The future response of marine ecosystem diversity to continued anthropogenic forcing is poorly constrained. Phytoplankton are a diverse set of organisms that form the base of the marine ecosystem. ...Currently, ocean biogeochemistry and ecosystem models used for climate change projections typically include only 2-3 phytoplankton types and are, therefore, too simple to adequately assess the potential for changes in plankton community structure. Here, we analyse a complex ecosystem model with 35 phytoplankton types to evaluate the changes in phytoplankton community composition, turnover and size structure over the 21st century. We find that the rate of turnover in the phytoplankton community becomes faster during this century, that is, the community structure becomes increasingly unstable in response to climate change. Combined with alterations to phytoplankton diversity, our results imply a loss of ecological resilience with likely knock-on effects on the productivity and functioning of the marine environment.
Non-invasive prenatal diagnosis (NIPD) makes use of cell-free fetal DNA (cffDNA) in the mother's bloodstream as an alternative to invasive sampling methods such as amniocentesis or CVS, which carry a ...0.5-1% risk of fetal loss. We describe a droplet digital PCR (ddPCR) assay designed to inform the testing options for couples whose offspring are at risk of suffering from cystic fibrosis via compound heterozygosity. By detecting the presence or absence of the paternal mutation in the cffDNA, it is possible to predict whether the fetus will be an unaffected carrier (absence) or whether further invasive testing is indicated (presence).
We selected a family in which the parents were known to carry different mutated CFTR alleles as our test system. NIPD was performed for three of their pregnancies during the first trimester (at around 11-12 weeks of gestation). Taqman probes were designed against an amplicon in exon 11 of the CFTR gene, to quantify the proportion of mutant (ΔF508-MUT; FAM) and normal (ΔF508-NOR; VIC) alleles at position c.1521_1523 of the CFTR gene.
The assay correctly and unambiguously recognized the ΔF508-MUT CFTR allele in the cffDNA of all three proband fetuses and none of the six unaffected control fetuses. In conclusion, the Bio-Rad QX100 was found to be a cost-effective and technically undemanding platform for designing bespoke NIPD assays.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary The ABCs of SLEEPING mnemonic was developed to serve as an organizing framework for common pediatric sleep recommendations. The mnemonic stands for 1) a ge appropriate b edtimes and ...wake-times with c onsistency, 2) s chedules and routines, 3) l ocation, 4) e xercise and diet, 5) no e lectronics in the bedroom or before bed, 6) p ositivity 7) i ndependence when falling asleep and 8) n eeds of child met during the day, 9) equal g reat sleep. This review examines the empirical evidence behind the practices and recommendations captured by the ABCs of SLEEPING mnemonic for children aged 1 to 12. A search was conducted of key electronic databases (PubMed, PsycINFO, CINAHL, & EMBASE) to identify English articles that included the concepts of sleep, insomnia, and/or bedtime. 77 articles were eligible for inclusion and were coded to extract key details and findings regarding the relations between sleep practices identified in the ABCs of SLEEPING mnemonic and sleep outcomes. Findings provided preliminary support for many of the recommendations that are commonly made to families regarding healthy sleep practices. However, more robust investigations are needed to better understand the causal contributions of healthy sleep practices to the onset and maintenance of children's sleep problems.
Statins are widely used to prevent major cardiovascular events by lowering serum cholesterol. There is evidence that statins have pleiotropic effects-that is, cholesterol-independent effects-that may ...also confer protection from cardiovascular disease and potentially numerous other pathologies, including cancer. Statins also have a number of well described adverse effects, including myopathy, rhabdomyolysis, liver damage, and type 2 diabetes. This paper examines the evidence of epigenetic modifications as a contributory factor to the pleiotropic and adverse effects of statins. In vitro and animal studies have shown that statins can inhibit histone deacetylase activity and increase histone acetylation. Similarly, there is evidence that statins may inhibit both histone and DNA methyltransferases and subsequently demethylate histone residues and DNA, respectively. These changes have been shown to alter expression of various genes, including tumor suppressor genes and genes thought to have anti-atherosclerotic actions. Statins have also been shown to influence the expression of numerous microRNAs that suppress the translation of proteins involved in tumorigenesis and vascular function. Whether the adverse effects of statins may also have an epigenetic component has been less widely studied, although there is evidence that microRNA expression may be altered in statin-induced muscle and liver damage. As epigenetics and microRNAs influence gene expression, these changes could contribute to the pleiotropic and adverse effects of statins and have long-lasting effects on the health of statin users.
