Cytogenomic array detects a subset of myelodysplastic syndrome with increased risk that is invisible to conventional karyotype

Conventional karyotyping is essential standard practice in the initial evaluation of myelodysplastic syndrome (MDS) and is the most impactful single component of the Revised International Prognostic Scoring System (IPSS‐R). While single nucleotide polymorphism array (SNP‐A) has demonstrated the ability to detect chromosomal defects with greater sensitivity than conventional karyotype, widespread adoption is limited by the unknown additional prognostic impact of SNP‐A analysis. Here, we investigate the significance of additional SNP‐A abnormalities in the setting of MDS and demonstrate differences in survival of patients with additional abnormalities, even those initially characterized as relatively lower risk either by cytogenetic score or IPSS‐R. Our findings identify specific abnormalities, particularly KMT2A partial tandem duplication, that are invisible to conventional karyotype and potentially contribute to the poor prognosis of MDS patients. Furthermore, these results demonstrate the added value of SNP‐A analysis in identifying patients who may benefit from more aggressive therapy, particularly those who would otherwise be classified into lower risk categories.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151357/1/gcc22783_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151357/2/gcc22783.pd

Long-term and recent trends in hypertension awareness, treatment and control in twelve high-income countries: an analysis of 123 nationally representative surveys

Background: Antihypertensive medicines are effective in reducing adverse cardiovascular events. Our aim was to compare hypertension awareness, treatment and control, and how they have changed over time, in high-income countries. Methods: We used data on 526,336 participants aged 40-79 years in 123 national health examination surveys from 1976 to 2017 in twelve high-income countries: Australia, Canada, Finland, Germany, Ireland, Italy, Japan, New Zealand, South Korea, Spain, the UK, and the USA. We calculated the percent of participants with hypertension – defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or being on pharmacological treatment for hypertension – who were aware of their condition, who were treated, and whose hypertension was controlled (i.e. lower than 140/90 mmHg). Findings: Canada, South Korea, Australia and the UK have the lowest prevalence of hypertension, and Finland the highest. In the 1980s and early 1990s, treatment rates were at most 40% and control rates were below 25% in most countries and age-sex groups. Over time, hypertension awareness and treatment increased and control rate improved in all twelve countries, with South Korea and Germany experiencing the largest improvements. Most of the increase occurred in the 1990s and early-mid 2000s, having plateaued since in most countries. Canada, Germany, South Korea and the USA have the highest rates of awareness, treatment and control, while Finland, Ireland, Japan and Spain the lowest. Even in the best performing countries, treatment coverage was at most 80% and control rates were below 70%. Interpretation: Hypertension awareness, treatment and control have improved substantially in high-income countries since the 1980s and 1990s. However, control rates have plateaued in the past decade, at levels lower than those in high-quality hypertension programmes. There is substantial variation across countries in the rates of hypertension diagnosis, treatment an

Safety and efficacy of direct- acting oral anticoagulants versus warfarin in kidney transplant recipients: a retrospective single- center cohort study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155941/1/tri13599.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155941/2/tri13599_am.pd

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries

Protein Tyrosine Phosphatase Receptor Type O Inhibits Trigeminal Axon Growth and Branching by Repressing TrkB and Ret Signaling

Axonal branches of the trigeminal ganglion (TG) display characteristic growth and arborization patterns during development. Subsets of TG neurons express different receptors for growth factors, but these are unlikely to explain the unique patterns of axonal arborizations. Intrinsic modulators may restrict or enhance cellular responses to specific ligands and thereby contribute to the development of axon growth patterns. Protein tyrosine phosphatase receptor type O (PTPRO), which is required for Eph receptor-dependent retinotectal development in chick and for development of subsets of trunk sensory neurons in mouse, may be such an intrinsic modulator of TG neuron development. PTPRO is expressed mainly in TrkB-expressing (TrkB(+)) and Ret(+) mechanoreceptors within the TG during embryogenesis. In PTPRO mutant mice, subsets of TG neurons grow longer and more elaborate axonal branches. Cultured PTPRO(-/-) TG neurons display enhanced axonal outgrowth and branching in response to BDNF and GDNF compared with control neurons, indicating that PTPRO negatively controls the activity of BDNF/TrkB and GDNF/Ret signaling. Mouse PTPRO fails to regulate Eph signaling in retinocollicular development and in hindlimb motor axon guidance, suggesting that chick and mouse PTPRO have different substrate specificities. PTPRO has evolved to fine tune growth factor signaling in a cell-type-specific manner and to thereby increase the diversity of signaling output of a limited number of receptor tyrosine kinases to control the branch morphology of developing sensory neurons. The regulation of Eph receptor-mediated developmental processes by protein tyrosine phosphatases has diverged between chick and mouse

Stress Increases Peripheral Axon Growth and Regeneration Through Glucocorticoid Receptor-Dependent Transcriptional Programs

Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. Findings: We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries.Bin Zhou, Yuan Lu, Kaveh Hajifathalian, James Bentham … Robert J. Adams … Anne Taylor … et al. (WNCD Risk Factor Collaboration

Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants

Background: Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods: We analysed, with use of a consistent protocol, population based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m² [underweight], 18·5 kg/m² to <20 kg/m², 20 kg/m² to <25 kg/m², 25 kg/m² to <30 kg/m², 30 kg/m² to <35 kg/m², 35 kg/m² to <40 kg/m², =40 kg/m² [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. Findings: We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m² (95% credible interval 21·3–22·1) in 1975 to 24·2 kg/m² (24·0–24·4) in 2014 in men, and from 22·1 kg/m² (21·7–22·5) in 1975 to 24·4 kg/m² (24·2–24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m² in central Africa and south Asia to 29·2 kg/m² (28·6–29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m² (21·4–22·3) in south Asia to 32·2 kg/m² (31·5–32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5–17·4) to 8·8% (7·4–10·3) in men and from 14·6% (11·6–17·9) to 9·7% (8·3–11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8–29·2) in men and 24·0% (18·9–29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4–4·1) in 1975 to 10·8% (9·7–12·0) in 2014 in men, and from 6·4% (5·1–7·8) to 14·9% (13·6–16·1) in women. 2·3% (2·0–2·7) of the world’s men and 5·0% (4·4–5·6) of women were severely obese (ie, have BMI =35 kg/m²). Globally, prevalence of morbid obesity was 0·64% (0·46–0·86) in men and 1·6% (1·3–1·9) in women. Interpretation: If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world’s poorest regions, especially in south Asia