Efficacy, Safety, and Subject Satisfaction After AbobotulinumtoxinA Treatment of Upper Facial Lines.

Background: Botulinum toxins are the treatment of choice for wrinkles in the upper third of the face.

Objective: The purpose of this study was to evaluate the efficacy, safety, and subject satisfaction of abobotulinumtoxinA (ABO) for treatment of upper facial lines.

Materials And Methods: Subjects aged 35 to 50 years with moderate-to-severe upper facial lines were included in this study.

Diabetes mellitus and hyperglycemia control on the risk of colorectal adenomatous polyps: a retrospective cohort study.

Background: Colorectal cancer (CRC) develops from colorectal adenomatous polyps. This study is to determine if diabetes mellitus (DM), its treatment, and hemoglobin A1c (HbA1c) level are associated with increased risk of colorectal adenomatous polyps.

Methods: This was a retrospective cohort study that included patients who had at least one colonoscopy and were continuously enrolled in a single managed care organization during a 10-year period (2002-2012).

Medical marijuana laws and workplace fatalities in the United States.

Aims: The aim of this research was to determine the association between legalizing medical marijuana and workplace fatalities.

Design: Repeated cross-sectional data on workplace fatalities at the state-year level were analyzed using a multivariate Poisson regression.

Setting: To date, 29 states and the District of Columbia have legalized the use of marijuana for medicinal purposes.

The "speed limit" for macromolecular crystal growth.

A simple "diffusion-to-capture" model is used to estimate the upper limit to the growth rate of macromolecular crystals under conditions when the rate limiting process is the mass transfer of sample from solution to the crystal. Under diffusion-limited crystal growth conditions, this model predicts that the cross-sectional area of a crystal will increase linearly with time; this prediction is validated by monitoring the growth rate of lysozyme crystals. A consequence of this analysis is that when crystal growth is diffusion-limited, micron-sized crystals can be produced in ~1 s, which would be compatible with the turnover time of many enzymes.

Complex disease management of pregnant young patient with familial hypercholesterolaemia complicated by coronary artery disease and cerebrovascular disease.

Inherited disorders of lipid metabolism may cause a heavy burden of cardiovascular disease early in life. Familial hypercholesterolaemia (FH) with abnormalities of LDL metabolism results in marked LDL elevations and accelerated, multivessel atherosclerosis presenting in teenage or young adulthood. We describe the case of a 33-year-old woman who presented with exertional angina in the setting of pregnancy who was found post-partum to have severe triple-vessel disease including left main disease on coronary angiography (Figs.

Evidence for Adipocyte-Derived Extracellular Vesicles in the Human Circulation.

Adipocyte-derived extracellular vesicles (EVs) may serve as novel endocrine mediators of adipose tissue and impact upon vascular health. However, it is unclear whether adipocyte-derived EVs are present in the human circulation. Therefore, the purpose of this study was to seek evidence for the presence of adipocyte-derived EVs in circulating plasma.

Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis.

Destruction of cancer cells by therapeutic antibodies occurs, at least in part, through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated by various Fc-receptor-expressing immune cells, including neutrophils. However, the mechanism(s) by which neutrophils kill antibody-opsonized cancer cells has not been established. Here, we demonstrate that neutrophils can exert a mode of destruction of cancer cells, which involves antibody-mediated trogocytosis by neutrophils.

Oxidative stress and phosphatidylserine exposure in red cells from patients with sickle cell anaemia.

Phosphatidylserine (PS) exposure increases as red cells age, and is an important signal for the removal of senescent cells from the circulation. PS exposure is elevated in red cells from sickle cell anaemia (SCA) patients and is thought to enhance haemolysis and vaso-occlusion. Although precise conditions leading to its externalisation are unclear, high intracellular Ca has been implicated.

Large magneto-optical Kerr effect and imaging of magnetic octupole domains in an antiferromagnetic metal.

When a polarized light beam is incident upon the surface of a magnetic material, the reflected light undergoes a polarization rotation. This magneto-optical Kerr effect (MOKE) has been intensively studied in a variety of ferro- and ferrimagnetic materials because it provides a powerful probe for electronic and magnetic properties as well as for various applications including magneto-optical recording. Recently, there has been a surge of interest in antiferromagnets (AFMs) as prospective spintronic materials for high-density and ultrafast memory devices, owing to their vanishingly small stray field and orders of magnitude faster spin dynamics compared to their ferromagnetic counterparts.

A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia.

