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PubMed2026

The bioinformatics approach to identifying pathogenic variants for colorectal cancer (CRC).

Colorectal cancer (CRC) is the third most prevalent cancer globally, accounting for 9.6% of newly diagnosed cases and 9.3% of cancer-related deaths. It develops from the uncontrolled proliferation of glandular cells in the colon and rectum and is categorized into three primary types: sporadic, hereditary, and colitis-associated. While genetic susceptibility is a key factor in CRC pathogenesis, identifying high-impact pathogenic variants remains a significant challenge. This study integrates bioinformatics and population genetics approaches to identify CRC-associated single-nucleotide polymorphisms (SNPs) with potential clinical significance. CRC-associated SNPs were extracted from the Genome-Wide Association Studies (GWAS) Catalog, functionally annotated via HaploReg, and validated via Ensembl. In addition, expression quantitative trait locus (eQTL) data from the GTEx database were used to assess the effects of these variants on gene expression across human tissues. Our analysis identified three high-priority SNPs (rs9379084, rs3184504, and rs11557154) associated with the RREB1, ATXN2, SH2B3, and DCAF12 genes, which exhibited marked allele frequency differences among populations. These findings suggest potential biomarkers for CRC risk assessment and highlight the importance of genetic screening across diverse populations.

Bioinformatics↗

PubMed1993

Contaminated weaning food: a major risk factor for diarrhoea and associated malnutrition.

Infections and the malnutrition associated with them are responsible for a significant proportion of the 13 million deaths among infants and children under 5 years of age worldwide each year. After respiratory infections, diarrhoeal diseases are the commonest illnesses and have the greatest negative impact upon the growth of infants and young children. The causes of diarrhoeal diseases have traditionally been ascribed to water supply and sanitation. In attempts to prevent such diseases, efforts by governments and nongovernmental organizations have been focused on and sometimes limited to improving water supply and sanitation as well as promoting and protecting breast-feeding. Based on studies reported in the literature, this review article demonstrates that weaning foods prepared under unhygienic conditions are frequently heavily contaminated with pathogens and thus are a major factor in the cause of diarrhoeal diseases and associated malnutrition. In the light of the evidence presented, it appears that current efforts are not sufficient to prevent diarrhoeal diseases: education of mothers in food safety principles, particularly weaning food, must also receive high priority. Educational programmes based on the hazard-analysis-critical-control-point approach, taking into consideration also sociocultural factors, should be integrated into all national infant feeding or food and nutrition programmes.

Adult↗

PubMed2004

New tools for antigen delivery to the MHC class I pathway.

At the beginning of this new millennium, pathogens and cancer remain the leading causes of death worldwide. The development of vaccines to prevent diseases for which no vaccine currently exists, such as AIDS or malaria, or to treat chronic infections or cancers, as well as the improvement of efficacy and safety of existing vaccines, remains a high priority. In most cases, the development of such vaccines requires strategies capable of stimulating CD8(+) cytotoxic T lymphocytes (CTLs) and thus, to deliver antigen to MHC class I molecules. There exists several different pathways for loading antigenic peptides onto MHC class I molecules, either based on the endogenous cytosolic MHC I pathway or on cross-presentation. The understanding of the relevance of each of these mechanisms in CTL activation will help vaccine design to progress more rationally.

Animals↗

PubMed2004

HIV/HCV coinfection in clinical practice.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) frequently co-exist due to shared routes of transmission. In the past, the impact of HCV on overall morbidity and mortality of coinfected patients was minimal due to the poor prognosis of HIV. However, since the introduction of highly active antiretroviral therapy (HAART), HCV has become a significant pathogen in this population. HIV clearly exacerbates HCV infection and accelerates progression to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There is debate over whether HCV influences the natural history of HIV. Given the high prevalence of coinfection and the accelerated liver damage, HCV treatment has become a priority in these patients. There are new data on pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for HCV in coinfected patients. The therapy is well tolerated and safe, although it appears to be slightly less effective than in monoinfected patients. The risk of HAART-related hepatotoxicity is greater in coinfected patients and therefore requires special consideration and close monitoring.

