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The Role Of B Cell Targeting In Chronic Graft-Versus-Host Disease., Ruben Rhoades, Md, Sameh Gaballa, Md Oct 2017

The Role Of B Cell Targeting In Chronic Graft-Versus-Host Disease., Ruben Rhoades, Md, Sameh Gaballa, Md

Department of Medical Oncology Faculty Papers

Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality following allogeneic stem cell transplantation. Current therapies, including corticosteroids and calcineurin inhibitors, are only effective in roughly 50% of cases; therefore, new treatment strategies are under investigation. What was previously felt to be a T cell disease has more recently been shown to involve activation of both T and B cells, as well as a number of cytokines. With a better understanding of its pathophysiology have come more expansive preclinical and clinical trials, many focused on B cell signaling. This report briefly reviews our current understanding of …


Sex Differential In 15-Hydroxyprostaglandin Dehydrogenase Levels In The Lumen Of Human Intracranial Aneurysms., Nohra Chalouhi, Pascal Jabbour, Mario Zanaty, Robert M. Starke, James Torner, Daichi Nakagawa, David M. Hasan Oct 2017

Sex Differential In 15-Hydroxyprostaglandin Dehydrogenase Levels In The Lumen Of Human Intracranial Aneurysms., Nohra Chalouhi, Pascal Jabbour, Mario Zanaty, Robert M. Starke, James Torner, Daichi Nakagawa, David M. Hasan

Department of Neurosurgery Faculty Papers

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs.

METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, …


Spinal Excitability Changes After Transspinal And Transcortical Paired Associative Stimulation In Humans, Maria Knikou Oct 2017

Spinal Excitability Changes After Transspinal And Transcortical Paired Associative Stimulation In Humans, Maria Knikou

Publications and Research

Paired associative stimulation (PAS) produces enduring neuroplasticity based on Hebbian associative plasticity. This study established the changes in spinal motoneuronal excitability by pairing transcortical and transspinal stimulation. Transcortical stimulation was delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Before and after 40 minutes of each PAS protocol, spinal neural excitability was assessed based on the amplitude of the transspinal-evoked potentials (TEPs) recorded from ankle muscles of both legs at different stimulation intensities (recruitment input-output curve). Changes in TEPs amplitude in response to low-frequency stimulation and paired transspinal stimuli were also established before and after each PAS protocol. TEP …


Human Herpesvirus 8 Infects And Replicates In Langerhans Cells And Interstitial Dermal Dendritic Cells And Impairs Their Function., Giovanna Rappocciolo, Mariel Jais, Paolo A Piazza, Diana C Delucia, Frank J Jenkins, Charles R Rinaldo Oct 2017

Human Herpesvirus 8 Infects And Replicates In Langerhans Cells And Interstitial Dermal Dendritic Cells And Impairs Their Function., Giovanna Rappocciolo, Mariel Jais, Paolo A Piazza, Diana C Delucia, Frank J Jenkins, Charles R Rinaldo

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The predominant types of dendritic cells (DC) in the skin and mucosa are Langerhans cells (LC) and interstitial dermal DC (iDDC). LC and iDDC process cutaneous antigens and migrate out of the skin and mucosa to the draining lymph nodes to present antigens to T and B cells. Because of the strategic location of LC and iDDC and the ability of these cells to capture and process pathogens, we hypothesized that they could be infected with human herpesvirus 8 (HHV-8) (Kaposi's sarcoma [KS]-associated herpesvirus) and have an important role in the development of KS. We have previously shown that HHV-8 …


Detection Of Activating Estrogen Receptor Gene (Esr1) Mutations In Single Circulating Tumor Cells, Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J. Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen E. Knudsen, Massimo Cristofanilli, Paolo Fortina Oct 2017

Detection Of Activating Estrogen Receptor Gene (Esr1) Mutations In Single Circulating Tumor Cells, Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J. Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen E. Knudsen, Massimo Cristofanilli, Paolo Fortina

