Model-guided therapy for hepatocellular carcinoma: A role for information technology in predictive, preventive and personalized medicine

Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM

Huomioita poronhoidosta Suonikylässä 1800-luvulla

Note on the reindeer breeding of the Suenjel Skolt Lapps in the 19th century (englanti

Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy

The thiol isomerase, protein disulfide isomerase (PDI), plays important intracellular roles during protein folding, maintaining cellular function and viability. Recent studies suggest novel roles for extracellular cell surface PDI in enhancing cellular activation and promoting their function. Moreover, a number of food-derived substances have been shown to regulate cellular PDI activity and alter disease progression. We hypothesized that PDI may have similar roles during mast cell-mediated allergic responses and examined its effects on IgE-induced mast cell activity during cell culture and food allergy. Mast cells were activated via IgE and antigen and the effects of PDI inhibition on mast cell activation were assessed. The effects of PDI blockade in vivo were examined by treating mice with the irreversible PDI inhibitor, PACMA-31, in an ovalbumin-induced model of food allergy. The role of dietary PDI modulators was investigated using various dietary compounds including curcumin and quercetin-3-rutinoside (rutin). PDI expression was observed on resting mast cell surfaces, intracellularly, and in the intestines of allergic mice. Furthermore, enhanced secretion of extracellular PDI was observed on mast cell membranes during IgE and antigen activation. Insulin turbidimetric assays demonstrated that curcumin is a potent PDI inhibitor and pre-treatment of mast cells with curcumin or established PDI inhibitors such as bacitracin, rutin or PACMA-31, resulted in the suppression of IgE-mediated activation and the secretion of various cytokines. This was accompanied by decreased mast cell proliferation, FcεRI expression, and mast cell degranulation. Similarly, treatment of allergic BALB/c mice with PACMA-31 attenuated the development of food allergy resulting in decreased allergic diarrhea, mast cell activation, and fewer intestinal mast cells. The production of TH2-specific cytokines was also suppressed. Our observations suggest that PDI catalytic activity is essential in the regulation of mast cell activation, and that its blockade may benefit patients with allergic inflammation. Keywords: PDI; food allergy; mast cells; propynoic acid carbamoyl methyl amide; protein disulfide isomerase

Skolt Sami Reindeer Ownership: Structural Changes as the Triggers of a New Era

This article combines views of economic and legal anthropology in its exploration of Skolt Sami reindeer ownership. The Skolt Sami culture and its key form of livelihood, reindeer herding, have adjusted to the modern industrial society fairly well so far, but it is getting more obvious that the aims and practices of a modern industrial economy endanger the continuity of Skolt Sami reindeer ownership. This article present accounts of Skolt Sami reindeer ownership in different time points, which indicates that we are witnessing a historical turning point in Skolt Sami culture. The centralization of reindeer ownership changes Skolt Sami culture in many ways, for example, by shrinking the traditional way of combining different forms of livelihood as a means of survival. The vulnerability of Skolt Sami reindeer herding has increased as a result of the changes. Therefore, this article develops questions and reasoning that could make it possible to increase the protection of Skolt Sami reindeer ownership. Anthropological researchers have stressed the importance of the social cultural whole of the community next to the economic features of culture. The emphasis on cultural continuity places sustainability before profitability in economic aims of reindeer husbandry

Aberrant Ulnar Artery and Ulnar Artery Thrombosis with Nerve Entrapment: A Case Report

Introduction: Vascular compromise causes hand pain, and physical examination requires to differentiate vascular causes from isolated ulnar nerve compression. Diagnostic studies visualize vascular abnormalities such as CT scans, MRA scans, and AV fistulograms. Ulnar artery aneurysms are quite rare discoveries, related to repetitive trauma, vasculitis, anatomic abnormalities, or infections. It is essential to repair any aneurysm when flow impediment causes significant symptoms. Blunt injury to the ulnar artery and superficial palmar arch damages the arterial wall and forms an aneurysm. The sensory branch of the ulnar nerve becomes compressed. Treatment here is to resect the thrombotic segment to relieve the compression. It is interesting to note, in this particular case, that a high origin and superficial ulnar artery had coursed along the forearm and entered along the ulnar side of the hand. The presence of such anatomic variations are essential in medical practice.Case presentation: A 73-year-old Haitian female was admitted to the hospital with complaints of numbness and weakness along the right forearm and wrist. According to the patient’s daughter, she has experienced these symptoms for at least two years’ duration after minimal trauma to her right hand. Upon physical examination of the right wrist, a 3-cm palpable, pulsatile ulnar mass was found. The Allen’s test showed no significant abnormalities, but the Tinel’s test and pinprick examination were diminished. An AV fistulogram was scheduled the same day and a repair followed soon after. IV contrast dye demonstrated an aneurysm of the ulnar artery, along with an adjacent superficial branch. The decision was made to resect the aneurysm and allow the superficial ulnar artery remain patent for continuous blood supply to the 4th and 5th digits of her right hand. She was discharged the same day and to follow up in the vascular clinic a week later.Conclusion: This particular case describes a couple important disciplines that establishes further insight about the human anatomy, pathophysiology and vascular surgical management. First, hypothenar hammer syndrome has been illustrated in a patient without any history of vasculitis, infections, or congenital anatomic abnormalities. A diagnostic and therapeutic approach is necessary to relieve ulnar nerve entrapment. Second, this particular patient underwent a simple repair but it was found that an aberrant ulnar artery was discovered, which coursed adjacent and superficial to the aneurysm. It is important to establish an early diagnosis prior to any surgical procedures. Intraoperatively, proper identification to isolate and establish a continuous blood flow is essential. Knowledge of such variations allows for improved care in the fields of radiology, angiography, surgery and the medical sciences.</p

Concurrent central nervous system infective pathology in a severely immunocompromised patient

To our knowledge and literature search, concurrent cryptococcal meningitis and neurosyphilis in a patient have rarely been reported. Here, we report a 37-year-old male with HIV infection presented with headache and dizziness for 5 days along with memory difficulty and personality changes for about 1 week. During the hospital stay, cryptococcal meningitis was confirmed with positive cerebral spinal fluid (CSF) cryptococcal antigen titer (1:320) and positive CSF culture. Diagnosis of neurosyphilis was made based upon CSF white blood cell count of 85 cells/mL, with CSF total protein of 87 mg/dL, reactive CSF treponemal antibody, and fluorescent treponemal antibody. The patient was treated with amphotericin B, flucytosine, fluconazole, and benzathine penicillin G, and the patient was recovered and discharged. HIV patients are at high risk of developing severe infections of the central nervous system. Awareness should be made not only to single infection but also for dual pathology for a better and life-saving management