bluuebunny/crossref_metadata_2025 huggingface dataset:
c-CBL E3 Ubiquitin Ligase Expression Increases Across the Spectrum of Benign and Malignant T-Cell Skin Diseases
Authors: Salva Katrin A. , Reeder Margo J. , Lloyd Rita , Wood Gary S.
Published: November 2016

Prolonged survival of lesional T cells plays a central role in the pathogenesis of T-cell-mediated dermatoses. We have recently shown that the ubiquitin ligase c-CBL is highly expressed in cutaneous T-cell lymphoma (CTCL) and that its knockdown increases activation-induced cell death, a key pathway for T-cell apoptosis. Here, we extend our work on c-CBL expression in malignant T cells to their nonneoplastic counterparts in benign inflammatory dermatoses. Immunohistochemical staining with anti-c-CBL antibody was performed on lesional biopsies from a total of 65 patients with atopic dermatitis, allergic contact dermatitis, pityriasis rosea, psoriasis vulgaris, lichen planus, mycosis fungoides (MF)/Sézary syndrome (SS) as well as on tonsil tissue from 5 individuals and on 5 human CTCL cell lines. Protein levels were measured in situ using multispectral image analysis, a quantitative method that is ×5 more sensitive than standard immunohistology for antigen detection. There was a significant (P < 0.05) and progressive increase of mean c-CBL expression across the spectrum of inflammatory dermatoses (2-fold), MF/SS (3-fold), and lymphoma cell lines (4-fold) as compared with tonsillar T lymphocytes. A subset of MF/SS cases expressed mean c-CBL levels above the ranges observed in inflammatory dermatoses. Given our prior finding that c-CBL inhibits activation-induced cell death, c-CBL might play a role in the pathogenesis of inflammatory dermatoses and CTCL.
Attachment Style and Obesity: Disordered Eating Behaviors as a Mediator in a Community Sample of Canadian Youth
Authors: Maras Danijela , Obeid Nicole , Flament Martine , Buchholz Annick , Henderson Katherine A. , Gick Mary , Goldfield Gary S.
Published: November 2016

Objective:

Obesity and overweight are associated with many negative health outcomes. Attachment style has been implicated in the development of obesity in youth. The present study examined if disordered eating behaviors mediate the relationship between attachment style and body mass index (BMI) in a large community sample of Canadian youth.

Method:

A total of 3,043 participants (1,254 males and 1,789 females, M
age = 14.20 years) completed self-report questionnaires including the Relationship Questionnaire and the Dutch Eating Behavior Questionnaire, and BMI was objectively measured. Disordered eating behaviors (restrained, emotional, and external) were examined as possible mediating mechanisms in the relationship between attachment style and BMI z-score, using a multiple mediation model using bootstrapping while controlling for socio-demographic covariates.

Results:

Insecure attachment was significantly associated with higher BMI, and disordered eating mediated this relationship. Restrained eating was the strongest mediator of this pathway.

Conclusion:

Results suggest that it may be important to take attachment history and restrained eating into account when designing treatment and prevention strategies for obesity in youth.
Age of menopause and fracture risk in postmenopausal women randomized to calcium + vitamin D, hormone therapy, or the combination: results from the Women's Health Initiative Clinical Trials
Authors: Sullivan Shannon D. , Lehman Amy , Nathan Nisha K. , Thomson Cynthia A. , Howard Barbara V.
Published: November 2016

Objective:

We previously reported that in the absence of hormone therapy (HT) or calcium/vitamin D (Ca/D) supplementation, earlier menopause age was associated with decreased bone mineral density and increased fracture risk in healthy postmenopausal women. Treatment with HT and Ca/D is protective against fractures after menopause. In this analysis, we asked if the age of menopause onset alters fracture risk in healthy postmenopausal women receiving HT, Ca/D, or a combination.

Methods:

Hazard ratios (HRs) for any fracture among 21,711 healthy postmenopausal women enrolled in the Women's Health Initiative Clinical Trial, who were treated with HT, Ca/D, or HT + Ca/D, and who reported age of nonsurgical menopause of <40, 40 to 49, and ≥50 years, were compared.

Results:

Women with menopause <40 years had significantly higher HR for fracture than women with menopause 40 to 49 or ≥50 years, regardless of treatment intervention (HR [95% CI]: menopause <40 y vs ≥50 y, 1.36 [1.11-1.67]; menopause <40 y vs 40-49 y, 1.30 [1.06-1.60]).

Conclusions:

In the overall Women's Health Initiative Clinical Trial cohort and within each treatment group, women with younger menopause age (<40 y) had a higher risk of any fracture than women reporting older menopause ages. The effect of menopause age on fracture risk was not altered by any of the treatment interventions (HT, Ca/D, HT + Ca/D), suggesting that early age of menopause is an independent contributor to postmenopausal fracture risk.
VITRECTOMY-ASSISTED BIOPSY FOR MOLECULAR PROGNOSTICATION OF CHOROIDAL MELANOMA 2 MM OR LESS IN THICKNESS WITH A 27-GAUGE CUTTER
Authors: Nagiel Aaron , McCannel Colin A. , Moreno Christian , McCannel Tara A.
Published: November 2016

Purpose:

Fine-needle aspiration biopsy of small choroidal melanomas 2 mm or less in thickness may be associated with a low biopsy yield. This report describes our center's experience using the 27-gauge vitreous cutter to perform tumor sampling in these small melanomas.