Department of Cancer Biology Faculty Papers

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and …


A Two-Biomarker Model Predicts Mortality In The Critically Ill With Sepsis., Carmen Mikacenic, Brenda L Price, Susanna Harju-Baker, D Shane O'Mahony, Cassianne Robinson-Cohen, Frank Radella, William O Hahn, Ronit Katz, David C Christiani, Jonathan Himmelfarb, W Conrad Liles, Mark M Wurfel Oct 2017

A Two-Biomarker Model Predicts Mortality In The Critically Ill With Sepsis., Carmen Mikacenic, Brenda L Price, Susanna Harju-Baker, D Shane O'Mahony, Cassianne Robinson-Cohen, Frank Radella, William O Hahn, Ronit Katz, David C Christiani, Jonathan Himmelfarb, W Conrad Liles, Mark M Wurfel

Articles, Abstracts, and Reports

RATIONALE: Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge.

OBJECTIVES: To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis.

METHODS: A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = …


Timing Of Pd-1 Blockade Is Critical To Effective Combination Immunotherapy With Anti-Ox40., David J Messenheimer, Shawn M. Jensen, Michael E Afentoulis, Keith W Wegman, Zipei Feng, David J Friedman, Michael J. Gough, Walter Urba, Bernard A Fox Oct 2017

Timing Of Pd-1 Blockade Is Critical To Effective Combination Immunotherapy With Anti-Ox40., David J Messenheimer, Shawn M. Jensen, Michael E Afentoulis, Keith W Wegman, Zipei Feng, David J Friedman, Michael J. Gough, Walter Urba, Bernard A Fox

Articles, Abstracts, and Reports

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 …


Plasmodium Falciparum Epcr-Binding Pfemp1 Expression Increases With Malaria Disease Severity And Is Elevated In Retinopathy Negative Cerebral Malaria., Estela Shabani, Benjamin Hanisch, Robert O Opoka, Thomas Lavstsen, Chandy C John Oct 2017

Plasmodium Falciparum Epcr-Binding Pfemp1 Expression Increases With Malaria Disease Severity And Is Elevated In Retinopathy Negative Cerebral Malaria., Estela Shabani, Benjamin Hanisch, Robert O Opoka, Thomas Lavstsen, Chandy C John

Pediatrics Faculty Publications

Background

Expression of group A and the A-like subset of group B Plasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). The question of whether children with clinical CM but no retinopathy represent a completely different disease process or a subgroup within the spectrum of CM …


Influenza Epidemiology And Immunization During Pregnancy: Final Report Of A World Health Organization Working Group, Deshayne B. Fell, Eduardo Azziz-Baumgartner, Michael G. Baker, Maneesh Batra, Julien Beauté, Philippe Beutels, Niranjan Bhat, Zulfiqar Ahmed Bhutta, Cheryl Cohen, Rehana Salam Oct 2017

Influenza Epidemiology And Immunization During Pregnancy: Final Report Of A World Health Organization Working Group, Deshayne B. Fell, Eduardo Azziz-Baumgartner, Michael G. Baker, Maneesh Batra, Julien Beauté, Philippe Beutels, Niranjan Bhat, Zulfiqar Ahmed Bhutta, Cheryl Cohen, Rehana Salam

Department of Paediatrics and Child Health

From 2014 to 2017, the World Health Organization convened a working group to evaluate influenza disease burden and vaccine efficacy to inform estimates of maternal influenza immunization program impact. The group evaluated existing systematic reviews and relevant primary studies, and conducted four new systematic reviews. There was strong evidence that maternal influenza immunization prevented influenza illness in pregnant women and their infants, although data on severe illness prevention were lacking. The limited number of studies reporting influenza incidence in pregnant women and infants under six months had highly variable estimates and underrepresented low- and middle-income countries. The evidence that maternal …


