Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum

Background

Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.

Methods

To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.

Results

We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.

Conclusion

Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.     

A Diagnostic Program for Patients Suspected of Having Lung Cancer

BackgroundA standardized diagnostic program, initiated to reduce the length of the diagnostic track and to improve application of diagnostic tools for patients referred with suspicious abnormalities on standard chest radiographs, was evaluated.MethodsThe findings on integrated positron emission tomography/computed tomography (PET-CT) determined the choice of invasive investigations to be performed the same day. Diagnostic results, time courses, and number and sorts of applied invasive investigations were assessed.ResultsIn 297 eligible patients, malignant disease was diagnosed in 72% and benign disease was diagnosed in 26% of patients. One percent of the patients had no abnormalities at all. For 85% of patients with malignancy, investigations were completed in 1 day, resulting in a diagnosis and definitive clinical disease stage. The median time from start of the analysis to informing the patient about diagnosis and tumor stage was 7 days. One invasive investigation was performed in 53% of patients in the study group, and at least 2 investigations were performed in 33% of patients. Bronchoscopies formed a part of the diagnostic process in 59% of patients. Surgical diagnostic procedures were performed in 8% of patients.ConclusionThe diagnostic program resulted in a short time to diagnosis, with finalization of invasive investigations in 1 day in the majority of patients. The imaging-based choice of invasive investigations precluded bronchoscopies in a substantial portion of the patients.     

Epidemiologic and Genomic Analysis of SARS-CoV-2 Delta Variant Superspreading Event in Nightclub,the Netherlands,June 2021

We report a severe acute respiratory syndrome coronavirus 2 superspreading event in the Netherlands after distancing rules were lifted in nightclubs, despite requiring a negative test or vaccination. This occurrence illustrates the potential for rapid dissemination of variants in largely unvaccinated populations under such conditions. We detected subsequent community transmission of this strain.     

Changes in peripheral blood CD5 (Bla) B-cell populations and autoantibodies following blood transfusion

BACKGROUND: CD5 B cells and the natural autoantibodies they produce play a role in antigen presentation, tolerance induction, and maintenance of an idiotypic immune network. The effects of transfusion on autoantibodies and peripheral blood CD5 B cells were studied. STUDY DESIGN AND METHODS: Eight previously transfused patients with sickle cell anemia and five patients who underwent orthopedic surgical procedures with transfusion were enrolled in the study. Patients in both groups received 1 to 2 units of allogeneic packed red cells. Ten untransfused healthy adults and five patients who underwent orthopedic surgery without transfusion were enrolled as controls. Peripheral blood CD5 B cells, serum levels of IgM, antinuclear antibodies, rheumatoid factor, and anticardiolipin IgM were quantitated either at the beginning of the study (baseline sample), before transfusion, or before surgery and either at 1-, 2-, 4-, 6-, and 8-week intervals after transfusion, after surgery, or after the baseline sample was obtained. RESULTS: IgM levels and the absolute number of B cells that coexpressed CD5 rose to twice pretransfusion levels in six of eight transfused sickle cell anemia patients and in four of five transfused orthopedic surgery patients. No comparable increases in CD5 B cells were noted in untransfused controls. Preexisting rheumatoid factor and antinuclear antibody levels increased in four of five transfused orthopedic surgery patients. One sickle cell anemia patient developed anti-Fya despite receiving Fya-negative blood. Increasing titers of anti-Fya paralleled the increases in IgM and CD5 B cells after transfusion. One patient who developed a positive direct antiglobulin test after transfusion had large increases in serum anticardiolipin IgM. Anticardiolipin IgM was subsequently eluted from direct antiglobulin test-positive red cells obtained after transfusion. Antibodies with anti-Fya-like activity and anticardiolipin IgM were produced in vitro by CD5 B cells and not by conventional CD5-negative B cells. CONCLUSION: An association was found between transfusion-induced increases in CD5 B cells and increased autoantibody production. These data may have implications for immunologic intervention to prevent the induction of red cell antibodies and other changes in the immune system caused by exposure to foreign antigens via blood transfusion.     

The behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with buserelin

This randomized double-blind placebo-controlled study was initiated to analyze the behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with a low dose (20 g) of a luteinizing hormone-releasing hormone analogue (Buserelin), administered daily, as a nasal spray, for a short period (28 days). Fifty-nine true cryptorchid boys were randomly assigned to 3 groups: buserelin, treatment [22], surgical treatment [18] or placebo control group [19]. The 3 groups of patients were similar before treatment in regard to testicular position, chronological and bone age, height and weight, luteinizing hormone, follicle-stimulating hormone, testosterone, penile size and the volume of the contralateral descended testis. None of the patients had retractile testes. Buserelin significantly induced testicular descent compared to the boys treated with a placebo (P<0.01). A normal epididymis was found more often in boys with successful descent (P<0.003). A closed processus vaginalis was also more frequently observed in the group treated with buserelin than in surgically treated one (P<0.05). In conclusion, buserelin was capable of inducing testicular descent besides provoking further development of the epididymis and closing the processus vaginalis.     

Management of Cardiogenic Shock: Focus on Tissue Perfusion

Cardiogenic shock (CS) may result from ischemic heart disease, cardiomyopathy, valvular heart disease, inflammation, myocardial contusion, and cardiac surgery. CS is the leading cause of in-hospital death in patients with acute myocardial infarction. Although early revascularization strategies have resulted in a better prognosis, in-hospital mortality from CS remains exceptionally high. Notably, long-term annual mortality is similar in survivors of CS relative to patients with myocardial infarction without shock. This underlines the importance of aggressive support of the failing heart in the acute phase of CS. Because CS reflects a state of hypoperfusion induced by heart failure, management of CS should aim at improving cardiac function as well as at optimization of tissue perfusion. This review evaluates the current treatment of CS. In addition, novel approaches to monitor and modulate peripheral circulation at the bedside are highlighted. It is expected that these techniques will improve our understanding of the pathogenesis of CS and will offer new opportunities to guide therapy in CS patients to improve long-term prognosis.     

Nitric oxide production during the early neonatal period in small-for-gestational-age infants

In a study of endogenous nitric oxide production in growth-retarded, very preterm newborns (<32 wk GA), urinary NOx/creatinine ratio and plasma guanosine 3',5'-cyclic monophosphate levels were determined during the early neonatal period. Newborns were divided into three groups: appropriate-for-gestational-age (AGA, n = 19), moderately small-for-gestational-age (SGA, n = 13) and severely SGA (n = 6) infants. Severely SGA infants showed significant higher values of nitric oxide derivatives during the first 24 h of life compared with the other groups. CONCLUSION: An increased NO production is found in SGA infants during the first 24 h after birth. This may reflect an increased intrauterine nitric oxide production in the feto-placental circulation found in cases with intrauterine growth retardation,     

Quantity not composition of dietary fats represents the dominant contributor to experimental obesity: Relevance to human pathophysiology

Plant fats are low in saturated fats but high in unsaturated fats compared to animal fats, and are supposedly less obesogenic. This study compared the obesogenic effects of plant and animal derived fatty diets in Wistar rats. Rats of each gender were divided into three dietary (standard chow (SC), high fat diet rich in animal fat (HFDaf) and a high fat diet rich in plant fat (HFDpf)) groups of ten each and fed for 17 weeks. Anthropometric, Adiposity and nutritive variables were assessed using standard methods. Comparing HFDpf to HFDaf: Abdominal circumference (AC),initial feed intaken (IFI), final feed intake(FFI), final body weight (FBW), white adipose tissue (WAT) were increased but brown adipose tissue (BAT) decreased in male rats fed with HFDpf; also, there were increased body length, IFI, FFI but decreased AC, FBW, BAT in female rats fed with HFDpf. Comparing male to female rats: Thoracic circumference, IFI, FFI, energy intake were increased while Adiposity index decreased across diet groups in male rats; the AC, FBW increased while WAT, BAT decreased in HFDpf fed group, also, BAT was increased but AC, FBW decreased in HFDaf fed group in male rats. Palatability and high feed efficiency of consumed diets were more associated with obesogenic risk than just the level of saturation. Therefore, Obesogenic effects of fatty diets in both genders is more dependent on the quantity (amount) of fatty diet consumed than the dietary fat composition alone.