bluuebunny/crossref_metadata_2025 huggingface dataset:
PDGFRβ translocates to the nucleus and regulates chromatin remodeling via TATA element–modifying factor 1
Authors: Papadopoulos Natalia , Lennartsson Johan , Heldin Carl-Henrik
Published: March 2018

Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB–induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells. In the nucleus, PDGFRβ formed ligand-inducible complexes with the tyrosine kinase Fer and its substrate, TATA element–modifying factor 1 (TMF-1). PDGF-BB stimulation decreased TMF-1 binding to the transcriptional regulator Brahma-related gene 1 (Brg-1) and released Brg-1 from the SWI–SNF chromatin remodeling complex. Moreover, knockdown of TMF-1 by small interfering RNA decreased nuclear translocation of PDGFRβ and caused significant up-regulation of the Brg-1/p53-regulated cell cycle inhibitor CDKN1A (encoding p21) without affecting PDGFRβ-inducible immediate-early genes. In conclusion, nuclear interactions of PDGFRβ control proliferation by chromatin remodeling and regulation of p21 levels.
Emergency Preparedness
Authors: Hurd Peter D , Lukas Stephenie , Hanson Ardis
Published: March 2018

Pharmacists, and pharmacy students, normally have a limited exposure to the principles and structures of emergency management necessary to help coordinate effective and rapid responses. However, pharmacists’ work in disaster preparedness has taken many focuses. Community pharmacists develop emergency preparedness manuals, organize health-system pharmacy teams to respond to terrorism attacks, and identify essential actions for effective emergency response. This chapter focuses on the US health care system and emergency preparedness within its borders, starting with basic terminology and concepts and then moving onto the key components of U.S. National Response Frameworks and the role of pharmacists in the Frameworks and larger emergency preparedness and planning efforts.
Neuromuscular Innervation
Authors: Fisch Adam J
Published: March 2018

This chapter focuses on learning the process and components of neuromuscular innervation. Instructions are given on how to draw the brachial plexus, terminal nerves, lumbosacral plexus, peroneal nerves, tibial nerves, and dermatomal maps of spinal nerve sensory innervation. The chapter provides key landmarks along the dermatomal maps of sensory innervation, as well as syndromes associated with the various structures involved in neuromuscular innervation.
The Spinal Cord & Spine
Authors: Fisch Adam J
Published: March 2018

This chapter focuses on learning the anatomy, elements, and histology of the spine and spinal cord. It gives instructions on how to draw the various components that make up the spinal cord, including ascending spinal cord pathways, descending spinal cord pathways, and spinal nerves. The chapter also outlines the mechanics of muscle stretch reflex. The major spinal cord disorders are discussed, to solidify understanding of spinal cord clinical anatomy. Finally, case histories of specific disorders are presented along with discussion of the elements involved in making the diagnosis.
The Cerebrum, Cerebellum, & Cognitive Disorders
Authors: Fisch Adam J
Published: March 2018

This chapter focuses on the cerebral lobes and some additional key features of the superior and inferior surfaces of the brain, as well as on the structures of the cerebellum. Instructions are provided on how to draw the multiple lobes and surfaces of the cerebrum, gyri, sulci, insula, Sylvian fissure, Brodmann areas, neocortical layers, cerebellum, cerebellar peduncles, the corticopontocerebellar pathway, cerebellar midline structures, arterial supply, cerebral white matter, and commissural fibers. Also discussed are features of histology of neurons and glia and cerebellar histology. Cerebral and cerebellar disorders are also presented, including cognitive disorders, apraxia, and neglect.
Proliferative Lesions and Breast Cancer Histopathology
Authors: Apple Sophia K. , Bassett Lawrence W.
Published: March 2018

Breast in situ lesions and invasive carcinomas are a heterogeneous group of tumors comprising many different morphological and biological subtypes. The majority of invasive breast cancers thought to arise in the terminal ductal lobular unit (TDLU). As multidisciplinary diagnosis and detection of early breast carcinomas is the gold standard, an understanding of histopathology in correlation with radiologic findings is critical. This chapter reviews the histopathology of high-risk proliferative lesions, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), and invasive breast carcinoma. Tumor progression and some of the frequently seen invasive breast cancer subtypes are described. Histopathology of other malignancies arising from mesenchymal origin, including phyllodes tumor, is also described.
An Overview of Digital Mammography Technology and MQSA Requirements
Authors: Oshiro Thomas , Bassett Lawrence W.
Published: March 2018

Understanding the fundamentals of mammographic imaging is essential for any practicing physician. The elements described in this section should serve as a brief review of how digital mammography systems acquire and generate images. Equipment including digital receptor design and technical factors to optimize the radiographic contrast and spatial resolution while reducing breast doses to lower levels are outlined. General image processing features as well as commonly encountered clinical artifacts will be reviewed. MQSA (Mammography Quality Standards Act) and ACR standards that define qualifications for personnel (interpreting physicians, radiologic technologists and medical physicists), minimum equipment performance characteristics and methodologies for routine quality control testing are summarized.
Breast Ultrasound Overview
Authors: Raghu Madhavi , Philpotts Liane E.
Published: March 2018