No Difference In Myosin Kinetics And Spatial Distribution Of The Lever Arm In The Left And Right Ventricles Of Human Hearts, Divya Duggal, S. Requena, Janhavi Nagwekar, Sangram Raut, Ryan Rich, Hriday Das, Vipul Patel, Ignacy Gryczynski, Rafal Fudala, Zygmunt Gryczynski, Cheavar Blair, Kenneth S. Campbell, Julian Borejdo Oct 2017

No Difference In Myosin Kinetics And Spatial Distribution Of The Lever Arm In The Left And Right Ventricles Of Human Hearts, Divya Duggal, S. Requena, Janhavi Nagwekar, Sangram Raut, Ryan Rich, Hriday Das, Vipul Patel, Ignacy Gryczynski, Rafal Fudala, Zygmunt Gryczynski, Cheavar Blair, Kenneth S. Campbell, Julian Borejdo

Physiology Faculty Publications

The systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles. Such a question cannot be answered by studying the entire ventricles or myocytes because any observed differences would be wiped out by averaging the information obtained from trillions of myosin molecules present in a ventricle or myocyte. …


A Pilot Study Evaluating Concordance Between Blood-Based And Patient-Matched Tumor Molecular Testing Within Pancreatic Cancer Patients Participating In The Know Your Tumor (Kyt) Initiative, Michael J. Pishvaian, R. Joseph Bender, Lynn M. Matrisian, Lola Rahib, Andrew Hendifar, William A. Hoos, Sam Mikhail, Vincent Chung, Vincent Picozzi, Craig Heartwell, Kimberly Mason, Katelyn Varieur, Metasebia Aberra, Subha Madhavan, Emanuel Petricoin Iii, Jonathan Brody Oct 2017

A Pilot Study Evaluating Concordance Between Blood-Based And Patient-Matched Tumor Molecular Testing Within Pancreatic Cancer Patients Participating In The Know Your Tumor (Kyt) Initiative, Michael J. Pishvaian, R. Joseph Bender, Lynn M. Matrisian, Lola Rahib, Andrew Hendifar, William A. Hoos, Sam Mikhail, Vincent Chung, Vincent Picozzi, Craig Heartwell, Kimberly Mason, Katelyn Varieur, Metasebia Aberra, Subha Madhavan, Emanuel Petricoin Iii, Jonathan Brody

Department of Surgery Faculty Papers

Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRBapproved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices. 23 of these patients also underwent traditional tumor tissue-based NGS testing. cfDNA was not detected in 9/34 (26%) patients. Overall concordance between blood and tumor tissue NGS …


Life After Being A Pathology Department Chair Ii: Lessons Learned., David N. Bailey, Mary F. Lipscomb, Fred Gorstein, David Wilkinson, Fred Sanfilippo Oct 2017

Life After Being A Pathology Department Chair Ii: Lessons Learned., David N. Bailey, Mary F. Lipscomb, Fred Gorstein, David Wilkinson, Fred Sanfilippo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The 2016 Association of Pathology Chairs annual meeting featured a discussion group of Association of Pathology Chairs senior fellows (former chairs of academic departments of pathology who have remained active in Association of Pathology Chairs) that focused on how they decided to transition from the chair, how they prepared for such transition, and what they did after the transition. At the 2017 annual meeting, the senior fellows (encompassing 481 years of chair service) discussed lessons they learned from service as chair. These lessons included preparation for the chairship, what they would have done differently as chair, critical factors for success …


