Pathology Commons^™

Dysregulation Of Mitochondrial Ca2+ Uptake And Sarcolemma Repair Underlie Muscle Weakness And Wasting In Patients And Mice Lacking Micu1, Valentina Debattisti, Adam Horn, Raghavendra Singh, Erin L. Seifert, Marshall W. Hogarth, Davi A. Mazala, Kai Ting Huang, Rita Horvath, Jyoti K. Jaiswal, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Muscle function is regulated by Ca²⁺, which mediates excitation-contraction coupling, energy metabolism, adaptation to exercise, and sarcolemmal repair. Several of these actions rely on Ca²⁺ delivery to the mitochondrial matrix via the mitochondrial Ca²⁺ uniporter, the pore of which is formed by mitochondrial calcium uniporter (MCU). MCU's gatekeeping and cooperative activation are controlled by MICU1. Loss-of-protein mutation in MICU1 causes a neuromuscular disease. To determine the mechanisms underlying the muscle impairments, we used MICU1 patient cells and skeletal muscle-specific MICU1 knockout mice. Both these models show a lower threshold for MCU-mediated Ca²⁺ uptake. Lack of …

Perceptions Of Health Professionals Regarding Minimally Invasive Tissue Sampling (Mits) To Identify The Cause Of Death In Stillbirths And Neonates: Results From A Qualitative Study, Anam Shahil Feroz, Anum Shiraz Ali, Mohsina Noor Ibrahim, Elizabeth M. Mcclure, Shiyam Sunder Tikmani, Sayyeda Reza, Zahid Abbasi, Afia Zafar, Sameen Siddiqi, Sarah Saleem

Community Health Sciences

Background: Pakistan is considered to be one of the riskiest places in the world for childbirth as measured by its high stillbirth and neonatal mortality rates. Complete diagnostic autopsy remains the gold standard to determine the cause of death (CoD); however, it is not routinely implemented due to religious objections, sociocultural beliefs, limited resources and low demand from physicians and families. Recently, minimally invasive tissue sampling (MITS) using needle biopsies of multiple tissues to obtain tissue for histological examination and organism identification with PCR has been developed and promoted to determine CoD in low-resource areas. To ensure successful implementation of …

Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed 'lipid-MERCs' (gap width <10 nm), while 'Ca2+-MERCs' (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons.This article has an associated First Person interview with the first author of the paper.

Mindfulness Based Stress Reduction Increases Pathology Resident Self Wellness, Kaitlin Collura, Md, Phd, Joanna Chan, Md

Department of Pathology, Anatomy, and Cell Biology Posters

Stress during medical residency is a common, complex issue influenced by time demands, level of social support, and environmental factors. Increased stress levels can lead to resident burnout, and may contribute to the high rates of depression and suicide seen among physicians. In 2015, the ACGME began a campaign to promote resident wellness by calling on programs to implement strategies to develop resiliency, identify problems, and promote wellbeing. Mindfulness based stress reduction (MBSR) strategies have been shown to decrease burnout, improve mood, and increase compassion in healthcare providers. We implemented a wellness retreat to educate residents on the principles of …

Wellness Initiative Program And Effect On Pathology Resident Burnout Rate, Kaitlin Collura, Md, Phd, Michelle Nagurney, Md, Joanna Chan, Md

Department of Pathology, Anatomy, and Cell Biology Posters

Increasing rates of physician burnout are reported across many medical specialties, including Pathology. In 2014, 52.5% of pathologists experienced symptoms of burnout compared to 37.6% in 2011. Suicide and depression rates in physicians are also higher than the average population. As a result, the ACGME began a campaign, in 2015, to foster resident wellness. The campaign calls for strategies to develop resiliency, identify problems, and promote well-being. While wellness initiatives may not change underlying mental illness, they may mitigate environmental factors that can exacerbate mental illness or suicidal behavior. Here we report results from a recently implemented resident wellness initiative …

Pigmented Melanoma Cell Migration Study On Murine Syngeneic B16f10 Melanoma Cells Or Tissue Transplantation Models, Maria-Cristina Predoi, Ion Mîndrilă, Sandra Alice Buteică, Ovidiu Marcel Mărginean, Bogdan Mîndrilă, Mihaela Niculescu

Journal of Mind and Medical Sciences

Melanoma is a lethal form of skin cancer with poor prognosis, especially due to the early metastatic feature. Recent studies have shown that the melanin pigment influences the nanomechanical properties and, therefore, the metastatic behavior of the melanoma cells. We aimed to study the growth of subcutaneously transplanted syngeneic melanoma tissue in female C57BL/6 mice harvested from a mouse with a four-week B16F10 melanoma. Also, we studied the effect of the melanin pigment loading on the peritumoral migratory abilities of melanoma cells. Even when the syngeneic transplant was different (cultured cells vs. tumor tissue), the morphological features and the tumor …

