bluuebunny/crossref_metadata_2025 huggingface dataset:
Progressive Multifocal Leukoencephalopathy
Authors: Swaminathan Arun , Berger Joseph R
Published: March 2017

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain that results from a ubiquitous virus in the polyoma family of viruses. PML occurs almost exclusively in individuals with altered immunity. Until the inception of the AIDS pandemic, PML was an extremely rare disorder. Its more recent association with natalizumab and other immunomodulatory therapies has heightened interest in the disorder. This brief review discusses the pathogenesis, clinical and radiographic features, pathology, and therapy of the disorder. Additionally discussed are future directions with respect to therapy and research into this unusual infectious disease of the brain. Effective treatment requires long-term antibiotics.
Sleep Apnea
Authors: Accardo Jennifer
Published: March 2017

Sleep apnea is a common condition involving breathing during sleep, which nonetheless has consequences beyond the scope of either sleep or breathing. Repeated, reversible respiratory obstructions are related to abnormal ventilatory drives and decreased upper airway neuromuscular activation. They result in dysautonomia, sleep fragmentation, and increased cardiovascular risks. Obstructive sleep apnea classically presents with daytime sleepiness and snoring, and its effects on learning, cognition, and mood are pervasive. On a neuropathologic basis, corresponding damage to widespread brain structures is noted. Obstructive sleep apnea is considered treatable, but it is unclear whether its cognitive effects are fully reversible with treatment.
Neurobiology of Intrauterine Opiate and Cocaine Exposure
Authors: Belcher Harolyn M.E. , Hutchison Samantha
Published: March 2017

Drug abuse results from a complex interplay among the drug, the individual and the socio-cultural environment. Current pain reliever, heroin, and OxyContin® use is reported in 0.9% (n = 19,000), 0.2% (n = 4,000), and 0.1% (n = 3,000), respectively, of pregnant women in the United States each year. Cocaine use was reported in 0.2% of pregnant women. Intrauterine drug exposure to opiates is associated with risk for narcotic abstinence syndrome, prenatal infections, and sudden infant death. Illicit drug use during pregnancy also places the mother-to-be at risk for reduced prenatal care, obstetric complications, including abruption placentae, prolonged rupture of membranes, and fetal distress. This chapter focuses on the neurobiological effects of intrauterine opiate and cocaine exposure on the developing fetus.
Electrolyte Disturbances
Authors: Rubin Mark N. , Rabinstein Alejandro A.
Published: March 2017

The neurological manifestations of abnormal electrolyte concentrations and acid-base disturbances can be multiple and often nonspecific. They are typically determined by the acuity and severity of the derangement. Detailed history and physical examination may guide appropriate laboratory testing and lead to prompt and accurate diagnosis. Neurological symptoms and signs are typically reversible if the underlying systemic disorder is detected and treated early. However, severe long-term neurologic sequelae can occur if treatment is delayed. The focus of this chapter is to detail the scientific fundamentals, clinical presentation, laboratory testing, and management of the various electrolyte and acid-base disorders associated with neurologic impairment.
Parathyroid, Adrenal, Gonadal, and Pituitary Disease
Authors: Abrams Gary M.
Published: March 2017

Endocrine disorders can cause diverse changes in cognition and affect as well as changes in neuromuscular function that may simulate primary neurologic disease, and they generally require a specialized endocrine workup to make a diagnosis. For example, hypoparathyroidism, which may be congenital (e.g., DiGeorge syndrome or Kearns-Sayre syndrome) or disease-acquired (e.g., autoimmune hypoparathyroidism) can present as neuromuscular irritability or tetany due to hypocalcemia, the most distinctive features, which may manifest as carpopedal spasm or laryngospasm. Primary hyperparathyroidism is the most common cause of hypercalcemia and is usually due to oversecretion of PTH by a solitary adenoma of the parathyroid glands. This chapter covers most common primary endocrine disorders that can present as neurological disorders.
Neurobiology of Brain Injury after Cardiac Arrest
Authors: Rivera-Lara Lucia , Geocadin Romergryko G.
Published: March 2017

The publication of two sentinel, multicenter, randomized controlled trials in The New England Journal of Medicine in 2002 provided evidence for the beneficial use of therapeutic hypothermia (TTH) to 32° to 34°C in resuscitated patients after cardiac arrest with a shockable rhythm. The number needed to treat to provide a favorable neurological outcome was 6, and TTH is a recommended treatment in the American Heart Association (AHA) Resuscitation Guidelines. This chapter describes the biological basis of disorders of arousal and awareness after cardiac arrest, the mechanisms of ischemic cell death, and the biological bases of the some therapeutic interventions.
Neurological Manifestations of Gastrointestinal and Hepatic Diseases
Authors: Bosworth Brian P. , Landzberg Brian R. , McEachern Elisa
Published: March 2017

