The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor. However, the MDM proteins modulate and respond to many other signalling networks in which they are embedded. Recent mechanistic studies and ...

Human biotin requirements are unknown and the identification of reliable markers of biotin status is necessary to fill this knowledge gap. Here, we used an outpatient feeding protocol to create states of biotin deficiency, sufficiency and supplementation in sixteen healthy men and women. A total of twenty possible markers of ...

The most critical unresolved issue associated with psychoanalysis is whether its core precepts belong in today's substance use armamentarium. Psychoanalytic theories have resisted the criterion of falsifiability, putting them at odds with the current paradigm for treating addiction. However, Freud's earliest pronouncement on the subject, "making the patient a collaborator ...

Injection of adeno-associated virus (AAV) into the cerebrospinal fluid (CSF) offers a means to achieve widespread transgene delivery to the central nervous system, where the doses can be readily translated from small to large animals. In contrast to studies with other serotypes (AAV2, AAV4 and AAV5) in rodents, we report ...

Cancer progression from microscopic dormant tumors into disseminated disease involves tumor angiogenesis, and is commonly referred to as the 'angiogenic switch'. CD11b(+)Gr1(+) immature myeloid cells (IMCs) were reported to promote angiogenesis and tumor progression. Here, we studied a model of tumor dormancy, in which Lewis Lung Carcinoma tumor cells were ...

We propose a novel and algorithmically simple Hough transform method that exploits the geometric properties of ellipses to enable the robust determination of the ellipse position and properties. We make use of the unique features of the evolute created by Hough voting along the gradient vectors of a two-dimensional image ...

This study determines the optimal clinical scenarios for gold nanoparticle dose enhancement as a function of irradiation conditions and potential biological targets using megavoltage x-ray beams. Four hundred and eighty clinical beams were studied for different potential cellular or sub-cellular targets. Beam quality was determined based on a 6 MV ...

Congenital rubella infection has been associated with a number of abnormalities including cardiac, central nervous system and placental complications. We present a case with multiple fetal abnormalities detected on prenatal ultrasound, and confirmed postnatally, including single umbilical artery, severe tricuspid regurgitation, micrognathia and agenesis of the inferior cerebellar vermis. Postnatal ...

Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of cardiovascular diseases in Asia. Its lignans are major components responsible for therapeutic action. A rapid and specific UPLC-Q-TOF/MS has been developed and validated for simultaneous quantification of the five main bioactive components, i.e. schisandrin, schisandrol B, ...

Abstract Objective: To evaluate the feasibility of a transdermal patch containing propranolol (PR). Method: Skin penetration enhancers (SPEs) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2(4) full factorial design. The permeation ...

Naphyrone (1-naphthalen-2-yl-2-pyrrolidin-1-yl-pentan-1-one; naphthylpyrovalerone, β-naphyrone) is a cathinone designer drug and was marketed as replacement for the synthetic cathinone derivative mephedrone. Meanwhile, naphyrone is also classified as a controlled drug in several countries. Therefore, the aim of this study was to identify the metabolites of naphyrone in rat urine using gas ...

We combined the high MR signal enhancement achieved using dissolution dynamic nuclear polarization (DNP) with a pulsed gradient double spin echo diffusion MR sequence to rapidly and accurately measure the diffusion coefficients of various hyperpolarized (13)C molecules in solution. Furthermore, with a diffusion-weighted imaging sequence we generate diffusion coefficient maps ...

BACKGROUND: Thrombolysis using tissue plasminogen activator (tPA) is the only treatment approved for acute ischemic stroke. Although tPA is an efficient clot lysis enzyme, it also produces damage of the neurovascular unit including hemorrhagic transformations and neurotoxicity. OBJECTIVES: Based on the mechanism of action of tPA on neurotoxicity, we aimed ...

Many haloarchaea are known as polyhydroxyalkanoates (PHAs) producers, but a global and integrated view of the PHA biosynthesis is still lacking in this group of archaea. In this study, a combined proteomic and transcriptomic approach was employed in Haloarcula hispanica, a model haloarchaeon that accumulates poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) under nutrient-limiting conditions ...

Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV-1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV-1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in ...

In a novel event method directed forgetting task, instructions to Remember (R) or Forget (F) were integrated throughout the presentation of four videos depicting common events (e.g., baking cookies). Participants responded more accurately to cued recall questions (E1) and true/false statements (E2-4) regarding R segments than F segments. This was ...

INTRODUCTION Diabetic macular edema is a common cause of visual acuity deterioration among patients with diabetes. Laser photocoagulation is a still most common treatment techniques of diabetic retinopathy and diabetic macular edema. OBJECTIVES To assess mean retinal sensitivity among patients with diabetic macular edema before and after laser photocoagulation treatment. ...