Methicillin Resistant Staphylococcus Aureus Outbreak In A Neonatal Intensive Care Unit, Seema Irfan, Imran Ahmed, Farida Lalani, Naureen Anjum, Nadia Mohammad, Maria Owais, Afia Zafar

Department of Pathology and Laboratory Medicine

The global and national burden of communicable and noncommunicable diseases continues to rise, thus making access to Healthcare workers (HCWs) colonized with methicillin-resistant Staphylococcus aureus (MRSA) may pose transmission risk to vulnerable patients including neonates. This study reports an MRSA outbreak in a level-II neonatal intensive care unit (NICU) of a secondary care hospital in Pakistan. Once identified, an infection control team from the parent hospital visited the facility, risk factors were listed and infection control measures taken to control the outbreak. Screening cultures of NICU staff and environmental cultures from NICU were obtained for the presence of MRSA. Five …

Labrad : Vol 45, Issue 3 - October 2019, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Therapeutic Drug Monitoring for Antibiotics in Infections
• Biomarkers of Sepsis
• Serum Procalcitonin Level - Marker of Bacterial Infection
• Bone Marrow Findings in Malaria
• Antibiogram: A Clinicians’ Reference for Antibiotic Selection
• Laboratory Diagnosis of Meningitis
• Detection of Pneumocystis Jirovecii by PCR
• Microbiology Quiz
• Radiology Pathology Correlation- Orthopedic Pathology
• Role of Imaging in the Diagnosis and Management of Hepatic Abscess
• The Best of the Past
• Microbiology Quiz’s Answer
• Polaroid

Assessment And Improvement Of Data Collection Errors Through Inter-Departmental Collaboration, Charlott Williams, Kelli L. Behr, Mary Moffatt, Rangaraj Selvarangan

Posters

Specific Aims:

1. To maintain the ED team's high rate of accuracy in data collection
2. To begin team participation in corrective action planning
3. To improve interdepartmental problem solving

Conclusion

Open communication about errors among all collaborating departments, combing with a shared approach to solving them:

• improved morale and perception of error tracking by the team
• led to a decrease in errors overall, and
• increased interdepartmental collaboration

When all members of the interdepartmental team work together with a positive approach to corrective action, improvement in error rates is a natural outcome of the solutions derived.

Infections In Patients With Multiple Myeloma Treated With Conventional Chemotherapy: A Single-Center, 10-Year Experience In Pakistan, Mohammad Faizan Zahid, Natasha Ali, Myra Nasir, Maria Haider Baig, Mustafa Iftikhar, Syed Usman Bin Mahmood, Arhama Malik, Sara Atif, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Introduction: Multiple myeloma (MM) is a common hematologic malignancy with variable degrees of immunodeficiency. Disease- and treatment-related compromise of the immune system predisposes patients to infections, which are a major cause of morbidity and mortality.
Objective: We aimed to establish the incidence and main characteristics of infections in MM patients treated at our center over a 10-year period.
Method and results: Of the 412 patients retrospectively analyzed, 154 (37.4%) were documented to have at least one episode of infection and were included in this study. A total of 244 infectious episodes were documented. The most common site of infection was …

Conceptualization Of A Parasympathetic Endocrine System., Jonathan Gorky, James Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We here propose a parasympathetic endocrine system (PES) comprised of circulating peptides released from secretory cells in the gut, significantly modulated by vagal projections from the dorsal motor nucleus of the vagus (DMV). While most of these gut peptides mediate well-described satiety and digestive effects that increase parasympathetic control of digestion (Lee et al., 1994; Gutzwiller et al., 1999; Klok et al., 2007), they also have actions that are far-reaching and increase parasympathetic signaling broadly throughout the body. The actions beyond satiety that peptides like somatostatin, cholecystokinin, glucagon-like peptide 1, and vasoactive intestinal peptide have been well-examined, but not in …

Don’T Be Blind To The Diagnosis: An Intriguing Case Of Monocular Blindness, Kourtney Erickson Do, Kaitlyn L. Buzard Do, Daniel Tseytlin Do, Carolyn Casey Do, Eugene Alexandrin Md

Department of Medicine

No abstract provided.

Xpert® Mtb/Rif Assay On Formalin-Fixed Paraffin-Embedded Tissues In The Diagnosis Of Extrapulmonary Tuberculosis, Allan Njau, Samuel Gakinya, Shahin Sayed, Zahir Moloo

Pathology, East Africa

Background: Diagnosis of extrapulmonary tuberculosis continues to be a challenge due to the complexity of the causative organism and the wide array of pathologic features seen in this infection. Xpert MTB/RIF can be used on fresh or frozen tissue specimens for diagnosis of tuberculosis with good results. However, there is little data on its use with formalin-fixed paraffin-embedded (FFPE) tissues.