Abstract
BACKGROUND
Approximately 50% of pregnancy losses are caused by chromosomal abnormalities, such as aneuploidy. The remainder has an apparent euploid karyotype, but it is plausible that there ...are cases of pregnancy loss with other genetic aberrations that are not currently routinely detected. Studies investigating the use of exome sequencing and chromosomal microarrays in structurally abnormal pregnancies and developmental disorders have demonstrated their clinical application and/or potential utility in these groups of patients. Similarly, there have been several studies that have sought to identify genes that are potentially causative of, or associated with, spontaneous pregnancy loss, but the evidence has not yet been synthesized.
OBJECTIVE AND RATIONALE
The objective was to identify studies that have recorded monogenic genetic contributions to pregnancy loss in euploid pregnancies, establish evidence for genetic causes of pregnancy loss, identify the limitations of current evidence, and make recommendations for future studies. This evidence is important in considering additional research into Mendelian causes of pregnancy loss and appropriate genetic investigations for couples experiencing recurrent pregnancy loss.
SEARCH METHODS
A systematic review was conducted in MEDLINE (1946 to May 2018) and Embase (1974 to May 2018). The search terms ‘spontaneous abortion’, ‘miscarriage’, ‘pregnancy loss’, or ‘lethal’ were used to identify pregnancy loss terms. These were combined with search terms to identify the genetic contribution including ‘exome’, ‘human genome’, ‘sequencing analysis’, ‘sequencing’, ‘copy number variation’, ‘single-nucleotide polymorphism’, ‘microarray analysis’, and ‘comparative genomic hybridization’. Studies were limited to pregnancy loss up to 20 weeks in humans and excluded if the genetic content included genes that are not lethal in utero, PGD studies, infertility studies, expression studies, aneuploidy with no recurrence risk, methodologies where there is no clinical relevance, and complex genetic studies. The quality of the studies was assessed using a modified version of the Newcastle–Ottawa scale.
OUTCOMES
A total of 50 studies were identified and categorized into three themes: whole-exome sequencing studies; copy number variation studies; and other studies related to pregnancy loss including recurrent molar pregnancies, epigenetics, and mitochondrial DNA aberrations. Putatively causative variants were found in a range of genes, including CHRNA1 (cholinergic receptor, nicotinic, alpha polypeptide 1), DYNC2H1 (dynein, cytoplasmic 2, heavy chain 1), and RYR1 (ryanodine receptor 1), which were identified in multiple studies. Copy number variants were also identified to have a causal or associated link with recurrent miscarriage.
WIDER IMPLICATIONS
Identification of genes that are causative of or predisposing to pregnancy loss will be of significant individual patient impact with respect to counselling and treatment. In addition, knowledge of specific genes that contribute to pregnancy loss could also be of importance in designing a diagnostic sequencing panel for patients with recurrent pregnancy loss and also in understanding the biological pathways that can cause pregnancy loss.
Dystrophinopathies are X-linked diseases, including Duchenne muscular dystrophy and Becker muscular dystrophy, due to DMD gene variants. In recent years, the application of new genetic technologies ...and the availability of new personalised drugs have influenced diagnostic genetic testing for dystrophinopathies. Therefore, these European best practice guidelines for genetic testing in dystrophinopathies have been produced to update previous guidelines published in 2010.These guidelines summarise current recommended technologies and methodologies for analysis of the DMD gene, including testing for deletions and duplications of one or more exons, small variant detection and RNA analysis. Genetic testing strategies for diagnosis, carrier testing and prenatal diagnosis (including non-invasive prenatal diagnosis) are then outlined. Guidelines for sequence variant annotation and interpretation are provided, followed by recommendations for reporting results of all categories of testing. Finally, atypical findings (such as non-contiguous deletions and dual DMD variants), implications for personalised medicine and clinical trials and incidental findings (identification of DMD gene variants in patients where a clinical diagnosis of dystrophinopathy has not been considered or suspected) are discussed.
