Screening and Testing in Multiples.

The choice of screening or invasive procedure in twin pregnancies is a personal choice of whether the patient wishes to take a small risk of having a baby with a serious disorder versus a small risk of having a complication because she wishes to avoid that. How to interpret such risks has profound effects on the perceived value of techniques, either leading to a decision to screening or going directly to chorionic villus sampling. There are profound issues surrounding the data and the interpretation of the data.

Cell-free DNA: Comparison of Technologies.

Cell-free fetal DNA screening for Down syndrome has gained rapid acceptance over the past few years with increasing market penetration. Three main laboratory methodologies are currently used: a massive parallel shotgun sequencing (MPSS), a targeted massive parallel sequencing (t-MPS) and a single nucleotide polymorphism (SNP) based approach. Although each of these technologies has its own advantages and disadvantages, the performance of all was shown to be comparable and superior to that of traditional first-trimester screening for the detection of trisomy 21 in a routine prenatal population.

Motor fluctuations due to interaction between dietary protein and levodopa in Parkinson's disease.

Background: The modulation of levodopa transport across the blood brain barrier by large neutral amino acids is well documented. Protein limitation and protein redistribution diets may improve motor fluctuations in patients with Parkinson's disease but the pharmacokinetics and pharmacodynamics of levodopa and amino acids are highly variable.

Methods: Clinical records of 1037 Parkinson's disease patients were analyzed to determine the proportion of patients with motor fluctuations related to protein interaction with levodopa.

Carotid Atherosclerosis and Stroke in Atrial Fibrillation: The Atherosclerosis Risk in Communities Study.

Background And Purpose: Whether consideration of carotid intima-media thickness (cIMT) and carotid plaque would improve risk prediction of ischemic stroke in persons with atrial fibrillation (AF) is unknown. The purpose of this study was to assess the improvement in risk prediction of stroke by adding cIMT and carotid plaque to the CHA2DS2-VASc (variables age, heart failure, hypertension, diabetes mellitus, myocardial infarction, and peripheral arterial disease) score.

Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study (mean age, 63 years) who developed AF within 5 years after carotid measurement, were not on warfarin, and had no prior stroke at AF diagnosis.

Split-face comparison between single-band and dual-band pulsed light technology for treatment of photodamage.

Background: Intense pulsed light (IPL) has a well-recognized role in the treatment of photodamaged skin.

Objective: To assess the safety and efficacy of a novel single-band IPL handpiece versus dual-band IPL handpiece in the treatment of photodamage.

Study Design/materials And Methods: This was a prospective, single-center split-face study with 20 enrolled participants.

Noninvasive prenatal screening or advanced diagnostic testing: caveat emptor.

The past few years have seen extraordinary advances in prenatal genetic practice led by 2 major technological advances; next-generation sequencing of cell-free DNA in the maternal plasma to noninvasively identify fetal chromosome abnormalities, and microarray analysis of chorionic villus sampling and amniotic fluid samples, resulting in increased cytogenetic resolution. Noninvasive prenatal screening of cell-free DNA has demonstrated sensitivity and specificity for trisomy 21 superior to all previous screening approaches with slightly lower performance for other common aneuploidies. These tests have rapidly captured an increasing market share, with substantial reductions in the number of chorionic villus sampling and amniocentesis performed suggesting that physicians and patients regard such screening approaches as an equivalent replacement for diagnostic testing.

Energy-Based Devices in Treatment of Acne Vulgaris.

Background: Acne vulgaris is a chronic dermatologic complaint with a multifactorial cause. Traditionally, antibiotics and retinoids have been used to manage the condition; patient compliance has been an ongoing issue. A variety of energy-based devices have been reported to be effective in the treatment of acne vulgaris.

Abnormal lipid processing but normal long-term repopulation potential of myc-/- hepatocytes.

Establishing c-Myc's (Myc) role in liver regeneration has proven difficult particularly since the traditional model of partial hepatectomy may provoke an insufficiently demanding proliferative stress. We used a model of hereditary tyrosinemia whereby the affected parenchyma can be gradually replaced by transplanted hepatocytes, which replicate 50-100-fold, over several months. Prior to transplantation, livers from myc-/- (KO) mice were smaller in young animals and larger in older animals relative to myc+/+ (WT) counterparts.

Metabolic Bone Disease in the Post-transplant Population: Preventative and Therapeutic Measures.

Post-transplant bone disease contributes significantly to patients' morbidity and mortality after transplantation and has an impact on their quality of life. This article discusses the major contributors to mechanisms causing bone loss, highlighting the role of preexisting disease in both kidney and liver failure and contributions from glucocorticoids and calcineurin inhibitors. Suggested monitoring and investigations are reviewed as well as treatment as far as the current literature supports, emphasizing the difference between kidney and liver recipients.

Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding.

