De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay.

Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies a genetic etiology in up to 30% of cases of intellectual disability (ID). Using WES, we identified seven unrelated patients with a similar clinical phenotype of severe intellectual disability or neurodevelopmental delay who were all heterozygous for de novo truncating variants in the AT-hook DNA-binding motif-containing protein 1 (AHDC1). The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors.

Using High Fluoride Concentration Products in Public Policy: A Rapid Review of Current Guidelines for High Fluoride Concentration Products.

Despite improvements in dental caries levels since the widespread introduction of fluoride toothpastes, it is still a disease which is considered to be a priority in many countries around the world. Individuals at higher risk of caries can be targeted with products with a high fluoride concentration to help reduce the amount and severity of the disease. This paper compares guidance from around the world on the use of products with a high fluoride concentration and gives examples of how guidance has been translated into activity in primary care dental practice.

Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia.

Through an international multi-center collaboration, 13 individuals from nine unrelated families and affected by likely pathogenic biallelic variants in TBC1-domain-containing kinase (TBCK) were identified through whole-exome sequencing. All affected individuals were found to share a core phenotype of intellectual disability and hypotonia, and many had seizures and showed brain atrophy and white-matter changes on neuroimaging. Minor non-specific facial dysmorphism was also noted in some individuals, including multiple older children who developed coarse features similar to those of storage disorders.

Assessing Perceived Challenges to Laboratory Testing at a Malawian Referral Hospital.

Adequate laboratory infrastructure in sub-Saharan Africa is vital for tackling the burden of infectious diseases such as human immunodeficiency virus and acquired immune deficiency syndrome, malaria, and tuberculosis, yet laboratories are ill-integrated into the diagnostic and care delivery process in low-resource settings. Although much of the literature focuses on disease-specific challenges around laboratory testing, we sought to identify horizontal challenges to the laboratory testing process through interviews with clinicians involved in the diagnostic process. Based on 22 interviews with physicians, nurses, clinical officers, medical students, and laboratory technicians, technologists and supervisors, we identified 12 distinct challenges in the areas of staff, materials, workflow, and the blood bank.

INVESTIGATING THE MANAGEMENT OF CARIOUS PRIMARY TEETH IN GENERAL DENTAL PRACTICE: AN OVERVIEW OF THE DEVELOPMENT AND CONDUCT OF THE FICTION TRIAL.

The management of carious primary teeth is a challenge for patients, parents and clinicians. Most evidence supporting different management strategies originates from a specialist setting and therefore its relevance to the primary care setting is questionable. The UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) has commissioned the FiCTION (Filling Children's Teeth: Indicated Or Not?) trial; a multi-centre primary dental care randomised controlled trial (RCT) to determine the most clinically and cost- effective approach to managing caries in the primary dentition in the UK.

Understanding the dispensary workflow at the Birmingham Free Clinic: a proposed framework for an informatics intervention.

Background: The Birmingham Free Clinic (BFC) in Pittsburgh, Pennsylvania, USA is a free, walk-in clinic that serves medically uninsured populations through the use of volunteer health care providers and an on-site medication dispensary. The introduction of an electronic medical record (EMR) has improved several aspects of clinic workflow. However, pharmacists' tasks involving medication management and dispensing have become more challenging since EMR implementation due to its inability to support workflows between the medical and pharmaceutical services.

Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration.

Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions.

Assessment of changes in potential nutrient limitation in an impounded river after application of lanthanum-modified bentonite.

With the advent of phosphorus (P)-adsorbent materials and techniques to address eutrophication in aquatic systems, there is a need to develop interpretive techniques to rapidly assess changes in potential nutrient limitation. In a trial application of the P-adsorbent, lanthanum-modified bentonite (LMB) to an impounded section of the Canning River, Western Australia, a combination of potential P, nitrogen (N) and silicon (Si) nutrient limitation diagrams based on dissolved molar nutrient ratios and actual dissolved nutrient concentrations have been used to interpret trial outcomes. Application of LMB resulted in rapid and effective removal of filterable reactive P (FRP) from the water column and also effectively intercepted FRP released from bottom sediments until the advent of a major unseasonal flood event.

An Twist Fatigue Test of Fabric Stent-Grafts Supported by Z-Stents Ringed Stents.

Whereas buckling can cause type III endoleaks, long-term twisting of a stent-graft was investigated here as a mechanism leading to type V endoleak or endotension. Two experimental device designs supported with Z-stents having strut angles of 35° or 45° were compared to a ringed control under accelerated twisting. Damage to each device was assessed and compared after different durations of twisting, with focus on damage that may allow leakage.

Geo-engineering experiments in two urban ponds to control eutrophication.

Many urban ponds experience detrimental algal blooms as the result of eutrophication. During a two year field experiment, the efficacy of five in situ treatments to mitigate eutrophication effects in urban ponds was studied. The treatments targeted the sediment phosphorus release and were intended to switch the ponds from a turbid phytoplankton-dominated state to a clear-water state with a low phytoplankton biomass.

