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ObjectiveWhile numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages.MethodsTwenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls.ResultsIntegrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched whereas all other parameters returned to baseline.ConclusionOur findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcome.

Introduction: The availability of a preventative vaccine, interferon, and nucleos(t)ide analogs have provided progress in the control of chronic hepatitis B (CHB). Despite this, it remains a major contributor to global morbidity and mortality. Developments in our understanding of the pathogenesis of CHB and the emergence of new therapies are paving the way, as we move toward HBV cure.Areas covered: We performed bibliographical searches of online databases to review the literature regarding conventional disease phases of CHB. We provide the latest evidence challenging the perception of the natural history of CHB, noting that previously considered quiescent disease phases may not represent benign disease states devoid of progression. We explore the use of potential novel immunological and viral tools which should enhance disease stratification and management decisions in the coming years. Finally, we discuss the timing of treatment and how this could be initiated earlier to improve treatment outcomes, preventing sequelae of chronic infection.Expert opinion: The treatment paradigm in CHB is set to change with multiple novel agents in early phase clinical trials with the aim of a functional cure. An improved understanding of disease pathogenesis and the timing of treatment will be critical to the success of new therapies.

Aim of these revised recommendations for the general management of Kawasaki disease is to encourage its prompter recognition and warrant the most appropriate therapy, based on ascertained scientific data, raising awareness of the complications related to misdiagnosis or delayed treatment. A set of 20 synthetic operative statements is herein provided, including the definition of Kawasaki disease, its protean presentations, clinical course and seminal treatment modalities of all disease phases. The application of these recommendations should improve prognosis of Kawasaki disease and prevent the progression to permanent vascular abnormalities, thereby diminishing morbidity and mortality.

We read with great interest the article entitled "HBV RNA profiles in chronic hepatitis B patients under different disease phases and anti-viral therapy" authored by Mak et al (1). In the reported study, the serum HBV RNA: DNA ratio was calculated to assess the reverse transcription efficiency of pregenomic RNA (pgRNA). Here, we would like to express our concerns on the rationale and interpretation of this specific assay.

BackgroundGovernments across the globe responded with different strategies to the COVID-19 pandemic. While some countries adapted draconic measures, which have been perceived controversial others pursued a strategy aiming for herd immunity. The latter is even more controversial and has been called unethical by the WHO Director-General. Inevitably, without proper control measure, viral diversity increases and multiple infectious exposures become common, when the pandemic reaches its maximum. This harbors not only a potential threat overseen by simplified theoretical arguments in support of herd immunity, but also deserves attention when assessing response measures to increasing numbers of infection.Methods and findingsWe extend the simulation model underlying the pandemic preparedness web interface CovidSim 1.1 (http://covidsim.eu/) to study the hypothetical effect of increased morbidity and mortality due to ‘multi infections’, either acquired at by successive infective contacts during the course of one infection or by a single infective contact with a multi-infected individual.The simulations are adjusted to reflect roughly the situation in the East Coast of the USA. We assume a phase of general contact reduction (‘lockdown’) at the beginning of the epidemic and additional case-isolation measures. We study the hypothetical effects of varying enhancements in morbidity and mortality, different likelihoods of multi-infected individuals to spread multi infections and different susceptibility to multi infectious in different disease phases. It is demonstrated that multi infections lead to a slight reduction in the number of infections, as these are more likely to get isolated due to their higher morbidity. However, the latter substantially increases the number of deaths. Furthermore, simulations indicate that a potential second lockdown can substantially decrease the epidemic peak, the number of multi-infections and deaths.ConclusionsEnhanced morbidity and mortality due to multiple disease exposure is a potential threat in the COVID-19 pandemic that deserves more attention. Particularly it underlines another facet questioning disease management strategies aiming for herd immunity.

