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Milk yield for Holstein cows has doubled over five decades due to genetic selection and changes to management, but the molecular mechanisms that facilitated this increase are mostly unknown. Epigenetic modifications to the cattle genome are a plausible molecular mechanism to cause variation in milk yield and our objective was to describe genome-wide DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from mature Holstein dairy cows with variable milk yield.
Whole genome MeDIP-seq was performed following DNA extraction from PBMC of 6 lactating dairy cows from 4 different herds that varied in milk yield from 13,556 kg to 23,105 kg per 305 day lactation. We describe methylation across the genome and for 13,677 protein coding genes. Repetitive element reads were primarily mapped to satellite (36.4%), SINE (29.1%), and LINE (23.7%) regions and the majority (78.4%) of CpG sites were sequenced at least once. DNA methylation was generally low upstream of genes with the nadir occurring 95 bp prior to the transcription start site (TSS). Methylation was lower in the first exon than in later exons, was highest for introns near the intron-exon junctions, and declined downstream as the distance from the gene increased. We identified 72 differentially methylated regions (DMR) between high milk yield cows and their control, and 252 DMR across herd environments.
This reference methylome for cattle with extreme variation in milk yield phenotype provides a resource to more fully evaluate relationships between DNA methylation and phenotype in populations subject to selection. The detection of DMR in cows of varying milk yield suggests potential to exploit epigenetic variation in cattle improvement programs.
Electronic supplementary material
The online version of this article (10.1186/s12864-018-5124-9) contains supplementary material, which is available to authorized users.
Epigenetics, Selection, Bos taurus, MeDIP-seq, DNA methylation
DNA methylation patterns in peripheral blood mononuclear cells from Holstein cattle with variable milk yield
Chad D Dechowcorresponding author and Wan-Sheng Liu
Malaria is an important cause of morbidity and mortality, in particular among children and pregnant women in sub‐Saharan Africa. Prompt access to diagnosis and treatment with effective antimalarial drugs is a central component of the World Health Organization’s (WHO) strategy for malaria control. Home‐ or community‐based programmes for managing malaria are one strategy that has been proposed to overcome the geographical barrier to malaria treatment.
To evaluate home‐ and community‐based management strategies for treating malaria.
We searched the Cochrane Central Register of Controlled Trials published in The Cochrane Library; MEDLINE; EMBASE; Science Citation Index; PsycINFO/LIT; CINAHL; WHO clinical trial registry platform; and the metaRegister of Controlled Trials up to September 2012.
Randomized controlled trials (RCTs) and non‐RCTs that evaluated the effects of a home‐ or community‐based programme for treating malaria in a malaria endemic setting.
Data collection and analysis
Two authors independently screened and selected studies, extracted data, and assessed the risk of bias. Where possible the effects of interventions are compared using risk ratios (RR), and presented with 95% confidence intervals (CI). The quality of the evidence was assessed using the GRADE approach.
We identified 10 trials that met the inclusion criteria. The interventions involved brief training of basic‐level health workers or mothers, and most provided the antimalarial for free or at a highly subsidized cost. In eight of the studies, fevers were treated presumptively without parasitological confirmation with microscopy or a rapid diagnostic test (RDT). Two studies trained community health workers to use RDTs as a component of community management of fever.
Home‐ or community‐based strategies probably increase the number of people with fever who receive an appropriate antimalarial within 24 hours (RR 2.27, 95% CI 1.79 to 2.88 in one trial; RR 9.79, 95% CI 6.87 to 13.95 in a second trial; 3099 participants, moderate quality evidence). They may also reduce all‐cause mortality, but to date this has only been demonstrated in rural Ethiopia (RR 0.58, 95% CI 0.44 to 0.77, one trial, 13,677 participants, moderate quality evidence).