Digestive diseases may have protean neurological manifestations, and should be considered during neurological evaluation of patients. Neurological manifestations of celiac disease (CD) may involve both central and peripheral nervous system, including syndromes of cerebellar and myoclonic ataxia, encephalopathy and dementia, seizures, CNS vasculitis and progressive multifocal leukoencephalopathy, peripheral neuropathy, and myopathy. Gluten sensitivity has been frequently implicated as a cause of neuropathy, with up to 49% of celiac disease patients experiencing some form of neuropathy and almost 40% meeting the criteria for peripheral neuropathy. Gluten ataxia is one of the most common neurological manifestations of celiac disease. Neurologic manifestations of inflammatory bowel disease (IBD) have long been recognized, with an incidence ranging from less than 1% to 35%. These manifestations may precede or, more commonly, follow a diagnosis of IBD. Hepatic encephalopathy, Wilson’s disease, and acute intermittent porphyria are examples of liver diseases associated with hepatic disorders.
Systemic Lupus Erythematosus
Authors: Rosenbaum Richard B.
Published: March 2017

The neurological manifestations of systemic lupus erythematosus are protean: headache, affective disorders, cognitive dysfunction, seizures, strokes, psychosis, acute confusional states, myelopathies, chorea, mimics of demyelinating disease, meningitis, polyneuropathy, mononeuropathy or mononeuritis multiplex, cranial neuropathies, autonomic dysfunction, Guillain-Barre syndrome, or myasthenia gravis make an incomplete list. Each neurological manifestation needs to be analyzed separately to understand pathogenesis, possible relation to primary lupus-related inflammation and vasculopathy, and optimal treatment.
Epigenetics of CD4+ T cells in autoimmune diseases
Authors: Wang Zijun , Chang Christopher , Lu Qianjin
Published: March 2017

Purpose of review

Autoimmune disorders are a group of overactive symptoms because of abnormal immune responses. Progress of novel mechanisms for autoimmune diseases has been restrained by incomplete understanding of immune disturbance. Recent advances in autoimmune diseases have been well documented by epigenetic alterations (DNA methylation, histone modification, and microRNAs), which alter the transcription activity of genes that are involved in autoimmune responses.

Recent findings

Multiple environmental factors (trichloroethylene, breast milk, and vitamin C) initiate aberrant epigenetic modifications in CD4+T cells, leading to a list of transcriptional deregulations in several genes (Ifng, Cd70, Tnf, Dnmt3a, and Foxp3) that determine T-cell identity. In addition, epigenetics target regulatory genes (Tim-3, cereblon, protein kinase C theta, octamer transcription factor 1, basic leucine zipper transcription factor ATF-like, p70 kinase, and lactate dehydrogenase A) to influence T-cell activation, differentiation, and metabolism.

In this review, we decipher findings that identify how epigenetic regulates CD4+T-cell functions and the advancement of novel epigenetic mechanisms in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Further researches could be conducted to explore new clinical application of epigenetic regulation based on T cells in autoimmune diseases.
Using Clinically Accessible Tools to Measure Sound Levels and Sleep Disruption in the ICU: A Prospective Multicenter Observational Study
Authors: Litton Edward , Elliott Rosalind , Thompson Kelly , Watts Nicola , Seppelt Ian , Webb Steven A. R.
Published: March 2017

Objectives:

To use clinically accessible tools to determine unit-level and individual patient factors associated with sound levels and sleep disruption in a range of representative ICUs.

Design:

A cross-sectional, observational study.

Setting:

Australian and New Zealand ICUs.

Patients:

All patients 16 years or over occupying an ICU bed on one of two Point Prevalence study days in 2015.

Interventions:

Ambient sound was measured for 1 minute using an application downloaded to a personal mobile device. Bedside nurses also recorded the total time and number of awakening for each patient overnight.

Measurements and Main Results:

The study included 539 participants with sound level recorded using an application downloaded to a personal mobile device from 39 ICUs. Maximum and mean sound levels were 78 dB (sd, 9) and 62 dB (sd, 8), respectively. Maximum sound levels were higher in ICUs with a sleep policy or protocol compared with those without maximum sound levels 81 dB (95% CI, 79–83) versus 77 dB (95% CI, 77–78), mean difference 4 dB (95% CI, 0–2), p < 0.001. There was no significant difference in sound levels regardless of single room occupancy, mechanical ventilation status, or illness severity. Clinical nursing staff in all 39 ICUs were able to record sleep assessment in 15-minute intervals. The median time awake and number of prolonged disruptions were 3 hours (interquartile range, 1–4) and three (interquartile range, 2–5), respectively.

