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PubMed1999

[Biological prevention and/or therapy possibility of radiation myelopathy. A discussion of recent perspectives].

BACKGROUND: Radiosensitivity of the spinal cord makes both curative first-line treatment of numerous malignancies and re-irradiation of recurrent or second tumors more difficult. This review discusses recent advances in basic research that alter the view on the pathogenesis of radiation myelopathy, possibly offering strategies for prevention and/or therapy. RESULTS: Available data of developmental neurobiology and preclinical studies of demyelinating diseases revealed interesting insights into oligodendrocyte development, intercellular signaling pathways, and myelination processes. Current findings suggest that administration of cytokines could increase proliferation of oligodendrocyte progenitor cells, enhance their differentiation, upregulate synthesis of myelin constituents, and promote myelin regeneration in the adult central nervous system (Table 1). Other compounds might also be able to modulate progression of pathogenic processes that eventually lead to radiation myelopathy. This offers several possible biological prevention and/or treatment strategies, which currently are being investigated in animal studies (Table 2). CONCLUSION: Technical options as well as optimization of fractionation parameters should be given priority in the attempt to reduce iatrogenic neurotoxicity. However, rational biological strategies could offer a new perspective for many patients.

Adult↗

PubMed1998

Epidemiology and pathogenesis of chronic suppurative otitis media: implications for prevention and treatment.

Despite advances in public health and medical care, chronic suppurative otitis media is still prevalent around the world. It is most common in developing countries and in certain high risk populations in developed nations, as well as among children who have tympanostomy tubes inserted. Since this chronic infection is caused by persistent acute otorrhea, which in turn is usually secondary to acute otitis media, prevention should be directed toward prompt and appropriate treatment of the acute middle-ear infection. Repair of chronic perforations should prevent recurrence, since reinfection is due either to reflux of pathogenic organisms from the nasopharynx into the middle ear, or water contamination from the external canal. Information from epidemiological studies, which show that populations can be categorized into highest, high, low and lowest prevalence, can be helpful in setting national priorities for prevention and treatment.

Acute Disease↗

PubMed2004

Global change and human vulnerability to vector-borne diseases.

Global change includes climate change and climate variability, land use, water storage and irrigation, human population growth and urbanization, trade and travel, and chemical pollution. Impacts on vector-borne diseases, including malaria, dengue fever, infections by other arboviruses, schistosomiasis, trypanosomiasis, onchocerciasis, and leishmaniasis are reviewed. While climate change is global in nature and poses unknown future risks to humans and natural ecosystems, other local changes are occurring more rapidly on a global scale and are having significant effects on vector-borne diseases. History is invaluable as a pointer to future risks, but direct extrapolation is no longer possible because the climate is changing. Researchers are therefore embracing computer simulation models and global change scenarios to explore the risks. Credible ranking of the extent to which different vector-borne diseases will be affected awaits a rigorous analysis. Adaptation to the changes is threatened by the ongoing loss of drugs and pesticides due to the selection of resistant strains of pathogens and vectors. The vulnerability of communities to the changes in impacts depends on their adaptive capacity, which requires both appropriate technology and responsive public health systems. The availability of resources in turn depends on social stability, economic wealth, and priority allocation of resources to public health.

Animals↗

PubMed2000

[Diffuse infiltrative lung diseases of infectious and neoplastic origin].

Among the causes of chronic diffuse infiltrative lung diseases, infection and neoplasia have to be suspected in priority because of their frequency and their therapeutic specificities. Diffuse infiltrative lung diseases related to infection, often acute and feverish, are due to Pneumocystis carinii pneumonia, miliary tuberculosis, or virus and atypical pneumonia. Strategy for microbiological diagnosis depends on the pathogen suspected and the pulmonary disease severity. By contrast, diffuse infiltrative lung diseases due to neoplasia, mostly chronic diseases, include lymphangitic carcinomatosis and more rarely diffuse bronchoalveolar carcinoma and lymphoproliferative diseases.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2026

Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.