Tyrosine kinase 2 (TYK2) is a widely expressed receptor-associated kinase that is involved in signaling by a variety of cytokines with important immune regulatory activities. Absence of TYK2 in mice results in impaired NK cell maturation and antitumor activity, although underlying mechanisms are largely unknown. Using conditional ablation of TYK2 in NK cells we show that TYK2 is required for IFN-γ production by NK cells in response to IL-12 and for an efficient immune defense against Listeria monocytogenes. Deletion of TYK2 in NK cells did not impact NK cell maturation and IFN-γ production upon NK cell activating receptor (actR) stimulation. Similarly, NK cell–mediated tumor surveillance was unimpaired upon deletion of TYK2 in NK cells only. In line with the previously reported maturation-associated Ifng promoter demethylation, the less mature phenotype of Tyk2−/− NK cells correlated with an increased CpG methylation at the Ifng locus. Treatment with the DNA hypomethylating agent 5-aza-2-deoxycytidine restored the ability of Tyk2−/− NK cells to produce IFN-γ upon actR but not upon IL-12 stimulation. NK cell maturation was dependent on the presence of TYK2 in dendritic cells and could be rescued in Tyk2-deficient mice by treatment with exogenous IL-15/IL-15Rα complexes. IL-15 treatment also rescued the in vitro cytotoxicity defect and the impaired actR-induced IFN-γ production of Tyk2−/− NK cells. Collectively, our findings provide the first evidence, to our knowledge, for a key role of TYK2 in the host environment in promoting NK cell maturation and antitumor activity.

Since the outbreak of COVID-19, global concern emerged inspiring scientists to dedicate more attention to this pandemic. The disease caused by a novel coronavirus requires urgent striking action to probe the disease phases and find a proper cure. In this regard, the necessity of brief and thorough explanations comes into view. In this study, we gathered useful information about the virology, pathogenesis, epidemiology, manifestations, diagnosis, and treatment with special consideration of pediatric patients. This review article helps medical caregivers to receive a quick and effective approach to deal with this disease in their practice.

Background Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with limited robust disease-modifying therapies presently available. While several treatments are aimed at improving health-related quality of life (HRQoL), longitudinal data on how QoL changes across the disease course are rare. Objectives To explore longitudinal changes in emotional well-being and HRQoL in ALS. Methods Of the 161 subjects initially recruited, 39 received 2 subsequent follow-up assessments at 6 and 12 months after baseline. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess physical impairment. HRQoL was assessed using the ALS Assessment Questionnaire (ALSAQ-40). The D50 disease progression model was applied to explore longitudinal changes in HRQoL. Results Patients were primarily in the early semi-stable and early progressive model-derived disease phases. Non-linear correlation analyses showed that the ALSAQ-40 summary index and emotional well-being subdomain behaved differently across disease phases, indicating that the response shift occurs early in disease. Both the ALSFRS-R and ALSAQ-40 significantly declined at 6- and 12-monthly follow-ups. Conclusion ALSAQ-40 summary index and emotional well-being change comparably over both actual time and model-derived phases, indicating that the D50 model enables pseudo-longitudinal interpretations of cross-sectional data in ALS.

Background: The excretion pathomechanisms of SARS-CoV-2 are actually unknown. No certain data exist about viral load in the different body compartments and fluids during the different disease phases. Material and Methods: Specific real-time reverse transcriptase–polymerase chain reaction targeting 3 SARS-CoV-e genes were used to detect the presence of the virus. Results: SARS-CoV-2 was detected in peritoneal fluid at a higher concentration than in respiratory tract. Conclusion: Detection of SARS-CoV-2 in peritoneal fluid has never been reported. The present article represents the very first positive result describing the presence of the virus in peritoneal fluid during an emergency surgical procedure in a COVID-19 sick patient. This article thus represents a warning for increasing the level of awareness and protection for surgeon especially in emergency surgical setting.

We read with great interest the article entitled "HBV RNA profiles in chronic hepatitis B patients under different disease phases and anti-viral therapy" authored by Mak et al(1). The authors proposed that the reverse transcription efficiency in HBeAg-positive patients was significantly higher than that in HBeAg-negative patients, based on the RNA: DNA ratio in the two groups of patients (0.79 vs. 0.53; p< 0.001). We had found that a higher ratio of serum HBV RNA to HBV DNA was inversely related with reverse transcription efficiency of HBV pgRNA(2), and HBeAg-positive patients had a lower reverse transcription efficiency of HBV pgRNA than HBeAg-negative patients did. We here suggest that the ratio of serum HBV DNA: (HBV DNA + HBV RNA) is more reliable to assess the reverse transcriptional efficiency of pgRNA. The medians of ratio in our cohort were 0.56 (n = 54), 0.56 (n = 23), 0.69 (n = 64) and 0.66 (n = 4), for patients with HBeAg-positive chronic infection, HBeAg-positive chronic hepatitis, HBeAg-negative chronic infection, and HBeAg-negative chronic hepatitis, respectively. Inconsistent with the report by Mak et al., our data showed that the reverse transcriptional efficiency was lower in HBeAg-positive patients than in HBeAg-negative patients (0.56 vs. 0.68; p< 0.001). A schematic diagram for illustrating the efficiencies of covalently closed circular DNA (cccDNA) transcription and reverse transcription of pgRNA are shown in Figure 1.