The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis.

The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review.

Objectives: The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community-based studies on IBS prevalence.

Design: Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages.

Polychlorinated biphenyls and their association with survival following breast cancer.

Background: Polychlorinated biphenyls (PCBs) are hypothesised to influence breast carcinogenesis due to their persistence and potential to induce oestrogenic and anti-oestrogenic effects. Whether PCBs influence survival following breast cancer is unknown.

Methods: A population-based cohort of women diagnosed with first primary invasive or in situ breast cancer in 1996-1997 and with blood-measured PCBs (n=627) collected shortly after diagnosis was followed for vital status through 2011.

In utero arsenic exposure and epigenome-wide associations in placenta, umbilical artery, and human umbilical vein endothelial cells.

Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n = 37), umbilical artery (n = 45) and human umbilical vein endothelial cells (HUVEC) (n = 52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways.

Strand-specific in vivo screen of cancer-associated miRNAs unveils a role for miR-21(∗) in SCC progression.

MicroRNAs play diverse roles in both normal and malignant stem cells. Focusing on miRs and/or miR(∗)s abundant in squamous cell carcinoma (SCC) stem cells, we engineer an efficient, strand-specific expression library, and apply functional genomics screening in mice to identify which of 169 cancer-associated miRs are key drivers in malignant progression. Not previously linked functionally to cancer, miR-21(∗) was the second top hit, surfacing in >12% of tumours.

HIV, highly active antiretroviral therapy and the heart: a cellular to epidemiological review.

The advent of potent highly active antiretroviral therapy (HAART) for persons infected with HIV-1 has led to a "new" chronic disease with complications including cardiovascular disease (CVD). CVD is a significant cause of morbidity and mortality in persons with HIV infection. In addition to traditional risk factors such as smoking, hypertension, insulin resistance and dyslipidaemia, infection with HIV is an independent risk factor for CVD.

Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome.

Objective: The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).

Methods: A multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing-remitting MS) and were also compared to two other population- and clinic-based PPMS cohorts.

Patient Preferences for Abdominal Incisions Used for Pelvic Organ Prolapse Surgery.

Objectives: Approaches for performing sacrocolpopexy (laparotomy, laparoscopy, and robotically assisted) differ with regard to length of surgery, postoperative pain, and cosmetic appearance of skin incisions. The aim of our study is to better understand what factors influence patient preferences for surgical approach.

Methods: A cross-sectional study was performed using a survey.

Neural crest defects in ephrin-B2 mutant mice are non-autonomous and originate from defects in the vasculature.

Ephrin-B2, a member of the Eph/ephrin family of cell signaling molecules, has been implicated in the guidance of cranial and trunk neural crest cells (NCC) and development of the branchial arches(BA), but detailed examination in mice has been hindered by embryonic lethality of Efnb2 null loss of function due to a requirement in angiogenic remodeling. To elucidate the developmental roles for Efnb2, we generated a conditional rescue knock-in allele that allows rescue of ephrin-B2 specifically in the vascular endothelium (VE), but is otherwise ephrin-B2 deficient. Restoration of ephrin-B2 expression specifically to the VE completely circumvents angiogenic phenotypes, indicating that the requirement of ephrin-B2 in angiogenesis is limited to the VE.

LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation.

Aims: Liver kinase B1 (LKB1) is a protein kinase that activates the metabolic regulator AMP-activated protein kinase (AMPK) and other related kinases. Deletion of LKB1 in mice leads to cardiomyopathy and atrial fibrillation (AF). However, the specific role of the LKB1 pathway in early atrial biology remains unknown.

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer.

Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients.

Background.  End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment.

Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings.

Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups.

Genome-Wide Loss of Heterozygosity and DNA Copy Number Aberration in HPV-Negative Oral Squamous Cell Carcinoma and Their Associations with Disease-Specific Survival.

Oral squamous cell cancer of the oral cavity and oropharynx (OSCC) is associated with high case-fatality. For reasons that are largely unknown, patients with the same clinical and pathologic staging have heterogeneous response to treatment and different probability of recurrence and survival, with patients with Human Papillomavirus (HPV)-positive oropharyngeal tumors having the most favorable survival. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we used Affymtrix 6.

Effect of Advanced Glycation End Products on Human Thyroglobulin's Antigenicity as Identified by the Use of Sera from Patients with Hashimoto's Thyroiditis and Gestational Diabetes Mellitus.

Advanced glycation end products (AGEs) are formed on proteins after exposure to high concentrations of glucose and modify protein's immunogenicity. Herein, we investigated whether the modification of thyroglobulin (Tg) by AGEs influences its antigenicity and immunogenicity. Human Tg was incubated in vitro with increasing concentrations of D-glucose-6-phosphate in order to produce Tgs with different AGE content (AGE-Tg).