs per patient were calculated for both years in both centres. Cost data from one centre were used to create ACG weights. These weights were then applied to patients at the other centre. Correlations between individual patient costs, age, gender and ACG weights were studied. Multiple linear regression analyses were performed in order to explain and estimate patient costs. RESULTS: The variation in individual patient costs was substantial within age groups as well as within ACG weight groups. About 37.7% of the individual patient costs could be explained by ACG weights, and age and gender added about 0.8%. The individual patient costs in 2001 estimated 22.0% of patient costs in 2002, whereas ACG weights estimated 14.3%. CONCLUSION: ACGs was an important factor in explaining and estimating individual patient costs in primary health care. Costs were explained to only a minor extent by age and gender. However, the usefulness of the ACG system appears to be sensitive to the accuracy of classification and coding of diagnoses by physicians