BACKGROUND Soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) play a role in immune regulation of chronic hepatitis B virus (HBV) infection. AIM To investigate the profiles of serum sPD-1 and sPD-L1 in chronic HBV-infected patients with different disease phases and after anti-viral treatment. METHODS A total of 99 chronic HBV-infected patients were enrolled and divided into HBeAg-positive chronic HBV infection (EPI) group, HBeAg-positive chronic hepatitis B (EPH) group, HBeAg-negative chronic hepatitis B (ENH) group and HBeAg-negative chronic HBV infection (ENI) group. Eleven healthy subjects were included as healthy controls (HCs). Thirty-two EPH patients received anti-viral treatment with nucleos(t)ide analogues and were followed up to 5 years. Serum sPD-1 and sPD-L1 levels were detected by Multiplex Immunoassays. RESULTS Serum sPD-1 and sPD-L1 levels of chronic HBV infected patients were significantly higher than that of HCs (P

We explore the emergence of persistent infection in two patches where the phases of disease progression of the individuals is given by the well known SIRS cycle modelling non-fatal communicable diseases. We find that a population structured into two patches with significantly different initial states, yields persistent infection, though interestingly, the infection does not persist in a homogeneous population having the same average initial composition as the average of the initial states of the two patches. This holds true for inter-patch links ranging from a single connection to connections across the entire inter-patch boundary. So a population with spatially uniform distribution of disease phases leads to disease extinction, while a population spatially separated into distinct patches aids the long-term persistence of disease. After transience, even very dissimilar patches settle down to the same average infected sub-population size. However the patterns of disease spreading in the patches remain discernibly dissimilar, with the evolution of the total number of infecteds in the two patches displaying distinct periodic wave forms, having markedly different amplitudes, though identical frequencies. We quantify the persistent infection through the size of the asymptotic infected set. We find that the number of inter-patch links does not affect the persistence in any significant manner. The most important feature determining persistence of infection is the disparity in the initial states of the patches, and it is clearly evident that persistence increases with increasing difference in the constitution of the patches. So we conclude that populations with very non-uniform distributions, where the individuals in different phases of disease are strongly compartmentalized spatially, lead to sustained persistence of disease in the entire population.

Background: Increasing evidences suggest that alterations in the gut microbiota may contribute to the pathogenesis and influence the clinical outcome of Rheumatoid arthritis (RA). Objectives: To characterize the gut microbiota composition in RA patients in different disease phases contingently to therapeutic regimens. Methods: Forty-four RA patients (7 naive to treatment, 13 MTX-IR and 24 in sustained clinical and ultrasound remission under conventional and bDMARD combination therapy, respectively) (age 55.2±11.4 years, 79.5% female and 59.1% positive for ACPA and/or RF) and 20 age/sex matched healthy controls (HC) were enrolled in the study. At study entry, RA specific data set were collected and dietary habits were recorded using the 14-items Mediterranean Diet Adherence Screener (MeDAS) questionnaire. DNA was extracted from stool samples of each patient, amplified and 16S rRNA gene V3–V4 region was sequenced using an Illumina MiSeqTM platform. For downstream sequence analysis, a combination of software packages QIIME (v1.9.1) and VSEARCH (v1.1) was used and a biological observation matrix (BIOM) at different taxonomic levels (from phylum to genus) was produced. The BIOM was analysed using the Web-based program MicrobiomeAnalyst. Statistical analyses were performed using the R phyloseq software package. Differences in the relative abundance of individual bacterial taxa between a priori defined groups were assessed by LEfSe analysis. Results: Microbiota composition analysis showed that RA patients had a decrease in the gut microbial species richness compared to HC (p 3.7) showed significant differences in α-diversity compared to RA patients in LDA or in sustained clinical and ultrasound remission (p=0.01) with a relative abundance of Haemophilus parainfluenzae in high disease activity patients (p Conclusion: Despite limited sample size, this study strengthen the concept of significant microbiota differences in RA, contingently with disease phases, compared to HC. The evaluation of microbiota composition in the patients follow-up according to response to therapies is ongoing. Disclosure of Interests: Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Francesco Cianci: None declared, Stefano Alivernini Speakers bureau: BMS, Giulia Menchinelli: None declared, Anna Laura Fedele: None declared, Barbara Tolusso: None declared, Brunella Posteraro: None declared, Maurizio Sanguinetti: None declared