Omega-6 Fatty Acid Biomarkers And Incident Type 2 Diabetes: Pooled Analysis Of Individual-Level Data For 39 740 Adults From 20 Prospective Cohort Studies, Jason H Y Wu, Matti Marklund, Fumiaki Imamura, Nathan L. Tintle, Andres V Ardisson Korat, Janette De Goede, Xia Zhou, Wei-Sin Yang, Marcia C De Oliveira Otto, Janine Kroger, Waqas Qureshi, Jyrki K. Virtanen, Julie K. Bassett, Alexis C. Frazier-Wood, Maria Lankinen, Rachel A. Murphy, Kalina Rajaobelina, Liana C. Del Gobbo, Nita G. Forouhi, Robert Luben, Kay-Tee Khaw, Nick Wareham, Anya Kalsbeek, Jenna Veenstra, Juhua Luo, Frank B. Hu, Hung-Ju Lin, David S. Siscovick, Heiner Boeing, Tzu-An Chen, Brian Steffen, Lyn M. Steffen, Allison Hodge, Gudny Eriksdottir, Albert V. Smith, Vilmunder Gudnason, Tamara B. Harris, Ingeborg A. Brouwer, Claudine Berr, Catherine Helmer, Cecilia Samieri, Markku Laakso, Michael Y. Tsai, Graham G. Giles, Tarja Nurmi, Lynne Wagenknecht, Matthias B. Schulze, Rozenn N. Lemaitre, Kuo-Liong Chien, Sabita S. Soedamah-Muthu, Johanna M. Geleijnse, Qi Sun, William S. Harris, Lars Lind, Johan Arnlov, Ulf Riserus, Renata Micha, Dariush Mozaffairian Oct 2017

Omega-6 Fatty Acid Biomarkers And Incident Type 2 Diabetes: Pooled Analysis Of Individual-Level Data For 39 740 Adults From 20 Prospective Cohort Studies, Jason H Y Wu, Matti Marklund, Fumiaki Imamura, Nathan L. Tintle, Andres V Ardisson Korat, Janette De Goede, Xia Zhou, Wei-Sin Yang, Marcia C De Oliveira Otto, Janine Kroger, Waqas Qureshi, Jyrki K. Virtanen, Julie K. Bassett, Alexis C. Frazier-Wood, Maria Lankinen, Rachel A. Murphy, Kalina Rajaobelina, Liana C. Del Gobbo, Nita G. Forouhi, Robert Luben, Kay-Tee Khaw, Nick Wareham, Anya Kalsbeek, Jenna Veenstra, Juhua Luo, Frank B. Hu, Hung-Ju Lin, David S. Siscovick, Heiner Boeing, Tzu-An Chen, Brian Steffen, Lyn M. Steffen, Allison Hodge, Gudny Eriksdottir, Albert V. Smith, Vilmunder Gudnason, Tamara B. Harris, Ingeborg A. Brouwer, Claudine Berr, Catherine Helmer, Cecilia Samieri, Markku Laakso, Michael Y. Tsai, Graham G. Giles, Tarja Nurmi, Lynne Wagenknecht, Matthias B. Schulze, Rozenn N. Lemaitre, Kuo-Liong Chien, Sabita S. Soedamah-Muthu, Johanna M. Geleijnse, Qi Sun, William S. Harris, Lars Lind, Johan Arnlov, Ulf Riserus, Renata Micha, Dariush Mozaffairian

Faculty Work Comprehensive List

Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled …


Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas Oct 2017

Role Of Microglial Amylin Receptors In Mediating Beta Amyloid (Aβ)-Induced Inflammation, Wen Fu, Vlatka Vukojevic, Aarti Patel, Rania Soudy, David Mactavish, David Westaway, Kamaljit Kaur, Valeri Goncharuk, Jack Jhamandas

Pharmacy Faculty Articles and Research

Background: Neuroinflammation in the brain consequent to activation of microglia is viewed as an important component of Alzheimer’s disease (AD) pathology. Amyloid beta (Aβ) protein is known to activate microglia and unleash an inflammatory cascade that eventually results in neuronal dysfunction and death. In this study, we sought to identify the presence of amylin receptors on human fetal and murine microglia and determine whether Aβ activation of the inflammasome complex and subsequent release of cytokines is mediated through these receptors.

