Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.

With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells.

Perivascular Spaces in Old Age: Assessment, Distribution, and Correlation with White Matter Hyperintensities.

Background And Purpose: The visual rating scales for perivascular spaces vary considerably. We sought to develop a new scale for visual assessment of perivascular spaces and to further describe their distribution and association with white matter hyperintensities in old age.

Materials And Methods: This population-based study included 530 individuals who did not have dementia and were not institutionalized (age, ≥60 years or older; mean age, 70.

MRI of the Swallow Tail Sign: A Useful Marker in the Diagnosis of Lewy Body Dementia?

Background And Purpose: There are, to date, no MR imaging diagnostic markers for Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia nigra pars compacta is hyperintense on SWI and has been called the swallow tail sign, disappearing with Parkinson disease. We aimed to study the swallow tail sign and its clinical applicability in Lewy body dementia and hypothesized that the sign would be likewise applicable in Lewy body dementia.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified mutations in 50% of patients with CM-AVM.

Cortical superficial siderosis: Prevalence and biomarker profile in a memory clinic population.

Objective: To gain further insight into cortical superficial siderosis (cSS), a new hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA), and to investigate the clinical, neuroimaging, genetic, and CSF biomarker profile of cSS in a large, consecutive memory clinic series.

Methods: We included 1,504 memory clinic patients undergoing dementia investigation including a brain MRI in our center. Routine CSF biomarker analysis was performed in 1,039 patients and APOE genotyping in 520 patients.

Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease.

Objective: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity.

Methods: In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE.

In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.

Objective: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated.

Pre-clinical formulation screening, development and stability of acetyl aspartic acid for cosmetic application.

Background: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap). Using an in silico and in vitro approach, A-A-A was found increased keratinocyte regeneration, inhibited dermal expression of MMP making this compound a potential active ingredient for cosmetic application.

Objectives: To determine the conditions to successfully formulate A-A-A for skin delivery investigation and in vivo clinical assessment by the systematic approach of pre-formulation testing of the active, screening of formulation type on active delivery and stability evaluations.

SWI or T2*: which MRI sequence to use in the detection of cerebral microbleeds? The Karolinska Imaging Dementia Study.

Background And Purpose: Cerebral microbleeds are thought to have potentially important clinical implications in dementia and stroke. However, the use of both T2* and SWI MR imaging sequences for microbleed detection has complicated the cross-comparison of study results. We aimed to determine the impact of microbleed sequences on microbleed detection and associated clinical parameters.

Cerebral microbleeds: different prevalence, topography, and risk factors depending on dementia diagnosis—the Karolinska Imaging Dementia Study.

Background And Purpose: Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia.

Materials And Methods: We analyzed 1504 patients (53% women; mean age, 63 ± 10 years; 10 different dementia diagnoses) in this study.

Lower versus higher hemoglobin threshold for transfusion in septic shock.

Background: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established.

Methods: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay.

Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.

Background: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the nonnucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.

Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), and dasabuvir (250 mg twice daily) with ribavirin (in doses determined according to body weight) (group A) or matching placebos (group B).

Comparison and functionalization study of microemulsion-prepared magnetic iron oxide nanoparticles.

Magnetic iron oxide nanoparticles (MION) for protein binding and separation were obtained from water-in-oil (w/o) and oil-in-water (o/w) microemulsions. Characterization of the prepared nanoparticles have been performed by TEM, XRD, SQUID magnetometry, and BET. Microemulsion-prepared magnetic iron oxide nanoparticles (ME-MION) with sizes ranging from 2 to 10 nm were obtained.

A double-blind and controlled study on the influence of the vehicle on the skin susceptibility to stinging from lactic acid.

Synopsis For patients with skin diseases, the process of treating the skin with topical medications adds to the burden of having the disease. Inconvenient skin reactions can make the treatment troublesome and lower the compliance. Moreover, epidemiological surveys indicate that 50% or more of female consumers believe they have sensitive skin.

On the formation and stability of high internal phase O/W emulsions.

High internal phase o/w emulsions have been investigated with respect to stability. A series of aliphatic hydrocarbons were used as the oil component. By matching the refractive index of both phases, transparent, concentrated emulsions were produced and these emulsions were found to have the highest long-term stability.

Percutaneous absorption of organic solvents.

Organic solvents pass the cutaneous barriers and may quickly be absorbed in substantial amounts, such that several solvents have "skin" denotations in lists of occupational exposure limit values. Solvents may be absorbed from liquids, upon direct skin contact, and in some cases also from contact with vapors. Environmental factors such as temperature, humidity, vehicle, and ventilation influence absorption.

The influence of salicylic acid on the in vitro release of anthralin from an o/w cream.

A diffusion cell with an artificial membrane (dialysis membrane) was used to study the in vitro release of antralin from an o/w cream (Locobase) in the presence of salicylic acid. The concentration range of antralin was 0.04-3.