9 páginas.-- L. Courtney Smith ... et al., The 13th Congress of the International Society of Developmental and Comparative Immunology took place in Murcia Spain from June 28 to July 3, 2015 at the Victor Villegas Auditorium and Convention Center. There were two or three parallel sessions during the Congress that covered a wide range of immunological topics and brought researchers together from around the world who work in different areas of immunology. The Congress included three plenary presentations, 12 oral sessions, two poster sessions, and a special symposium. Here we report on some of the talks and a few of the posters that were presented at the meeting, Funding from the US National Science Foundation (IOS-1461716) awarded to LCS and Louise Rollins-Smith (Vanderbilt University, USA) supported students and postdocs from laboratories in the US to attend the 13th Congress of ISDCI

Cardiovascular diseases (CVDs), especially the coronary arterial diseases (CADs), have become the main cause of death all around the world, attracting attentions from the whole society. Even though considerable progresses have been made for the treatment of CADs, many clinical challenges remain to be overcome. In particular, effective biomarkers for CADs need to be developed to facilitate the early diagnosis and thus early treatment of the disease. Recently, the dysregulation of microRNAs (miRNAs) has been found to be involved in the progression of multiple CADs, manifested as altered levels of miRNAs at different disease phases, suggesting that miRNAs may be capable of serving as promising biomarkers for CADs. Here, we attempt to evaluate the possibility of miRNAs as biomarkers for CADs and compare these markers with previously reported ones. In this review, we will summarize the basic concepts and advances for CADs and miRNAs, with a special emphasis on miRNAs in the progression of CADs.

Gastrointestinal (GI) malignancies (esophageal, gastric, pancreatic, intra- and extra-biliary ductal, hepatocellular, and colorectal cancers) are an important cause of cancer incidence and mortality in the US and globally. GI cancers account for 15.4% and 23.8% of incident cancers and cancer-related deaths respectively in the US alone. Although earlier diagnosis and treatment advances have improved outcomes for some GI malignancies, the need for improved therapies in all disease phases (adjuvant, neoadjuvant and advanced) is paramount. Utilization of monoclonal antibodies targeting against vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) has shown the success in selected colorectal carcinoma patients. More investigations of immunotherapy are on going in the treatment of GI malignances with different mechanisms and methods. In this article, we review data for established and evolving immunotherapy-related treatment options in GI malignancies.

Osteopontin (OPN) was shown to be involved in inflammatory and degenerative processes of the nervous system. In multiple sclerosis, the role of OPN has been studied in the inflammatory phase, where it was shown that the protein levels increase during disease relapses. Moreover, it was shown that subjects who carry a genotype associated with decreased protein levels tend to display a benign course. Taken altogether, these findings suggest that OPN may play a detrimental role in multiple sclerosis, at least in the inflammatory phase. In common neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, OPN seems to act as a double-edged sword triggering neuronal toxicity and death in some contexts and functioning as a neuroprotectant in others. The involvement of OPN in several biological pathways and networks calls for more extensive research in order to unravel its role in the different disease phases and its potential as a therapeutic target.

Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients' classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one. We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters. Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT. These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT.

and MMSE was found in the occipital lobes for the combined AD+MCI+HC (Pearson 0.82, p1⁄40.0465) and AD (Pearson 0.99, p1⁄40.01) groups. Conclusions:Based on relatively small number of studies, no apparent relationship between change on brain amyloid burden and cognition in AD was found. In contrast, the negative correlation seen in MCI suggests that PiB PET changes may be a useful biomarker in earlier disease phases. The significant finding in the correlation between changes in amyloid deposition in the occipital lobe and MMSE warrants further study. Limitation included the paucity of studies having longitudinal data on both brain amyloid burden and clinical measures and heterogeneity amongst studies.