11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) catalyzes the inactivation of cortisol (F) to cortisone (E) in aldosterone target tissues, thereby protects mineralocorticoid receptor from F. Failure of 11β-HSD2 function is the basis of apparent mineralocorticoid excess, and its mild disturbances are suggested to lead to hypertension. The aim of the study ...

Objective: Functional Electrical Stimulation (FES) for correction of dropped foot has been shown to increase mobility, reduce the incidence of falls and to improve quality of life. This study aimed to determine how long the intervention is of benefit, and the total cost of its provision. Design: Retrospective review of ...

OBJECTIVES: To assess the long-term effects of the EXBELT intervention program, which was designed to reduce belt restraint use and was found to be effective immediately after implementation, after 24 months. DESIGN: Quasi-experimental longitudinal design. SETTING: Thirteen nursing homes: seven assigned to control group and six to intervention group. PARTICIPANTS: A ...

When starved, Bacillus subtilis cells can enter the developmental program of endospore formation by activation of the master transcriptional regulator Spo0A. Correct chromosome copy number is crucial for the production of mature and fully resistant spores. The production and maintenance of one chromosome for the mother cell and one copy ...

Objective: In a simultaneous care model, patients have concurrent access to both cancer-directed therapies and palliative care. As oncologists play a critical role in determining the need/timing of referral to palliative care programs, their understanding of the service and ability to communicate this with patients is of paramount importance. Our ...

Anaerobic digestion is an environmental key technology in the future bio-based economy. To achieve functional stability, a minimal microbial community diversity is required. This microbial community should also have a certain 'elasticity', i.e. the ability to rapidly adapt to suboptimal conditions or stress. In this study it was evaluated whether ...

OBJECTIVE: To validate the efficacy and safety of our clinical protocol for expectant management of selected women diagnosed with tubal ectopic pregnancy. METHODS: This was a prospective observational study carried out in the Early Pregnancy Unit (EPU) of a London inner city university teaching hospital from the 1(st) of January ...

Abstract As the use of silver nanoparticles is increasing fast in industry, food, medicines, etc., exposure to silver nanoparticles is increasing in quantity day by day. So, it is imperative to know the adverse effects of silver nanoparticles in man. In this study, we selected mice as an animal model ...

The goals of this study were to better understand the ecology of oral subgingival communities in health and periodontitis and elucidate the relationship between inflammation and the subgingival microbiome. Accordingly, we used 454-pyrosequencing of 16S rRNA gene libraries and quantitative PCR to characterize the subgingival microbiome of 22 subjects with ...

The current study uses data from the genetic subsample from the National Longitudinal Study of Adolescent Health (Add Health) in waves I and II (ages of 11-19 and 12-20 respectively) to investigate the interaction of the TaqIA polymorphism and poor parental socialization on changes in adolescent marijuana use. Results reveal ...

Native chemical ligation (NCL) has become the method of choice in synthesizing large or cyclic peptides/proteins. To overcome the limitation of NCL requiring N-terminal cysteine to mediate ligation, a strategy involving thiol-mediated ligation followed by desulfurization has been developed and advanced to realize peptide ligation at other amino acid sites, ...

Experimental evidence suggests that endogenous opioids play an important role in the development of ethanol addiction. In this study, we employed two mouse lines divergently bred for opioid-mediated stress-induced analgesia. In comparison with HA (high analgesia line) mice, LA (low analgesia line) mice, having lower opioid receptor system activity, manifest ...

Because of the increased availability of price data over the past 15 years, several studies have estimated the demand for illicit drugs, providing 462 estimates of the price elasticity. Results from estimating several meta-regressions reveal that these price elasticity estimates are influenced by a number of study characteristics. For instance, the ...

We report a new and rare case of recurrent anencephaly in a family with no other apparent abnormalities. The karyotypes of the family and all affected subjects were normal. Thorough mutational analyses of VANGL1 of chromosome 1p13.1 and FOXN1 of chromosome 17q11-q12, genes that are associated with phenotypes of the ...

MicroRNAs (miRNAs) negatively regulate target gene expression by binding to 3'-untranslated region of target mRNA. Single-nucleotide polymorphisms (SNPs) that reside in the miRNA target sites can affect the bindings of miRNAs to mRNAs. Compelling evidence has shown that miRNAs contribute to the etiology of type 2 diabetes (T2DM). We hypothesized ...

BACKGROUND: Eczema is common in infancy; there is little evidence about its natural history to adulthood. OBJECTIVES: To study the natural history of eczema from birth to young adult life with particular reference to its relation to atopy. METHODS: A birth cohort of children with atopic family histories was followed ...

Physical restraints are commonly used in intensive care units to reduce the risk of injury and ensure patient safety. However, there is still controversy regarding the practice of physical restraints in such units. The purpose of this study was to investigate the practices of physical restraints among critical care nurses ...