Methods:

This was a retrospective analysis of all patients who underwent a 27-gauge vitreous cutter biopsy for molecular prognostication at the time of iodine-125 plaque placement for local treatment of choroidal melanoma ≤2.0 mm in height.

Results:

Seventeen consecutive patients with a mean baseline tumor height of 1.67 mm (range, 1.31–2.03 mm) and median follow-up time of 7.0 months (range, 3.3–19.5 months) were included. The 27-gauge cutter biopsy yielded sufficient material for multiplex-ligation probe amplification (MLPA) or gene expression profiling (GEP) in 17/17 (100%) patients. Complications were limited to focal vitreous hemorrhage in 13/17 patients and diffuse vitreous hemorrhage in 1/17 patients, with no instance of retinal detachment or nonclearing vitreous hemorrhage.

Conclusion:

Tumor sampling of small choroidal melanoma with a 27-gauge vitreous cutter is safe and offers excellent biopsy yield for molecular prognostication when cancer prognosis is desired by patients.
STICKY SILICONE OIL
Authors: Ghoraba Hamouda Hamdi , Zaky Adel Galal , Abd Al Fatah Haithem Mamoun , El Gemai Emad El Din Mohamed , Heikal Mohamed Amin
Published: November 2016

Objective:

To report and analyze the phenomenon of sticky silicone oil on the retina at the time of its removal.

Background:

Silicone oil has been used for more than 25 years as a long-term retinal tamponade in the surgical management of patients with complex retinal detachments. When a decision to remove silicone oil was made at the end of the tamponade period, the system involved a number of different materials: silicone oil, aqueous solution with or without remnants of perfluorocarbon liquid plus the material of the cannula used to aspirate Silicone oil. This, in effect, may lead to an abnormal adherence of large bubbles of residual silicone oil to the posterior pole of the retina.

Patients and methods:

A retrospective, interventional case study was performed. We consecutively reviewed 796 patients of silicone oil removal (5,000 or 5,500 centistokes) after primary pars plana vitrectomy at one vitreoretinal center operated by a single surgeon (HG). Chart review was performed to identify potential patients or procedural factors that could predispose to sticky silicone oil formation at the macular area.

Results:

Large silicone oil bubbles were sticky to the macula in eight out of 796 silicone oil removal procedures between January 2014 and August 2015. The use of perfluorooctane was related to the occurrence of the phenomenon (P < 0.001).

Conclusion:

The sticky silicone oil bubble at the macular region was not related to internal limiting membrane peeling, epiretinal membrane, viscosity, duration, or brand of silicone oil used, but to the use of perfluorooctane.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CHORIORETINAL LESIONS DUE TO IDIOPATHIC MULTIFOCAL CHOROIDITIS
Authors: Zahid Sarwar , Chen Kevin C. , Jung Jesse J. , Balaratnasingam Chandrakumar , Ghadiali Quraish , Sorenson John , Rofagha Soraya , Freund K. Bailey , Yannuzzi Lawrence A.
Published: November 2016

Purpose:

To evaluate the spectrum of macular chorioretinal lesions occurring in idiopathic multifocal choroiditis using optical coherence tomography angiography (OCTA) to evaluate those showing neovascular flow.

Methods:

This was a descriptive, retrospective study of 18 eyes of 14 patients with multifocal choroiditis. Macular lesions were characterized as subretinal pigment epithelium, subretinal, or mixed and evaluated during active and presumed inactive states of multifocal choroiditis. Correlations between structural optical coherence tomography and OCTA were performed. In select cases, correlations between OCTA, fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes, quantitative measurements of neovascular lesions were compared at baseline and following intravitreal anti–vascular endothelial growth factor therapy.

Results:

Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography angiography flow signatures consistent with neovascularization were identified in 83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal, and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of fluorescein angiography leakage were frequently found to have neovascularization using OCTA. There was no change in quantitative measurements of neovascular lesions after anti–vascular endothelial growth factor therapy (all tested variables P > 0.05).

Conclusion:

Optical coherence tomography angiography may be a useful imaging modality for understanding the pathophysiology of multifocal choroiditis and monitoring its clinical course.
GEMCITABINE-INDUCED RETINOPATHY
Authors: Kovach Jaclyn L.
Published: November 2016

Purpose:

To report a case of Purtscher-like retinopathy associated with gemcitabine.

Methods:

The author reports a 68-year-old woman who presented with a 4-month history of bilateral vision loss. She had a history of diabetes, hypertension, and leiomyosarcoma, diagnosed 5 months before presentation and had completed 5 cycles of combination treatment with gemcitabine and docetaxel. Clinical examination revealed a Purtscher-like retinopathy that improved after gemcitabine cessation without the development of cystoid macular edema or retinal neovascularization.

