The importance of endothelin-1 for microvascular dysfunction in diabetes

Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ETA receptor antagonists are discussed

Selective endothelin A-receptor blockade attenuates coronary microvascular dysfunction after coronary stenting in patients with type 2 diabetes

Nikolaos Östlund Papadogeorgos, Mattias Bengtsson, Majid KalaniKarolinska Institute, Department of Clinical Sciences, Department of Cardiology, Danderyd Hospital, Stockholm, SwedenBackground: Endothelin-1 may be involved in the development of diabetic microangiopathy. We studied the effect of endothelin-1 blockade on myocardial microcirculation during coronary stenting.Patients and methods: Patients with type 2 diabetes and stable coronary artery disease undergoing elective percutaneous coronary intervention (PCI) were randomized to bolus dose of 500 mg bosentan (n = 4), a dual endothelin receptor blocker, or intracoronary administration of 0.03 mmol BQ123 (n = 6), a selective endothelin A-receptor blocker, or placebo (n = 5), respectively. Coronary flow reserve (CFR) was measured immediately post-PCI. CFR was also measured in five nondiabetic controls post-coronary stenting.Results: Patients in the placebo group had (P < 0.05) lower values of CFR (2.3 ± 1.2) as compared to those who received endothelin blockade (n = 10; 3.1 ± 0.7) and nondiabetic controls (4.9 ± 2.3). Patients who received BQ123 showed significantly higher CFR (3.3 ± 0.5; P < 0.05) as compared to those on placebo. Nondiabetic patients had significantly higher CFR as compared to patients with diabetes (4.9 ± 2.3 and 2.8 ± 1.0, respectively; P < 0.05). Conclusion: Coronary microvascular dysfunction is present during coronary stenting in patients with type 2 diabetes and may be reversed by selective endothelin A-receptor blockade. Targeting endothelin system may be of importance in protecting the myocardium against ischemic events during elective PCI in type 2 diabetic patients.Keywords: coronary flow reserve, diabetes, endothelin-1, coronary artery disease, coronary angioplast

The Relationship between Motor Function and Behavioral Function in Infants with Low Birth Weight