The liver serves the triple functions of metabolism, detoxification, and immune surveillance. Its unique immune microenvironment is shaped by continuous exposure to gut-derived antigens, pathogen-associated molecular patterns (PAMPs), and metabolites arriving via the portal vein, necessitating a delicate equilibrium between immune tolerance and effector activation. This equilibrium relies on the coordinated activities of diverse liver-resident immune cell populations-including Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), dendritic cells (DCs), tissue-resident memory T cells (TRM), innate-like T cells, including mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδ T cells, innate lymphoid cells (ILCs, encompassing conventional NK cells and helper ILC subsets), and neutrophils. With advancing age and chronic injury, these resident immune cell populations undergo profound senescence-associated phenotypic reprogramming that is spatially organized along the portal-to-central axis of the hepatic lobule. Key mechanisms include: telomere dysfunction and DNA damage accumulation driving persistent activation of p53/p21 and p16/Rb pathways; mitochondrial dysfunction with mitochondrial DNA (mtDNA) leakage fueling the senescence-associated secretory phenotype (SASP) via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway; epigenetic age acceleration, including genome-wide H3K27me3 heterochromatinization; and metabolic reprogramming toward glycolysis and lipid accumulation. This review proposes a "spatial niche remodeling" framework to integrate these cell-intrinsic senescence programs with their lobular context, intercellular communication network rewiring, and pathogenic roles across the spectrum of chronic liver disease-from steatosis through steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. We critically evaluate emerging senotherapeutic strategies targeting specific liver-resident immune cell subsets, discuss the barriers to clinical translation, and identify priority areas for future investigation, including the application of spatial multi-omics, humanized models, and epigenetic clock-guided clinical trials.

Kupffer cells↗

PubMed1998

[Surveillance of multiresistant bacteria: justification, role of the laboratory, indicators, and recent French data].

In France, several organizations have given priority status to programs aimed at controlling outbreaks of nosocomial infections due to multiresistant bacteria (MRB), most notably methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE), thus recognizing the widespread distribution and marked pathogenic potential of MRB. To evaluate the impact of preventive measures, surveillance systems have been set up by bacteriology laboratories. These systems rest on a number of indicators: (1) the percentage of strains of a given bacterial species recovered from diagnostic specimens that were multiresistant; (2) the number of new patients (cases) with recovery of a MRB strain from at least one diagnostic specimen (or at least one screening specimen); (3) the incidence, or incidence density, of cases per 1000 hospital days or 100 admissions; (4) the distinction between cases acquired in and transported to the hospital or department. Studies conducted in France between 1990 and 1995 found that the percentage of Klebsiella pneumoniae that were multiresistant was around 20% overall and 25 to 35% among nosocomial strains, and that the prevalence and incidence of cases were about 0.1 to 0.3 per 100 admissions. The proportion of S. aureus strains exhibiting resistance to methicillin was 35 to 40% overall and 50% among nosocomial strains, and the prevalence and incidence of cases ranged from 0.5 to 1 per 100 admissions.

Bacteria↗

PubMed2026

Cohesin variants associated with human reproductive and developmental disorders.

The cohesin complex is an evolutionarily conserved multi-subunit protein assembly essential for sister chromatid cohesion, meiotic recombination, DNA double-strand break repair, and transcriptional regulation. Pathogenic variants in its subunits are implicated in a spectrum of reproductive and developmental disorders, including non-obstructive azoospermia, premature ovarian insufficiency, reproductive aging, aneuploidy, Cornelia de Lange syndrome, Roberts syndrome, cancer, and neuropsychiatric disease. Consequently, identifying cohesin mutations is a priority for precision diagnostics and personalized medicine. This review systematically summarizes the cohesin variants linked to these pathologies, exploring their molecular mechanisms and clinical manifestations. A deeper understanding of these variants is crucial not only for deciphering disease etiology but also for guiding the development of targeted diagnostic strategies and therapeutic interventions, ultimately improving patient management and outcomes.

Humans↗

PubMed2003

Prevalence of nosocomial infections in Italy: result from the Lombardy survey in 2000.

A one-day survey was carried out in 88 out of 113 public hospitals in Lombardy to obtain prevalence rates of hospital-acquired infections (HAIs) by hospital departments and to identify the pathogens more frequently involved. In total 18667 patients were surveyed, representing 72% of the average daily total of occupied beds in public hospitals in Lombardy. The overall prevalence of HAI was 4.9%. The highest prevalence was observed in intensive care units and in spinal units. The prevalence of bloodstream infections was 0.6%; pneumonia 1.1%; urinary tract infections 1.6% and gastrointestinal infections 0.4%. In surgical patients the prevalence of surgical site infections was 2.7%. The most frequently isolated pathogen from all sites of infections was Escherichia coli (16.8%), followed by Staphylococcus aureus (15.0%), Pseudomonas aeruginosa (13.2%) and Candida spp. (8.7%). Methicillin-resistant S. aureus accounted for 23% of all isolated S. aureus. The results provide baseline data for rational priorities in allocation of resources, for further studies and for infection control activities.