Algorithms↗

PubMed1993

Prophylaxis for HIV-associated infections in the developing world.

Prophylaxis for specific HIV-associated infections has made a major difference in the industrialized world to patient survival and the quality of life. However, the HIV epidemic is spreading most rapidly in the poor developing world, where prophylaxis is neither currently used nor recommended. Streptococcus pneumoniae. Mycobacterium tuberculosis and non-typhi salmonellae are the pathogens responsible for much of the morbidity and mortality associated with HIV infection in the tropics. Because these problems often present relatively early in the course of the HIV disease, prophylaxis may be cost-effective and increase the years of productive life. Prevention of pneumococcal disease has not been considered a priority in the developing world. Penicillin chemoprophylaxis may be efficacious; immunization which is recommended for all HIV seropositive adults in the USA, has not been used. The importance of studies to test both efficacy and cost compared to benefit is discussed. The problem of HIV-associated tuberculosis is of major importance and several intervention studies are now in progress. The efficacy of chemoprophylaxis may be limited if the problem is largely acute infection rather than reactivated disease and if shown to be effective compliance will present a major operational difficulty. Systemic salmonellosis is greatly underdiagnosed but may be the leading cause of death. Recurrent infection can be prevented by chemoprophylaxis but this will be costly. The use of novel or currently unlicensed vaccines may eventually prove to be the most effective means of controlling the burden of disease and death caused by salmonellosis.

AIDS-Related Opportunistic Infections↗

PubMed2003

Emergency response vaccines: lessons learned in response to communicable diseases.

In response to recent political and epidemiological events, the availability of emergency response vaccines has received high priority on the global agenda. An emergency response vaccine is defined as a vaccine of public health importance that should be available to all people at risk against epidemic, pandemic or global threat situations. This review focuses on global threat vaccines, those that would be used in the case of an emerging pathogen or the intentional release of an agent to which there is a low level of population immunity. The development and use of such vaccines requires attention to simultaneous actions on seven fronts: development, forecasting, supply sources, regulation, procurement, financing and allocation. Neglect of any one of these aspects will threaten the success of the project. A case study on smallpox vaccines illustrates this. Although many public health experts fear that attention to stockpiling emergency response vaccines could draw resources from other areas, some aspects of such an effort could positively impact the supply of other needed vaccines.

Communicable Disease Control↗

PubMed2004

Etiology, antimicrobial susceptibility profiles, and mortality associated with bacterial meningitis among children in Egypt.

PURPOSE: Surveillance for patients with meningitis is a high priority in order to determine the etiology of disease and design prevention strategies. This study presents data on the causes of bacterial meningitis among children <6 years of age treated in a network of hospitals throughout Egypt. METHODS: Training was provided to standardize the collection of clinical information and optimize recovery of bacterial pathogens. Bacterial isolates were tested for antimicrobial resistance patterns using Kirby Bauer disk diffusion, E-test and/or Beta-lactamase (BL) testing methods. RESULTS: Patients with culture-confirmed bacterial meningitis (228 children<6 years) were identified including 89 (39%) patients with H. influenzae (HI), 68 (30%) with Streptococcus pneumoniae (SP), 30 (13%) with N. meningitidis (NM), 18 (8%) with Mycobacterium tuberculosis (MTB) and 23 (10%) with other bacteria. The overall case fatality ratio was high (24%) and increased among children with TB meningitis (56%). The susceptibility for HI to ampicillin (AMP), chloramphenicol (C) and ceftriaxone (CRO) was 21%, 13%, and 100% respectively. The susceptibility for SP to C and CRO was 79% and 100%, respectively. CONCLUSIONS: HI and SP are the leading causes of bacterial meningitis among children in Egypt. The majority of HI strains tested were resistant to AMP or C suggesting the need for routine use of CRO as first line therapy. Among older children TB emerges as a significant cause of bacterial meningitis in Egypt.