Ultrasound of the breast is comfortable, widely available, and does not involve ionizing radiation. Indications for a breast ultrasound study include evaluation of a palpable lump, further evaluation of a mammographic or MRI abnormality, screening among women who are at increased cancer risk, and to provide guidance for a percutaneous biopsy. This chapter provides an overview of breast ultrasound, which is a key modality for diagnostic evaluation and, increasingly, for supplemental screening. Topics that will be covered here include the breast anatomy on ultrasound, imaging techniques, medical physics associated with breast ultrasound (including spatial compounding, Doppler imaging, and harmonic imaging), and clinical indications.
Emerging Breast Imaging Technologies
Authors: Umphrey Heidi R.
Published: March 2018

Emerging breast imaging technologies may provide improved care across the entire breast cancer care continuum; however, assessment of these technologies and their added value will require further development and research. Contrast-enhanced mammography was first described in 1985, utilizing digital subtraction angiography of the breast. Molecular techniques in breast imaging are expanding as advances in technology allow for decreased radiotracer dose and reveal high sensitivity for the detection of breast cancers. Molecular breast imaging (MBI) tools may have a role as we develop personalized breast imaging protocols based on risk. This chapter, appearing in the section on breast cancer overview, describes the new emerging technologies in breast imaging, including contrast-enhanced spectral mammography and molecular breast imaging.
Circumscribed Mass: Intramammary Lymph Node
Authors: Kettler Mark D.
Published: March 2018

This chapter, appearing in the section on circumscribed mass, reviews the key clinical and imaging features, differential diagnosis, and management recommendations for intramammary lymph nodes. Benign intramammary lymph nodes are ubiquitous on screening mammography, and whenever it is possible to do so, they should be differentiated from solid masses in order to avoid unnecessary recalls for diagnostic imaging. Three-dimensional tomosynthesis can facilitate the diagnosis of benign intramammary lymph nodes and decrease the number of recalls for supplemental breast imaging. Ultrasound may help in distinguishing between benign lymph nodes and other breast masses when this cannot be accomplished by using mammography alone.
Large Circumscribed Mass in Young Female
Authors: Kettler Mark D.
Published: March 2018

Fibroepithelial lesions account for the overwhelming majority of solid breast masses affecting women younger than age 20. Nearly all present as self-detected or provider-detected palpable masses. All fibroepithelial lesions are composed of stromal (fibrous) and glandular (epithelial) elements and variable histology. Rapidly growing mobile breast masses in girls or female adolescents may represent juvenile fibroadenomas, which have different but benign histological features when compared to typical fibroadenomas. Benign phyllodes tumors closely resemble usual fibroadenomas and juvenile fibroadenomas on imaging. Decisions whether to biopsy these tumors are made clinically; the diagnosis of phyllodes tumor depends on histological assessment.

This chapter, appearing in the section on circumscribed mass, reviews the key clinical and imaging features, differential diagnosis, and management recommendations of large solid breast masses affecting young women, including typical fibroadenomas, giant fibroadenomas, juvenile fibroadenomas, and phyllodes tumors.
Complex Cystic and Solid Mass
Authors: Stein Matthew A.
Published: March 2018

The breast ultrasound (US) finding known as “complex mass” has undergone a labeling revision with the fifth edition of the BI-RADS Atlas and is now designated as complex cystic and solid mass (CCSM). The updated BI-RADS sought to unambiguously define and differentiate an actionable finding often requiring biopsy from a lesser finding requiring, at most, imaging follow-up to confirm expected stability. This chapter, appearing in the section on nipple, skin and lymph nodes, reviews key imaging and clinical features, imaging protocols and pitfalls, differential diagnosis, and clinical recommendations for complex cystic and solid masses. Topics include the rationale for the updated BI-RADS lexicon, the important differentiation of a complex cystic and solid mass from a complicated cyst, and a framework for the differentiation and management of actionable and non-actionable masses with complex cystic and solid features at ultrasound.
Thrombophlebitis (Mondor Disease)
Authors: Stein Matthew A.
Published: March 2018

This chapter, appearing in the section on nipple, skin, and lymph nodes, reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnosis, and clinical recommendations of superficial thrombophlebitis of the breast and anterior chest wall (Mondor disease). The condition is quite rare; incidence rates in the literature are reported as being less than 0.1%. Mondor disease is often temporally associated with a history of recent breast surgery, core needle biopsy, inflammatory process, or episode of trauma. Topics in this chapter include discussions of the incidence of Mondor disease, its presumptive pathophysiology, typical and atypical clinical/imaging presentations, and management considerations.
Stereotactic Core Biopsy
Authors: Lee Bonmyong
Published: March 2018