Conclusion:

This case highlights the importance of recognizing gemcitabine-induced ischemic retinopathy that can be associated with life-threatening myocardial or renal ischemia.
Respiratory Syncytial Virus in Older Adults
Authors: Talbot H. Keipp , Belongia Edward A. , Walsh Edward E. , Schaffner William
Published: November 2016

Respiratory syncytial virus (RSV) is a common cause of medically significant respiratory tract illnesses in adults 65 years and older. The clinical presentation of RSV is largely indistinguishable from other respiratory infections including influenza, limiting awareness of its burden and impact among health care professionals and the public. Although no specific treatment in adults or licensed vaccine to prevent the disease is currently available, several promising candidate vaccines and treatments are on the horizon. Recognizing and defining the impact of RSV in older adults is important to evaluate the impact of these new prevention and treatment options. Public health and health care professionals need to be aware about RSV so they can advise the general public and older patients about the importance of prevention.
Genetic variant rs3750625 in the 3′UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site
Authors: Linnstaedt Sarah D. , Walker Margaret G. , Riker Kyle D. , Nyland Jennifer E. , Hu JunMei , Rossi Catherine , Swor Robert A. , Jones Jeffrey S. , Diatchenko Luda , Bortsov Andrey V. , Peak David A. , McLean Samuel A.
Published: November 2016

α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3′UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3′UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.
Resuscitative endovascular balloon occlusion of the aorta: promise, practice, and progress?
Authors: Perkins Zane B. , Lendrum Robbie A. , Brohi Karim
Published: November 2016

Purpose of review

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive damage control procedure for life-threatening abdominal or pelvic haemorrhage. The purpose of this review is to summarize the current understanding and experience with REBOA, outline potential future applications of this technology, and highlight priority areas for further research.

Recent findings

REBOA is a feasible method of achieving temporary aortic occlusion and can be performed rapidly, with a high degree of success, in the emergency setting (including at the scene of injury) by appropriately trained clinicians. The procedure supports central perfusion, controls noncompressible haemorrhage, and may improve survival in certain profoundly shocked patient groups; but is also associated with significant risks, including ischaemic tissue damage and procedural complications. Evolutions of this strategy are being explored, with promising proof-of-concept studies in the fields of partial aortic occlusion and the combination of REBOA with extracorporeal support.

Noncompressible torso haemorrhage is the leading cause of preventable trauma deaths. The majority of these deaths occur soon after injury, often before any opportunity for definitive haemorrhage control. For a meaningful reduction in trauma mortality, novel methods of rapid haemorrhage control are required.
Survey on Clinical Practice of Primary Prophylaxis in Portal Hypertension in Children
Authors: Jeanniard‐Malet Odile , Duché Mathieu , Fabre Alexandre
Published: November 2016

Primary prophylaxis in portal hypertension in children is controversial, because there are few studies documenting its efficacy on the risk of bleeding. Twenty‐eight centres out of the 38 we contacted returned a completed questionnaire about their clinical practices. More than 75% of the centres use endoscopy to screen patients diagnosed with portal cavernoma, biliary atresia, cystic fibrosis, and other fibrotic chronic liver diseases with suspected portal hypertension. In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation. Noncardioselective beta‐blockers were used by approximately 20% of centres. In conclusion, despite the absence of scientific recommendations there is a tacit consensus concerning the need to screen children with clinical signs of portal hypertension, and to provide primary prophylaxis in cases of endoscopic patterns of high‐risk varices.
Simulation to Teach Nursing Students About End-of-Life Care
Authors: Hjelmfors Lisa , Strömberg Anna , Karlsson Katarina , Olsson Louise , Jaarsma Tiny
Published: November 2016

There is minimal education on death and dying in undergraduate nursing programs, leaving the students unprepared to provide sufficient care to dying patients and their families. This article describes a teaching innovation on how end-of-life care simulation can provide a successful and appreciated learning situation for nursing students, teaching them communication skills in challenging situations. Modifications in the setup of the simulation might help the students to focus more on communication and existential issues instead of mostly practical ones.
Evaluation of a Multifaceted Educational Intervention to Improve Palliative Care in the Intensive Care Unit
Authors: Constantine Lori
Published: November 2016

Currently, palliative care needs are inconsistently implemented in intensive care units (ICUs). To remedy this problem, a multifaceted educational intervention was delivered to interdisciplinary ICU team members to promote the adoption of the Care and Communication Bundle for patients identified as being at a high risk of death. A preintervention/postintervention evaluation design was used to determine the extent to which the nine quality measures of the Care and Communication Bundle, patient length of stay, and patient mortality were changed after this educational intervention. On the basis of statistical results, documentation of an appropriate decision maker, advance directives, resuscitation status, and social work contact significantly improved after the multifaceted educational intervention to integrate palliative care measures into the ICU.
The Introduction of Patient’s Own Drug Scheme in a Specialist Palliative Care Inpatient Unit
Authors: Wright Marie , Moran Sue , Doody Owen
Published: November 2016

