Management of Mammographic Architectural Distortion Based on Contrast-enhanced MRI and US Correlation.

Objective: The objective was to evaluate outcomes of mammographic architectural distortion (AD) with and without MRI and US correlates.

Methods: A retrospective review of unexplained mammographic AD with subsequent MRI from January 1, 2007 to September 30, 2017 was performed using a reader-based study design. Mammographic, MRI, and US features and outcomes were documented.

Environmental oxygen affects ex vivo growth and proliferation of mesenchymal progenitors by modulating mitogen-activated protein kinase and mammalian target of rapamycin signaling.

Background Aims: Stem and progenitor cells of hematopoietic and mesenchymal lineages reside in the bone marrow under low oxygen (O) saturation. O levels used in ex vivo expansion of multipotent mesenchymal stromal cells (MSCs) affect proliferation, metabolism and differentiation.

Methods: Using cell-based assays and transcriptome and proteome data, the authors compared MSC cultures simultaneously grown under a conventional 19.

Helicobacter pylori Infection and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Since numerous studies have stated that there may be a relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease, and because of the high prevalence of both conditions worldwide, this study investigated the risk of non-alcoholic fatty liver disease in patients infected with H. pylori. Following a systematic review of PubMed, Scopus, Web of Science and Embase, and a search in Google Scholar using MeSH terms such as H.

Factors Associated With Background Parenchymal Enhancement on Contrast-Enhanced Mammography.

The purpose of this study was to determine the relationship between background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM) and breast tissue density, menstrual status, endocrine therapy, and risk factors for breast cancer and also to evaluate interreader agreement on classification of BPE on CEM. Five subspecialty-trained breast radiologists independently and blindly graded tissue density (with fatty tissue and scattered fibroglandular tissue classified as nondense tissue and with heterogeneously dense and extremely dense classified as dense tissue) and BPE (with minimal or mild BPE categorized as low BPE and moderate or marked BPE categorized as high BPE) on CEM examinations performed from 2014 to 2018. Electronic medical charts were reviewed for information on menstrual status, endocrine therapy, history of breast surgery, and other risk factors for breast cancer.

Contrast-enhanced Mammography: Current Applications and Future Directions.

Contrast-enhanced mammography (CEM) is a developing modality used for the workup and management of breast cancer. Although diagnostic imaging modalities such as mammography and US have historically been the mainstays of initial breast cancer workup, recent advances in breast MRI have allowed better disease evaluation. However, MRI is not always readily available, can be time consuming, and is contraindicated in certain patients.

Comparison of Contrast-Enhanced Mammography With Conventional Digital Mammography in Breast Cancer Screening: A Pilot Study.

Purpose: To perform a pilot evaluation of contrast-enhanced mammography (CEM) for screening to determine whether it can improve accuracy and reader confidence in diagnosis.

Methods And Materials: This institutional review board-approved reader study was comprised of 64 de-identified CEM cases acquired from December 1, 2014, to June 7, 2016, including 48 negative, 5 biopsy-proven benign, and 11 biopsy-proven malignancies. Negative cases were followed for at least 2 years without evidence of cancer.

CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis.

Organelle biogenesis requires proper transport of proteins from their site of synthesis to their target subcellular compartment. Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and traffic through the Golgi complex before being transferred to the endolysosomal system, but how they are transferred from the ER to the Golgi is unknown. Here, we show that ER-to-Golgi transfer of lysosomal enzymes requires CLN8, an ER-associated membrane protein whose loss of function leads to the lysosomal storage disorder, neuronal ceroid lipofuscinosis 8 (a type of Batten disease).

Lysosome biogenesis in health and disease.

This review focuses on the pathways that regulate lysosome biogenesis and that are implicated in numerous degenerative storage diseases, including lysosomal storage disorders and late-onset neurodegenerative diseases. Lysosomal proteins are synthesized in the endoplasmic reticulum and trafficked to the endolysosomal system through the secretory route. Several receptors have been characterized that execute post-Golgi trafficking of lysosomal proteins.

Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency.

Unlabelled: The accumulation of undegraded molecular material leads to progressive neurodegeneration in a number of lysosomal storage disorders (LSDs) that are caused by functional deficiencies of lysosomal hydrolases. To determine whether inducing macroautophagy/autophagy via small-molecule therapy would be effective for neuropathic LSDs due to enzyme deficiency, we treated a mouse model of mucopolysaccharidosis IIIB (MPS IIIB), a storage disorder caused by deficiency of the enzyme NAGLU (alpha-N-acetylglucosaminidase [Sanfilippo disease IIIB]), with the autophagy-inducing compound trehalose. Treated naglu mice lived longer, displayed less hyperactivity and anxiety, retained their vision (and retinal photoreceptors), and showed reduced inflammation in the brain and retina.

