Facilitating text reading in posterior cortical atrophy

Objective We report 1) the first quantitative investigation of text reading in posterior cortical atrophy (PCA); and 2) the effects of two novel software-based reading aids that result in dramatic improvements in PCA patients' reading ability. Methods Reading performance, eye movements and fixations were assessed in PCA and typical Alzheimer’s disease (tAD) patients and healthy controls (Experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (Experiment 2). Results PCA patients’ mean reading accuracy was significantly worse (57%) compared to both tAD patients (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of PCA patients’ fixations and eye movements under the single-word reading aid. Conclusions These findings demonstrate how neurological characterisation of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence This study provides Class III evidence that for patients with posterior cortical atrophy, two software-based reading aids (single-word and double-word) improve reading accuracy

Sarcomatoid Carcinoma of Lung Presenting as Localized Bronchiectasis: A Case Report and Review of Literature

© 2018 The Authors Sarcomatoid carcinoma (SC) of the lung is a rare and aggressive biphasic lung tumor with a 5-year survival of 20%. Early detection and treatment is the only way to improve outcomes in patients with SC of the lung. We present a case of primary SC identified early based on high suspicion. A 56-year-old female with a history of chronic obstructive pulmonary disease (COPD) presented with hemoptysis and exertional dyspnea. Chest X-ray revealed right upper lobe (RUL) opacity and patient was started on antibiotics for pneumonia. Due to the persistence of hemoptysis, a computed tomography scan was performed which showed RUL bronchiectasis with scattered nodular opacities suggestive of an infectious process. The patient underwent bronchoscopy which revealed a pedunculated mass in the RUL biopsy of which was consistent with poorly differentiated SC. Positron-emission tomography scan revealed Flourdeoxyglucose-avid right peri-hilar mass and another nodule in the RUL. The patient was not a surgical candidate because of severe COPD and was started on chemoradiation therapy. SC of the lung can have various presentations and is usually detected at a later stage and hence, difficult to treat. Our case highlights the importance of critical thinking and prompt diagnostic evaluation in high-risk patients with localized bronchiectasis even without an obvious lung mass on imaging

Septic emboli of the lung due to Fusobacterium necrophorum, a case of Lemierre\u27s syndrome

© 2019 The Authors Fusobacterium necrophorum plays a causal role in a rare and life-threatening condition, Lemierre\u27s syndrome. It is characterized by infection involving the posterior compartment of the lateral pharyngeal space complicated by septic suppurative thrombophlebitis of the internal jugular vein with F. necrophorum bacteremia and metastatic abscesses, primarily to the lung and pulmonary septic emboli. Herein, we present a very rare case of oropharyngeal infection complicated by Lemierre\u27s syndrome with characteristic septic emboli to the lungs presenting as sore throat in a previously healthy patient. A 23-year-old woman presented with sore throat and was found to be in sepsis and acute kidney injury. She was found to have septic emboli in lung and Streptococcus anginosus and F. necrophorum in blood. She was diagnosed with Lemierre\u27s syndrome and successfully treated with antibiotics. Lemierre\u27s syndrome should be included in the differential diagnosis in young patients who deteriorate in the setting of a sore throat. If the suspicion is high, throat swabs from young patients with nonstreptococcal group A tonsillitis should be cultured anaerobically on selective medium to detect the presence of F. necrophorum. While clinicians of the infectious disease team may be familiar with this condition other departments including internal medicine and critical care team may less so. Unless clinicians are aware of this syndrome, diagnosis and treatment can be delayed leading to higher morbidity and mortality

Giant cell carcinoma of the lung successfully treated with surgical resection and adjuvant vinorelbine and cisplatin

© 2018 Giant Cell Carcinoma of the lung, a subtype of Sarcomatoid lung cancer is a poorly differentiated Non-Small-Cell Lung Cancer. GCCL has exceptionally aggressive characteristics, and its prognosis is much poorer than any other NSCLCs. Herein, we present a rare case of Giant Cell Carcinoma of lung treated successfully with surgical resection and adjuvant vinorelbine and cisplatin. A 48-year-old African American man with a history of smoking and chronic obstructive pulmonary disease was admitted to the hospital for chief complaints of shortness of breath. He was found to have a 3.5 cm × 3.3 cm x 2.8 cm cavitary right upper lobe mass which turned out to be poorly differentiated Giant Cell Carcinoma with extensive necrosis and deemed similar to stage 1b non-small cell lung cancer. He was successfully treated with right upper lobectomy and adjuvant chemotherapy with vinorelbine and cisplatin. He was followed for seven years with no evidence of recurrent disease. Giant Cell Carcinoma\u27s existing literature is limited, and hence our case is reportable. Our case is unique because of the better outcome which we believe might be the result of early detection and treatment with surgical resection along with adjuvant chemotherapy. More studies are needed to deeply understand the need for adjuvant chemotherapy in stage 1 b GCCL, and proper guidelines are required for the indications of adjuvant chemotherapy in Stage 1b GCCL

Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of cancer death in the United States. Surgery offers the only chance for cure. However, less than twenty percent of patients are considered operative candidates at the time of diagnosis. A common reason for being classified as unresectable is advanced loco-regional disease.</p> <p>A review of the literature indicates that almost nine hundred patients with pancreatic cancer have received regional chemotherapy in the last 15 years. Phase I studies have shown regional administration of chemotherapy to be safe. The average reported response rate was approximately 26%. The average 1-year survival was 39%, with an average median survival of 9 months. Of the patients that experienced a radiographic response to therapy, 78 (78/277, 28%) patients underwent exploratory surgery following regional chemotherapy administration; thirty-two (41%) of those patients were amenable to pancreatectomy. None of the studies performed analyses to identify factors predicting response to regional chemotherapy.</p> <p>Progressive surgical techniques combined with current neoadjuvant chemoradiotherapy strategies have already yielded emerging support for a multimodality approach to treatment of advanced pancreatic cancer.</p> <p>Intravenous gemcitabine is the current standard treatment of pancreatic cancer. However, >90% of the drug is secreted unchanged affecting toxicity but not the cancer per se. Gemcitabine is converted inside the cell into its active drug form in a rate limiting reaction. We hypothesize that neoadjuvant regional chemotherapy with continuous infusion of gemcitabine will be well tolerated and may improve resectability rates in cases of locally advanced pancreatic cancer.</p> <p>Design</p> <p>This is a phase I study designed to evaluate the feasibility and toxicity of super-selective intra-arterial administration of gemcitabine in patients with locally advanced, unresectable pancreatic adenocarcinoma. Patients considered unresectable due to locally advanced pancreatic cancer will receive super-selective arterial infusion of gemcitabine over 24 hours via subcutaneous indwelling port. Three to six patients will be enrolled per dose cohort, with seven cohorts, plus an additional six patients at the maximum tolerated dose; accrual is expected to last 36 months. Secondary objectives will include the determination of progression free and overall survival, as well as the conversion rate from unresectable to potentially resectable pancreatic cancer.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01294358">NCT01294358</a></p

Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection

Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity

Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty

Langmuir Monolayer as a Tool toward Visualization of a Specific DNA-Protein Complex

Immobilization and imaging of protein molecules and protein-DNAcomplexes on a Langmuir-Blodgett (LB) substrate have been explored here. We have prepared a nickel-arachidate (NiA) monolayer and characterized it through pressure-area isotherm on a LB trough. Recombinant RNA polymerase from Escherichia coli, where the largest subunit was replaced with the same gene having a series of histidine amino acids at the C-terminus end of the protein, was immobilized over the Ni-arachidate monolayer through a Ni(II)-histidine interaction. A single molecule of RNA polymerase could be seen through intermittent-contact atomic force microscopy (AFM). Under the condition of the formation of the LB monolayer, the enzyme molecules were arrayed and transcriptionally active. Interestingly, they could pick up sequence specificDNAmolecules from the subphase in an oriented fashion.Onthe other hand, preformed RNA polymerase Ni(II)-arachidate monolayers bound DNA haphazardly when no surface pressure was employed

Langmuir Monolayer as a Tool toward Visualization of a Specific DNA-Protein Complex

Immobilization and imaging of protein molecules and protein-DNAcomplexes on a Langmuir-Blodgett (LB) substrate have been explored here. We have prepared a nickel-arachidate (NiA) monolayer and characterized it through pressure-area isotherm on a LB trough. Recombinant RNA polymerase from Escherichia coli, where the largest subunit was replaced with the same gene having a series of histidine amino acids at the C-terminus end of the protein, was immobilized over the Ni-arachidate monolayer through a Ni(II)-histidine interaction. A single molecule of RNA polymerase could be seen through intermittent-contact atomic force microscopy (AFM). Under the condition of the formation of the LB monolayer, the enzyme molecules were arrayed and transcriptionally active. Interestingly, they could pick up sequence specificDNAmolecules from the subphase in an oriented fashion.Onthe other hand, preformed RNA polymerase Ni(II)-arachidate monolayers bound DNA haphazardly when no surface pressure was employed