Genetic variants at three quantitative trait loci (QTL) for fetal haemoglobin (HbF), BCL11A, HBS1L-MYB and the β-globin gene cluster, have attracted interest as potential targets of therapeutic strategies for HbF reactivation in sickle cell anaemia (SCA). We carried out the first systematic evaluation of critical single nucleotide polymorphisms at these disease modifier loci in Nigerian patients with SCA. Common variants for BCL11A and HBS1L-MYB were strongly associated with HbF levels.

Fragment-Based Discovery of a Potent, Orally Bioavailable Inhibitor That Modulates the Phosphorylation and Catalytic Activity of ERK1/2.

Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signaling through ERK1/2. Here, we describe the fragment-based generation of ERK1/2 inhibitors that block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK.

White matter integrity and processing speed in sickle cell anemia.

Objective: The purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia.

Methods: Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8-37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed.

Polycystic Ovary Syndrome Is Associated With Adverse Mental Health and Neurodevelopmental Outcomes.

Context: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and subfertility, but the effects on mental health and child neurodevelopment are unclear.

Objectives: To determine if (1) there is an association between PCOS and psychiatric outcomes and (2) whether rates of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are higher in children of mothers with PCOS.

Design: Data were extracted from the Clinical Practice Research Datalink.

Organic synthesis provides opportunities to transform drug discovery.

Despite decades of ground-breaking research in academia, organic synthesis is still a rate-limiting factor in drug-discovery projects. Here we present some current challenges in synthetic organic chemistry from the perspective of the pharmaceutical industry and highlight problematic steps that, if overcome, would find extensive application in the discovery of transformational medicines. Significant synthesis challenges arise from the fact that drug molecules typically contain amines and N-heterocycles, as well as unprotected polar groups.

Application of Chloroplast Phylogenomics to Resolve Species Relationships Within the Plant Genus Amaranthus.

Amaranthus species are an emerging and promising nutritious traditional vegetable food source. Morphological plasticity and poorly resolved dendrograms have led to the need for well resolved species phylogenies. We hypothesized that whole chloroplast phylogenomics would result in more reliable differentiation between closely related amaranth species.

Proteomic analysis of plasma from children with sickle cell anemia and silent cerebral infarction.

Silent cerebral infarction is the most common neurological abnormality in children with sickle cell anemia, affecting 30-40% of 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts, and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts.

Parturition and the perinatal period: can mode of delivery impact on the future health of the neonate?

Caesarean section and instrumental delivery rates are increasing in many parts of the world for a range of cultural and medical reasons, with limited consideration as to how 'mode of delivery' may impact on childhood and long-term health. However, babies born particularly by pre-labour caesarean section appear to have a subtly different physiology from those born by normal vaginal delivery, with both acute and chronic complications such as respiratory and cardio-metabolic morbidities being apparent. It has been hypothesized that inherent mechanisms within the process of labour and vaginal delivery, far from being a passive mechanical process by which the fetus and placenta are expelled from the birth canal, may trigger certain protective developmental processes permissive for normal immunological and physiological development of the fetus postnatally.

A randomised, double-blind, cross-over trial to evaluate bread, in which gluten has been pre-digested by prolyl endoprotease treatment, in subjects self-reporting benefits of adopting a gluten-free or low-gluten diet.

The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour.

The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia.

Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, activities of the main red cell dehydration pathways (P , Gardos channel, and KCl cotransporter [KCC]), and cell volume were measured at 100, 30, and 0 mmHg O , together with deoxygenation-induced nonelectrolyte hemolysis.

Generation of Maternal Obesity Models in Studies of Developmental Programming in Rodents.

Mother-child cohort studies have established that both pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are independently associated with cardio-metabolic risk factors in juvenile and adult offspring, including systolic and diastolic blood pressure. In rodent studies maternal obesity confers many facets of the metabolic syndrome including a persistent sympathy-excitatory hyperresponsiveness and hypertension acquired in the early stages of development. Insight from these animal models raises the possibility that early life exposure to the nutritional and hormonal environment of obesity in pregnancy in humans may lead to early onset of metabolic syndrome and/or essential hypertension.

How I manage red cell transfusions in patients with sickle cell disease.

Sickle cell disease is one of the commonest serious inherited diseases in the world, and red cell transfusion is still one of the few effective treatments for acute and chronic complications. Transfusion corrects anaemia and dilutes out the number of red cells able to cause vaso-occlusion and vascular damage. Urgent red cell transfusions are used to correct acute anaemia, treat acute chest syndrome and patients with acute neurological symptoms.