Gene regulatory activity associated with polycystic ovary syndrome revealed DENND1A-dependent testosterone production.

Polycystic ovary syndrome (PCOS) is among the most common disorders affecting up to 15% of the menstruating population globally. It is the leading cause of anovulatory infertility and a major risk factor for type 2 diabetes. Elevated testosterone levels are a core endophenotype.

Impact of 'the Q word' on hospital speciality activity levels: a narrative systematic review.

Background: Healthcare professionals commonly believe that saying the word 'quiet' can jinx a shift and lead to increased workload or particularly unwell patients. A previous small integrative review found no effect but had some methodological limitations. This narrative systematic review aimed to synthesise the evidence from studies on the impact of saying 'quiet' on clinical workload measures.

Salbutamol for analgesia in renal colic: a prospective, randomised, placebo-controlled phase II trial.

Background: The pain of renal colic, mediated in part by ureteral spasm and inflammation, is often severe and difficult to control. Salbutamol has been shown to cause ureteral relaxation, but its effects on the pain of renal colic have never been studied. The objective of this trial was to investigate whether the use of intravenous salbutamol in addition to standard analgesia was associated with greater pain reduction compared with standard analgesia alone in patients presenting to emergency departments (EDs) with renal colic.

Experiences and perceptions of acute testicular pain, with a focus on reasons for delayed presentation to hospital: a qualitative evidence synthesis.

Background: The annual incidence of testicular torsion is approximately 1 in 4000 males under the age of 25. Despite the 97% testicular salvage rate when surgical intervention is within 6 hours of onset, orchidectomy is required in 40% of cases. These comparatively poor outcomes are driven by delays to intervention, the majority of which take place prior to presentation to healthcare.

Use of emergency departments by children and young people following telephone triage: a large database study.

Background: Although one objective of NHS 111 is to ease the strain on urgent and emergency care services, studies suggest the telephone triage service may be contributing to increased demand. Moreover, while parents and caregivers generally find NHS 111 satisfactory, concerns exist about its integration with the healthcare system and the appropriateness of advice. This study aimed to analyse the advice provided in NHS 111 calls, the duration between the call and ED attendance, and the outcomes of such attendances made by children and young people (C&YP).

Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.

Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes functional elements that descended from previously neutral regions. Here, we demonstrate that the fastest-evolved regions of the human genome, which we term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged in an episodic burst of directional positive selection prior to the human-Neanderthal split, before transitioning to constraint within hominins.

Correcting signal biases and detecting regulatory elements in STARR-seq data.

High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial analytical challenges. Here, we identify technical biases that explain most of the variance in STARR-seq data.

Handheld electronic device use in patient care: the emergency department patient perspective-a cross-sectional survey.

Background: Staff use of smartphones and tablets in the healthcare setting is increasingly prevalent, but little is known about whether this use is acceptable to patients. Staff are concerned that the use of handheld electronic devices (HEDs) may be negatively misconstrued by patients. The HED can be a valuable tool, offering the emergency clinician access to a wealth of resources; it is therefore vital that patient views are addressed during their widespread adoption into clinical practice.

Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy.

Background: Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy.

Aims: To assess the association between codeine use and acute pancreatitis in patients with a previous cholecystectomy.

Methods: We conducted a retrospective nested case-control study using the 2005-2015 MarketScan Commercial Claims and Encounters Database.

Bayesian estimation of genetic regulatory effects in high-throughput reporter assays.

Motivation: High-throughput reporter assays dramatically improve our ability to assign function to noncoding genetic variants, by measuring allelic effects on gene expression in the controlled setting of a reporter gene. Unlike genetic association tests, such assays are not confounded by linkage disequilibrium when loci are independently assayed. These methods can thus improve the identification of causal disease mutations.

Human genome-wide measurement of drug-responsive regulatory activity.

Environmental stimuli commonly act via changes in gene regulation. Human-genome-scale assays to measure such responses are indirect or require knowledge of the transcription factors (TFs) involved. Here, we present the use of human genome-wide high-throughput reporter assays to measure environmentally-responsive regulatory element activity.

Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia.

Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability.

β-Adrenoreceptor agonists in the management of pain associated with renal colic: a systematic review.

Objectives: To determine whether β-adrenoreceptor agonists are effective analgesics for patients with renal colic through a systematic review of the literature.

Setting: Adult emergency departments or acute assessment units.

Participants: Human participants with proven or suspected renal colic.

Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events.

Nuclear remodeling to a condensed state is a hallmark of spermatogenesis. This is achieved by replacement of histones with protamines. Regions retaining nucleosomes may be of functional significance.

Oxidative DNA damage in mouse sperm chromosomes: Size matters.

Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models that display high levels of sperm oxidative DNA damage, a common alteration encountered both in in vivo and in vitro reproduction. Immunoprecipitation of oxidized sperm DNA coupled to deep sequencing showed that mouse chromosomes may be largely affected by oxidative alterations.

Chromatin and extracellular vesicle associated sperm RNAs.

A diverse pool of RNAs remain encapsulated within the transcriptionally silent spermatozoon despite the dramatic reduction in cellular and nuclear volume following cytoplasm/nucleoplasm expulsion. The impact of this pronounced restructuring on the distribution of transcripts inside the sperm essentially remains unknown. To define their compartmentalization, total RNA >100 nt was extracted from sonicated (SS) mouse spermatozoa and detergent demembranated sucrose gradient fractionated (Cs/Tx) sperm heads.

Stability, delivery and functions of human sperm RNAs at fertilization.

Increasing attention has focused on the significance of RNA in sperm, in light of its contribution to the birth and long-term health of a child, role in sperm function and diagnostic potential. As the composition of sperm RNA is in flux, assigning specific roles to individual RNAs presents a significant challenge. For the first time RNA-seq was used to characterize the population of coding and non-coding transcripts in human sperm.

Local and global factors affecting RNA sequencing analysis.

High-throughput RNA sequencing (RNA-seq) continues to provide unparalleled insight into transcriptome complexity. Now the "gold standard" for assessing global transcript levels, RNA-seq is poised to revolutionize our understanding of transcription and posttranscriptional regulation of RNA. Despite significant advantages over prior experimental strategies, RNA-seq is not without pitfalls.

Interrogating the transgenic genome: development of an interspecies tiling array.

A single expressing copy of the human protamine domain was randomly inserted into an intron of Cyp2c38. The transgenic locus was shown to recapitulate the level of expression observed in normal human testis while not perturbing endogenous protamine expression. The development of an interspecies tiling array was pursued to enable direct comparison of the orthologous protamine domains in a single experiment.

The sperm nucleus: chromatin, RNA, and the nuclear matrix.

Within the sperm nucleus, the paternal genome remains functionally inert and protected following protamination. This is marked by a structural morphogenesis that is heralded by a striking reduction in nuclear volume. Despite these changes, both human and mouse spermatozoa maintain low levels of nucleosomes that appear non-randomly distributed throughout the genome.

Real-time PCR quantification using a variable reaction efficiency model.

The quantitative real-time polymerase chain reaction (PCR) remains a cornerstone technique in gene expression analysis and sequence characterization. Despite the importance of the approach to experimental biology, the confident assignment of reaction efficiency to the early cycles of real-time PCR reactions remains problematic. Considerable noise may be generated when few cycles in the amplification are available to estimate peak efficiency.