Methods: The presence of dimeric components of the amylin receptor (calcitonin receptor and receptor activity modifying protein 3) …


Anthropometric Factors And Cutaneous Melanoma: Prospective Data From The Population-Based Janus Cohort, Jo S. Stenehjem, Marit B. Veierød, Lill Tove Nilsen, Reza Ghiasvand, Bjørn Johnsen, Tom K. Grimsrud, Ronnie Babigumira, Judy R. Rees, Trude E. Robsahm Oct 2017

Anthropometric Factors And Cutaneous Melanoma: Prospective Data From The Population-Based Janus Cohort, Jo S. Stenehjem, Marit B. Veierød, Lill Tove Nilsen, Reza Ghiasvand, Bjørn Johnsen, Tom K. Grimsrud, Ronnie Babigumira, Judy R. Rees, Trude E. Robsahm

Dartmouth Scholarship

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking …


Necrotizing Fasciitis Of The Neck: Case Presentation, Emil Marginean, Ciprian Venter, Maria Domuta, Oana Valenas, Ildiko Sorban, Alina Pantis, Bogdan Popescu, Razvan V. Scăunașu Oct 2017

Necrotizing Fasciitis Of The Neck: Case Presentation, Emil Marginean, Ciprian Venter, Maria Domuta, Oana Valenas, Ildiko Sorban, Alina Pantis, Bogdan Popescu, Razvan V. Scăunașu

Journal of Mind and Medical Sciences

Necrotizing fasciitis represents a severe and rare infectious disease, which is accompanied by extended necrosis of subcutaneous tissues and fascia layers, having as a result gangrene of the teguments. To reduce mortality associated with this disease, a rapid diagnosis is necessary as well as aggressive surgical treatment, accompanied by adequate, aggressive antibiotic therapy. As a rule, etiology is teeth related, with the condition more common in immunology-depressed patients. This article presents the experience of the authors regarding a case presentation of necrotizing fasciitis with typical clinical expression and management of the disease in an immunological-depressed patient. Further data on diagnosis, …


Zenker’S Diverticulum And Squamous Esophageal Cancer: A Case Report, Ion Dina, Octav Ginghina, Corina D. Toderescu, Cristian Bălălău, Bianca Galateanu, Carolina Negrei, Claudia Iacobescu Oct 2017

Zenker’S Diverticulum And Squamous Esophageal Cancer: A Case Report, Ion Dina, Octav Ginghina, Corina D. Toderescu, Cristian Bălălău, Bianca Galateanu, Carolina Negrei, Claudia Iacobescu

Journal of Mind and Medical Sciences

Zenker’s diverticulum represents a rare esophageal lesion developed especially in the elderly population due to herniation of esophageal mucosa above the cricopharyngeus muscle. The condition leads to food retention, regurgitation, aspiration, and dysphagia in affected patients. Progressive dysphagia also characterizes malignant diseases of the esophagus like squamous esophageal carcinoma that typically appears in male patients in the seventh decade of life, with a history of cigarette smoking and alcohol abuse. We report a case of a male patient who presented with dysphagia for both solids and liquids along with significant weight loss, and who was diagnosed with medium esophageal cancer …


Therapeutic Challenges In A Case Of Psoriasis With Nail Onset, Mădălina I. Mitran, Cristina I. Mitran, Maria I. Sârbu, Vasile Benea, Mircea Tampa, Simona R. Georgescu Oct 2017

Therapeutic Challenges In A Case Of Psoriasis With Nail Onset, Mădălina I. Mitran, Cristina I. Mitran, Maria I. Sârbu, Vasile Benea, Mircea Tampa, Simona R. Georgescu

Journal of Mind and Medical Sciences

Nail psoriasis affects a large number of patients with psoriasis and has a major psychosocial impact. Furthermore, it may be regarded as a predictor of more severe forms of psoriasis and early sign of psoriatic arthritis. The clinical presentations vary depending on the structure affected (nail matrix or nail bed), the nail lesions may range from minor to severe, but they are not specific. Treatment is a challenge, in most cases the lesions being resistant to therapy. We present a rare case of psoriasis with nail onset in a 59-year-old woman. The nail involvement confined to the fingernails was severe, …