Stereotactic biopsy systems utilize angled mammography images and parallax shift to localize and sample a target. The most common indication for stereotactic core biopsy is to sample suspicious/indeterminate calcifications, but it can be used to biopsy any mammographic finding (mass, developing asymmetry, architectural distortion). In benign cases, core biopsy may avoid unnecessary surgery. In malignant cases, core biopsy allows for a pathological diagnosis prior to lumpectomy, and better surgical planning. This chapter, appearing in the section on interventions and surgical procedures, provides a practical guide to stereotactic core biopsy. Topics discussed include stereotactic core biopsy equipment, procedure protocols and pitfalls, clinical management, and imaging follow-up.
Ultrasound-Guided Core Biopsy
Authors: Di Carlo Philip A.
Published: March 2018

Prior to 1993, when ultrasound-guided core breast biopsy was first described by Parker and colleagues, surgery following image-guided needle localization was necessary to obtain a histological diagnosis of breast lesions. But there are many financial, practical, and clinical advantages of image-guided core biopsy over surgical excisional biopsy. There are also many advantages to ultrasound-guided biopsy over stereotactic- or MRI-guided biopsy, detailed in this chapter. Ultrasound is now usually the modality of choice by which to perform core biopsies if the lesion is visualized by multiple imaging modalities. This chapter, appearing in the section on interventions and surgical changes, reviews the key points of performing ultrasound-guided core biopsy. Topics discussed include protocols for both spring-loaded and vacuum-assisted devices; pre-procedure and post-procedure management, and imaging follow-up.
MRI-Guided Core Biopsy
Authors: Mullen Lisa A.
Published: March 2018

MRI-guided breast biopsy techniques were developed to sample indeterminate and suspicious breast lesions visible only on MRI. Breast MRI performed for high-risk screening, problem solving, or assessment of extent of disease in patients with newly diagnosed breast cancer may demonstrate indeterminate findings, such as enhancing foci, masses or non-mass enhancement. If the lesion is not visible by mammography or ultrasound, and MRI follow-up is not appropriate, then MRI-guided biopsy is indicated. This chapter, appearing in the section on interventions and surgical changes, reviews the key points and procedural protocols and pitfalls for performance of magnetic resonance imaging (MRI)–guided breast core biopsy. Pre-, peri-, and post-procedure clinical management, radiology–pathology correlation, and imaging follow-up are also reviewed.
Reduction Mammoplasty
Authors: Horvath Laura J.
Published: March 2018

Reduction mammoplasty is a surgical procedure performed to decrease breast size. Breast parenchyma and skin are resected, and the nipple is repositioned to a more superior location on the smaller breast mound. The goals of the procedure are to alleviate a variety of physical and psychological complaints. Because women with a history of reduction surgery are commonly seen for screening mammography and other breast imaging studies, it is important to be aware of the normal post-operative appearance. This chapter, appearing in the section on intervention and surgical change, reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnoses, and management recommendations for reduction mammoplasty. Topics discussed include clinical indications, surgical technique, and benign post-operative changes, including scars, oil cysts, fat necrosis, and calcifications.
Depression in Neurological Disorders
Authors: Kanner Andres M.
Published: March 2018

Depression is a common psychiatric comorbidity in the major neurologic disorders (e.g, stroke, epilepsy, migraine, Alzheimer’s dementia, multiple sclerosis, and Parkinson’s disease), with average prevalence rates of 25% to 40%. The relation between depression and several of these neurologic disorders is bidirectional, that is not only are patients with these neurologic conditions at greater risk of developing depression, but patients with depression are at greater risk of developing these neurologic disorders. Furthermore, the presence of comorbid depression has been associated with a worse course of the neurologic disorder and a higher risk of failure to respond to the neurologic therapies. This chapter reviews the epidemiologic and clinical characteristics of depression in the major neurologic disorder and describes the impact it has on the course of the neurologic condition and response to treatment. Finally, it identifies those neurologic disorders in with a bidirectional relation has been identified and suggests potential pathogenic mechanisms that may be operant in their complex relation.
Pathogenesis
Authors: Lam Raymond W.
Published: March 2018

Depression is a heterogeneous condition, and its aetiology and pathophysiology likely involve multiple processes involving combinations of biological, psychological, and social factors. Neurobiological hypotheses include dysregulation in monoamine and other neurotransmitter systems, alterations in stress hormones and neuroimmune systems, disturbances in sleep and circadian rhythms, and neuropsychological and neurocircuitry dysfunction. Disturbed circadian rhythms, stressful life events, and stress reactivity can also modify genetic and biological processes (gene-by-environment interactions and epigenetics) to contribute to depression. Endophenotypes, or genetic expressions of neural systems involved in depression, are important in the study of the pathogenesis of depression and the development of biomarkers and novel treatments.
Injecting While Incarcerated
Authors: Milloy M-J
Published: March 2018