Age Factors↗

PubMedDate not supplied

Nosocomial respiratory infections.

Nosocomial respiratory tract infections are major causes of excessive morbidity and mortality in US hospitals, affecting an estimated five to ten of every 1,000 patients. Patients with serious underlying diseases have an especially high risk of acquiring these infections, and that risk is magnified by exposure to respiratory therapy. Until recently, contaminated respiratory care devices were a major cause of infection, but procedures for the management of these devices have decreased their role substantially. Now, aspiration of oropharyngeal flora appears to be responsible for most cases of bacterial respiratory infections. Therefore, techniques to alter the flora of the oropharynx and to diminish the risk of aspiration are important priorities for infection control. Exposure to intensive care units (ICUs) is also a major risk factor for nosocomial pulmonary infection, and person-to-person spread of microorganisms within ICUs seems to be responsible for some of these infections. Increasing numbers of pulmonary infections are being caused by newly identified or previously uncommon pathogens, and this shift requires that traditional control techniques be reevaluated to assure that they remain relevant. Few new techniques have been developed recently to alter host susceptibility, prevent acquisition of virulent pathogens, or eradicate infectious organisms from their sources, but effective infection control programs in hospitals appear to reduce the incidence of nosocomial pulmonary infection, and implementation of these programs deserves serious consideration in all hospitals.

Cross Infection↗

PubMed2003

11beta-hydroxysteroid dehydrogenase type 1 as a novel therapeutic target in metabolic and neurodegenerative disease.

11beta-hydroxysteroid dehydrogenase Type 1 (11HSD1) catalyses regeneration of active 11-hydroxy glucocorticoids from inactive 11-keto metabolites within target tissues. Inhibition of 11HSD1 has been proposed as a novel strategy to lower intracellular glucocorticoid concentrations, without affecting circulating glucocorticoid levels and their responsiveness to stress. Increased 11HSD1 activity may be pathogenic, for example, in adipose tissue in obesity. Experiments in transgenic mice and using prototype inhibitors in humans show benefits of 11HSD1 inhibition in liver, adipose and brain tissue in treating features of the metabolic syndrome and cognitive dysfunction with ageing. The clinical development of potent selective 11HSD1 inhibitors is now a high priority.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1995

[Post-partum cardiomyopathy: medical aspects, role of heart transplantation].

The incidence of post-partum cardiomyopathies (PPCM) represents 5% of all cardiomyopathies and 10-13% of cardiomyopathies in women. The outcome of PPCM may be: a) death in the acute phase, b) evolution to chronic myocardial disease or c) complete recovery, in which PPCM differs from dilated cardiomyopathy. Another difference is that PPCM may not recur in subsequent pregnancies. The aetiology and pathogenesis of PPCM are still unknown. Infectious diseases, nutritional disorders have been reported but they do not account for the majority of cases. Immune responses to the foreign tissue of the placenta and foetus may explain alteration of immune function associated with myocardial lesion. In the author's experience, the most common pathogenic mechanism is latent myocardial insufficiency observed in each woman in the normal post-partum period. The different noted "causes" could be factors which reveal this latent common condition. Recently, cardiac transplants for PPCM have been reported. As patients with PPCM may recover completely, we believe that PPCM is not a special priority for transplantation. Two recent studies have compared the outcome of women undergoing transplantation for PPCM and those for dilated cardiomyopathy. The risk of rejection and infection was greater in PPCM (but the difference was significant in only one report). The long-term survival was favourable in both groups.

Adult↗

PubMed1988

Live viral vaccines for respiratory and enteric tract diseases.

In its programme for accelerated development of vaccines for viral respiratory and enteric tract diseases the WHO has assigned a very high priority to respiratory syncytial virus (RSV), parainfluenza viruses and rotaviruses. There is also some interest in alternative approaches to immunization against influenza viruses because of the failure of inactivated vaccines to provide complete and reasonably durable immunity. Current attempts to develop satisfactorily attenuated viruses for use in prevention of disease caused by the above viral pathogens are described.