Patient’s own drug scheme (PODS) involves the use of patient’s own medicines that they have obtained in the community setting and bring to the hospital. The purpose of this study is to evaluate the effectiveness of PODS implementation in an Irish specialist palliative care inpatient unit. Administration time for drug rounds (PODS vs drug trolley); experience of nurses, doctors, and pharmacists using PODS; and the cost effectiveness of PODS were evaluated. Time spent on PODS-related tasks was documented for 1 month; focus groups were undertaken with nursing staff (n = 9), pharmacy staff (n = 3), and doctors (n = 5) to determine their experience of the PODS; and a cost/savings analysis was conducted. Although a minimal difference in the number of minutes to administer drugs per patient was noted, using PODS enabled simultaneous administration of drugs that potentially reduced drug round time by up to 75%. Nursing, doctors, and pharmacy staff demonstrated a good understanding of PODS and identified many benefits (and few disadvantages) for the organization, patient, and team. The PODS resulted in a median pharmacy drug cost saving of approximately €77.50 ($86.79) per patient. The introduction of PODS was successful and is being implemented across all units of the specialist palliative care inpatient service.
Mentoring in Palliative Nursing
Authors: Mazanec Polly , Aslakson Rebecca A. , Bodurtha Joann , Smith Thomas J.
Published: November 2016

Mentoring is a responsibility of the nurse to advance the nursing profession and can be viewed from an ethical perspective. Little has been reported about mentoring in hospice and palliative nursing, and data to support this concept are lacking. Yet, nowhere is mentoring more essential than in this specialty, which is filled with the often difficult issues of caring for those with serious illnesses and their families. Educational and emotional support, which are important components in the mentoring relationship, are critical for nurses who need a hospice or palliative care nursing colleague to guide and coach them in caring for this patient population and to advance the profession of palliative nursing. Although all nurses can benefit from finding a mentor and being a mentor, it is extremely important for those caring for patients and families facing serious illnesses.
Cessation of Smoking and Alcohol Addiction Following Thalamic Hemorrhage
Authors: Najeeb Fatima , Silver Brian , Khan Muhib
Published: November 2016

Introduction:

We describe a case of thalamic intracerebral hemorrhage leading to cessation of smoking.

Case Report:

A 53-year-old female presented to the emergency department with right-sided weakness and dysarthria. Initial systolic blood pressure was 220 mm Hg. Computed tomography scan showed a left thalamic hemorrhage with associated edema and hemorrhage extending into the left lateral and third ventricle. She recovered uneventfully and was discharged to inpatient rehabilitation and eventually transitioned home. Three months later in the clinic, she reported that following the stroke, she abruptly stopped smoking without any smoking cessation aid. She reported that she had no craving for cigarettes. She also developed an aversion to drinking alcohol.

Discussion:

Cessation of smoking following a thalamic intracerebral hemorrhage is not reported earlier. This observation suggests that the thalamus may play a role in nicotine and alcohol addiction. Further studies are needed to elucidate the possible involvement of the thalamic circuits in addiction pathways and as a potential target for modulation.
Pontine Warning Syndrome
Authors: Enriquez-Marulanda Alejandro , Amaya-Gonzalez Pablo , Orozco Jorge L.
Published: November 2016

Introduction:

Crescendo transient ischemic attacks or “Stroke Warning Syndromes” consist of stereotyped frequent short-lasting episodes of focal neurological deficits. This is explained by intermittent hypoperfusion of the vascular territory of terminal arteries with insufficient collateral flow, presenting a high risk for subsequent infarction. Pontine warning syndrome (PWS) is a subtype of this atypical presentation of stroke/transient ischemic attack and is considered a challenge for diagnosis.

Case Report:

We describe 2 cases of patients with PWS who were admitted to our institution. They presented acute neurological deficits that fluctuated during the course of their hospitalization; interestingly, this neurological worsening and improvement was associated with blood pressure fluctuations. In both cases, brain magnetic resonance imaging revealed an ischemic lesion in the paramedian pons due to basilar artery branch disease. No outstanding infectious or metabolic factors contributed to neurological worsening/fluctuations. These patients received standard medical care without IV-thrombolysis because of the presence of contraindications for IV tissue plasminogen activator. Permissive hypertension was promoted to achieve adequate perfusion during hospitalization. At discharge and follow-up, the patients showed partial resolution from their stroke symptoms.

Conclusions:

PWS is a diagnostic and management challenge for the clinician. Because of its low incidence, this syndrome has been underestimated and understudied. There is, currently, no standard treatment for this condition; however, it is paramount, during treatment, that hypotension/hypoperfusion be avoided, with the goal being asymptomatic normotension to permissive hypertension. The probable mechanism of disease is hypoperfusion due to basilar artery branch disease and perhaps cerebral vascular dysregulation in the affected area.
Severe Relapse After Cessation of Immunosuppressive Therapy in a Patient With Neuromyelitis Optica Spectrum Disorder
Authors: Hyun Jae-Won , Kim Gayoung , Kim Yeseul , Jeong In Hye , Kim Su-Hyun , Kim Ho Jin
Published: November 2016

Introduction:

The optimal duration of immunosuppressive therapy (IT) for neuromyelitis optica spectrum disorder (NMOSD) has not been established. Here, we report a case of severe relapse after early cessation of IT.

Case Report:

A 32-year-old woman presented with a 2-week history of intractable vomiting and hiccups followed by quadriplegia with respiratory insufficiency. Spinal cord MRI showed longitudinally extensive transverse myelitis (LETM) and aquaporin-4-immunoglobulin-G (AQP4-IgG) was positive. She was diagnosed with NMOSD and IT was initiated. She did not experience any clinical attacks during 42 months of IT and her AQP4-IgG status was negative. IT was discontinued on her own decision; 36 months later, the patient experienced a severe LETM relapse with paraplegia, and her AQP4-IgG status reverted to positive.