Conclusions:

Across a large number of ICUs, patients were exposed to high sound levels and substantial sleep disruption irrespective of factors including previous implementation of a sleep policy. Sound and sleep measurement using simple and accessible tools can facilitate future studies and could feasibly be implemented into clinical practice.
The association between plasma C-peptide concentration and the risk of prostate cancer: a nested case–control study within a Japanese population-based prospective study
Authors: Kiyabu Grace Y. , Sawada Norie , Iwasaki Motoki , Yamaji Taiki , Shimazu Taichi , Sasazuki Shizuka , Inoue Manami , Tsugane Shoichiro
Published: March 2017

The association between plasma C-peptide concentration and prostate cancer is unclear. Inconsistency of results from previous studies motivates this study. Using the Japan Public Health Center-based Prospective study, 201 prostate cancer cases and 402 controls were matched by age, public health center area, residence, date and time of blood collection, and fasting duration before blood collection. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated by conditional logistic regression models. Out of 201 cases, 144 were localized and 48 were advanced. The overall association between median plasma C-peptide concentration and prostate cancer was not significant (OR for the highest tertile=0.81, 95% CI: 0.43–1.56, P-trend=0.54). Although stratification of prostate cancer by stage indicated different effects of plasma C-peptide on localized and advanced cases, there was no association between plasma C-peptide concentration and advanced prostate cancer (OR=2.82, 95% CI: 0.30–26.36 for the highest category, P-trend=0.37) and localized cases (OR=0.49, 95% CI: 0.23–1.04 for the highest category, P-trend=0.06) for patients fasting at the time of blood collection. The association between plasma C-peptide concentration and prostate cancer risk differed by cancer stage. Differentiation of localized and advanced prostate cancer cases is crucial when investigating the association between plasma C-peptide concentration and the risk of prostate cancer.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO DISTINGUISH CHOROIDAL NEOVASCULARIZATION FROM MACULAR INFLAMMATORY LESIONS IN MULTIFOCAL CHOROIDITIS
Authors: Astroz Polina , Miere Alexandra , Mrejen Sarah , Sekfali Rim , Souied Eric H. , Jung Camille , Nghiem-Buffet Sylvia , Cohen Salomon Y.
Published: March 2017

Purpose:

To characterize the macular lesions in multifocal choroiditis using multimodal imaging (MMI) and to evaluate optical coherence tomography angiography (OCTA) in distinguishing neovascular from inflammatory lesions.

Methods:

Retrospective review of medical records of consecutive patients diagnosed with multifocal choroiditis and macular involvement, between September 2014 and May 2016, were included. All patients underwent standard examination and MMI, including fundus color photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography. They also underwent OCTA examination. Multimodal imaging and OCTA characteristics of inflammatory lesions and choroidal neovascularization (CNV) were compared.

Results:

Eighteen eyes of 13 patients (11 females) were analyzed. The mean age was 42.9 ± 13.4 years. The lesions were first categorized as active or inactive CNV and active or inactive inflammatory lesions through conventional MMI. Using OCTA, an abnormal blood flow was observed in all active CNV (9/9) and most inactive CNV (5/6), but also in 2 of 14 lesions previously classified as active inflammatory lesions. On the contrary, no case of inactive inflammatory lesions showed abnormal blood flow. Therefore, the use of OCTA allowed a diagnosis of CNV that was not made through conventional MMI in 14% of cases of active inflammatory lesions.

Conclusion:

The combined findings of conventional imaging and OCTA demonstrate distinctive features of inflammatory lesions and CNV in multifocal choroiditis, allowing an appropriate management of these sight-threatening lesions. However, OCTA alone did not distinguish between active and inactive CNVs and should be integrated into an MMI approach.
Influence of Pilocarpine and Timolol on Human Meibomian Gland Epithelial Cells
Authors: Zhang Yi , Kam Wendy R. , Liu Yang , Chen Xiaomin , Sullivan David A.
Published: March 2017

Purpose:

Investigators have discovered that topical antiglaucoma drugs may induce meibomian gland dysfunction. This response may contribute to the dry eye disease commonly found in patients with glaucoma taking such medications. We hypothesize that drug action involves a direct effect on human meibomian gland epithelial cells (HMGECs). To test this hypothesis, we examined the influence of the antiglaucoma drugs, pilocarpine and timolol, on the morphology, survival, proliferation, and differentiation of HMGECs.

Methods:

Immortalized (I) HMGECs (n = 2–3 wells/treatment/experiment) were cultured with multiple concentrations of pilocarpine or timolol for up to 7 days. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract) and differentiation (azithromycin). Cells were enumerated using a hemocytometer and evaluated for morphology, neutral lipid staining, and lysosome accumulation.

Results:

Our results demonstrate that pilocarpine and timolol cause a dose-dependent decrease in the survival of IHMGECs. The clinically used concentrations are toxic and lead to cell atrophy, poor adherence, or death. By contrast, drug levels that are known to accumulate within the conjunctiva, adjacent to the meibomian glands, do not influence IHMGEC survival. These latter concentrations also have no effect on IHMGEC proliferation or differentiation, and they do not interfere with the ability of azithromycin to stimulate cellular neutral lipid and lysosome accumulation. This dose of pilocarpine, though, did suppress the epidermal growth factor+bovine pituitary extract–induced proliferation of IHMGECs.

Conclusions:

Our results support our hypothesis and demonstrate that these antiglaucoma drugs, pilocarpine and timolol, have direct effects on HMGECs that may influence their morphology, survival, and proliferative capacity.
Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril
Authors: Davidson Eric P. , Coppey Lawrence J. , Shevalye Hanna , Obrosov Alexander , Kardon Randy H. , Yorek Mark A.
Published: March 2017

Purpose:

This study investigated the efficacy of monotherapy versus combination of menhaden oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes.