Beginning approximately coincident with the advent of the global HIV pandemic, a growing number of qualitative and quantitative epidemiological studies have investigated the phenomenon of the injection of illicit psychoactive substances by individuals held within correctional settings. Empirical studies reveal that incarceration is a common experience for people who use illicit drugs, and injection while incarcerated (IWI) is an unintended if widespread consequence of the prohibition-based approach to regulating psychoactive drugs. Analyses of the spread of HIV, hepatitis C virus (HCV), and other blood-borne pathogens among injection drug users have identified IWI as an important risk factor. Although a number of evidence-based responses have been developed to mitigate the risks associated with IWI, they are unavailable to the vast majority of imprisoned people who use injection drugs.
Prisoners With a Substance Use Disorder and a Mental Illness
Authors: Dolan Kate , Farrell Michael , Moghaddam Sahar Saeedi
Published: March 2018

Globally more than 10 million people are held in prisons on any given day, giving an imprisonment rate of 144 per 100,000 population. Clear evidence indicates that the burden of substance use disorders and mental illnesses is much higher among prisoners than among the general population. The co-occurrence of these two conditions is termed dual diagnosis. The high occurrence of multiple disorders is a critical challenge for the prison health system and, regrettably, most prisoners have inadequate access to health services, particularly mental health services while in custody. This chapter explores the prevalence, incidence, and effective treatment of substance use, mental disorders, and dual diagnosis among prison populations around the world. The impact of imprisonment on drug use and mental health is discussed, and gaps in knowledge and practice are highlighted. Recommendations for future approaches to addressing substance use disorders, mental illnesses, and dual diagnoses among prisoners and detainees are explored.
Understanding the Risk Environment Surrounding Drug Use in Prisons
Authors: Small Will , McNeil Ryan
Published: March 2018

Qualitative research is uniquely positioned to advance understanding of the role of social and structural factors in shaping drug use and drug-related harms in prison settings and following release. This chapter critically reviews the qualitative literature examining drug use within the prison risk environment and following release, while identifying research gaps and directions for future inquiry. The extant literature has documented: (1) how drug use in prisons is shaped by which drugs are available, their pharmacological effects, and correctional policies; (2) how injection-related risk and syringe sharing are shaped by social and structural forces within prisons (including policies restricting syringe access) which increase the potential for drug-related harm; (3) how withdrawal and detoxification experiences in custody both foster participation in high-risk injecting practices (eg, syringe-sharing) and facilitate injection cessation and drug abstinence; (4) how inmates and staff view prison-based methadone maintenance therapy, the experiences of those receiving treatment, and barriers to scaling up methadone programs; and, (5) how transitions from prison to community shape health access, harms, and drug use patterns. By documenting prisoners’ drug-related experiences, and situating these experiences within their social, structural, and environmental contexts, these studies have generated insights beyond what is possible using other research approaches. In doing so, they have identified features of prison and post-release risk environments amenable to modification. There is an urgent need to scale up qualitative studies of prison and post-release risk environments, to better inform targeted public health interventions. Emerging interventions, including prison-based syringe exchange, should similarly be examined using qualitative approaches to more fully document their potential impacts on drug-related risks and harms.
Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma
Authors: Schneider Julia R , Shatzkes Deborah R , Scharf Stephen C , Tham Tristan M , Kulason Kay O , Buteau François-Alexandre , Del Prete Michela , Chakraborty Shamik , Anderson Todd A , Asiry Saeed , Beauregard Jean-Mathieu , Langer David J , Costantino Peter D , Boockvar John A
Published: March 2018

BACKGROUND AND IMPORTANCE

Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB.

CLINICAL PRESENTATION

A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease.

CONCLUSION

We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.
The Role of the Visor Flap in Scalp Reconstruction: A Case Series of 21 Patients
Authors: Ellis Marco , Hwang Lisa , Ford Ni-Ka , Slavin Konstantin
Published: March 2018

BACKGROUND

Full-thickness scalp defects pose a reconstructive problem, especially in the setting of infection, chemotherapy/radiation, and underlying cranial defects. Current options include dermal matrices, skin grafts, and local flaps. Local flaps often fail, requiring subsequent microvascular free flap reconstruction.

OBJECTIVE

To describe the visor flap, a novel bipedicled advancement flap design, and its role in reconstruction of scalp defects.

METHODS

A retrospective review of 21 adult patients who developed scalp defects reconstructed using the visor flap from 2013 to 2017. The visor flap is a large bipedicled advancement flap design with a triangular extension at the base, which allows redistribution of a large surface area of the scalp.