The Psychological Influence Of The Diagnosis Of Breast Cancer On Therapeutic Options Selection, Razvan V. Scaunasu, Stefan Voiculescu, Bogdan Popescu, Cristina Cozma, Radu Jecan, Cristian Balalau Oct 2017

The Psychological Influence Of The Diagnosis Of Breast Cancer On Therapeutic Options Selection, Razvan V. Scaunasu, Stefan Voiculescu, Bogdan Popescu, Cristina Cozma, Radu Jecan, Cristian Balalau

Journal of Mind and Medical Sciences

The therapeutic management decision-making process for breast cancer is complex, and is influenced by multiple factors including patient age, comorbidities, ethnicity, education, and availability of immediate or delayed reconstruction options. Our study analysed 276 patients diagnosed with breast cancer in the “Colțea” Clinical Hospital between 2014 and 2015. Mean patients age was 61.24, median 62, with a range of 31 to 89 years. Younger age was associated with a less advanced local disease and younger patients were more likely to choose and benefit from conservative surgery. Most patients (61.76%) came from rural areas. Place of origin had a significant influence …


Finasteride As A Model For Personalized Medicine, Ion G. Motofei, David L. Rowland, Ioana Păunică, Octavian C. Tănăsescu, Petrişor Banu, Stana Păunică Oct 2017

Finasteride As A Model For Personalized Medicine, Ion G. Motofei, David L. Rowland, Ioana Păunică, Octavian C. Tănăsescu, Petrişor Banu, Stana Păunică

Journal of Mind and Medical Sciences

The side effects of Finasteride are currently a subject of controversy. Some studies report minor or acceptable adverse effects, which decrease after a variable period of time so that they do not necessitate terminating Finasteride administration. However, several clinical and neuro-endocrine studies show that some adverse effects persist indefinitely in the form of post-Finasteride syndrome, even after the drug cessation. This paper presents a possible explanation for these inconsistent findings. First, the study design of either informing or not informing patients prior therapy about possible adverse effects can influence the incidence and magnitude of reported adverse effects. Second, structural and …


Non-Compaction Cardiomyopathy – Brief Review, Oana Mirea, Mihaela Berceanu, Anca Constantin, Mirela Mănescu, Georgică Costinel Târtea, Ionuț Donoiu, Constantin Militaru, Octavian Istrătoaie Oct 2017

Non-Compaction Cardiomyopathy – Brief Review, Oana Mirea, Mihaela Berceanu, Anca Constantin, Mirela Mănescu, Georgică Costinel Târtea, Ionuț Donoiu, Constantin Militaru, Octavian Istrătoaie

Journal of Mind and Medical Sciences

Left ventricular non-compaction cardiomyopathy is a genetic disorder characterized by the presence of two myocardial layers with numerous prominent trabeculations and deep inter-trabecular recesses that communicate with the ventricular cavity. The diagnosis is often challenging because excessive trabeculations may also be a normal finding in performance athletes and black people. Echocardiography is the gold standard for diagnosis of this condition, but other useful diagnostic techniques may include cardiac magnetic resonance imaging, computed tomography, and contrast ventriculography. Moreover, newer echocardiographic methods such as three-dimensional imaging and speckle tracking analysis promise to improve the diagnosis of left ventricular non-compaction cardiomyopathy. The purpose …


End-Stage Head And Neck Cancer: Coping Mechanism, Bogdan Popescu, Oana Paun, Razvan V. Scăunaşu, Serban V.G. Berteşteanu Oct 2017

End-Stage Head And Neck Cancer: Coping Mechanism, Bogdan Popescu, Oana Paun, Razvan V. Scăunaşu, Serban V.G. Berteşteanu