Conclusion:

This case suggests that clinicians should exercise caution before discontinuing effective IT in patients with NMOSD.
Dehydration Status is Associated With More Severe Hemispatial Neglect After Stroke
Authors: Bahouth Mona N. , Bahrainwala Zainab , Hillis Argye E. , Gottesman Rebecca F.
Published: November 2016

Background:

Many stroke patients are clinically dehydrated at the time of hospital presentation, which could lead to an increase in blood viscosity and alteration in cerebral perfusion. Impaired cerebral perfusion can cause hemispheric dysfunction, which can be rapidly quantified with bedside tests of hemispatial neglect. We hypothesized that hospitalized patients with laboratory markers consistent with dehydration or a volume contracted state (VCS) would have more severe cerebral dysfunction defined by greater degree of neglect.

Methods:

Subjects were a consecutive series of right-handed patients with acute right hemispheric stroke admitted within the Johns Hopkins Health System. All participants had clinical syndrome and magnetic resonance imaging consistent with acute infarction. The primary definition of a VCS was a urea/creatinine ratio >15, with secondary definition including urine specific gravity over 1.010. Acute infarct volume was measured on magnetic resonance imaging. Neglect was evaluated using a standardized battery of bedside tests.

Results:

Of 201 patients meeting inclusion criteria, 131/201 (65%) had elevated BUN/creatinine ratios at admission. Approximately 61% (122/201) had some degree of neglect. Elevated BUN/creatinine ratio was associated with an increased odds of severe neglect in unadjusted models (OR=4.1; 95% CI, 1.2, 14.4), with loss of significance in adjusted models (OR=4.43; 95% CI, 0.99, 19.8) after adjustment for age, infarct volume, sex, and NIHSS score.

Conclusions:

Our data suggest that patients who are in a VCS at the time of stroke may have more frequent and severe neglect, with attenuation of results after adjustment for factors related to stroke size and age. If proven clinically relevant, a formalized rehydration strategy based on objective lab markers may represent an opportunity for improvement in outcome with low-cost, broadly available treatment for acute stroke patients.
Asymmetric Acute Motor Axonal Neuropathy With Unilateral Tongue Swelling Mimicking Stroke
Authors: Chi Man Sum , Ng Shi Hon , Chan Lok Yiu
Published: November 2016

A 60-year-old man presented with acute onset of left hemiparesis and left hypoglossal nerve palsy with ipsilateral tongue swelling. He then progressed to tetraparesis in a few days. Cerebrospinal fluid showed cell protein dissociation. A nerve conduction study showed motor axonal neuropathy with sensory sparing. A subsequent blood test revealed anti-GD1b IgG antibody positivity. He was diagnosed to have acute motor axonal neuropathy (AMAN) and treated with a course of intravenous immunoglobulin with slow improvement. This is probably the first AMAN with asymmetrical presentation mimicking stroke reported in the literature in detail. The anti-GD1b IgG antibody is also not commonly associated with AMAN.
Chemotherapy-associated Posterior Reversible Encephalopathy Syndrome
Authors: How Joan , Blattner Margaret , Fowler Susan , Wang-Gillam Andrea , Schindler Suzanne E.
Published: November 2016

Introduction:

There are increasing reports of posterior reversible encephalopathy syndrome (PRES) associated with the use of chemotherapeutic agents. Recognition of PRES is crucial given its reversibility with appropriate supportive management. We report a patient presenting with PRES after treatment with Rituximab, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone (R-CHOP) and intrathecal methotrexate. We also perform a systematic review of the literature on chemotherapy-associated PRES.

Case Report:

A 72-year-old man with recently diagnosed diffuse large B-cell lymphoma became unresponsive 4 days after initiation of R-CHOP and intrathecal methotrexate. Brain magnetic resonance imaging showed interval development of occipital and temporal fluid attenuation inversion recovery hyperintensities consistent with PRES. The patient’s blood pressure was aggressively controlled and he received 5 days of high-dose methylprednisone. He subsequently regained consciousness and his mental status gradually improved. Repeat magnetic resonance imaging showed interval resolution of the bilateral fluid attenuation inversion recovery hyperintensities.

Review Summary:

We performed a systematic review of the literature and included a total of 70 unique cases involving chemotherapy-associated PRES. Platinum-containing drugs, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone/R-CHOP regimens, and gemcitabine were the agents most commonly used in patients who developed suspected chemo-associated PRES. Median onset of symptoms occurred 8 days after chemotherapy. Hypertension was the most commonly reported risk factor associated with the development of chemotherapy-associated PRES. In most cases, PRES improved with supportive management alone within 2 weeks.

Conclusions:

Chemotherapy-associated PRES is an increasingly encountered syndrome. Both neurologists and non-neurologists should be familiar with the most commonly implicated agents, symptoms, risk factors, and clinical course of chemotherapy-associated PRES, given its favorable prognosis with appropriate management.
Histopathology of Subcapsular Cataract in a Patient with Atopic Dermatitis
Authors: Shu Daisy Yao , Ong Keith , Lovicu Frank J.
Published: November 2016

Purpose

To report the histopathological features of anterior subcapsular cataract associated with atopic dermatitis.