Lysosomes and Brain Health.

One of the fundamental properties of the cell is the capability to digest and remodel its own components according to metabolic and developmental needs. This is accomplished via the autophagy-lysosome system, a pathway of critical importance in the brain, where it contributes to neuronal plasticity and must protect nonreplaceable neurons from the potentially harmful accumulation of cellular waste. The study of lysosomal biogenesis and function in the context of common and rare neurodegenerative diseases has revealed that a dysfunctional autophagy-lysosome system is the shared nexus where multiple, interconnected pathogenic events take place.

Corrigendum: mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases.

This corrects the article DOI: 10.1038/ncomms14338.

mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases.

Neurodegenerative diseases characterized by aberrant accumulation of undigested cellular components represent unmet medical conditions for which the identification of actionable targets is urgently needed. Here we identify a pharmacologically actionable pathway that controls cellular clearance via Akt modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathways. We show that Akt phosphorylates TFEB at Ser467 and represses TFEB nuclear translocation independently of mechanistic target of rapamycin complex 1 (mTORC1), a known TFEB inhibitor.

NADPH oxidase promotes Parkinsonian phenotypes by impairing autophagic flux in an mTORC1-independent fashion in a cellular model of Parkinson's disease.

Oxidative stress and aberrant accumulation of misfolded proteins in the cytosol are key pathological features associated with Parkinson's disease (PD). NADPH oxidase (Nox2) is upregulated in the pathogenesis of PD; however, the underlying mechanism(s) of Nox2-mediated oxidative stress in PD pathogenesis are still unknown. Using a rotenone-inducible cellular model of PD, we observed that a short exposure to rotenone (0.

Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB.

Sanfilippo syndrome Type B or Mucopolysaccharidosis IIIB (MPS IIIB) is a neurodegenerative autosomal recessive lysosomal storage disorder in which patients suffer severe vision loss from associated retinopathy. Here we sought to study the underlying retinal functional and morphological changes associated with MPS IIIB disease progression using the established model of MPS IIIB, the B6.129S6-Naglu(tm1Efn)/J mouse line.

Papilloma on core biopsy: excision vs. observation.

Background: Intraductal papillomas (IPs) are commonly seen breast lesions with variable clinical presentation. For a palpable lesion and/or evidence of cellular atypia and/or pathologic nipple discharge, excision is warranted to rule out adjacent carcinoma, while for asymptomatic IPs lacking atypia current data for excision vs. observation are controversial.

2-Hydroxypropyl-β-cyclodextrin promotes transcription factor EB-mediated activation of autophagy: implications for therapy.

2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a Food and Drug Administration-approved excipient used to improve the stability and bioavailability of drugs. Despite its wide use as a drug delivery vehicle and the recent approval of a clinical trial to evaluate its potential for the treatment of a cholesterol storage disorder, the cellular pathways involved in the adaptive response that is activated upon exposure to HPβCD are still poorly defined. Here, we show that cell treatment with HPβCD results in the activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and in enhancement of the cellular autophagic clearance capacity.

A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells.

A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG) activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB) due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB.

Control of neural interfacing in peripheral nerves through regenerative molecular guidance.

Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, random axonal pathfinding during peripheral nerve regeneration leads to mixed populations of sensory and motor neurons at the electrode interfaces preventing the precise identification of the modality nature of the recorded action potentials; motor or specific sensory sub-modalities. This study present evidence that supports the notion that type-specific neurotrophins can be used to preferentially entice and segregate the growth of defined axonal populations from transected peripheral nerves.

Modality-specific axonal regeneration: toward selective regenerative neural interfaces.

Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed sub-modality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments.

The effect of incorporation of SDF-1alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response.

Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design.

Can breast MRI predict axillary lymph node metastasis in women undergoing neoadjuvant chemotherapy.

Background: Axillary lymph node status provides important staging information. We sought to evaluate the predictive value of breast magnetic resonance imaging (MRI) in detecting axillary lymph node metastases prior to initiation of neoadjuvant chemotherapy (NAC) and in detecting residual lymph node metastases after NAC in women found to be node positive prior to NAC.

Methods: Women underwent breast MRI with axillary evaluation prior to initiation of NAC and again after completion of NAC.