Journal of Mind and Medical Sciences

Coping mechanisms are patients’ means of adapting to stressful situations and involve psychological and physical changes in behavior. Patients adapt to head and neck cancer in a variety of ways. Head and neck cancers are extremely debilitating, especially in advanced stages of the disease or in end-of-life situations. While an oncology team needs to address the needs of all oncology patients, the advanced terminal patients require special attention. Most of these patients do not cope well with their situation and have a tendency to cease social interactions. Pain is the most frequentlyexperienced medical disability in patients having an end-stage illness …


Targeting Cysteine Thiols For In Vitro Site-Specific Glycosylation Of Recombinant Proteins, Yoo Jung Choi, Jinhui Zhu, Steve Chung, Naveed Siddiqui, Qingping Feng, Peter B. Stathopulos Oct 2017

Targeting Cysteine Thiols For In Vitro Site-Specific Glycosylation Of Recombinant Proteins, Yoo Jung Choi, Jinhui Zhu, Steve Chung, Naveed Siddiqui, Qingping Feng, Peter B. Stathopulos

Paediatrics Publications

Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1 regulates the activity of PM Orai1 channels in a process known as store operated calcium (Ca2+) entry which is the principal Ca2+ signaling process that drives the immune response. STIM1 undergoes post-translational N-glycosylation at two luminal Asn sites within the Ca2+ sensing domain of the molecule. However, the biochemical, biophysical, and structure biological effects of N-glycosylated STIM1 were poorly understood until recently due to an inability to readily obtain high levels of homogeneous N-glycosylated protein. Here, we describe the …


Syntaphilin Controls A Mitochondrial Rheostat For Proliferation-Motility Decisions In Cancer., M Cecilia Caino, Jae Ho Seo, Yuan Wang, Dayana B. Rivadeneira, Dmitry I. Gabrilovich, Eui Tae Kim, Ashani T Weeraratna, Lucia R. Languino, Dario C. Altieri Oct 2017

Syntaphilin Controls A Mitochondrial Rheostat For Proliferation-Motility Decisions In Cancer., M Cecilia Caino, Jae Ho Seo, Yuan Wang, Dayana B. Rivadeneira, Dmitry I. Gabrilovich, Eui Tae Kim, Ashani T Weeraratna, Lucia R. Languino, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II-dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility. Conversely, introduction of stress stimuli to the microenvironment, including hypoxia, acutely lowered SNPH levels, resulting in bioenergetics defects and increased superoxide production. In …


Patients' And Caregivers' Needs, Experiences, Preferences And Research Priorities In Spiritual Care: A Focus Group Study Across Nine Countries., Lucy Ellen Selman, Lisa Jane Brighton, Shane Sinclair, Ikali Karvinen, Richard Egan, Peter Speck, Richard A Powell, Ewa Deskur-Smielecka, Myra Glajchen, Shelly Adler, Christina Puchalski, Joy Hunter, Nancy Gikaara, Jonathon Hope Oct 2017

Patients' And Caregivers' Needs, Experiences, Preferences And Research Priorities In Spiritual Care: A Focus Group Study Across Nine Countries., Lucy Ellen Selman, Lisa Jane Brighton, Shane Sinclair, Ikali Karvinen, Richard Egan, Peter Speck, Richard A Powell, Ewa Deskur-Smielecka, Myra Glajchen, Shelly Adler, Christina Puchalski, Joy Hunter, Nancy Gikaara, Jonathon Hope

Medicine Faculty Publications

Background:

Spiritual distress is prevalent in advanced disease, but often neglected, resulting in unnecessary suffering. Evidence to inform spiritual care practices in palliative care is limited.

Aim:

To explore spiritual care needs, experiences, preferences and research priorities in an international sample of patients with life-limiting disease and family caregivers.

Design:

Focus group study.

Setting/participants:

Separate patient and caregiver focus groups were conducted at 11 sites in South Africa, Kenya, South Korea, the United States, Canada, the United Kingdom, Belgium, Finland and Poland. Discussions were transcribed, translated into English and analysed thematically.