Gastrointestinal Diseases↗

PubMed2002

Antifungal chemoprophylaxis after blood and marrow transplantation.

Invasive fungal infections are common and deadly in recipients of blood and marrow transplants. Current diagnostic techniques do not allow accurate early diagnosis, especially of infection with mould pathogens, and delays in diagnosis are associated with treatment failure. This lack of early diagnosis has provided the impetus for the development of antifungal prophylaxis. Fluconazole prophylaxis is highly effective for the control of invasive yeast infections and associated with few breakthrough infections. The development of antimould prophylaxis in this patient population is a high priority.

Antifungal Agents↗

PubMed2003

New approaches in vaccine development.

In the last century, vaccines have been one of the most powerful tools for preventing infectious diseases. Smallpox has been eradicated and other diseases such as poliomyelitis or measles have been reduced to very low levels in many regions of the world. However, infectious diseases remain the leading cause of death worldwide. Thus, the development of vaccines to prevent diseases for which no vaccine currently exists such as AIDS or malaria as well as the improvement of efficacy and safety of existing vaccines remains a high priority. Achieving such ambitious goals in a near future will certainly require a strong modification of the methods that have been used so far to identify vaccine candidates. In particular, modern vaccinology could strongly benefit of the latest developments of molecular biology and immunology. Here, we will discuss some potential applications of the increasing knowledge of pathogen genomes as well as the immune system for the discovery of new antigenic targets and the development of new strategies of vaccination.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Assessing the consequences of global change for forest disturbance from herbivores and pathogens.

Herbivores and pathogens impact the species composition, ecosystem function, and socioeconomic value of forests. Herbivores and pathogens are an integral part of forests, but sometimes produce undesirable effects and a degradation of forest resources. In the United States, a few species of forest pests routinely have significant impacts on up to 20 million ha of forest with economic costs that probably exceed $1 billion/year. Climatic change could alter patterns of disturbance from herbivores and pathogens through: (1) direct effects on the development and survival of herbivores and pathogens; (2) physiological changes in tree defenses; and (3) indirect effects from changes in the abundance of natural enemies (e.g. parasitoids of insect herbivores), mutualists (e.g. insect vectors of tree pathogens), and competitors. Because of their short life cycles, mobility, reproductive potential, and physiological sensitivity to temperature, even modest climate change will have rapid impacts on the distribution and abundance of many forest insects and pathogens. We identify 32 syndromes of biotic disturbance in North American forests that should be carefully evaluated for their responses to climate change: 15 insect herbivores, browsing mammals; 12 pathogens; 1 plant parasite; and 3 undiagnosed patterns of forest decline. It is probable that climatic effects on some herbivores and pathogens will impact on biodiversity, recreation, property value, forest industry, and even water quality. Some scenarios are beneficial (e.g. decreased snow cover may increase winter mortality of some insect pests), but many are detrimental (e.g. warming tends to accelerate insect development rate and facilitate range expansions of pests and climate change tends to produce a mismatch between mature trees and their environment, which can increase vulnerability to herbivores and pathogens). Changes in forest disturbance can produce feedback to climate through affects on water and carbon flux in forest ecosystems; one alarming scenario is that climate warming may increase insect outbreaks in boreal forests, which would tend to increase forest fires and exacerbate further climate warming by releasing carbon stores from boreal ecosystems. We suggest a list of research priorities that will allow us to refine these risk assessments and adopt forest management strategies that anticipate changes in biotic disturbance regimes and mitigate the ecological, social, and economic risks.

Animal Nutritional Physiological Phenomena↗

PubMed1984

The impact of new technologies on vaccine development.

