Intralymphatic allergen administration renders specific immunotherapy faster and safer: A randomized controlled trial

The only causative treatment for IgE-mediated allergies is allergen-specific immunotherapy. However, fewer than 5% of allergy patients receive immunotherapy because of its long duration and risk of allergic side effects. We aimed at enhancing s.c. immunotherapy by direct administration of allergen into s.c. lymph nodes. The objective was to evaluate safety and efficacy compared with conventional s.c. immunotherapy. In a monocentric open-label trial, 165 patients with grass pollen-induced rhinoconjunctivitis were randomized to receive either 54 s.c. injections with pollen extract over 3 years [cumulative allergen dose 4,031,540 standardized quality units (SQ-U)] or 3 intralymphatic injections over 2 months (cumulative allergen dose 3,000 SQ-U). Patients were evaluated after 4 months, 1 year, and 3 years by nasal provocation, skin prick testing, IgE measurements, and symptom scores. Three low-dose intralymphatic allergen administrations increased tolerance to nasal provocation with pollen already within 4 months (P < 0.001). Tolerance was long lasting and equivalent to that achievable after standard s.c. immunotherapy (P = 0.291 after 3 years). Intralymphatic immunotherapy ameliorated hay fever symptoms (P < 0.001), reduced skin prick test reactivity (P < 0.001), decreased specific serum IgE (P < 0.001), caused fewer adverse events than s.c. immunotherapy (P = 0.001), enhanced compliance (P < 0.001), and was less painful than venous puncture (P = 0.018). In conclusion, intralymphatic allergen administration enhanced safety and efficacy of immunotherapy and reduced treatment time from 3 years to 8 weeks.     

The cardiovascular outcomes,heart failure and kidney disease trials tell that the time to use Sodium Glucose Cotransporter 2 inhibitors is now

Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5 years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of the evidence. SGLT2i improve cardiorenal outcomes and have a beneficial risk benefit ratio across populations with cardiovascular disease, HFrEF and kidney disease. In this quantitative review, we synthesize the data from the large outcomes trials about the benefits and risks of SGLT2i. SGLT2i reduce all cause, cardiovascular mortality, heart failure hospitalizations, need for dialysis and acute kidney injury as a class effect across a broad range of populations with diabetes Type 2 at risk for cardiovascular disease, patients with HFrEF or CKD with or without diabetes. While certain adverse events for example, diabetic ketoacidosis and genital mycotic infections are reproducibly increased by SGLT2i, the absolute increase in the risk of these complications is smaller than the absolute risk reductions conferred by SGLT2i. Other complications such as amputations, fractures and urinary tract infections are increased to a lesser degree, or not at all (e.g., hypoglycemia). Overall, SGLT2is appear to have a favorable safety profile and thus should be used by cardiologists, nephrologists, endocrinologists, primary care physicians when managing the cardiorenal risk of their patients.     

Formation of Pseudomonas aeruginosa inhibition zone during tobramycin disk diffusion is due to transition from planktonic to biofilm mode of growth

Pseudomonas aeruginosa PAO1 (tobramycin MIC?=?0.064 µg/mL) was used to perform agar diffusion tests employing tobramycin-containing tablets. Bacterial growth and formation of inhibition zones were studied by stereomicroscopy and by blotting with microscope slides and staining with methylene blue, Alcian blue and a fluorescent lectin for the P. aeruginosa PSL, which was studied by confocal laser scanning microscopy. Diffusion of tobramycin from the deposit was modelled using a 3D geometric version of Fick's second law of diffusion. The time-dependent gradual increase in the minimum biofilm eradication concentration (MBEC) was studied using a Calgary Biofilm Device. The early inhibition zone was visible after 5 h of incubation. The corresponding calculated tobramycin concentration at the border was 1.9 µg/mL, which increased to 3.2 µg/mL and 6.3 µg/mL after 7 h and 24 h, respectively. The inhibition zone increased to the stable final zone after 7 h of incubation. Bacterial growth and small aggregate formation (young biofilms) took place inside the inhibition zone until the small aggregates contained less than ca. 64 cells and production of polysaccharide matrix including PSL had begun; thereafter, the small bacterial aggregates were killed by tobramycin. Bacteria at the border of the stable inhibition zone and beyond continued to grow to a mature biofilm and produced large amount of polysaccharide-containing matrix. Formation of the inhibition zone during agar diffusion antimicrobial susceptibility testing is due to a switch from a planktonic to biofilm mode of growth and gives clinically important information about the increased antimicrobial tolerance of biofilms.     

Systemic immunogenicity of para-Phenylenediamine and Diphenylcyclopropenone: two potent contact allergy-inducing haptens

p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1 % w/v or 0.01 % w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1 % PPD, 0.01 % DPCP or 0.1 % DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8⁺ T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-γ- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases.     

Identification of Candida species in the clinical laboratory: a review of conventional,commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species.     

The influence of epigenetics in relation to oral health

The immune response is influenced by genetic and epigenetic factors, as well as disease and environmental factors. The term ‘epigenetics’ describes changes in the genome that influence the gene expression without altering the DNA sequence. In contrast to genetic changes in the DNA, epigenetic changes are reversible and are influenced by environmental factors. The aim of this study is to review the literature on epigenetic modifications with respect to oral health and inflammatory conditions in the oral cavity and to discuss the potential use of this new research field for the dental hygienists' and/or dentists' clinical work. Relevant publications were identified using the PubMed database without limits. The searches were conducted during January to March 2012 and resulted in articles published between 1912 and 2012. Key factors such as environment, diet, smoking, bacteria and inflammation were identified to be relevant to oral health. The result of this review article shows that there is a void in the research on epigenetics in relation to oral health. Identification of epigenetic modifications correlating with oral health may not only present a link between the influence of genetics and that of the environment on oral diseases but also provide new treatment models and tools for the dental professionals.     

Low Seroprevalence among Undetected COVID-19 Cases,Faroe Islands,November 2020

We conducted a second nationwide severe acute respiratory syndrome coronavirus 2 seroprevalence study in the Faroe Islands during November 2020. We found crude seroprevalence was 0.3% and prevalence was 0.4% after adjusting for test sensitivity and specificity. This low seroprevalence supports the prevention strategies used in the Faroe Islands.