Periodontal Diseases in Patients with Special Health Care Needs

A wide variation of people with an impairment or disability requires a “special care dentistry” once their general manifestations directly act in the oral cavity. This target public is inserted into the following categories: neuromotor disability, sensory disability, mental disorder, infecto-contagious diseases, chronic systemic diseases, and systemic conditions. Among the several oral illnesses found in these groups, periodontal diseases have been the most frequent, becoming a major challenge for the dental practitioners. Thus, we described the microbiological, histopathological, and clinical features of periodontal diseases in each “special health care needs” group. Advances in “Omic” technologies have suggested the application of molecular biology methods to assess the genomics (genes), proteomics (proteins), transcriptomics (mRNA), and metabolomics (metabolites) aspects of periodontal diseases. These researches aim to promote a better understanding of the mechanisms involved in the pathogenesis and in the identification of new biomarkers of periodontal diseases that help in diagnosis of periodontal diseases and in tissue responses after treatments of gingivitis and periodontitis. As an alternative therapy, some bioactive materials and photobiomodulation may be indicated once they strongly stimulate the periodontal tissue regeneration, attenuate the inflammatory processes, and/or promote the reconstruction of the microstructure of the periodontium

Mass spectrometry-based proteomic exploration of the human immune system : focus on the inflammasome, global protein secretion, and T cells

Introduction: The immune system is our defense system against microbial infections and tissue injury, and understanding how it works in detail is essential for developing drugs for different diseases. Mass spectrometry-based proteomics can provide in-depth information on the molecular mechanisms involved in immune responses.Areas covered: Summarized are the key immunology findings obtained with MS-based proteomics in the past five years, with a focus on inflammasome activation, global protein secretion, mucosal immunology, immunopeptidome and T cells. Special focus is on extracellular vesicle-mediated protein secretion and its role in immune responses.Expert commentary: Proteomics is an essential part of modern omics-scale immunology research. To date, MS-based proteomics has been used in immunology to study protein expression levels, their subcellular localization, secretion, post-translational modifications, and interactions in immune cells upon activation by different stimuli. These studies have made major contributions to understanding the molecular mechanisms involved in innate and adaptive immune responses. New developments in proteomics offer constantly novel possibilities for exploring the immune system. Examples of these techniques include mass cytometry and different MS-based imaging approaches which can be widely used in immunology.Peer reviewe

Salivary Genomics, Transcriptomics and Proteomics: The Emerging Concept of the Oral Ecosystem and their Use in the Early Diagnosis of Cancer and other Diseases

There is an increasingly growing interest world-wide for the genomics, transcriptomics and proteomics of saliva and the oral cavity, since they provide a non-invasive source of unprecedently rich genetic information. The complexity of oral systems biology goes much beyond the human genome, transcriptome and proteome revealed by oral mucosal cells, gingival crevicular fluid, and saliva, and includes the complexity of the oral microbiota, the symbiotic assembly of bacterial, fungal and other microbial flora in the oral cavity. In our review we summarize the recent information on oral genomics, transcriptomics and proteomics, of both human and microbial origin. We also give an introduction and practical advice on sample collection, handling and storage for analysis. Finally, we show the usefulness of salivary and oral genomics in early diagnosis of cancer, as well as in uncovering other systemic diseases, infections and oral disorders. We close the review by highlighting a number of possible exploratory pathways in this emerging, hot research field

Human ascariasis: diagnostics update

Soil-transmitted helminths (STHs) infect over one billion people worldwide. Ascariasis may mimic a number of conditions, and individual clinical diagnosis often requires a thorough work-up. Kato-Katz thick smears are the standard detection method for Ascaris and, despite low sensitivity, are often used for mapping and monitoring and evaluation of national control programmes. Although increased sampling (number of stools) and diagnostic (number of examinations per stool) efforts can improve sensitivity, Kato-Katz is less sensitive than other microscopy methods such as FLOTAC®. Antibody-based diagnostics may be a sensitive diagnostic tool; however, their usefulness is limited to assessing transmission in areas aiming for elimination. Molecular diagnostics are highly sensitive and specific, but high costs limit their use to individual diagnosis, drug - efficacy studies and identification of Ascaris suum. Increased investments in research on Ascaris and other STHs are urgently required for the development of diagnostic assays to support efforts to reduce human suffering caused by these infections

“Omics”-Informed drug and biomarker discovery : opportunities, challenges and future perspectives

The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the “data-heavy” outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences—genomics, transcriptomics, proteomics and metabolomics—have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process

Chagas Disease Diagnostic Applications: Present Knowledge and Future Steps

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout Latin America and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stresses the necessity of developing new methods operational in point-of-care settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery.Fil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Fernandez Aguero, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin

Development and validation of blood-based proteomic biomarker-sociodemographic diagnostic prediction models to identify major depressive disorder among symptomatic individuals