Hospital admissions in children were reported in one small trial from urban Uganda, with no effect detected (437 participants, very low quality evidence). No studies reported on severe malaria. For parasitaemia prevalence, the study from urban Uganda demonstrated a reduction in community parasite prevalence (RR 0.22, 95% CI 0.08 to 0.64, 365 participants), but a second study in rural Burkina Faso did not (1006 participants). Home‐ or community‐based programmes may have little or no effect on the prevalence of anaemia (three trials, 3612 participants, low quality evidence). None of the included studies reported on adverse effects of using home‐ or community‐based programmes for treating malaria.
In two studies which trained community health workers to only prescribe antimalarials after a positive RDT, prescriptions of antimalarials were reduced compared to the control group where community health workers used clinical diagnosis (RR 0.39, 95% CI 0.18 to 0.84, two trials, 5944 participants, moderate quality evidence). In these two studies, mortality and hospitalizations remained very low in both groups despite the lower use of antimalarials (two trials, 5977 participants, low quality evidence).
Home‐ or community‐based interventions which provide antimalarial drugs free of charge probably improve prompt access to antimalarials, and there is moderate quality evidence from rural Ethiopia that they may impact on childhood mortality when implemented in appropriate settings.
Programmes which treat all fevers presumptively with antimalarials lead to overuse antimalarials, and potentially undertreat other causes of fever such as pneumonia. Incorporating RDT diagnosis into home‐ or community‐based programmes for malaria may help to reduce this overuse of antimalarials, and has been shown to be safe under trial conditions.
Child, Child, Preschool, Humans, Infant, Infant, Newborn, Antimalarials, Antimalarials/supply & distribution, Antimalarials/therapeutic use, Community Health Services, Community Health Services/methods, Community Health Services/organization & administration, Community Health Workers, Community Health Workers/education, Fever, Fever/drug therapy, Home Care Services, Home Care Services/organization & administration, Malaria, Malaria/drug therapy, Malaria/mortality, Mothers, Mothers/education, Randomized Controlled Trials as Topic
Home‐ or community‐based programmes for treating malaria
Charles I Okwundu,corresponding author Sukrti Nagpal, Alfred Musekiwa, and David Sinclair
Background: Whether human insulin may affect lung cancer risk requires investigation.
Methods: All patients with a diagnosis of diabetes mellitus from 1996 to 2009 were enrolled from Taiwan’s National Health Insurance. An entry date was set on January 1, 2004, and 1,007,617 patients with type 2 diabetes mellitus diagnosed before 2004 were followed up for new-onset lung cancer until December 31, 2009. Incidence rates of lung cancer for never-users, ever-users, and tertiles of three dose-response exposure parameters (i.e., time since starting insulin, cumulative dose, and cumulative duration) were calculated. Adjusted hazard ratios were estimated by Cox proportional hazards models. The joint effect of insulin and chronic obstructive pulmonary disease was also evaluated.
Results: There were 156,720 ever-users and 850,897 never-users. The respective case numbers of incident lung cancer were 3,007 (1.92%) and 13,677 (1.61%), and the respective incidence rates were 424.45 and 313.60 per 100,000 person-years. The adjusted hazard ratio comparing ever-users vs. never-users was 1.545 (95% confidence interval: 1.478-1.614). The hazard ratios for the different subgroups of the three dose-response parameters all suggested a significantly higher risk of lung cancer associated with insulin use (P trend < 0.0001). Compared to patients without insulin use and without chronic obstructive pulmonary disease, insulin users who also had chronic obstructive pulmonary disease had the highest risk of lung cancer (adjusted hazard ratio: 1.891, 95% confidence interval: 1.767-2.024). Conclusions: This study suggests a significant association between human insulin use and lung cancer risk in patients with type 2 diabetes mellitus.
retrospective cohort study, insulin, lung cancer, type 2 diabetes mellitus, Taiwan
Human Insulin Therapy Is Associated With an Increased Risk of Lung Cancer: A Population-Based Retrospective Cohort Study