RESULTS

All 21 patients achieved complete and viable soft tissue coverage of the recipient site, but 19.0% developed complications unrelated to flap viability, requiring reoperation (infected bone flap, epidural hematoma, and recurrent glioblastoma with subdural abscess). Only 1 patient required conversion to free flap reconstruction due to cerebrospinal fluid leak. Etiologies included cancer (76.1%), cerebrovascular disease (19.0%), and traumatic brain injury (4.8%). Preoperative radiation (42.9%), bone/hardware exposure (57.1%), and previous craniotomy (85.7%) were widely prevalent. Defect size ranged from 3 to 50 cm2 (mean, 16.9 cm2), and flap size ranged from 90 to 500 cm2 (mean, 222 cm2).

CONCLUSION

The visor flap provides an innovative solution for closure of scalp defects. This technique optimizes immediate closure of tissue compromised by infection or chemotherapy/radiation without burning bridges to more complex reconstructive options.
Determinants of Lactic Acidosis in Acute Cyanide Poisonings
Authors: Baud Frédéric J. , Haidar Mohamad K. , Jouffroy Romain , Raphalen Jean-Herlé , Lamhaut Lionel , Carli Pierre
Published: March 2018

Objectives:

To investigate the magnitude of lactic acidosis in response to cyanide poisoning compared with the secondary response caused by cardiovascular shock.

Design:

Retrospective case-control observational study.

Setting:

University Hospital of Assistance Publique – Hôpitaux de Paris.

Subjects:

Patients admitted for suspicion of cyanide poisoning or drug overdose. Medical charts provided by Assistance Publique - Hôpitaux de Paris of patients between January 1988 and December 2015.

Intervention:

None.

Measurements and Main Results:

Twelve cyanide poisoned patients were matched to 48 controls by age, sex, systolic blood pressure, catecholamine administration, and outcome at discharge from ICU. Extracted data included age, sex, vital signs, symptoms, biochemical parameters, toxicological analysis, treatment, and outcome. Non-parametric tests were used. Multivariable analysis was used to adjust for confounders causing hyperlactacidemia. The median blood lactate concentration was significantly greater in the cyanide group (15.6 mmol/L) compared to the control group (4.1 mmol/L; p = 0.0003). Similarly, blood lactate concentration greater than or equal to 8 mmol/l was observed in 83% of the cyanide cases versus 27% of the matched controls. Multivariate analysis conferred hyperlactacidemia as the lone factor which significantly predicted cyanide poisoning at an odds of 73.0 (5.7-936.1). Moreover, blood cyanide level significantly correlated with the increase of blood lactate (p = 0.0033).

Conclusions:

This study supports the hypothesis lactic acidosis primarily results from the direct toxicity of cyanide.
RETINAL NEOVASCULARIZATION FROM A PATIENT WITH CUTIS MARMORATA TELANGIECTATICA CONGENITA
Authors: Sassalos Thérèse M. , Fields Taylor S. , Levine Robert , Gao Hua
Published: March 2018

Purpose:

To report a rare case of peripheral retinal neovascularization in a patient diagnosed with cutis marmorata telangiectatica congenita (CMTC).

Methods:

Observational case report.

Results:

A 16-year-old girl was referred to clinic for retinal evaluation. The patient had a clinical diagnosis of CMTC later confirmed by skin biopsy. Examination revealed temporal peripheral retinal sheathing, as well as lattice degeneration in both eyes. Wide-field fluorescein angiogram showed substantive peripheral retinal nonperfusion with evidence of vascular leakage from areas of presumed retinal neovascularization. The patient subsequently had pan retinal photocoagulation laser treatment to each eye without complication.

Discussion:

Cutis marmorata telangiectatica congenita is a rare vascular condition known to affect multiple organ systems including the eyes. Although ocular manifestations of CMTC are rare, instances of congenital glaucoma, suprachoroidal hemorrhage, and bilateral total retinal detachments resulting in secondary neovascular glaucoma have been reported. Our patient demonstrates the first reported findings of peripheral nonperfusion and retinal neovascularization related to CMTC in a 16-year-old girl. We propose early retinal examination, wide-field fluorescein angiogram, and early pan retinal photocoagulation laser treatment in patients with peripheral nonperfusion and retinal neovascularization from CMTC.
Maternal Carriage of Group B Streptococcus and Escherichia coli in a District Hospital in Mozambique
Authors: Madrid Lola , Maculuve Sonia Amós , Vilajeliu Alba , Sáez Emma , Massora Sergio , Cossa Anelsio , Varo Rosauro , Sitoe Antonio , Mosqueda Noraida , Anselmo Rui , Munguambe Khatia , Soto Sara M. , Moraleda Cinta , Macete Eusebio , Menéndez Clara , Bassat Quique
Published: March 2018

Background:

In low-income countries, data on prevalence and effects of group B Streptococcus (GBS) and Escherichia coli (E. coli) colonization among pregnant women are scarce, but necessary to formulate prevention strategies. We assessed prevalence of GBS and E. coli colonization and factors associated among pregnant women, its effect in newborns and acceptability regarding the utilized sampling methods in a semirural Mozambican hospital.