Methods:

Male Sprague-Dawley rats (aged 12 weeks) were fed a high-fat diet for 8 weeks followed by 30 mg/kg streptozotocin. After 16 weeks of hyperglycemia, 12-week treatments consisting of menhaden oil, α-lipoic acid, enalapril, or their combination were initiated. Before and after treatments, we performed analyses of multiple neural and vascular endpoints including corneal sensitivity, corneal nerve density, vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, intraepidermal nerve fiber density, and thermal nociception.

Results:

Before treatment, all the neural and vascular endpoints in diabetic rats were impaired. Treating diabetic rats with monotherapy was effective in improving neural and vascular deficits with menhaden oil being most efficacious. However, the combination therapy provided the greatest benefit and improved/reversed all nerve and vascular deficits. The effect of combination therapy on corneal relative sensitivity and structure (in mm/mm2), primary endpoints for this study, for control, diabetic, and diabetic treated rats was 4.2 ± 1.4 and 7.5 ± 0.5, 12.1 ± 1.3* and 3.8 ± 0.2*, and 6.6 ± 2.3+ and 7.3 ± 0.5+, respectively (*P < 0.05 compared with control rats; +
P < 0.05 compared with diabetic rats).

Conclusions:

These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
Corneal K-Values as a Diagnostic Screening Tool for Marfan Syndrome
Authors: Luebke Jan , Boehringer Daniel , Eberwein Philipp , Reinhard Thomas
Published: March 2017

Purpose:

Marfan syndrome (MFS) is diagnosed based on Ghent nosology, including major and minor criteria such as increased axial length (AXL) and flattened corneal curvature (higher K-values) or myopia of more than -3 diopters (D) in its latest revision. Because corneal flattening may, in part, be caused by AXL increase, it may be helpful to consider K-values separately. We present statistical evaluation of using corneal K-values for identifying MFS.

Methods:

A retrospective study of K-values of 74 right eyes of 74 patients with MFS, who were compared with an age- and AXL-matched group of 74 right eyes of 74 patients without MFS. After multivariate analysis, receiver operating characteristic curves were calculated.

Results:

Mean age was 44.1 years versus 44.9 years (P = 0.834). Mean AXL was 25.22 mm versus 25.47 mm (P = 0.661). K-values showed significant differences: mean Kmax was 8.25 mm (40.91 D) versus 7.9 mm (42.72 D) (P < 0.001) and mean Kmin was 8.22 mm (41.06 D) versus 7.69 mm (43.89 D) (P < 0.001). The area under the curve in receiver operating characteristic analysis was 0.82 for Kmax and 0.78 for Kmin; the best cutoff was seen at a Kmax of at least 8.16 mm (41.36 D; sensitivity 73% and specificity 81%).

Conclusions:

Although both K-values differ significantly, Kmax is the better marker to identify MFS. A Kmax of more than 8.16 mm (41.36 D) seems to be a reasonable cutoff (specificity of 81% and sensitivity of 73%). Because this biometric value is easily obtained and standardized, we see it as a good supporting screening tool for MFS suspects.
Nursing and Focal Dyscognitive Seizures: A Clinical Update When Managing Risk Using Advanced Nursing Skills
Authors: Holland Christine , Edward Karen-leigh , Giandinoto Jo-Ann
Published: March 2017

Focal seizures are divided into simple and dyscognitive, with the latter resulting in the alteration of consciousness. In the ictal and postictal stages, patients may present with confusion, delirium, and psychosis, presenting a risk of safety to themselves and others. This article presents 3 case studies where patients have been admitted for visual and electroencephalographic monitoring. Seizure activity is provoked for the diagnosis and development of a management plan. These cases illustrate the unique nursing implications when caring for patients experiencing focal dyscognitive seizures, highlighting the unique circumstances for the neuroscience nurse regarding risk management, safe administration of radioactive isotopes, detection of subtle seizure manifestation, and use of family as experts in patient-centered care. Through a deliberate onset of seizures, neuroscience nurses are placed in nontypical nursing situations, thus managing risk in unpredictable conditions and displaying advanced and distinctive nursing skills.
Genetic Determinants of Circulating Lipoproteins in Nonalcoholic Fatty Liver Disease
Authors: Jiang Zhenghui G. , Tapper Elliot B. , Kim Misung , Connelly Margery A. , Krawczyk Sarah A. , Yee Eric U. , Herman Mark A. , Mukamal Kenneth J. , Lai Michelle
Published: March 2017

Background:

Recent genome-wide association studies have identified 2 genetic polymorphisms in association with nonalcoholic fatty liver disease (NAFLD): patatin-like phospholipase domain containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2), both of which appear to influence the production of very low density lipoprotein (VLDL). The impact of these genetic variations on lipoprotein metabolism in the setting of nonalcoholic steatohepatitis and liver fibrosis are not fully characterized.

