Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.

MYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type-specific enhancer leads to increased MYC expression.

Cost-Effectiveness of Vaccination of Older Adults with an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden.

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years.

Expectations and Experiences of Internet-Based Therapy for Adolescents with TMD Pain.

Aims: To investigate expectations and experiences of internet-based therapy (IBT) in adolescents with temporomandibular disorder (TMD) pain.

Methods: Seven adolescents were strategically selected for this study. All patients had received IBT for their TMD pain in a previous randomized controlled trial.

A "spindle and thread" mechanism unblocks p53 translation by modulating N-terminal disorder.

Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of "life on the edge of solubility.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation.

Rationale: Asthma phenotyping requires novel biomarker discovery.

Objectives: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).

Methods: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR.

Gene-environment interaction: Oxytocin receptor (OXTR) polymorphisms and parenting style as potential predictors for depressive symptoms.

Depression is a common mental health problem that is thought to develop through a combination of genetic, psychological, and environmental factors, including parental behaviours and parental mental health. The present study investigated the potential interaction between oxytocin receptor (OXTR) single nucleotide polymorphisms (SNPs) (rs53576, rs237880, rs237887, rs237889, rs237898, rs1042778, rs2268490, rs2268491, rs4686302, rs6770632, rs13316193) and parenting style in adolescence in relation to depressive symptoms among young adults. The sample consisted of 1,098 Caucasian participants (63.

Comparative quantitative systems pharmacology modeling of anti-PCSK9 therapeutic modalities in hypercholesterolemia.

Since the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) as an attractive target in the treatment of hypercholesterolemia, multiple anti-PCSK9 therapeutic modalities have been pursued in drug development. The objective of this research is to set the stage for the quantitative benchmarking of two anti-PCSK9 pharmacological modality classes, monoclonal antibodies (mAbs) and small interfering RNA (siRNA). To this end, we developed an integrative mathematical model of lipoprotein homeostasis describing the dynamic interplay between PCSK9, LDL-cholesterol (LDL-C), VLDL-cholesterol, HDL-cholesterol (HDL-C), apoB, lipoprotein a [Lp(a)], and triglycerides (TGs).

Sexually dimorphic effects of ancestral exposure to vinclozolin on stress reactivity in rats.

How an individual responds to the environment depends upon both personal life history as well as inherited genetic and epigenetic factors from ancestors. Using a 2-hit, 3 generations apart model, we tested how F3 descendants of rats given in utero exposure to the environmental endocrine-disrupting chemical (EDC) vinclozolin reacted to stress during adolescence in their own lives, focusing on sexually dimorphic phenotypic outcomes. In adulthood, male and female F3 vinclozolin- or vehicle-lineage rats, stressed or nonstressed, were behaviorally characterized on a battery of tests and then euthanized.

"As long as I'm in good health". The relationship between medical diagnoses and life satisfaction in the oldest-old.

Background And Aims: Life satisfaction in the elderly has usually been found to be closely related to self-rated health, and less to diagnoses and more objective measures of health status. However, few studies have examined the relative importance of various specific diagnoses in population-based samples.

Methods: In this study, we investigate the relationship between life satisfaction and medical diagnoses in a non-demented sample of 392 participants aged 80 and older.

Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen.

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.

Effects of intramuscular omeprazole on gastric acid secretion in horses over a twenty-four hour period.

The effect of intramuscular (i.m.) omeprazole (0.

Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats.

The present study investigates whether tumor:normal tissue uptake ratios of radiolabeled monoclonal antibodies can be further improved by a combination of extracorporeal immunoadsorption (ECIA) and preload with unlabeled idiotypic monoclonal antibody. Athymic rats, heterotransplanted with human lung carcinoma under the kidney capsule (SR tumor) and i.m.

Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.

Background: Several epidemiological studies have shown an inverse relation between high-density lipoprotein (HDL) cholesterol levels and coronary heart disease. Recently, observational studies have suggested a similar inverse relation between HDL and restenosis after coronary balloon angioplasty. Despite these observations, it is unclear whether this inverse relation reflects a direct vascular protective effect of HDL or apolipoprotein (apo) A-I, the major apolipoprotein component of HDL.

A procedure for the analysis by mass spectrometry of the structure of oligosaccharides from high-mannose glycoproteins.

A strategy, based on mass spectrometry, for analysis of the structure of oligosaccharides obtained from high-mannose glycoproteins, is described. The oligosaccharides are analysed first by f.a.

Cardiovascular complications of estrogen therapy for nondisseminated prostatic carcinoma. A preliminary report from a randomized multicenter study.

In a prospective multicenter study, 244 men with highly or moderately differentiated prostatic cancer in stage I, II or III (VACURG) were consecutively randomized to three groups of treatment: Group A (77 patients) received polyestradiol phosphate (Estradurin, Leo) 80 mg i.m. every fourth week + ethinyl estradiol (Etivex, Leo) 150 micrograms daily, group B (72 patients) estramustine phosphate (Estracyt, Leo) 280 mg twice daily, and group C (76 patients) no therapy.

Interferon therapy in multiple myeloma.

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m.