Methods:

Pregnant women were recruited from June 2014 to January 2015, during routine antenatal clinics at gestational age ≥ 34 weeks (n = 200); or upon delivery (n = 120). Maternal risk factors were collected. Vaginal and vagino-rectal samples for GBS and E. coli determination were obtained and characterized in terms of antimicrobial resistance and serotype. Anti-GBS antibodies were also determined. Neonatal follow-up was performed in the first 3 months after birth. Semistructured interviews were performed to investigate acceptability of sample collection methods.

Results:

In total, 21.3% of women recruited were GBS carriers, while 16.3% were positive for E. coli. Prevalence of HIV was 36.6%. No association was found between being colonized by GBS and E. coli and maternal risk factors. GBS isolates were fully susceptible to penicillin and ampicillin. Serotypes V (32.4%), Ia (14.7%) and III (10.3%) were the most commonly found and 69.2% of the women tested had immunoglobuline G antibodies against GBS. E. coli isolates showed resistance to ampicillin in 28.9% and trimethoprim/sulfamethoxazole in 61.3% of the cases.

Conclusion:

Prevalence of GBS and/or E. coli colonization among pregnant women is high in this semirural community and comparable with those reported in similar settings. Four serotypes accounted for nearly 70% of all isolates of GBS. Population-based data on infant GBS infections would enable the design of prevention strategies for GBS disease in Mozambique.
Human Parechovirus 1, 3 and 4 Neutralizing Antibodies in Dutch Mothers and Infants and Their Role in Protection Against Disease
Authors: Karelehto Eveliina , Wildenbeest Joanne G. , Benschop Kimberley S. M. , Koen Gerrit , Rebers Sjoerd , Bouma-de Jongh Saskia , Westerhuis Brenda M. , de Jong Menno D. , Pajkrt Dasja , Wolthers Katja C.
Published: March 2018

Background:

Human parechoviruses (HPeVs) are common pathogens in young children, and in the Netherlands, HPeV1, HPeV3 and HPeV4 are the most frequently detected genotypes. HPeV3 in particular has been associated with severe disease in young infants below 3 months of age while the other genotypes more often infect older children and elicit mild symptoms. We investigated if maternal neutralizing antibodies (nAbs) against HPeV1, HPeV3 and HPeV4 protect young Dutch infants from severe disease related to HPeV infection.

Methods:

We conducted a prospective case–control study of Dutch mother–infant pairs. Thirty-eight HPeV-infected infants and their mothers were included as cases, and 65 HPeV-negative children and their mothers as controls.

Results:

In control infants, we observed nAb seropositivity rates of 41.4%, 33.3% and 27.6%, with median nAb titers of 1:16, 1:12 and 1:8, against HPeV1, HPeV3 and HPeV4, respectively. In control mothers, nAb seropositivity rates were 84.6%, 55.4% and 60.0% with median nAb titers of 1:128, 1:32 and 1:45 against HPeV1, HPeV3 and HPeV4, respectively. The HPeV3 nAb seroprevalence was significantly lower in HPeV3-infected infants and their mothers (0.0% with P < 0.05 and 10.0% with P < 0.001, respectively). In contrast, no differences in nAb seroprevalence against HPeV1 or HPeV4 could be detected between case and control infants or mothers.

Conclusions:

Our results suggest that young Dutch infants are protected against severe disease related to HPeV1 and HPeV4 by maternal nAbs, but less so against HPeV3 explaining the distinct age distributions and disease severity profiles of children infected with these HPeV genotypes.
Brown adipose tissue and lipid metabolism
Authors: Heeren Joerg , Scheja Ludger
Published: March 2018

Purpose of review

This article explores how the interplay between lipid metabolism and thermogenic adipose tissues enables proper physiological adaptation to cold environments in rodents and humans.

Recent findings

Cold exposure triggers systemic changes in lipid metabolism, which increases fatty acid delivery to brown adipose tissue (BAT) by various routes. Next to fatty acids generated intracellularly by de-novo lipogenesis or by lipolysis at lipid droplets, brown adipocytes utilize fatty acids released by white adipose tissue (WAT) for adaptive thermogenesis. WAT-derived fatty acids are internalized directly by BAT, or indirectly after hepatic conversion to very low-density lipoproteins and acylcarnitines. In the postprandial state, chylomicrons hydrolyzed by lipoprotein lipase – activated specifically in thermogenic adipocytes – are the predominant fatty acid source. Cholesterol-enriched chylomicron remnants and HDL generated by intravascular lipolysis in BAT are cleared more rapidly by the liver, explaining the antiatherogenic effects of BAT activation. Notably, increased cholesterol flux and elevated hepatic synthesis of bile acids under cold exposure further promote BAT-dependent thermogenesis.

