BACKGROUND:The Chikungunya (CHIK) virus was recently reported by the CDC to have spread to the United States. We report an early documented case of CHIK from the state of Pennsylvania after a patient recently returned from Haiti in June of 2014. METHODS:A 39-year-old man presented to the emergency department complaining of fever, fatigue, polyarthralgias and a diffuse rash for two days. Four days before, he returned from a mission trip to Haiti and reported that four of his accompanying friends had also become ill. A CHIK antibody titer was obtained and it was found to be positive. During his hospital stay, he responded well to supportive care, including anti-inflammatories, intravenous hydration and anti-emetics. RESULTS:His condition improved within two days and he was ultimately discharged home. CONCLUSIONS:Manifestations of CHIK can be similar to Dengue fever, which is transmitted by the same species of mosquito, and occasionally as a co-infection. Clinicians should include Chikungunya virus in their differential diagnosis of patients who present with fever, polyarthralgia and rash with a recent history of travel to endemic areas, including those within the United States.

BACKGROUND: Chronic aortic regurgitation (AR) patients demonstrate left ventricular (LV) remodeling with increased LV mass and volume but may have a preserved LV ejection fraction (EF). We hypothesize that in chronic AR, global longitudinal systolic and diastolic function will be reduced despite a preserved LV EF. METHODS: We studied with Doppler echocardiography 27 normal subjects, 87 patients with chronic AR with a LV EF > 50% (AR + PEF), 66 patients with an EF < 50% [AR + reduced LV ejection fraction (REF)] and 82 patients with hypertensive heart disease. LV volume, transmitral spectral and tissue Doppler were obtained. Myocardial velocities and their timing and longitudinal strain of the proximal and mid wall of each of the 3 apical views were obtained. RESULTS: As compared to normals, global longitudinal strain was reduced in AR + PEF (13.8 +/- 4.0%) and AR + REF (11.4 +/- 4.7%) vs. normals (18.4 +/- 3.6%, both p < 0.001). As an additional comparison group for AR + PEF, global longitudinal strain was reduced as compared to patients with hypertensive heart disease (p = 0.032). The average peak diastolic annular velocity (e') was decreased in AR + PEF (6.9 +/- 3.3 cm/s vs. 13.4 +/- 2.6 cm/s, p < 0.001) and AR + REF (4.8 +/- 2.1 cm/s, p < 0.001). Peak rapid filling velocity/e' (E/e') was increased in both AR + PEF (14.4 +/- 6.2 vs. 6.2 +/- 1.3, p < 0.001) and AR + REF (18.8 +/- 6.4, p < 0.001 vs. normals). Independent correlates of global longitudinal strain (r = 0.6416, p < 0.001) included EF (p < 0.0001), E/e' (p < 0.0001), and tricuspid regurgitation velocity (p = 0.0176). CONCLUSION: With chronic AR, there is impaired longitudinal function despite preserved EF. Moreover, global longitudinal strain was well correlated with noninvasive estimated LV filling pressures and pulmonary systolic arterial pressures.
Aortic Valve Insufficiency* ; Arterial Pressure ; Echocardiography, Doppler ; Heart Diseases ; Humans ; Tricuspid Valve Insufficiency ; Ventricular Function, Left ; Ventricular Remodeling

Antineoplastic Agents ; therapeutic use ; Antineoplastic Protocols ; standards ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Guidelines as Topic ; Humans ; Lung Neoplasms ; drug therapy ; Neoplasm Staging ; Societies, Medical ; United States

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence ; Antigens, CD ; chemistry ; genetics ; pharmacology ; Autoimmunity ; Biological Assay ; Cell Line ; Cytotoxicity, Immunologic ; genetics ; immunology ; Dose-Response Relationship, Immunologic ; Humans ; Immunoglobulins ; immunology ; metabolism ; Immunologic Factors ; chemistry ; genetics ; pharmacology ; Kinetics ; Leukocyte Immunoglobulin-like Receptor B1 ; Lymphocyte Activation ; genetics ; immunology ; Major Histocompatibility Complex ; genetics ; immunology ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mutagenesis, Site-Directed ; Peptide Library ; Polyethylene Glycols ; Protein Binding ; genetics ; immunology ; Receptors, Immunologic ; chemistry ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

The National Cancer Institute (NCI) Division of Cancer Prevention (DCP) convened the “Translational Advances in Cancer Prevention Agent Development (TACPAD) Workshop on Immunomodulatory Agents” as a virtual 2-day workshop on September 13 to 14, 2021. The main goals of this workshop were to foster the exchange of ideas and potentially new collaborative interactions among leading cancer immunoprevention researchers from basic and clinical research and highlight new and emerging trends in immunoprevention. The workshop included an overview of the mechanistic classes of immunomodulatory agents and three sessions covering the gamut from preclinical to clinical studies. The workshop convened individuals working in immunology and cancer prevention to discuss trends in discovery and development of immunomodulatory agents individually and in combination with other chemopreventive agents or vaccines.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

Background and Objective: Colorectal cancer (CRC) has the third highest incidence in the Philippines. Currently, there is a paucity in literature that is focused on the knowledge, attitudes, and perceptions of Filipinos regarding CRC screening. This is the first study in the Philippines that describes this. Methods: This is a cross-sectional study that validated a 52-item Filipino questionnaire on the knowledge on colorectal cancer, willingness to undergo CRC screening, and perceived benefits and barriers to fecal occult blood test (FOBT) and colonoscopy. The study enrolled household heads more than 20 years of age residing in both urban and rural communities in the Philippines. Results: The UP-PGH CRC KAP (University of the Philippines – Philippine General Hospital Colorectal Cancer Knowledge, Attitudes, and Practices) and Rawl Questionnaire’s validity and internal consistency were established in a pilot study of 30 respondents. A total of 288 respondents were then enrolled to the main study group with a median age of 54.0. Knowledge scores for prognosis and utility of CRC screening were modest (6.3/12 and 8.4/20, respectively). Perceived benefit scores to FOBT and colonoscopy were high (9.9/12 and 13.9/16, respectively).Median scores to barriers to FOBT and colonoscopy were intermediate (22.5/36 and 35.8/60, respectively). Notably, a vast majority (86.1%) were willing to participate in CRC screening programs initiated by the government, and 46.9% agreed to undergo screening tests even as out-of-pocket expense. Conclusion The UP-PGH CRC KAP Questionnaire as well as the Filipino translation of the Rawl Questionnaire are reliable and valid tools in extensively assessing the knowledge of Filipinos on CRC and willingness to undergo screening, as well as the benefits of and barriers to FOBT and colonoscopy. Knowledge scores were modest suggesting that directed educational campaigns and awareness programs can aid in increasing awareness about CRC and its screening. Household income and highest educational attainment were significantly positively correlated with knowledge scores, and perceived benefits of and barriers to CRC screening. Scores were generally comparable between urban and rural communities.
Knowledge ; Attitudes