Materials and Methods:

We measured comprehensive lipoprotein profiles by nuclear magnetic resonance among 170 serially recruited patients in an NAFLD registry, and determined their relationships with PNPLA3 and TM6SF2 genotypes.

Results:

In this cohort, 72% patients had at least 1 allele of either PNPLA3 I148M or TM6SF2 E167K, and 30% carried 2 alleles. In multivariate models adjusting for histologic features of nonalcoholic steatohepatitis and liver fibrosis, PNPLA3 I148M is associated with a decrease in VLDL particle size. Both PNPLA3 I148M and TM6SF2 E167K genotypes were associated with increases in the size of low density lipoprotein (LDL) and high density lipoprotein particles, phenotypes considered atheroprotective. When adjusted for both genotypes, NAFLD activity score, in particular the degree of hepatic steatosis was strongly associated with increases in the size of VLDL particles, the concentration of LDL, especially small LDL particles, and a decrease in the size of high density lipoprotein particles, all of which are linked with a proatherogenic phenotype.

Conclusions:

PNPLA3 and TM6SF2 are common genetic variants among NAFLD patients and impact lipoprotein profiles in slightly different ways. The interactions between genotypes, hepatic steatosis, and lipoprotein metabolism shed lights on the pathophysiology of NAFLD, and provide opportunities for personalized treatment in the era of emerging NAFLD therapeutics.
Dermatofibrosarcoma Protuberans: An Immunomarker Study of 57 Cases That Included Putative Mesenchymal Stem Cell Markers
Authors: Song Joon Seon , Kim Eun-Ju , Park Chan-Sik , Cho Kyung-Ja
Published: March 2017

Dermatofibrosarcoma protuberans (DFSP) is a low-grade fibroblastic sarcoma with a superficial location that has been suggested to potentially be a type of mesenchymal stem cell tumor. We studied the expression of various immunomarkers, including putative stem cell markers, in a series of 57 DFSPs including variants, and 12 dermatofibromas (DFs). CD105, a mesenchymal stem cell marker, was weakly expressed in 24 DFSPs, whereas other stem cell markers, including CD133, ALK-1, and Oct3/4, were completely negative in all samples. The expression rates of CD105 and CD34 were significantly higher in DFSP (42% and 93%) than in DF (0% and 17%), and CD10 and D2-40 were significantly lower in DFSP (40% and 3.5%) than in DF (100% and 33%), respectively. CD99, CD117, PDGFB, and PDGFRβ expression was comparable between the groups. CD105+ mesenchymal cells were not observed in non-neoplastic dermis. In summary, we did not obtain sufficient immunohistochemical evidence to support the DFSP as a cutaneous mesenchymal stem cell tumor. CD34 alone was the most consistent marker of DFSP, irrespective of its variants. Because CD34+ non-neoplastic mesenchymal cells were distributed in a location similar to that of DFSP, we suggest that DFSP might have originated from CD34+ mesenchymal cells in the dermis.
The Usefulness of Phospholipase A2 Receptor and IgG4 Detection in Differentiation Primary Membranous Nephropathy From Secondary Membranous Nephropathy in Renal Biopsy
Authors: Yeo Min-kyung , Kim Yoo Hyung , Choi Dae Eun , Choi Song-Yi , Kim Kyung-Hee , Suh Kwang-Sun
Published: March 2017

Membranous nephropathy (MGN) is the most common cause of the nephrotic syndrome in adults. Most cases of MGN are primary, but secondary MGN are frequently encountered. Determination of secondary MGN is crucial for initiation of appropriate treatment. The diagnostic performance of the phospholipase A2 receptor (PLA2R) and immunoglobulin G4 (IgG4) detection based on immunohistochemistry were evaluated using biopsy tissues of 59 primary and 56 secondary MGN cases for discrimination between primary MGN and secondary MGN. The PLA2R and IgG4 detection based on immunohistochemistry were dominantly positive in primary MGN cases. Sensitivity and specificity values for identification of primary MGN were 83% and 88% for PLA2R, and 76% and 86% for IgG4. Both PLA2R and IgG4 positivity showed a high specificity of 96.4% for identifying primary MGN. A meta-analysis was performed for analysis of the diagnostic accuracy of histologic PLA2R and IgG4 deposition for differentiation of primary from secondary MGN. The overall sensitivity, specificity, and area under curve of summary receiver operating characteristics were 76%, 86%, 0.93 for histologic PLA2R deposition, and 80%, 69%, 0.82 for histologic IgG4 deposition. PLA2R and IgG4 detection based on immunohistochemistry can be useful for differentiation of primary MGN from secondary MGN.
Napsin-A, a Possible Diagnostic Marker for Differentiating Clear Cell Ovarian Carcinoma From Other High-grade Ovarian Carcinomas
Authors: Alshenawy Hanan A. , Radi Dina A.
Published: March 2017