Eutrophication management in surface waters using lanthanum modified bentonite: A review.

This paper reviews the scientific knowledge on the use of a lanthanum modified bentonite (LMB) to manage eutrophication in surface water. The LMB has been applied in around 200 environments worldwide and it has undergone extensive testing at laboratory, mesocosm, and whole lake scales. The available data underline a high efficiency for phosphorus binding.

Combined trabeculotomy-trabeculectomy with antimetabolite and releasable suture: outcome with primary congenital glaucoma in a north Indian population.

Objective: To determine the surgical outcomes of combined trabeculotomy- trabeculectomy with mitomycin-C and releasable suture in children with primary congenital glaucoma (PCG) in a North Indian population.

Design: Retrospective, interventional, consecutive, non-comparative case series.

Materials And Methods: The medical records of 137 eyes of 77 patients who underwent combined trabeculotomy- trabeculectomy with 0.

Management of eutrophication in Lake De Kuil (The Netherlands) using combined flocculant - Lanthanum modified bentonite treatment.

Eutrophication of Lake De Kuil (The Netherlands, 6.7 ha, maximum depth 9 m) has frequently caused cyanobacterial blooms resulting in swimming bans or the issue of water quality warnings during summer. The eutrophication was mainly driven by sediment phosphorus (P)-release.

The cost-effectiveness of smoking cessation services provided by general dental practice, general medical practice, pharmacy and NHS Stop Smoking Services in the North of England.

Objectives: To compare the cost-effectiveness of smoking cessation services in general dental practice (dental), general medical practice (GMP), pharmacy and NHS Stop Smoking Services (NHS SSS) from the perspective of the provider and the perspective of the NHS.

Methods: Retrospective monitoring data from NHS Bradford were accessed for any client attending a smoking cessation advisor within one of four commissioned smoking cessation services delivered by and within dental, GMP, pharmacy and NHS SSS (July 2011-December 2011). The treatment outcome of interest was 'quits' (effectiveness), and costs were assessed using incremental cost-effectiveness ratios (ICER) which compared each service setting against usual care (NHS SSS).

An electronic register for vital registration in a rural village with no electricity in Malawi.

Setting: Chalasa village, Traditional Authority Mtema, Lilongwe District, Malawi.

Objectives: To report on the deployment of an electronic register in a rural village with no electricity. Specific objectives were to document 1) challenges in setting up the electronic village register (EVR); 2) demographics of village residents, along with births and deaths over three quarters; and 3) the costs of setting up the system.

Primary care dentists' experience of treating avulsed permanent teeth.

Introduction: An avulsed permanent tooth is one of the few true emergencies in dentistry. Children who suffer this injury require urgent dental care and prompt follow-up care. There is very limited evidence available regarding the provision of treatment for avulsion injuries in primary dental care.

POL5551, a novel and potent CXCR4 antagonist, enhances sensitivity to chemotherapy in pediatric ALL.

The importance of the cell surface receptor CXCR4 and the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is well-established in normal and malignant hematopoiesis. The Protein Epitope Mimetic POL5551 is a novel and potent antagonist of CXCR4. POL5551 efficiently mobilizes hematopoietic stem and progenitor cells, but its effects in acute lymphoblastic leukemia (ALL) have not been reported.

Outcomes of Childhood Asthma and Wheezy Bronchitis. A 50-Year Cohort Study.

Rationale: Cohort studies suggest that airflow obstruction is established early in life, manifests as childhood asthma and wheezy bronchitis, and continues into early adulthood. Although an association between childhood asthma and chronic obstructive pulmonary disease (COPD) in later life has been demonstrated, it is unclear if childhood wheezy bronchitis is associated with COPD.

Objectives: To investigate whether childhood wheezy bronchitis increases the risk of COPD in the seventh decade.

Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF-2 pathway.

Ventilatory sensitivity to hypoxia increases in response to continued hypoxic exposure as part of acute acclimatisation. Although this process is incompletely understood, insights have been gained through studies of the hypoxia-inducible factor (HIF) hydroxylase system. Genetic studies implicate these pathways widely in the integrated physiology of hypoxia, through effects on developmental or adaptive processes.

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death.

Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation.

Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2) and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts) and a villous pathway (giving rise to multinucleated syncytiotrophoblast). Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries.

Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.

Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane.

Barriers to using eHealth data for clinical performance feedback in Malawi: A case study.

Introduction: Sub-optimal performance of healthcare providers in low-income countries is a critical and persistent global problem. The use of electronic health information technology (eHealth) in these settings is creating large-scale opportunities to automate performance measurement and provision of feedback to individual healthcare providers, to support clinical learning and behavior change. An electronic medical record system (EMR) deployed in 66 antiretroviral therapy clinics in Malawi collects data that supervisors use to provide quarterly, clinic-level performance feedback.