Candidiasis↗

PubMed2005

Methodologic factors affect the measurement of anti-basal ganglia antibodies.

An autoimmune etiology has been proposed for a variety of movement disorders, making the detection of autoantibodies a high investigative priority. Recognizing the existence of different methodologic approaches to identify these antibodies, we sought to investigate the effects of tissue preparation, antibody selection, and Western immunoblot detection methods on outcome. ELISA and immunoblotting studies were performed in healthy controls evaluating non-pathogenic autoantibodies. Our results indicate that enhanced data can be obtained by using fresh, rather than frozen, postmortem tissue homogenates for Western immunoblots and enzyme-linked immunosorbent assays and support the use of electrochemiluminescent detection for Western immunoblots. Molecular localization is significantly affected by the selected standard. Removal of lipids from homogenates does not affect anti-basal ganglia antibody (ABGA) results. Methodological variables should be taken into consideration when performing and interpreting neuroimmunological assays using sera or isolated IgG.

Adult↗

PubMed2026

Proteomic and phosphoproteomic profiles of time-dependent dynamic changes in LPS-induced macrophage polarization.

The temporal proteomic and phosphoproteomic reprogramming during early M1 macrophage polarization (0-6 h) remains poorly understood. We performed time-resolved proteomic and phosphoproteomic analyses of LPS-stimulated RAW264.7 macrophages at seven time points within 6 h. Time-clustering of differentially expressed molecules revealed two patterns: initial change with partial recovery, and sustained dysregulation. Upregulated proteins and phosphorylation sites were enriched in the Rho GTPase signaling pathway, T-cell receptor signaling pathway, NF-κB cascade, osteoclast differentiation pathway, and antiviral immune pathway. Downregulated pathways were associated with cell cycle regulation, chromatin remodeling, RNA metabolism, and mRNA processing, indicating resource reallocation to prioritize acute inflammatory responses. Kinase-substrate network analysis confirmed the mitogen-activated protein kinase (MAPK), cyclin-dependent kinase (CDK), protein kinase B (AKT), and ribosomal S6 kinase (RSK) families as core upstream phosphorylation regulators. Integrated analysis revealed synergistic and antagonistic relationships between proteomic and phosphoproteomic changes. This study provides a temporal molecular atlas of M1 polarization, delineating inflammatory signaling dynamics and offering a basis for therapeutic target discovery in inflammatory diseases. SIGNIFICANCE: Macrophage M1 polarization is a central event in innate immune defense against pathogenic invasion, yet its dysregulation is a pivotal driver of the onset and progression of a broad spectrum of inflammation-associated disorders, spanning autoimmune diseases, infectious conditions and inflammatory bone diseases, making the dissection of its molecular regulatory mechanisms an urgent research priority in immunology and translational medicine. Dynamic molecular events within 0-6 h after LPS stimulation are critical for initiating and shaping M1 inflammatory activation, yet systematic time-resolved proteomic and phosphoproteomic profiling remains insufficient.In this study, we comprehensively characterized temporal proteome and phosphoproteome changes at seven consecutive time points during macrophage polarization, clarified two distinct dynamic molecular patterns, identified core signaling pathways and key kinase regulators involved in inflammatory reprogramming, and uncovered the leading role of post-translational phosphorylation modifications in initiating polarization. This work delineates the time-series molecular atlas of early macrophage activation, provides novel insights into the temporal regulatory mechanism of inflammatory signaling networks, and lays a solid experimental foundation for exploring new intervention targets and regulatory nodes in clinical translational research.

Lipopolysaccharides↗

PubMed2026

Genomic Medicine Sweden: Advancing precision medicine at the national level.