The objective of this review is to summarize the pharmacology, efficacy, and safety of cerliponase alfa for the treatment of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). Cerliponase ...alfa is recombinant human tripeptidyl peptidase 1 enzyme replacement therapy. A phase 1/2 trial established the efficacy and safety of cerliponase alfa for treatment of neuronal ceroid lipofuscinosis type 2. Treatment with intracerebroventricular cerliponase alfa resulted in slower decline of motor and language functions compared with natural history controls. Common adverse events include convulsions, electrocardiography abnormalities, pyrexia, vomiting, and upper respiratory tract infections. Intracerebroventricular device–related adverse events also occur. Cerliponase alfa is the first therapy for neuronal ceroid lipofuscinosis type 2 that targets the disease etiology. Cerliponase alfa is effective in delaying the progression of motor language decline for patients with neuronal ceroid lipofuscinosis type 2.
Measurement of Emergency Obstetric Care capability is common, and measurement of newborn and overall routine childbirth care has begun in recent years. These assessments of facility capabilities can ...be used to identify geographic inequalities in access to functional health services and to monitor improvements over time. This paper develops an approach for monitoring the childbirth environment that accounts for the delivery caseload of the facility.
We used data from the Kenya Service Provision Assessment to examine facility capability to provide quality childbirth care, including infrastructure, routine maternal and newborn care, and emergency obstetric and newborn care. A facility was considered capable of providing a function if necessary tracer items were present and, for emergency functions, if the function had been performed in the previous three months. We weighted facility capability by delivery caseload, and compared results with those generated using traditional "survey weights".
Of the 403 facilities providing childbirth care, the proportion meeting criteria for capability were: 13% for general infrastructure, 6% for basic emergency obstetric care, 3% for basic emergency newborn care, 13% and 11% for routine maternal and newborn care, respectively. When the new caseload weights accounting for delivery volume were applied, capability improved and the proportions of deliveries occurring in a facility meeting capability criteria were: 51% for general infrastructure, 46% for basic emergency obstetric care, 12% for basic emergency newborn care, 36% and 18% for routine maternal and newborn care, respectively. This is because most of the caseload was in hospitals, which generally had better capability. Despite these findings, fewer than 2% of deliveries occurred in a facility capable of providing all functions.
Reporting on the percentage of facilities capable of providing certain functions misrepresents the capacity to provide care at the national level. Delivery caseload weights allow adjustment for patient volume, and shift the denominator of measurement from facilities to individual deliveries, leading to a better representation of the context in which facility births take place. These methods could lead to more standardized national datasets, enhancing their ability to inform policy at a national and international level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Nurse-Patient Assignment Allen, Stephanie B.
The Journal of nursing administration,
2015-December, Letnik:
45, Številka:
12
Journal Article
Recenzirano
OBJECTIVE:Identify purposes and decision factors of the nurse-patient assignment process.
BACKGROUND:Nurse-patient assignments can positively impact patient, nurse, and environmental outcomes.
...METHODS:This was an exploratory study involving interviews with 14 charge nurses from 11 different nursing units in 1 community hospital.
RESULTS:Charge nurses identified 14 purposes and 17 decision factors of the nurse-patient assignment process.
CONCLUSIONS:The nurse-patient assignment is a complex process driven by the patient, nurse, and environment. Further study is needed to identify factors linked to patient safety, nurse, and environmental outcomes.
Bacterial pilin nanowires are protein complexes, suggested to possess electroactive capabilities forming part of the cells' bioenergetic programming. Their role is thought to be linked to ...facilitating electron transfer between cells and the external environment to permit metabolism and cell-to-cell communication. There is a significant debate, with varying hypotheses as to the nature of the proteins currently lying between type-IV pilin-based nanowires and polymerised cytochrome-based filaments. Importantly, to date, there is a very limited structure-function analysis of these structures within whole bacteria. In this work, we engineered Cupriavidus necator H16, a model autotrophic organism to express differing aromatic modifications of type-IV pilus proteins to establish structure-function relationships on conductivity and the effects this has on pili structure. This was achieved via a combination of high-resolution PeakForce tunnelling atomic force microscopy (PeakForce TUNA™) technology, alongside conventional electrochemical approaches enabling the elucidation of conductive nanowires emanating from whole bacterial cells. This work is the first example of functional type-IV pili protein nanowires produced under aerobic conditions using a Cupriavidus necator chassis. This work has far-reaching consequences in understanding the basis of bio-electrical communication between cells and with their external environment.
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