Case Report

A 29-year-old man with atopic dermatitis presented with bilateral anterior subcapsular cataract. After routine cataract surgery, the anterior subcapsular cataractous tissue was obtained as an anterior capsulorhexis flap and prepared as a wholemount for histological analysis. The wholemount consisted of a well-demarcated central grayish-white plaque surrounded by transparent capsule, corroborating the slit-lamp biomicroscopic appearance. Higher magnification of the plaque revealed a fibrous and amorphous mass, most likely extracellular matrix owing to the presence of irregularly arranged bundled strands of fibrils, typical of collagen. Lens epithelial cells at the plaque were densely packed and myofibroblast-like and immunoreactive for alpha-smooth muscle actin. In contrast, lens epithelial cells more distant from the plaque retained their regular cuboidal arrangement and regular spacing, and were not labeled for alpha-smooth muscle actin, similar to lens epithelial cells obtained from a non-cataractous case.

Conclusions

The presence of alpha-smooth muscle actin-reactive elongated cells at the plaque suggests that the cuboidal lens epithelial cells making up the anterior subcapsular cataract have transdifferentiated into spindle-shaped myofibroblastic cells that produce and deposit aberrant extracellular matrix. This transdifferentiation process, more commonly known as an epithelial-mesenchymal transition, contributes to a fibrotic response leading to the development of human anterior subcapsular cataract.
Richter Syndrome With Plasmablastic Lymphoma at Primary Diagnosis: A Case Report With a Review of the Literature
Authors: Ronchi Andrea , Marra Laura , Frigeri Ferdinando , Botti Gerardo , Franco Renato , De Chiara Annarosaria
Published: November 2016

Richter syndrome (RS) is considered as the rare development of an aggressive lymphoid malignancy in a preexisting small lymphocytic lymphoma/chronic lymphocytic leukemia. The most common aggressive lymphoma developing in this setting is diffuse large B-cell lymphoma, but classical Hodgkin lymphoma and other much rarer entities such as prolymphocytic lymphoma and dendritic cell sarcoma are also described, most frequently in the progression of the disease over time. A clonal relation between the 2 neoplastic proliferations can be frequently found, whereas clonally unrelated cases are commonly considered as independent tumors, probably due to a variable combination of multiple causes, responsible independently for the 2 neoplasms. RS with plasmablastic lymphoma is reported very rarely, during the clinical course of the small lymphocytic lymphoma/chronic lymphocytic leukemia. Herein, an unusual case of RS with the coexistence of plasmablastic lymphoma and B-small lymphocytic lymphoma in the same lymph node at the time of first diagnosis is described.
Fading With Time of PD-L1 Immunoreactivity in Non–Small Cells Lung Cancer Tissues: A Methodological Study
Authors: Giunchi Francesca , Degiovanni Alessio , Daddi Niccolò , Trisolini Rocco , Dell’Amore Andrea , Agostinelli Claudio , Ardizzoni Andrea , Fiorentino Michelangelo
Published: November 2016

Blockade of inhibitory immune checkpoints is currently arising as a potential immunologic option for tumor therapy. Inhibition of programmed cell death protein 1 and/or its specific ligand programmed death-ligand 1 (PD-L1) was effective in clinical trials in advanced melanoma, non–small cell lung cancer (NSCLC) bladder and kidney cancer. The predictive role of the immunohistochemical (IHC) expression of PD-L1 is highly debated. Different reagents, clones, cutoffs of cell expression and subjective interpretation of PD-L1 immunoreactivity in epithelial cells and lymphocytes are the main issue. In this study we selected 58 consecutive NSCLC surgical specimens that underwent pathologic examination from January 2014 to July 2015. Using a tissue microarray approach we evaluated the IHC expression of PD-L1 in tumor-infiltrating lymphocytes and tumor cells (TCs) and compared the ICH staining with tumor histology, grade and the age of the tissue blocks. The main new finding was the fading of PD-L1 IHC expression in TCs in tissues processed in 2014 compared with 2015. PD-L1 expression in tumor-infiltrating lymphocytes in the 2 years was similar. We also found a significant higher immunoreactivity of TCs in high grade NSCLC and in the squamous carcinoma histotype compared with low grade tumors and the adenocarcinoma histology (P=0.013). We demonstrated that the IHC evaluation of PD-L1 in NSCLC archival tissues is feasible and can be implemented in a routine pathology setting, but it should be carefully assessed in tissue blocks older than 1 year.
Value of Pathology Review in a Population-based Series of Ovarian Tumors
Authors: Stewart Colin J.R. , Stewart Louise M. , Holman C. D’Arcy J. , Jordan Susan , Semmens James , Spilsbury Katrina , Threlfall Timothy
Published: November 2016