The ability to move genetic determinants between species using in vitro gene-manipulation techniques has opened up new approaches to vaccine development. This has rapidly grown into an exciting area of research in both academic and industrial laboratories. There are numerous scientific challenges which require multidisciplinary teams to solve problems in creating new immunogens. This has challenged our existing knowledge about protein structure and conformation, microbial pathogenicity and the immune system. Recombinant-DNA techniques are invaluable as tools of analysis and antigen production. The surface of micro-organisms can also be minutely explored with the use of synthetic peptides and monoclonal antibodies. Nevertheless, these new technologies do not allow us to circumvent the need for detailed understanding of pathogens and the disease process. What is apparent from the work carried out so far is that there are few easy answers to vaccine development and it is not realistic to expect rapid solutions to these problems. As there are many potential targets for constructing novel vaccines for both human and animal diseases, it is helpful to establish some priorities. There is a tendency to look at the existing effective vaccines and simply direct research at producing them more economically or with enhanced safety and stability. The advantage of this approach is that considerable background work will have already been carried out establishing the basis for the application of recombinant DNA techniques. However, this can also lead to conflicts (often within the same institute or company) between the new and old technologies. This could be to the detriment of the new technologies which are still only partly developed and may not be good enough yet to compete with existing vaccines in cost or efficacy. The more ambitious, and eventually more rewarding, approach is to attempt to develop new vaccines where none had existed before. There is a vast untapped market, especially in the parasitic diseases, but the scientific problems may be considerable and much more background work is likely to be necessary. Indeed, most of the work in this area is more accurately referred to as basic research rather than vaccine development as totally new, effective vaccines are still some way off. Having directed research towards a specific organism or disease there are still many options available as to the scientific strategy to adopt. As discussed in this review it may be possible to consider subunits, synthetic antigens and live (attenuated or heterologous) organisms as possible vaccines.(ABSTRACT TRUNCATED AT 400 WORDS)

Adjuvants, Immunologic↗

PubMed2006

Quantitative MR imaging in Alzheimer disease.

Alzheimer disease (AD) is the most common type of dementia. It currently affects approximately 4 million people in the United States. AD is a progressive neurodegenerative disorder characterized by the gradual deposition of neuritic plaques and neurofibrillary tangles in the brain, which is thought to occur decades before the onset of clinical symptoms. Identification of people at risk before the clinical appearance of dementia has become a priority due to the potential benefits of therapeutic intervention. Although atrophy of medial temporal lobe structures has been shown to correlate with progression of AD, a growing number of recent reports have indicated that such atrophy may not be specific to AD. To improve diagnostic specificity, new quantitative magnetic resonance (MR) imaging methods are being developed that exploit known pathogenic mechanisms exclusive to AD. This article reviews the MR techniques that are currently available for the diagnostic assessment of AD.

Alzheimer Disease↗

PubMed1999

[How I explore ... vitiligo].

Vitiligo is likely a syndrome rather than a disease. Several pathogenic causes are indeed recognized. The exploration of such condition encompasses three distinct facets. Establishing the diagnosis and a precise typing of the skin clinical presentation represents the first step. The ophthalmologic examination is mandatory in order to detect infraclinical signs of uveitis and retinopathy. Auditory problems can also be present. Searching for associated diseases should be oriented in priority toward alopecia areata and some specific autoimmune endocrinopathies.

Alopecia↗

PubMed2006

[Research advance in antibacterial immunity ecology of earthworm].

Earthworm lives in the environment flocked with pathogens, but few are infected due to the earthworm's unique antibiotic and immune system. In this paper, the research advance in this domain was reviewed from the aspects of antibiotic barrier, cell immunity, and humoral immunity. Antibiotic barrier mainly includes body wall, alimentary canal and parietal mucus, cell immunity represents phagocytosis and encapsulation responses, while humoral immunity gives priority to unspecific immune system. The main antibacterial materials in the coelomic fluid of earthworm are antigen-binding proteins, agglutinins, antibacterial proteins, and lysozyme.

Animals↗