Major depressive disorder (MDD) is a highly prevalent and disabling condition with a complex pathophysiology that has not been fully elucidated to date. While the socioeconomic burden of the disease is significant, many individuals remain undiagnosed or misdiagnosed. This is largely because the current diagnostic approach that relies on clinical evaluations of signs and symptoms can be subjective, and time and resources tend to be rather limited in primary care where the majority seek help for depression. Therefore, there is a significant and pressing need for an objective, reliable and readily accessible diagnostic test to enable earlier and more accurate diagnosis of MDD. In particular, as individuals experiencing subthreshold levels of depressive symptoms have an increased risk of developing MDD, it would be clinically relevant for such a diagnostic test to be able to identify depressed patients and/or individuals with high risks of incident MDD among symptomatic individuals. This thesis sought to develop risk prediction models that could potentially be utilised within a clinical setting to facilitate earlier and more accurate diagnosis of MDD. Such models were used to obtain probability estimates of the investigated individuals having or developing MDD based on their blood-based proteomic profiles and other characteristics, including sociodemographic and lifestyle factors. A targeted mass spectrometry approach was used to measure the abundances of a panel of peptides representing proteins, many of which have been previously associated with psychiatric disorders. Biomarkers were investigated in serum samples, which are widely used for blood-based biomarker discovery, as well as in dried blood spot samples, which are relatively novel in the field and carry several advantages. Importantly, this thesis focused on adopting appropriate statistical methods to ensure that the diagnostic predictions made by the models were accurate and reproducible, by addressing problems of model overfitting and model selection uncertainty. A particularly significant aspect of this was the development and application of a multimodel-based approach combining feature extraction and model averaging, which resulted in improved model predictive performance and generalisability. Diagnostic prediction models based on serum proteomic, sociodemographic/lifestyle and clinical data were shown to be able to differentiate between subthreshold symptomatic individuals who developed and did not develop MDD. Additionally, diagnostic prediction models based on dried blood spot proteomic and digital mental health assessment data were shown to be able to identify currently depressed patients without an existing MDD diagnosis as well as currently not depressed patients with an existing MDD diagnosis among subthreshold symptomatic individuals. These results clearly demonstrate the potential of such prediction models to be used as an aid to the diagnosis of MDD in clinical practice, especially within the primary care setting. Moreover, MDD was found to be associated with several blood-based proteomic biomarkers, which mainly represented an immune/inflammatory profile, as well as with various other patient features, most notably body mass index and childhood trauma. Although further investigations are needed, these associations reveal disturbances in the stress response pathways involving the hypothalamic-pituitary-adrenal axis in the pathophysiology of depression

16th Baltic Congress in Laboratory Medicine

Eesti Arst 2022;101(Supplement 4):1–4

Residential green and blue spaces and working memory in children aged 6–12 years old. Results from the INMA cohort

Availability of green and blue spaces in the area of residence has been related to various health outcomes during childhood, including neurodevelopment. Some studies have shown that children living in greener and/or bluer areas score better on cognitive tasks although the evidence is inconsistent. These protective effects are hypothesized to occur in part through reductions in air pollution exposure and odds of attention-deficit/hyperactivity disorder (ADHD). This study analysed the effects of residential green and blue spaces on working memory of children in the Spanish INfancia y Medio Ambiente (INMA) birth cohort and the potential joint mediating role of air pollution and ADHD. The study samples were composed of 1738 six-to eight-year-olds (M = 7.53, SD = 0.68, 49% female) and 1449 ten-to twelve-year-olds (M = 11.18, SD = 0.69, 50% female) living in Asturias, Gipuzkoa, Sabadell or Valencia, Spain. Individual Normalized Difference Vegetation Index (NDVI) values in 100-, 300- and 500-m buffers and availability of green and blue spaces &gt;5000 m2 in 300-m buffers were calculated using Geographic Information Systems software. Individual NO2 values for the home environment were estimated using ESCAPE's land use regression models. ADHD diagnosis was reported by participants' parents via a questionnaire. Working memory was measured with numbers and colours (in the younger group only) N-back tests (2- and 3-back d’). Mixed-effects models informed of the beneficial effects of NDVI in a 300-m buffer on numerical working memory in the younger sample although the results were not consistent for all d’ scores considered and failed to detect significant effects through the candidate mediators. Availability of major blue spaces did not predict working memory performance. Provision of green spaces may play a role in children's working memory but further research is required.</p

Biomarker identification in HIV and non-HIV related lymphomas

DLBCL is the most common lymphoma subtype occurring in older populations as well as in younger HIV infected patients. The current treatment options for DLBCL are effective for most patients yet the relapse rate is high. While many biomarkers for DLBCL exist, they are not in clinical use due to low sensitivity and specificity. In addition, these biomarkers have not been studied in the HIV context. Therefore, the identification of new biomarkers for HIV negative and HIV positive DLBCL, may lead to a better understanding of the disease pathology and better therapeutic design. Initially differences in the clinicopathological features between HIV negative and HIV positive DLBCL patients were determined by conducting a retrospective study of patients treated at GSH. Subsequent to this, potential protein biomarkers for DLBCL were determined using MALDI imaging mass spectrometry (IMS) and characterised using LCMS. The expression of one of the biomarkers, heat shock protein (Hsp) 70, was confirmed on a separate cohort of samples using immunohistochemistry. Our results indicate that the clinicopathological features for HIV negative and HIV positive DLBCL are similar except for median age, and frequency of elevated LDH levels. Several clinicopathological factors were prognostic for all DLBCL cases including age, gender, stage and bone marrow involvement. In addition, tumour extranodal site was also a prognostic indicator for the HIV negative cohort. The biomarkers identified in the study consisted of four protein clusters including glycolytic enzymes, ribosomal proteins, histones and collagen. These proteins could differentiate between control and tumour tissue, and the DLBCL subtypes in both cohorts. The majority (41/52) of samples in the confirmation cohort were negative for Hsp70 expression. The HIV positive DLBCL cases had a higher percentage of cases expressing Hsp70 than their HIV negative counterparts. The non-GC subtype also frequently overexpressed Hsp70, confirming MALDI IMS data. Expression of Hsp70 correlated with poor outcome in the HIV negative cohort. In conclusion, this study identified potential biomarkers for HIV negative and HIV positive DLBCL from both clinical and molecular sources. These may be used as diagnostic and prognostic markers complementary to current clinical management for DLBCL