Ovarian clear cell carcinoma (CCC) is divergent from other types of epithelial ovarian carcinoma in terms of clinicopathologic and molecular features. It should be separated from other high-grade carcinomas of the ovary for appropriate treatment. Napsin A is a reliable marker for adenocarcinoma of the lungs, but its role in ovarian epithelial carcinomas is vague. We investigated the expression of a panel of TTF-1, paired box 8, estrogen receptor, Wilms tumor 1, and Napsin A in 100 cases of high-grade ovarian carcinomas. All the examined cases were TTF-1 negative and paired box 8 positive. The 2 biomarkers estrogen receptor together with Wilms tumor 1 can separate CCC from endometriod carcinoma, yet this cannot be carried out in the case of serous and mucinous carcinomas of high grade. Napsin A can differentiate CCC with high sensitivity and specificity. It can be concluded that Napsin A is a sensitive and specific marker for CCC of the ovary. However, an entire marker panel may be useful for distinguishing ovarian CCC from other mimics.
Production and purification of human Hsp90β inEscherichia coli
Authors: Radli Martina , Veprintsev Dmitry B. , Rüdiger Stefan G. D.
Published: March 2017

The molecular chaperone Hsp90 is an essential member of the cellular proteostasis system. It plays an important role in the stabilisation and activation of a large number of client proteins and is involved in fatal disease processes e.g. Alzheimer disease, cancer and cystic fibrosis. This makes Hsp90 a crucial protein to study. Mechanistic studies require large amounts of protein but the production and purification of recombinant human Hsp90 inE. coliis challenging and laborious. Here we identified conditions that influence Hsp90 production and optimised a fast and efficient purification protocol. We found that the nutrient value of the culturing medium and the length of induction had significant effect on Hsp90 production inEscherichia coli. Our fast, single-day purification protocol resulted in a stable, well-folded and pure sample that was resistant to degradation in a reproducible manner. We anticipate that our results provide a useful tool to produce higher amount of pure, well-folded and stable recombinant human Hsp90β inEscherichia coliin an efficient way.
Estimating the contribution of folding stability to non-specific epistasis in protein evolution
Authors: Dasmeh Pouria , Serohijos Adrian W.R.
Published: March 2017

The extent of non-additive interaction among mutations or epistasis reflects the ruggedness of the fitness landscape, the mapping of genotype to reproductive fitness. In protein evolution, there is strong support for the importance and prevalence of epistasis, but whether there is a universal mechanism behind epistasis remains unknown. It is also unclear which of the biophysical properties of proteins—folding stability, activity, binding affinity, and dynamics—have the strongest contribution to epistasis. Here, we determine the contribution of selection for folding stability to epistasis in protein evolution. By combining theoretical estimates of the rates of molecular evolution and protein folding thermodynamics, we show that simple selection for folding stability implies that at least ~30% to ~60% of among amino acid substitutions would have experienced epistasis. Additionally, our model predicts substantial epistasis at marginal stabilities therefore linking epistasis to the strength of selection. Estimating the contribution of governing factors in molecular evolution such as protein folding stability to epistasis will provide a better understanding of epistasis that could improve methods in molecular evolution.
Guidance of circumnutation of climbing bean stems: An ecological exploration
Authors: Calvo Paco , Raja Vicente , Lee David N.
Published: March 2017

In this report we explore the guidance of circumnutation of climbing bean stems under the light of general rho/tau theory, a theory that aims to explain how living organisms guide goal-directed movements ecologically. We present some preliminary results on the control of circumnutation by climbing beans, and explore the possibility that the power of movement in plants, more generally, is controlled under ecological principles.
Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through Promyelocytic Leukemia Zinc Finger
Authors: Kim Yeung-Hyen , Kumar Ajay , Chang Cheong-Hee , Pyaram Kalyani
Published: March 2017

Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological and pathological conditions as second messengers. ROS are essential for antigen specific activation of T cells, but little is known about what role ROS play in NKT cells. In the current study, we investigated the role of ROS in NKT cell function. We found that ROS levels are similar among CD4, CD8 and NKT cell subsets in the thymus. However, NKT cells, but neither CD4 nor CD8 T cells, showed dramatically increased ROS in the spleen and liver but not in adipose tissues. ROS in the peripheral NKT cells were primarily produced by NADPH oxidases not mitochondria. Accordingly, ROS-high NKT cells were susceptible to oxidative stress and underwent apoptotic cell death. Furthermore, ROS play an important role in regulating the inflammatory function of NKT cells because antioxidant treatment of NKT cells showed reduced frequencies of IFN-γ+and IL-17+cells. In line with this, freshly isolated ROS-high NKT cells had more NKT1 and NKT17 cells but less NKT2 than ROS-low cells. These characteristics are regulated by promyelocytic leukemia zinc finger (PLZF) as evidenced by low ROS in NKT cells from PLZF haplodeficient mice and also from adipose tissues that do not express PLZF. Conversely, ROS were highly elevated in CD4 T cells from mice ectopically expressing PLZF. Together, our study revealed for the first time that ROS regulate NKT cell functions through PLZF.
Epidemiology and antimicrobial resistance characteristics of the ST131-H30subclone among extraintestinalEscherichia colicollected from US children
Authors: Miles-Jay Arianna , Weissman Scott J. , Adler Amanda L. , Tchesnokova Veronika , Sokurenko Evgeni V. , Baseman Janet G. , Zerr Danielle M.
Published: March 2017

Background

E. coliST131-H30is a globally important pathogen implicated in rising rates of multidrug resistance amongE. colicausing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology ofH30among children undefined.