High-throughput sequencing has transformed clinical diagnostics of rare diseases (RD), cancer and infectious diseases by enabling the identification of disease-causing genetic alterations and facilitating individualised treatment and care. In response to these advances, Genomic Medicine Sweden (GMS) was established in 2017 as a national collaborative effort to accelerate implementation of genomics-based precision medicine within Sweden's regionally organized, publicly funded healthcare system. GMS brings together the seven university healthcare regions and their associated medical faculties, in collaboration with healthcare regions across Sweden, Science for Life Laboratory, patient organizations, industry and governmental agencies. Activities are coordinated through national disease-specific expert groups, supported by cross-cutting functions in bioinformatics, health economics, ethics, education and patient engagement. At the operational level, seven Genomic Medicine Centres, embedded at university hospitals, develop and deliver harmonised genomic diagnostics nationwide. The National Genomics Platform provides secure infrastructure for large-scale data storage, analysis, and national and international data sharing. Following initial project-based funding, GMS now receives long-term governmental support. This review describes the national implementation of genomic-based precision diagnostics, discusses challenges and lessons learnt, and highlights key milestones across disease areas, including whole-genome sequencing in RD and paediatric cancer, comprehensive genomic profiling of haematological malignancies and solid tumours, pathogen genomics in microbiology, pharmacogenomic testing and emerging applications of polygenic risk scores in complex diseases. Collectively, these efforts have contributed to more than 500,000 genomic tests being performed within Swedish healthcare between 2017 and 2025. Finally, we outline future diagnostic needs and priority areas to ensure sustainable, scalable and equitable access to precision medicine.

Precision Medicine↗

PubMed1995

[Nosocomial infections: new agents, incidence, prevention].

Nosocomial infection is one of the major health problems confronting clinicians in intensive care units. Incidence has been estimated to vary from 5 to 10%, leading to death in one of every 5000 persons hospitalized. This situation is not however static since hospital epidemics and nosocomial infections evolve as a consequence of advances in antibiotic drug therapy and surgical and intensive care techniques. Microbial investigations themselves are of major importance as the collection of epidemiological data and its communication to hospital partners affects their approach to patient management. Nosocomial pneumonia, particularly in ventilated patients, urinary infection in those with indwelling catheters and wound colonization after surgery are still major problems and explain part of the variations between wards and hospitals. The main changes concern the bacteria involved. Classical agents with new mechanisms of resistance (Klebsiella pneumoniae, extended spectrum beta-lactamase producers) have been joined by other "new" agents emerging as pathogens (Xanthomonas maltophilia, Acinetobacter baumannii). The incidence of resistance in Staphylococcus and Enterococcus strains as well as new Gram positive species including Corynebacterium jeikeium and Rhodococcus equi, now recognized as opportunistic agents, has also increased. The multiresistance of these pathogens is often responsible for failure of antibiotic therapy and emphasizes the need both for rigorous prevention through active cooperation between bacteriologists, ward clinicians and intensive care units, and further research in the fields of microbial resistance mechanisms and antibiotics. Preventive measures have become a priority creating an international challenge to health care policy makers.

Cross Infection↗

PubMed1999

Toward the development of antibacterial vaccines: report of a symposium and workshop. Organizing Committee.

On 26 and 27 October 1998, the Department of Medicine at the University of California, San Francisco (UCSF), hosted a symposium and workshop on bacterial vaccines. The symposium featured invited speakers who are internationally recognized authorities in their fields and who discussed selected topics related to specific pathogens or specific principles of bacterial vaccine development. The workshop, held on the day following the symposium, brought together the invited speakers and members of the organizing committee, who came from UCSF and the University of California, Berkeley, to discuss 4 specific topics and to define priorities for future vaccine development. Considerable knowledge has been gained from successful and unsuccessful vaccine development efforts, and large gains in knowledge relevant to vaccine development have resulted from studies of basic immunology and microbial pathogenesis. This report summarizes the presentations at the symposium and the discussions of the workshop sessions.

Bacterial Vaccines↗

PubMed2005

Hepatitis B immunisation status among health care workers in two Kuala Lumpur hospitals.

Health care workers (HCW) are at higher risk of acquiring blood borne infections such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus from patients. To minimise exposure, Universal Precautions Policy guidelines were introduced. This study looked into one of the aspects of hepatitis B prevention among HCW in the Malaysian context. The objective of this study was to assess hepatitis B vaccine coverage among HCW. A cross sectional study involving pre-tested questionnaires was undertaken from February 2001 to August 2001. Hospital staff in Hospital Kuala Lumpur and Hospital Universiti Kebangsaan Malaysia as well as undergraduate students undergoing clinical attachments were randomly chosen. A total of 625 subjects were enrolled. Only 58.4% had taken a complete hepatitis B vaccination. However, 82.2% have taken at least one dose of the hepatitis B vaccine and were supposed to complete the schedule in due course. Not all HCW were protected against hepatitis B. Preventing hepatitis B in HCW should be one of the priorities of the hospital management as it is definitely cheaper than managing chronic hepatitis B cases.