How to Cite This Article: Amini M, Aliabadi F, Alizade M, Kalani M, Qorbani M. The Relationship between Motor Function and Behavioral Function in Infants with Low Birth Weight. Iran J Child Neurol. Autumn 2016; 10(4):49-55. AbstractObjectiveNowadays, the evaluation of all aspects of infant development is important. However, in practice, some of these assessments, especially those requiring more manipulation on high-risk infants, may impose additional stress on them.Therefore, sometimes it is essential to utilize the results of a developmental assessment for the prediction of some other aspects of development. This study evaluated the relationship between the scores of the behavioral tests and the motor function test. Materials & MethodsThis cross-sectional study and was undertaken in the Neonatal Intensive Care Center and Clinic of Shahid Akbar Abadi Hospital, Tehran, Iran. A group of 50 infants with low birth weights was selected based on the easy non-contingency method and the inclusion criteria, and served as the participants. In order to assess the motor function and the behavioral performance, the motor function test (a test of infant motor performance (TIMP)) and the neonatal behavioral assessment scale (neonatal behavioral assessment scale (NBAS)) were used respectively. TIMP has both stimulation and observation sections. The items include habituation, social interaction, motor system, state organization, state regulation, autonomic system, smile, supplementary items, and the reflex. ResultsNo significant association was found between the items of the habituation of behavioral testing and the observation of the movement test. There was no statistically significant relationship between the habituation and stimulation sections as well as between the system autonomous of the behavioral test and the observation section of the motor test (P>0.05). The relationship between other variables was statistically significant (P<0.05). ConclusionThe scores of some behavioral performance items could be a good predictor of the scores of the motor function items for low birth weight infants in the neonatal period. References1. Wright-Ott C. Mobility. In: Case-smith J, editors. Occupational Therapy for Children. 5th ed. USA: Mosbey; 2005.P. 657-684.2. Case-smith J. Fine motor outcomes in preschool children who receive occupational therapy services. Am J Occup Ther 1996;50(6):466-74.3. Soleimani F, Zaheri F, Abdi F. Long-term neurodevelopmental outcomes after preterm birth. Iran Red Crescent Med J 2014;16(6):1-8.4. Hunter JG. Neonatal Intensive Care Unite. In: Case-smith J, editors. Occupational Therapy for Children. 5th ed. USA: Mosbey; 2005.P. 688-754.5. Arpino C, Compagnone E, Montanaro ML, Cacciatore D, De Luca A, Cerulli A, Di Girolamo S, Curatolo P. Preterm birth and neurodevelopmental outcome: a review. Childs Nerv Syst 2010;50:10-20.6. Pedersen SJ, Sommerfelt K, Markestad T. Early motor development of premature infants with birthweight less than 2000 grams. Acta Pediatr 2000;89:1450-61.7. Aliabadi F, Amini M, Alizade M, Kalani M, Qorbani M. Prediction of infant motor performance through performance evaluation of behavior. J Modern Rehab 2011;5 (3): 54-59.8. Orton J, Spittle A, Doyle L, Anderson P, Boyd R. Do early intervention programs improve cognitive and motor outcomes for preterm infants after discharge: a systematic review. Dev Med Child Neurol 2009;51(11):851-9.9. Spittle AJ, Doyle LW, Boyd RN. A systematic review of clinimetric properties of neuromotor assessment for preterm infants during the first year of life. Dev Med Child Neurol 2008;50(10):254-66.10. Brazeltone B. Neonatal Behavioral Assessment Scale. 3rd ed. University of Masschusetts and Harvard Medical School: Mac Keit Press; 1995. 8-10, 67, P. 104-5.11. Falk B, Eliakim A, Dotan R, Liebermann DG, Regev R, Bar-Or O. Birth weight and physical ability in 5- to -8-yr old healthy children born prematurely. Med Sci Sports Exerc 1997;29(9):1124-30.12. Burns Y, O’Callaghan M, McDonell B, Rogers Y. Movement and motor development in ELBW infant at 1 year is related to cognitive and motor abilities at 4 years. Early Hum Dev 2004;80:19-29.13. Tavasoli A, Aliabadi F, Eftekhari R. Motor Developmental Status of Moderately Low Birth Weight Preterm Infants. Iran J Pediatr 2014;24 (5), 581-586.14. Islam M. The Effects of Low Birth Weight on School Performance and Behavioral Outcomes of Elementary School Children in Oman. Oman Med J 2015;30(4):241-51.15. Ohgi S, Arisawa K, Takahashi T, Kusumoto T, Goto Y, Akiyama T, Saito H. Neonatal behavioral assessment scale as a predictor of later developmental disabilities of low-birth weight and/or premature infants. Brain Dev 2003;25:313-21.16. Ho YB, Lee RS, Chow CB, Pang MY. Impact of massage therapy on motor outcomes in very low-birth weight infants: Randomized controlled pilot study. Pediatr Int 2010; 52(3):378-85.17. Craciunoiu O, Holsti L. A Systematic Review of the Predictive Validity of Neurobehavioral Assessments During the Preterm Period. Phys Occup Ther Pediatr 2016; 17:1-16.18. Tirosh E, Abadi J, Berger A, Cohen A. Relationship between neonatal behavior and subsequent temperament. Acta Pediatr 1992;81(8):29-31

The Prevalence of Acute Kidney Injury in Neonates with Asphyxia

Introduction: Asphyxia is a common cause of mortality and morbidity among neonates. Following severe asphyxia and ischemia, reperfusion occurs which damages vital organs like the kidneys. This study was conducted to determine the prevalence of AKI based on the definition of a serum creatinine level higher than 1.5 mg/dL, in neonates with asphyxia.Materials and Methods: This retrospective study was performed in Ali-Asghar and Shahid-Akbar-Abadi Hospitals, Tehran, Iran in a period of one year. The medical documents of all newborns diagnosed with asphyxia were studied. The asphyxia grade was determined according to the asphyxia Sarnat criteria. The kidney function was evaluated based on the serum creatinine level.Results: Thirty-eight cases met the inclusion criteria. There were 13 Sarnat grade-1 cases (34.2%), 19 grade 2 cases (50%), and 6 grade 3 patients (17.6%).  Three (7.8%) patients (2 patients in grade 3 and one patient in grade 2 of the Sarnat grading scale) developed AKI. AKI was detected in 33% of the patients in grade 3 and 5.2% of the patients in grade 2 of the Sarnat grading scale. Nine patients (23%) died, of whom 83% were in grade 3 and 16.9% in grade 2 of asphyxia.Conclusions: AKI developed in 7.8% of the cases, of whom 33% were in grade 3 and 5.2% were in grade 2 of the Sarnat grading scale. The low rate of AKI development in our study might be duo to the small sample size and patient mortality in the first 3 days of life.Keywords: Acute kidney injury; Neonates; Asphyxia

Increased Urine IgM and IgG2 Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes

Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n = 28), or physiological saline, (n = 26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG2 were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG2 indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P < 0.001) and serum IGFBP-1 (P < 0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG2 despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG2 might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019