Ovarian neoplasia comprises a heterogenous group of tumors with distinct clinicopathologic and molecular features and therefore assessment of potential risk factors should be tumor subtype specific. As part of ongoing epidemiological investigations of ovarian neoplasia in Western Australia, we performed an initial review of original pathology reports followed, in selected cases, by reassessment of histology material to optimize accurate diagnosis. Additional immunohistochemistry, often using antibodies unavailable at the time of initial assessment, was also performed as required. From an initial cohort of 1660 cases identified through the Western Australia Cancer Registry, benign, nonepithelial, nonovarian, miscellaneous, and indeterminate cases were excluded. Also excluded were 33 cases that were reclassified as ovarian metastases rather than primary ovarian tumors. Following exclusions there remained 1321 borderline and malignant epithelial neoplasms. The diagnosis was considered accurate in 1186 cases (89.8%) based upon information in the initial pathology reports and clinical follow-up data but uncertain in 135 cases (10.2%). Histologic review was possible in 92 of the latter tumors leading to an amended diagnosis in 63 cases (68.5%). The most common types of diagnostic amendment were the reclassification of high-grade carcinomas of undifferentiated, endometrioid, or transitional appearance as high-grade serous carcinoma, and the reclassification of most carcinomas of mixed epithelial type as “pure” carcinomas. This review illustrated specific pitfalls in the diagnosis of ovarian epithelial neoplasia and helped to maintain the accuracy of the Western Australia Cancer Registry. Accurate diagnosis will optimize further epidemiological studies assessing risk factors in specific subtypes of ovarian neoplasia.
Metastatic Urothelial Carcinoma to the Uterine Cervix: A Case Report of a Rare Entity and Review of the Diagnostic Differential
Authors: Sams Sharon B. , Rosser Julie A.
Published: November 2016

Urothelial carcinoma (UC) rarely metastasizes to the gynecologic tract, occurring in descending order of frequency, within the vagina, uterus, ovaries, and cervix. Significant morphologic overlap exists between primary gynecologic squamous lesions (both benign and malignant) and metastatic UC, thus potentially hindering a timely and accurate diagnosis. We present a case of UC metastatic to the uterine cervix in a 69-year-old female initially found to have noninvasive high-grade papillary UC of the bladder. Complaints of vaginal spotting lead to identification and biopsy of a mass in the uterine cervix. Histologic evaluation of the cervical mass showed a neoplastic proliferation of atypical epithelioid cells arranged in a papillary architecture. The differential in this case included primary uterine cervical tumors such as condyloma acuminatum, immature condyloma, verrucous carcinoma, warty/condylomatous carcinoma, and papillary squamotransitional cell carcinoma, as well as metastatic UC. A careful evaluation of histologic variances and a selective immunohistochemical panel allows differentiation of these tumors. We herein review the subtle, albeit significant, histologic and immunohistochemical differences of the aforementioned lesions.
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quantum dots as colouring agents of Art Nouveau and contemporary stained glass: a combined transmission electron microscopy and Raman study
Authors: Fornacelli C. , Sciau Ph. , Colomban Ph.
Published: November 2016

The use of cadmium chalchogenide nanoprecipitates to obtain brightly coloured glasses enormously expanded by the beginning of the twentieth century, when the production of cadmium-based pigments was already well established. Six historical stained glass pieces produced between the late 1920s and modern days have been investigated in order to delineate the average size and the elemental composition of the nanocrystals. As non-invasive conditions are now mandatory when considering objects belonging to cultural heritage, Raman spectroscopy is used to measure the (average) elemental composition of the nanoparticles. Zinc substitution is also detected by the shifting of the Raman peak position. Moreover, a tentative evaluation of size distribution and crystallinity of the nanoparticles has been performed considering those parameters that are mainly influenced by the disorder of the system, such as Raman band width, surface phonons and the ratio between second and first order band intensities. A confirmation of the above-mentioned conclusion is searched by means of transmission electron microscopy (TEM) and local elemental analysis. Raman investigations allowed identifying a different and more pronounced disorder characterizing the oldest glasses, also verified by TEM observations, suggesting a different manufacture.

This article is part of the themed issue ‘Raman spectroscopy in art and archaeology’.
Virtuous colours for Mary. Identification of lapis lazuli, smalt and cochineal in the Andean colonial image of Our Lady of Copacabana (Bolivia)
Authors: Tomasini Eugenia P. , Marte Fernando , Careaga Valeria P. , Landa Carlos Rúa , Siracusano Gabriela , Maier Marta S.
Published: November 2016

The image of Our Lady of Copacabana, a gilded polychrome sculpture carved in maguey wood in 1583, is one of the most important devotions in the Americas. In former research, we have identified the use of gypsum, Armenian bole, cerussite and atacamite in its polychromy. In this study, a red sample taken from the Virgin's tunic and a blue sample extracted from the cloak have been analysed with the aim to identify both pigments and offer insights into the painting technique. Analysis by micro-Raman spectroscopy complemented with scanning electron microscopy–energy dispersive spectroscopy and high-performance liquid chromatography allowed the identification of carmine lake in the red sample. Analysis by micro-Raman spectroscopy of the surface of the blue sample and its cross section showed the presence of smalt—the blue-glass pigment—over a cerussite layer, bathed by a very thin ultramarine layer—from a probable native origin—following a pictorial tradition that would last even until the eighteenth century. This is the first time that lapis lazuli has been scientifically identified in a Spanish American colonial painted layer.