Objectives: The aim of this study was to demonstrate the potential utility of Xpert MTB/RIF and to compare its performance to Ziehl-Neelsen staining for the detection of Mycobacterium tuberculosis from FFPE tissues using histological features from haematoxylin and eosin staining …

Comparison Of Two Commercial Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry (Maldi-Tof Ms) Systems For Identification Of Nontuberculous Mycobacteria., Barbara A. Brown-Elliott, Thomas R. Fritsche, Brooke J. Olson, Sruthi Vasireddy, Ravikiran Vasireddy, Elena Iakhiaeva, Diana Alame, Richard J. Wallace, John A. Branda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Objectives: This multi-center study’s aim was to assess the performance of two commercially-available matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems in identifying a challenge collection of clinically-relevant nontuberculous mycobacteria (NTM).

Methods: NTM clinical isolates (N=244) belonging to 23 species/subspecies were identified by gene sequencing and analyzed using the Bruker Biotyper with Mycobacterial Library v5.0.0 and the bioMérieux VITEK MS with v3.0 database.

Results: Using the Bruker or bioMérieux systems, 92% or 95% of NTM strains, respectively, were identified at least to the complex/group level; 62% and 57%, respectively, were identified to the highest taxonomic level. Differentiation between members …

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C. Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Rabia Hussain, Najeeha Talat Iqbal

Department of Pathology and Laboratory Medicine

Background: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.
Methods and Findings: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

Incidence Rates Of Critical Low Glucoses (<40 Mg/Dl) By Poct Before And After New Policies For Treatment Of Clinically Significant Hypoglycemia (<54 Mg/Dl): A Comparison Between Two Hospitals, Lilah Evans, Douglas F. Stickle, Barbara Goldsmith

Department of Pathology, Anatomy, and Cell Biology Posters

Glucose <54 mg/dL was recently defined as Clinically Significant Hypoglycemia (CSH, American Diabetes Association, Standards of Medical Care in Diabetes, 2017). In January 2018, our hospitals instituted a callback policy for inpatient CSH from the central laboratory, and instituted a new nursing procedure for response to CSH. We examined whether the new policies had affected the incidence rate of low glucose critical values (CRITICAL, <40 mg/dL) among POCT glucose measurements. This was investigated for two hospitals within our system: A, a 950-bed academic medical center hospital, and B, a 200-bed community hospital.

Helicobacter Pylori Pathophysiology, Alisha Smith

Nursing Student Class Projects (Formerly MSN)

Abstract

This poster provides current research evidence on Helicobacter Pylori pathophysiology, treatment guidelines, and the potential etiology of associated disorders. The purpose is to provide a detailed overview of the functional changes within the intestinal cells caused by the microorganism. Furthermore, explaining of the mechanism and clinical manifestations of symptoms. The research focuses on risk factors, transmission, diagnostic evaluation, and the implications for nursing care. The best-available evidence offers concrete data examining the detrimental effects of the immune and inflammatory response stimulated by H. pylori. A description of the functional structures of H. pylori and its’ ability to survive. …

Antimicrobial Sensitivity Pattern, Demographic Findings And Risk Factors Amongst Meningitis And Non-Meningitis Invasive Streptococcus Pneumoniae At Aga Khan University Hospital Clinical Laboratory, Karachi, Pakistan, Seema Irfan, Joveria Farooqi, Afia Zafar, Haresh Kumar

Department of Pathology and Laboratory Medicine

Objective: To determine the resistance rate of penicillin and ceftriaxone amongst invasive meningitis and nonmeningitis isolates of streptococcus pneumoniae. Methods: The prospective cross-sectional study was conducted from January 2011 to March 2014 at the Clinical Microbiology Laboratory of Aga Khan University, Karachi, and comprised all invasive strains of streptococcus pneumoniae. Penicillin and ceftriaxone susceptibilities were performed and interpreted based on minimum inhibitory concentration breakpoints recommended by Clinical and Laboratory Standards Institute guidelines. Data was analysed using Stata 12.
Result: There were 163 strains isolated from sterile body fluids of 109 patients. Of the total, 46(28%) samples were meningitic while 117(72%) …

The Society Of Abdominal Radiology At 10 Years: Reflections, Status Report, And Look To The Future, Manju Ambelil, David M Saulino, Atilla Ertan, Andrew W Dupont, Mamoun Younes

Faculty, Staff and Student Publications

CONTEXT.—: Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV.

OBJECTIVES.—: To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies.

DESIGN.—: Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history.

RESULTS.—: Fifty-two cases (24% of all tested, …

Beyond Sequencing: Re-Visiting Annotations For Pjl As A Test Case, Waqasuddin Khan, Aisha Ghani, Muhammad Bilal Azmi, Safina Abdul Razzak

Department of Paediatrics and Child Health

Objectives: Current developments in sequencing techniques have enabled rapid and high-throughput generation of sequence data. however, there is a growing gap between the generation of raw sequencing data and the extraction of meaningful biological information. variant annotation is a crucial step in the analysis of genome sequencing data. incorrect or incomplete annotations can cause researchers to dilute interesting variants in a pool of false positives. we require consistent, accurate and reliable annotation of variants for making diagnostic and treatment decisions. current annotation depends on the set of transcripts, and software used can be managed, with sufficient care, in the research …