Although pathways providing fatty acids for activated BAT have been identified, more research is needed to understand the integration of lipid metabolism in BAT, WAT and liver, and to determine the relevance of BAT for human energy metabolism.
Mucosal Impedance Measurements Differentiate Pediatric Patients With Active Versus Inactive Eosinophilic Esophagitis
Authors: Lowry Mary Allyson , Vaezi Michael F. , Correa Hernan , Higginbotham Tina , Slaughter James C. , Acra Sari
Published: March 2018

Background and Aims:

Eosinophilic esophagitis (EoE) is a chronic disorder in children that requires continued assessment of disease activity, involving repeated sedation, endoscopy, and biopsy analysis. We investigated whether mucosal impedance measurements can be used to monitor disease activity in pediatric patients with EoE.

Methods:

We measured mucosal impedance at 3 locations in the esophagus in pediatric patients (1–18 years old; 32 with active EoE, 10 with inactive EoE, 32 with nonerosive reflux disease [NERD]) and 53 children with symptoms but normal findings from histologic analyses (controls) undergoing routine esophagogastroduodenoscopy at the Vanderbilt Pediatric Gastroenterology Clinic. Pathologists reviewed biopsies per routine protocol, determined eosinophilic density, and graded spongiosis on an ordinal visual scale. Mucosal impedance measurements were compared within patient groups. The primary outcome was correlation of mucosal impedance measurements with disease activity, based on severity of spongiosis and eosinophil counts.

Results:

Mucosal impedance measurements were significantly lower in patients with active EoE at 2, 5, and 10 cm above the squamo‐columnar junction (median values of 1069, 1368, and 1707, respectively) compared to patients with inactive EoE (median values of 3663, 3657, and 4494, respectively), NERD (median values of 2754, 3243, and 4387), and controls (median values of 3091, 3760, and 4509) (P < 0.001 for all comparisons to patients with active EoE). We found inverse correlations between mucosal impedance measurements and eosinophil count (P < 0.001), and spongiosis severity (P < 0.001).

Conclusions:

Mucosal impedance measurements may provide immediate information about mucosal inflammation in children. Patients with active EoE have significantly lower mucosal impedance values than patients with inactive EoE, NERD, or controls; mucosal impedance measurements correlate inversely with eosinophil counts and spongiosis severity. Mucosal impedance is a promising rapid and less‐invasive method to monitor EoE activity in pediatric patients with EoE; it could reduce costs and risks of disease monitoring.
Anatomic Study on Sphenoidal Emissary Foramen by Using Cone-Beam Computed Tomography
Authors: Bayrak Seval , Kurşun-Çakmak Emine Şebnem , Atakan Cemal , Orhan Kaan
Published: March 2018

Objectives:

The goal of this retrospective study is to evaluate the radiologic anatomy of sphenoidal emissary foramen (SEF) by using cone-beam computed tomography (CBCT) scans.

Methods:

Three hundred seventeen (189 female and 128 male) full-head CBCT images were evaluated in this study. Incidence, diameter, shape, confluence to foramen ovale, and distance to anatomic structures of SEF were noted.

Results:

In the 317 analyzed images, the SEF was identified in 89 (28.1%) images. Of these, 67 (21.1%) were unilateral, 22 were (6.9%) bilateral. The maximum mean diameter of SEF was measured 2.66 mm on the right side and 2.82 mm on the left side (P = 0.16). The most observed SEF shape was oval with the incidence of 68.5% (P ≤ 0.05). Confluence was observed in 23.4% of SEF whereof 84.6% were in the left side (P ≤ 0.05).

Conclusion:

Observations in this study tender new anatomic parameters regarding SEF incidence, characteristics, and distances to proximate anatomic structures. Knowledge related to SEF variations will be helpful for neurosurgeons and radiologist.
Neurological syndromes driven by postinfectious processes or unrecognized persistent infections
Authors: Johnson Tory P. , Nath Avindra
Published: March 2018

Purpose of review

The immune system serves a critical role in protecting the host against various pathogens. However, under circumstances, once triggered by the infectious process, it may be detrimental to the host. This may be as a result of nonspecific immune activation or due to a targeted immune response to a specific host antigen. In this opinion piece, we discuss the underlying mechanisms that lead to such an inflammatory or autoimmune syndrome affecting the nervous system. We examine these hypotheses in the context of recent emerging infections to provide mechanistic insight into the clinical manifestations and rationale for immunomodulatory therapy.

Recent findings

Some pathogens endure longer than previously thought. Persistent infections may continue to drive immune responses resulting in chronic inflammation or development of autoimmune processes, resulting in damage to the nervous system. Patients with genetic susceptibilities in immune regulation may be particularly vulnerable to pathogen driven autoimmune responses.