Results:

A total of 74 patients participated: median age …


Circulating Early- And Mid-Pregnancy Micrornas And Risk Of Gestational Diabetes., Pandora L Wander, Edward J Boyko, Karin Hevner, Viraj J Parikh, Mahlet G Tadesse, Tanya K Sorensen, Michelle A Williams, Daniel A Enquobahrie Oct 2017

Circulating Early- And Mid-Pregnancy Micrornas And Risk Of Gestational Diabetes., Pandora L Wander, Edward J Boyko, Karin Hevner, Viraj J Parikh, Mahlet G Tadesse, Tanya K Sorensen, Michelle A Williams, Daniel A Enquobahrie

Articles, Abstracts, and Reports

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex.

METHODS: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen …


Role Of 5-Ala In Improving Extent Of Tumour Resection In Patients With Glioblastoma Multiforme, Muhammad Waqas, Inamullah Khan, Muhammad Shahzad Shamim Oct 2017

Role Of 5-Ala In Improving Extent Of Tumour Resection In Patients With Glioblastoma Multiforme, Muhammad Waqas, Inamullah Khan, Muhammad Shahzad Shamim

Section of Neurosurgery

Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use …


Video Microscope Robotic Arm-Assisted, Neuronavigation-Guided Glioma Resection And Regional Sampling, Muhammad Waqas, Ather Enam, Fauzan A Hashmi, Fatima Mubarak, Fazal Arain Oct 2017

Video Microscope Robotic Arm-Assisted, Neuronavigation-Guided Glioma Resection And Regional Sampling, Muhammad Waqas, Ather Enam, Fauzan A Hashmi, Fatima Mubarak, Fazal Arain

Section of Neurosurgery

High-grade gliomas possess internal pathological heterogeneity. Selective sampling of different tumor regions can help in the study of this heterogeneity. In this report, we have described the use of a novel navigation and optical system for the selective regional sampling of a high-grade glioma lesion. A 45-year-old gentleman presented to us with complaints of intermittent frontal headaches for past eight months. On examination, he had subtle pyramidal weakness in left upper and lower extremities. Magnetic resonance imaging (MRI) showed a large contrast-enhancing, space-occupying lesion in the right frontal lobe causing perilesional edema and midline shift. We marked four different regions …


Internal Mammary Artery Flow In Different Racial Groups Of Pakistan, Mudassir Iqbal Dar, Asim Hassan Dar, Mansoor Ahmed, Abdul Haseeb, Muhammad Bilal Oct 2017

Internal Mammary Artery Flow In Different Racial Groups Of Pakistan, Mudassir Iqbal Dar, Asim Hassan Dar, Mansoor Ahmed, Abdul Haseeb, Muhammad Bilal

Department of Biological & Biomedical Sciences

Objective: To find out any differences in free flow of internal mammary artery among different ethnic groups.
Methods: This observational, cross-sectional study was conducted at the Civil Hospital, Karachi, from January 2013 to December 2015, and comprised patients who underwent coronary artery bypass grafting. The participants were divided into 5 groups, i.e. Sindhi, Muslim migrants from India, Punjabi, Pathan and Balochi patients. Free flow of internal mammary artery was measured immediately after harvesting within a syringe, and its flow was measured in 30 seconds. SPSS 18 was used for data analysis.
Results: Of the 158 patients, 44(27.8%) …


Exosomal Microrna For Detection Of Cardiac Sarcoidosis., Elliott D Crouser, Nabeel Y Hamzeh, Lisa A Maier, Mark W Julian, May Gillespie, Mohammad Rahman, David Baxter, Xiaogang Wu, S Patrick Nana-Sinkam, Kai Wang Oct 2017

Exosomal Microrna For Detection Of Cardiac Sarcoidosis., Elliott D Crouser, Nabeel Y Hamzeh, Lisa A Maier, Mark W Julian, May Gillespie, Mohammad Rahman, David Baxter, Xiaogang Wu, S Patrick Nana-Sinkam, Kai Wang

Articles, Abstracts, and Reports

No abstract provided.