Purpose: Although the translocation t(4;14) is supposed to be a primary event in multiple myeloma, we have been surprised to observe that in large relapse series of patients, the t(4;14) can be observed only in subpopulations of plasma cells, in contrast to what is seen at diagnosis. This observation raised the question of possible subclones harboring the translocation that would be observable only at the time of relapse. Experimental Design: To address this issue, we analyzed by FISH a cohort of 306 patients for whom we had at least two samples obtained at different disease phases. Results: We observed a “gain” of the t(4;14) in 14 patients, and conversely, a “loss” of the translocation in 11 patients. Two hypotheses were raised: either an acquisition of the translocation during evolution or the existence of small t(4;14)-positive subclones at the time of diagnosis. To address this question, we had the opportunity to analyze two patients at the time of diagnosis by RT-PCR (reverse transcription-polymerase chain reaction) to look for the chimeric Eμ-MMSET transcript, and one patient positive at diagnosis, but negative at relapse. The samples were positive, supporting the second hypothesis. Furthermore, the IGH sequences of two patients who “lose” the t(4;14) were identical at diagnosis and relapse, confirming the existence of a common ancestral clone. Conclusion: Thus, the conclusion of this study is that the t(4;14) is not a primary event in multiple myeloma and that it can be present in silent subclones at diagnosis, but also at relapse. Clin Cancer Res; 19(17); 4634–7. ©2013 AACR.

The ultimate goal of periodontal therapy is the regeneration of the tissues destroyed as a result of periodontal disease. Conventional surgical approaches continue to put forward time-tested and consistent methods to access and attain improved periodontal architecture. However, these techniques offer only limited potential towards recovering tissues destroyed during earlier disease phases. There is limited data available for the clinical effectiveness of other biologically active molecules, such as growth factors and platelet concentrates, and although promising results have been reported, further clinical trials are required in order to confirm their effectiveness. Current active areas of research are centered on tissue engineering and gene therapy strategies which may result in more predictable regenerative outcomes in the future.

A symptomless phase of Alternaria macrospora leaf blight that occurs in commercial cultivation of cotton between visible disease outbreaks was studied to determine its cause and effect. Most plants between the two outbreaks of leaf blight epidemics in the field were infected but symptomless; yet during the outbreaks the number of infected symptomless plants was minimal. Drought, high temperature, low humidity, and high salinity increased plant resistance to leaf blight by decreasing visible symptoms and causing symptomless infections. Symptomless plants provided inoculum to infect and produce a visible disease in healthy plants when favorable conditions for disease development resumed. Plant age had minimal influence on symptom-lessness, and sunlight exposure had none. Defoliation was related to the density of spots on leaves and to the virulence of the strain. Polyphenoloxidase activity and phenol accumulation were similar in both disease phases. Plants having visible symptoms produced more spores, but spores from symptomless plants were detached more easily by air currents. Symptom-lessness apparently is a common manifestation of alternaria leaf blight of cotton. It is probably influenced by agroenvironmental parameters that induce the two phases of disease expression. Key words: Alternaria macrospora, cotton leaf blight, leaf spot of cotton, symptomless infections.

Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longi- tudinal, questionnaire-based study comparing an "entry" inquiry addressed to patients before an entry thermal cycle, and a "return" inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermato- logic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year ("index year") were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to "non-spa" rehabilita- tion therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with rando- mised controlled studies.

Infectious diseases are continuing to threaten humankind. While some diseases have been controlled, new diseases are constantly appearing. Others are now reappearing in forms that are resistant to drug treatments. A capacity for continual re-adaptation furnishes pathogens with the power to escape our control efforts through evolution. This makes it imperative to understand the complex selection pressures that are shaping and reshaping diseases. Modern models of evolutionary epidemiology provide powerful tools for creating, expressing, and testing such understanding. Bringing together international leaders in the field, this volume offers a panoramic tour of topical developments in understanding the mechanisms of disease evolution. The volume's first part lucidates the general concepts underlying models of disease evolution. Methodological challenges addressed include those posed by spatial structure, stochastic dynamics, disease phases and classes, single- and multi-drug resistance, the heterogeneity of host populations and tissues, and the intricate coupling of disease evolution with between-host and within-host dynamics. The book's second part shows how these methods are utilized for investigating the dynamics and evolution of specific diseases, including HIV/AIDS, tuberculosis, SARS, malaria, and human rhinovirus infections. This volume is particularly suited for introducing young scientists and established researchers with backgrounds in mathematics, computer science, or biology to the current techniques and challenges of mathematical evolutionary epidemiology.