This article is part of the themed issue ‘Raman spectroscopy in art and archaeology’.
Validation of self-administered nasal swabs and postage for the isolation of Staphylococcus aureus
Authors: Harrison Ewan M. , Gleadall Nicholas S. , Ba Xiaoliang , Danesh John , Peacock Sharon J. , Holmes Mark
Published: November 2016

Staphylococcus aureus carriers are at higher risk of S. aureus infection and are a reservoir for transmission to others. Detection of nasal S. aureus carriage is important for both targeted decolonization and epidemiological studies. Self-administered nasal swabbing has been reported previously, but the effects of posting swabs prior to culture on S. aureus yield have not been investigated. A longitudinal cohort study was performed in which healthy volunteers were recruited, trained in the swabbing procedure and asked to take weekly nasal swabs for 6 weeks (median: 3 weeks, range 1–6 weeks). Two swabs were taken at each sampling episode and randomly assigned for immediate processing on arrival to the laboratory (Swab A) or second class postage prior to processing (Swab B). S. aureus was isolated using standard methods. A total of 95 participants were recruited, who took 944 swabs (472 pairs) over a median of 5 weeks. Of these, 459 swabs were positive for S. aureus. We found no significant difference (P=0.25) between 472 pairs of nasal self-swabs processed immediately or following standard postage from 95 study participants (51.4 % vs. 48.6 %, respectively). We also provide further evidence that persistent carriers can be detected by two weekly swabs with high degrees of sensitivity [92.3 % (95 % CI 74.8–98.8 %)] and specificity [95.6 % (95 % CI 84.8–99.3 %)] compared with a gold standard of five weekly swabs. Self-swabbing and postage of nasal swabs prior to processing has no effect on yield of S. aureus, and could facilitate large community-based carriage studies.
Minimal-assumption inference from population-genomic data
Authors: Weissman Daniel B. , Hallatschek Oskar
Published: November 2016

Samples of multiple complete genome sequences contain vast amounts of information about the evolutionary history of populations, much of it in the associations among polymorphisms at different loci. Current methods that take advantage of this linkage information rely on models of recombination and coalescence, limiting the sample sizes and populations that they can analyze. We introduce a method, Minimal-Assumption Genomic Inference of Coalescence (MAGIC), that reconstructs key features of the evolutionary history, including the distribution of coalescence times, by integrating information across genomic length scales without using an explicit model of recombination, demography or selection. Using simulated data, we show that MAGIC’s performance is comparable to PSMC’ on single diploid samples generated with standard coalescent and recombination models. More importantly, MAGIC can also analyze arbitrarily large samples and is robust to changes in the coalescent and recombination processes. Using MAGIC, we show that the inferred coalescence time histories of samples of multiple human genomes exhibit inconsistencies with a description in terms of an effective population size based on single-genome data.
Ploidy tug-of-war: evolutionary and genetic environments influence the rate of ploidy drive in a human fungal pathogen
Authors: Gerstein Aleeza C. , Lim Heekyung , Berman Judith , Hickman Meleah A.
Published: November 2016

Variation in baseline ploidy is seen throughout the tree of life, yet the factors that determine why one ploidy level is selected over another remain poorly understood. Experimental evolution studies using asexual fungal microbes with manipulated ploidy levels intriguingly reveals a propensity to return to the historical baseline ploidy, a phenomenon that we term ‘ploidy drive’. We evolved haploid, diploid, and polyploid strains of the human fungal pathogenCandida albicansunder three different nutrient limitation environments to test whether these conditions, hypothesized to select for low ploidy levels, could counteract ploidy drive. Strains generally maintained or acquired smaller genome sizes in minimal medium and under phosphorus depletion compared to in a complete medium, while mostly maintained or acquired increased genome sizes under nitrogen depletion. Surprisingly, improvements in fitness often ran counter to changes in total nuclear genome size; in a number of scenarios lines that maintained their original genome size often increased in fitness more than lines that converged towards diploidy. Combined, this work demonstrates a role for both the environment and genotype in determination of the rate of ploidy drive, and highlights questions that remain about the force(s) that cause genome size variation.
Phenopolis: an open platform for harmonization and analysis of sequencing and phenotype data
Authors: Pontikos Nikolas , Yu Jing , Blanco-Kelly Fiona , Vulliamy Tom , Wong Tsz Lun , Murphy Cian , Cipriani Valentina , Fiorentino Alessia , Arno Gavin , Greene Daniel , Jacobsen Julius OB , Clark Tristan , Gregory David S , Nemeth Andrea , Halford Stephanie , Downes Susan , Black Graeme C , Webster Andrew R , Hardcastle Alison , Plagnol Vincent
Published: November 2016

Phenopolis is an open-source web server which provides an intuitive interface to genetic and phenotypic databases. It integrates analysis tools which include variant filtering and gene prioritisation based on phenotype. The Phenopolis platform will accelerate clinical diagnosis, gene discovery and encourage wider adoption of the Human Phenotype Ontology in the study of rare disease.

Availability and Implementation

A demo of the website is available athttp://phenopolis.github.io(username: demo, password: demo123). If you wish to install a local copy, souce code and installation instruction are available athttps://github.com/pontikos/phenopolis. The software is implemented using Python, MongoDB, HTML/Javascript and various bash shell scripts.

Contact

n.pontikos@ucl.ac.uk

Supplementary information

http://phenopolis.github.io