Adult↗

PubMed2003

Agronomic approach: cropping systems and plant diseases.

This paper deals with the effects of agronomic practices on parasite life cycles, and the design of integrated crop protection strategies. Cropping systems have a large effect on the size of the primary inoculum and its localisation, on the development and spread of epidemics, and on the coordination of the life cycle of cultivated plants and that of their parasites. They can disrupt ecological equilibria, either favouring or disfavouring the pathogens. By combining information concerning the effects of agricultural techniques on diseases and the physiological effects of diseases on growth and crop production, it is now possible to develop new crop management systems, in which the use of non-chemical methods for preventing diseases is a priority. However, the current knowledge need to be completed by studies on other scales, particularly of the effect of cropping systems on the genetics of disease populations integrating more completely the 'long-term' dimension of sustainable agriculture.

Agriculture↗

PubMed2000

The burden of infection in long-term care.

Available data, although fragmentary, indicate that infections impose a large burden on long-term-care facilities (LTCFs) in the United States. Endemic infections occur with frequencies estimated to range between 1.64 and 3.83 million per year. These estimates rival or exceed the annual tally for nosocomial infections in acute-care settings. Infections associated with outbreaks caused by respiratory, gastrointestinal, and antimicrobial-resistant pathogens burden LTCFs even further. As judged by antimicrobial use, transfers to hospital, and mortality figures, infections in LTCFs are not trivial. Moreover, annual costs associated with these infections appear to exceed $1 billion. Recognition of the burden associated with infection in LTCFs helps to identify research priorities for this rapidly growing area of healthcare.

Bacterial Infections↗

PubMed2006

OIE philosophy, policy and procedures for the development of food safety standards.

Food safety was identified as a high priority area in the 2001-2005 World Organisation for Animal Health (OIE) Strategic Plan. Member Countries of the OIE considered that the organisation should be more active in issues of public health and consumer protection and that this should include more involvement in the area of diseases or pathogens transmissible through food, whether or not animals are affected by such diseases or pathogens. A permanent Working Group on Animal Production Food Safety was established in 2002 to coordinate the OIE's activities in food safety. The Working Group was requested to focus on food safety measures applicable at farm level and to monitor the ongoing cooperation between the OIE and Codex Alimentarius. More emphasis is now placed on the public health aspects of a disease when OIE standards are developed or revised. For example, the revised chapter on bovine tuberculosis in the Terrestrial Animal Health Code includes food safety recommendations for meat and meat products and for milk and milk products. The revised chapter was approved by the OIE International Committee of Member Countries at their 73rd General Session in May 2005. More chapters will follow, beginning with a chapter addressing bovine brucellosis.

Animal Diseases↗

PubMed1999

Sharps injuries: defining prevention priorities.

OBJECTIVE: An institutional review of sharps injuries was conducted to assist in establishing priorities for resource allocation in a sharps prevention program. DESIGN: A retrospective review of 221 sharps injuries occurring during a 1-year period was conducted by a 4-member multidisciplinary team. Each injury was categorized as either moderate/high, low, or unknown risk for acquisition of bloodborne diseases by using modified provincial definitions of occupational risk for exposure to bloodborne pathogens. RESULTS: A total of 119 injuries were considered to be moderate/high risk, and 93 were at low risk for acquisition of bloodborne disease. Nine injuries could not be categorized. In 59% of high-risk injuries, education or changes in technique were identified as the primary preventive intervention. Passive devices such as needleless intravenous administration sets could theoretically address prevention of the majority of low-risk injuries. Known available safety devices could have prevented 33 (28%) high-risk injuries. CONCLUSION: Disposition of resources must take into consideration the risk of bloodborne disease acquisition and the efficiency and expense of the preventable methods employed. Institutional review of injuries combined with a cost analysis revealed that resources were best allocated to protective devices at source (eg, safety syringes) and on a comprehensive, multidisciplinary, and sustained educational program. Needleless intravenous infusion sets would mainly prevent low-risk injuries at significant cost.

British Columbia↗