Methods

We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistantE. coliconducted at four US children’s hospitals to estimate the burden and identify host correlates of infection withH30. H30isolates were identified using two-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status.

Results

A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptibleE. coliisolates were available for analyses. The estimated period prevalence ofH30was 5.3% among all extraintestinalE. coliisolates (95% confidence interval [CI] 4.6%-7.1%);H30made up 43.3% (81/187) of ESBL-producing isolates in this study. Host correlates of infection withH30differed by extended-spectrum cephalosporin resistance status: among resistant isolates, age ≤5 years was positively associated withH30infection (relative risk [RR] 1.83, 95% CI 1.19-2.83); among susceptible isolates, age ≤5 years was negatively associated withH30(RR 0.48, 95% CI 0.27-0.87), while presence of an underlying medical condition was positively associated (RR 4.49, 95% CI 2.43-8.31).

Conclusions

ST131-H30is less common among extraintestinalE. colicollected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. TheH30subclone appears to disproportionately affect young children relative to other extendedspectrum cephalosporin-resistantE. coli.

ST131-H30was responsible for 5.3% of all extraintestinalE. coliinfections and 43.3% of ESBL-producing extraintestinalE. coliinfections among US children. The clinical and demographic correlates of infection with ST131-H30differed between extended-spectrum cephalosporin-resistant and -sensitive isolates.
miniMDS: 3D structural inference from high-resolution Hi-C data
Authors: Rieber Lila , Mahony Shaun
Published: March 2017

Motivation

Recent experiments have provided Hi-C data at resolution as high as 1 Kbp. However, 3D structural inference from high-resolution Hi-C datasets is often computationally unfeasible using existing methods.

Results

We have developed miniMDS, an approximation of multidimensional scaling (MDS) that partitions a Hi-C dataset, performs high-resolution MDS separately on each partition, and then reassembles the partitions using low-resolution MDS. miniMDS is faster, more accurate, and uses less memory than existing methods for inferring the human genome at high resolution (10 Kbp).

Availability

A Python implementation of miniMDS is available on GitHub:https://github.com/seqcode/miniMDS.
Genome graphs and the evolution of genome inference
Authors: Paten Benedict , Novak Adam M. , Eizenga Jordan M. , Garrison Erik
Published: March 2017

The human reference genome is part of the foundation of modern human biology and a monumental scientific achievement. However, because it excludes a great deal of common human variation, it introduces a pervasive reference bias into the field of human genomics. To reduce this bias, it makes sense to draw on representative collections of human genomes, brought together into reference cohorts. There are a number of techniques to represent and organize data gleaned from these cohorts, many using ideas implicitly or explicitly borrowed from graph-based models. Here, we survey various projects underway to build and apply these graph-based structures—which we collectively refer to as genome graphs—and discuss the improvements in read mapping, variant calling, and haplotype determination that genome graphs are expected to produce.
Low-dose fixed-target serial synchrotron crystallography
Authors: Owen Robin L. , Axford Danny , Sherrell Darren A. , Kuo Anling , Ernst Oliver P. , Schulz Eike C. , Miller R. J. Dwayne , Mueller-Werkmeister Henrike M.
Published: March 2017

The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.
Living arrangements, coresidence preference, and mortality risk among older Taiwanese
Authors: Yang Wen-Shan , Shih Yao-Chi , Li Yang-Tzu
Published: March 2017

Purpose

Although coresidence with children when one becomes old is an ideal in Chinese society, the drastic socio-economic development in Taiwan has brought some fundamental changes to living arrangements of the elderly population. The purpose of this paper is to examine the relationship between family living arrangements and elderly health in Taiwan, given the secular trend of more elderly persons choosing to live with their spouse or to live independently.

Design/methodology/approach

The authors utilized panel data from the “1989 Survey of Health and Living Status of the Elderly in Taiwan” with follow-ups up to 2007 to examine how living arrangements of the elderly affect the risk of mortality using discrete-time hazard models. The authors stratified the analyses by the elderly’s preference to coreside with children, and examined whether the effects of living arrangement varied by age, controlling for sociodemographics, health status, health behaviors, and social relationships observed at the baseline.

Findings

The authors found that both the associations of living arrangements and coresidence preference with that mortality risk were largely weakened when controlling for other variables. Only among respondents expressing preference for coresidence were living arrangements associated with mortality risks, and these effects increased with age. For those who did not intend to live with children, the authors found no evidence suggesting living arrangements were associated with mortality risks. The dynamics of living arrangements among the elderly and elderly care policies in Taiwan are discussed for further research.