The aim of the present study is to explore the relationship between depression and psychotic symptoms of schizophrenia over the course of illness. Sixty-eight patients meeting DSM-IV criteria for schizophrenia were enrolled, 27 in an acute episode, 41 when stable. Assessments were performed using the Calgary Depression Scale for Schizophrenia (CDSS) for depression and the Positive and Negative Syndrome Scale (PANSS) for psychotic symptoms. When considering patients in an acute episode (52% depressed), the CDSS score was correlated only with the PANSS positive sub-scale score. For patients in the stable period (38% depressed), the CDSS score was correlated with positive as well as negative and general psychopathology sub-scale scores. Hence, the relationship between depression and other symptoms of schizophrenia appear to differ during different stages of illness.

In this chapter, we will adopt a more finely grained look at the HIV scenario and those psychological. issues that are evoked by the various HIV-related threats. The point of departure is the qualitative analysis of Dr. Schonnesson’s psychotherapeutic notes of the 38 gay men with HIV. The most salient HIV-related psychological issues are portrayed in the light of the constructs of persecution, death anxiety, existential death anxiety and awareness, loss and mourning, control, despair versus hope, and psychological defenses. Table 2 illustrates that different psychological. issues and the defenses occur with different intensity over the four disease phases (asymptomatic, mild symptomatic, severe symptomatic, and terminal).

3625 Background: Three new biologics have been approved to treat metastatic colorectal cancer (mCRC) since 2004. This study describes the medical care and its costs among patients diagnosed with mC...

We aimed to study the level of CNPase activity in the cerebrospinal fluid of patients with demyelinating diseases and other neurological diseases, particularly multiple sclerosis, with reference to CSF myelin basic protein content. CNPase activity was measured paper chromatographically using radioactive 2',3'-cAMP as a substrate. Myelin basic protein content was measured with a radioimmunoassay. The mean level of CNPase activity was significantly higher for multiple sclerosis than for nonneurological controls. Dividing the disease phases of multiple sclerosis into the three periods, the CNPase activity was found to be significantly elevated in the worsening period and reduced in the improving period and the inactive period. The level of CNPase activity in the cerebrospinal fluid of multiple sclerosis coincided with the clinical activity of the disease. The level of CNPase activity correlated well (r = 0.84) with the level of myelin basic protein content in cerebrospinal fluid. The ratio for CNPase activity and myelin basic protein content in cerebrospinal fluid was almost the same as that in human central nerve myelin. We concluded that CNPase activity in the cerebrospinal fluid from neurological patients is an indicator of destruction of myelin in the central nervous system, and the measurement of CNPase activity in the cerebrospinal fluid of multiple sclerosis could be useful in the clinical management.

does not appear. First page follows. Losses from obscure causes on certain California turkey ranges, where green feed is limited during much of the growing season, suggested the need for studies on vitamin-A deficiency in turkeys. The experiments reported herein were outlined to determine the possible relation of A-avitaminosis4 to turkey mortality and to obtain information concerning the effect on turkeys of various vitamin-A levels. A-avitaminosis in chickens has been fully described by Beach(1), Emmett and Peacock?(3), Seifried(10), Elvehjem and Neu(4), and many other investigators, so that the pathological changes in chickens are well established. Chicks were included in one experiment as a control on the methods used and as a basis for comparing A-avitaminosis in the two species. Scott and Hughes(9), using yellow corn as the source of vitamin A, showed that turkeys required more vitamin A than did chickens. This paper is concerned chiefly with the disease phases of the problem. Because published data on the vitamin-A requirements of turkeys are limited, the results on the comparative value of dehydrated alfalfa-leaf meal for turkeys and chickens are also included. Certain vitamin-A liver storage data collected in connection with the experiments have already been published by Guilbert and Hinshaw.(6)

MiR-155/miR-150 network regulates progression through the disease phases of chronic lymphocytic leukemia