The presence of prolonged pathogens may result in chronic immune stimulations that drives immune-mediated neurologic complications. Understanding the burden and mechanisms of these processes is challenging but important.
Effects of Temperatures and High Pressures on the Growth and Survivability of Methanogens and Stable Carbon Isotope Fractionation: Implications for Deep Subsurface Life on Mars
Authors: Sinha Navita , Nepal Sudip , Kral Timothy , Kumar Pradeep
Published: March 2018

In order to examine the potential survivability of life in the Martian deep subsurface, we have investigated the effects of temperature (45°C, 55°C, and 65°C) and pressure (1 atm, 400 atm, 800 atm, and 1200 atm) on the growth, carbon isotopic data, and morphology of chemolithoautotrophic anaerobic methanogenic archaea,Methanothermobacter wolfeii. The growth and survivability of this methanogen were determined by measuring the methane concentration in headspace gas samples after the cells were returned to their conventional growth conditions. Interestingly, this methanogen survived at all the temperatures and pressures tested.M. wolfeiidemonstrated the highest methane concentration following exposure to pressure of 800 atm and a temperature of 65°C. We found that the stable carbon isotopic fractionation of methane, δ13C(CH4), was slightly more enriched in12C at 1 atm and 55°C than the carbon isotopic data obtained in other temperature and pressure conditions. A comparison of the images of the cells before and after the exposure to different temperatures and pressures did not show any obvious alteration in the morphology ofM. wolfeii. The research reported here suggests that at least one methanogen,M. wolfeii, may be able to survive under hypothetical Martian subsurface conditions with respect to temperature and pressure.
Discrete Modeling Dynamical Systems That Determine the Role of Biodiversity in Different Regimes of Using Resources at Different Levels of Organization of Living Matter
Authors: Bespalov Yu.G.
Published: March 2018

The paper aims at mathematical modeling of dynamic systems that determine the role of biodiversity in different modes of resource usage at different levels of the organization of living matter. As a measure of biodiversity, the number of different strategies of the performance of a biological system is used, which differ in ways of usage of the resources by this system. This measure can be supplemented, and in some cases, replaced by the degree of evenness of the intensity of different ways of using resources. As a result of modeling with use of a new class of mathematical models called Discrete Models of Dynamical Systems, the appearance of matrices representing the sets of these strategies corresponding to combinations of values of the system’s parameters in columns, strategies observed for the regimes of maximum and limited usage of resources was analyzed. Using the case study related to a local fish population in a pond, it was shown that, in comparison with the regimes of limited use of resources, the regime of maximum usage distinguishes by a larger degree of evenness of the intensities of different ways of using resources by the system. Different size-age groups of the population play the role of resources. A similar result was obtained earlier for different regimes of the performance of the human cardiovascular system; in this case, the heart rate and blood pressure played the role of different ways of resources usage. The similarity of the results obtained for such different biological systems allows us to hope for the prospects of developing universal system approaches to the use of generalized biodiversity parameters for the diagnosis of the state of bioobjects, in particular, with the help of aerospace methods. The necessity of such methods is significantly increasing in the context of global climate change.
Spatiotemporal manipulation of ciliary glutamylation reveals its roles in intraciliary trafficking and Hedgehog signaling
Authors: Hong Shi-Rong , Wang Cuei-Ling , Huang Yao-Shen , Chang Yu-Chen , Chang Ya-Chu , Pusapati Ganesh V. , Lin Chun-Yu , Hsu Ning , Cheng Hsiao-Chi , Chiang Yueh-Chen , Huang Wei-En , Shaner Nathan C. , Rohatgi Rajat , Inoue Takanari , Lin Yu-Chun
Published: March 2018

Tubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells and are suggested to be involved in a wide range of cellular activities. However, the complexity and dynamic distribution of tubulin PTMs within cells have hindered the understanding of their physiological roles in specific subcellular compartments. Here we develop a method to rapidly deplete tubulin glutamlyation inside the primary cilia, a microtubule-based sensory organelle protruding on the cell surface, by targeting an engineered deglutamylase to the cilia in minutes. This rapid deglutamylation quickly leads to altered ciliary functions such as kinesin-2-mediated anterograde intraflagellar transport and Hedgehog signaling, along with no apparent crosstalk to other PTMs such as acetylation and detyrosination. Our study offers a feasible approach to spatiotemporally manipulate tubulin PTMs in living cells. Future expansion of the repertoire of actuators that regulate PTMs may facilitate a comprehensive understanding of how diverse tubulin PTMs encode ciliary as well as cellular functions.
High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of secondary mechanical hyperalgesia
Authors: Manresa José Biurrun , Andersen Ole Kæseler , Mouraux André , van den Broeke Emanuel N.
Published: March 2018

High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin (secondary hyperalgesia). Moreover, it has been shown that brief high intensity CO2 laser stimuli, activating both Aδ- and C-fiber nociceptors, are perceived as more intense when delivered in the area of secondary hyperalgesia. To investigate the contribution of A-fiber nociceptors to secondary hyperalgesia the present study assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating Aδ-fiber nociceptors, are increased in the area of secondary hyperalgesia. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. HFS induced a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive inputs conveyed by AMH-II nociceptors. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that AMH-II nociceptors do not contribute to HFS-induced secondary hyperalgesia.