Originality/value

To the authors knowledge, no previous research has examined living arrangements and mortality risks with respect to coresidence preference.
Ultra-low fertility, gender equity and policy considerations
Authors: Tu Edward Jow-Ching , Yan Yuruo , Zhao Jiaying
Published: March 2017

Purpose

The purpose of this paper is to focus on the issue and the reasons why fertility patterns in many industrialized and post-industrialized societies decline so rapidly, primarily in newly industrialized countries, particularly in East Asia, and especially after the countries have adopted the capitalist and market economy as the preferred approach to improve the lives of their population.

Design/methodology/approach

The authors discuss gender equality and the relationship between fertility and female labor force participation in industrialized and post-industrialized countries, in the context of role incompatibility, mainly for women and the level of the strength and rigidity of family- and gender-role norms/attitudes that affect the behaviors of men and women.

Findings

The existing family-related policies and programs which have reduced the role conflict and incompatibility experienced by working mothers are reviewed and discussed under national orientations toward the resolution of work–family conflict since they could affect the relevance, acceptance, significance and effectiveness of policies being developed and approved to carry on under institutional context within a nation.

Originality/value

Specific strategies and policies to reduce role incompatibility and childcare arrangements and their costs are discussed, especially for East Asian nations.
Women and leadership: challenges and opportunities in Saudi higher education
Authors: Abalkhail Jouharah M.
Published: March 2017

Purpose

The purpose of this paper is to examine women managers’ perceptions of forces influencing their career progression to leadership positions in Saudi Arabian higher education (HE).

Design/methodology/approach

A qualitative, interpretive approach is adopted for analysing in-depth interviews with women managers in Saudi HE.

Findings

The findings of this study provide an in-depth understanding of Saudi women’s experience in management in HE. This study shows that women face a number of challenges preventing them from achieving equitable representation in leadership positions; conversely, they do have some opportunities which help them in their careers. Additionally, it provides more explanation of how the macro factors trickle down to the organizational level to shape organizational process and practices, and have an impact on women accessing leadership positions. Furthermore, this study suggests that socio-cultural background does matter when studying women in management in the Saudi context.

Research limitations/implications

The paper, mainly focussing on women managers in Saudi HE, gives a clear picture of women’s careers and influencing factors.

Practical implications

The research has implications for government and other related institutions to formulate effective policies and appropriate strategies to help Saudi women access leadership posts.

Originality/value

The novelty of this paper is in its focus on the under-researched topic of careers of Saudi women managers. The paper is also valuable as it emphasizes the societal context for researchers wishing to study women’s careers in the Arab world.
Mentoring and other valued components of counselor educator doctoral training: a Delphi study
Authors: Perera-Diltz Dilani , Duba Sauerheber Jill
Published: March 2017

Purpose

Counselor educators graduating from accredited doctoral programs complete training in counseling, supervision, teaching, research, scholarship, leadership, and advocacy. The purpose of this paper is to investigate the valued components of doctoral degree training in counselor education among new graduates.

Design/methodology/approach

Recent graduates in full-time counselor education positions were surveyed using the Delphi method to determine which aspects of their doctoral training best prepared them for their current positions.

Findings

The participants valued or desired training in teaching, research, supervision, and potential mentorship.

Research limitations/implications

A serendipitous finding of the research was that mentorship, which was not a deliberate training feature, was highly valued by new counselor educators. Further research on which mentorship styles are best suited for counselor educator training is necessary. Continued training in teaching, research, and supervision is also necessary.

Practical implications

Some form of mentoring is desirable in counselor educator training programs to facilitate transition from year to year of doctoral study, as well as to assist transition from the role of student to faculty.

Originality/value

A desire to be mentored by faculty, specifically for students in counselor education doctoral programs, is revealed.
Lining up for charity
Authors: Salonen Anna Sofia
Published: March 2017

Purpose

Recent decades have witnessed a rise in food charity provided by faith-based and other charitable agencies. Previous research has noted that besides material assistance, these occasions provide a social and communal event for many participants. The purpose of this paper is to examine this notion by exploring how the social organization of breadlines contributes to the social relationships between the food recipients and their experiences of these places as communities, and what qualities these communities eventually develop.

Design/methodology/approach

The study is based on ethnographic data from four breadlines in one Finnish city. The study approaches the breadlines as queues, that is, social systems that govern waiting, mutual order and access.

Findings

The social organization of queue practices mirrors the users’ experiences of the breadlines as communities with many concurrent faces: as communities of mutual surveillance and as demanding communities that call for skills and resources from the participants, as well as socially significant communities. The findings show how the practices of organizing charitable assistance influence the complex social relationships between charitable giver and recipient, and how the food recipients accommodate themselves to the situations and social roles available on a given occasion.

Originality/value

Analysing breadlines as queues and using qualitative data from the everyday assistance events gives voice to the experiences of food charity recipients and allows a more nuanced picture to be painted of the breadline communities than studies based merely on surveys or interviews.