ABSTRACT: BACKGROUND: Catgut implantation at acupoints has been used in China to treatment allergic rhinitis (AR) for a long time. However, its efficacy and safety in the treatment of AR is controversial due to the poor quality of the clinical trial of this therapy. This study aims to identify whether ...

OBJECTIVE: To analyze the association between objectively assessed physical activity (PA) and markers of insulin resistance (IR) in European adolescents and to examine whether the association of objectively assessed PA and markers of IR is modified by cardiorespiratory fitness (CRF). METHODS: A cross-sectional study at school setting was conducted in ...

Abstract Objective. Myelomeningocele is the most common physically disabling birth defect in humans. It is caused by the failure of the neural tube to close and is most common in the lumbosacral area. Because of associated neurogenic bladder dysfunction, children with myelomeningocele have an increased risk of urinary tract infections ...

Which factors limit metabolite accumulation in plant cells? Are theories on flux control effective at explaining the results? Many biotechnologists cling to the idea that every pathway has a rate limiting enzyme and target such enzymes first in order to modulate fluxes. This often translates into large effects on metabolite ...

OBJECTIVES: To examine the relationship between resting pulse rate (RPR) and longevity in individuals aged 70 to 90. DESIGN: The Jerusalem Longitudinal Cohort Study (1990-2010) is a prospective longitudinal study of a representative cohort born in 1920-21. SETTING: Home-based comprehensive assessment in 1990, 1998, and 2005. PARTICIPANTS: Individuals aged 70 ...

BACKGROUND AND AIM: Increased basal release of nitric oxide (NO) in the splanchnic circulation contributes to elevated plasma levels of NO observed in decompensated cirrhosis. We evaluated in rat mesenteric arteries whether the differences in basal release of NO, revealed by asymmetric dimethylarginine (ADMA)- and N(G) -nitro-L-arginine methyl ester (L-NAME)-induced ...

Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to published studies presented in this review article, FLG mutations are observed in approximately 7.7% of Europeans and ...

Peptidoglycan (PG), also designated as murein, forms a skeletal mesh within the periplasm of bacterial membrane. PG is a metabolically stable cell architecture in Escherichia coli, but under as yet ill-defined conditions, a portion of PG is degraded, of which both amino sugar and peptide moieties are either recycled or ...

Selective oxidation of alkyl C-H bonds constitutes one of the highest challenges for chemical synthesis. In this work we show that mononuclear iron coordination complexes containing highly structured active sites catalyze the efficient oxidation of alkyl C-H bonds employing H2O2 as terminal oxidant. These catalysts are very reactive and can ...

Linear Zn(ii)-Ce(iii)-Zn(ii) complex, which involves only one 4f electron as a spin source, behaves as an SMM. Easy-axis magnetic anisotropy for the ground (2)F(5/2) state of Ce(iii) was achieved by a uni-axial crystal field, which is formed with four phenoxo oxygens as axial donors with the other five oxygens as ...

The current knowledge of trehalose biosynthesis under stress conditions is incomplete and needs further research. Since trehalose finds industrial and pharmaceutical applications, enhanced accumulation of trehalose in bacteria seems advantageous for commercial production. Moreover, physiological role of trehalose is a key to generate stress resistant bacteria by metabolic engineering. Although ...

Abstract Objective. The aim of this study was to investigate the functional and oncological outcomes of orthotopic neobladders in women with urothelial cancer. Material and methods. From 1993 to 2007, 61 women underwent radical cystectomy and orthotopic ileal neobladder using the hemi-Kock pouch or Skinner T pouch. Sixteen of them ...

Morriss R, Yang M, Chopra A, Bentall R, Paykel E, Scott J. Differential effects of depression and mania symptoms on social adjustment: prospective study in bipolar disorder. Bipolar Disord 2013: 15: 80-91. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. Objectives:  Previous studies of social adjustment ...

A novel Cu(ii)-catalyzed cyclization of α-diazo-β-oxoamides with amines has been developed, constituting a straightforward method to construct pyrrol-3(2H)-one rings. The intramolecular hydrogen bonding effect in α-diazo-β-oxoamides plays an essential role in this reaction. A plausible reaction mechanism involving divergent generation and subsequent [2 + 3] cyclization of ketene and α-diazoimine ...

Dietary behavior can worsen or prevent hypertension. However, data on the association between dietary behavior and the risk of hypertension in Asians are limited. The aim of this study was to determine these associations in Japanese male workers. We conducted a prospective study of 30-71-year-old Japanese male workers in Osaka, ...

AIMS: Dietary modifications may play an important role in the prevention of diabetes. We aimed to assess the temporal association between diet quality and both impaired fasting glucose and Type 2 diabetes among older adults. METHODS: A total of 2564 participants aged 49+ years at baseline were examined between 1992 and ...