High indoor microbial levels are associated with reduced Th1 cytokine secretion capacity in infancy

Background: Exposure to microbes and their components may affect the maturation of the immune system. We examined the association of house dust microbial content with cytokine-producing capacity at birth and at the age of 1 year. Methods: Production of TNF-α, IFN-γ, IL-5, IL-8 and IL-10 at birth (n = 228) and at the age of 1 year (n = 200) following 24- and 48-hour whole-blood stimulation with staphylococcal enterotoxin B (SEB), lipopolysaccharide and the combination of phorbol ester and ionomycin was measured. Concentrations of ergosterol (marker for fungal biomass), muramic acid (marker for Gram-positive bacteria) and 3-hydroxy fatty acids with a carbon chain length from 10 to 14 (marker for Gram-negative bacteria) in living room floor dust were analyzed using gas chromatography-tandem mass spectrometry. Five single microbial species or groups were determined using a quantitative polymerase chain reaction method. Results: A high total level of the studied Gram-positive bacteria in general or Mycobacterium spp. in house dust was associated with decreased SEB-stimulated IFN-γ production, especially at the age of 1 year. The total level of indoor fungi analyzed (Penicillium spp., Aspergillus spp. and Paecilomyces variotii group, Trichoderma viride/atroviride/koningii,Wallemia sebi) was also inversely associated with IFN-γ production at the age of 1 year, but this association did not remain significant after adjustment for potential confounders. A few associations were found between microbial exposures and other measured cytokines. Conclusions: High indoor microbial exposures may affect immune development in early life by reducing T helper type 1 cytokine secretion capacity. The observed hyporesponsiveness may reflect the adaptation of the immune system to environmental antigens. In future, more attention should be paid especially to the immunomodulatory role of exposures to Gram-positive bacteria.     

Odour annoyance and physical symptoms among residents living near waste treatment centres

Waste treatment processes produce odours and biological emissions to the environment, but their health effects are controversial. The aim of our study was to assess odour-associated self-reported physical symptoms among residents living near waste treatment centres. The study was conducted in the surroundings of five large-scale Finnish waste treatment centres with composting plants. In 2006, 1142 randomly selected residents living within 1.5, 3.0 and 5.0 km of these centres were interviewed by telephone. A questionnaire with 102 items asked about respondent's personal characteristics, odour exposure and symptoms during the preceding 12 months. Physical symptoms were analysed by distance to the waste treatment centre and by the respondent's perception and annoyance of waste treatment odour. The residents who were classified as “annoyed of the odour” reported following physical symptoms more than the others did: unusual shortness of breath (OR 1.5, 95% CI 1.0–2.2), eye irritation (1.5, 1.1–2.1), hoarseness/dry throat (1.5, 1.1–2.0), toothache (1.4, 1.0–2.1), unusual tiredness (1.5, 1.1–2.0), fever/shivering (1.7, 1.1–2.5), joint pain (1.5, 1.1–2.1) and muscular pain (1.5, 1.1–2.0). Moreover, the ORs for almost all other physical symptoms were elevated among the annoyed respondents. Reported odour annoyance near the waste treatment centres showed an association with many physical symptoms among residents living in the neighbouring areas.     

Increased levels of lipid peroxides in aged rat brain as revealed by direct assay of peroxide values

Lipid peroxide concentrations in brain tissues of young and aged rats were determined by a direct method for measuring peroxide values. Three different brain regions were analyzed for lipid peroxides. The peroxide levels increased in all three regions of aged as compared to those of young rats, while lipid peroxides in plasma appeared to be stable along with age. Lipid peroxides in cerebrum and cerebellum increased 1.6-2.0 times in aged brains compared with young ones, and about 3-fold in the brain stem. Increased levels of lipid peroxides in aged brains seem not merely due to increased pools of precursor polyene fatty acids, but rather due to altered protection systems for lipid peroxidase formation.     

Effects of Preoperative Atorvastatin Treatment On Erectile Function After Radical Prostatectomy: Results From a Subgroup of ESTO1, a Randomized,Double-Blind,Placebo-Controlled Study

IntroductionErectile dysfunction is common after radical prostatectomy because of damage to the cavernous nerves. Thus, it is important to identify new ways to avoid this problem. For example, statins have shown positive effects on erectile function and may have anti-inflammatory effects that improve recovery after surgery.AimThe aim of this exploratory analysis of a subgroup from ESTO1, a randomized, double-blind, placebo-controlled study, was to evaluate the preoperative use of atorvastatin on erectile function after radical prostatectomy.MethodPatients were randomized to either 80 mg atorvastatin or placebo daily before undergoing radical prostatectomy from study inclusion to the day of surgery. Altogether 118 men with prostate cancer and scheduled for radical prostatectomy were asked to fill out the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire before surgery and at 3, 6, 9, and 12 months after surgery.Main Outcome MeasurementsThe study was exploratory, with the main outcome being the overall difference between IIEF-5 scores in the 2 groups at 12 months. Several hypotheses generating sub-analyses were conducted.ResultsOverall, 85% filled out the IIEF-5 questionnaire before their operation and 85%, 81%, 78%, and 78% completed it at 3, 6, 9, and 12 months follow-up, respectively. 52% of men had information available at all time points. There were no statistically significant differences between the groups at baseline in either erectile function, comorbidities, or tumor characteristics. The median duration of use of atorvastatin and placebo before surgery was 27 and 25 days, respectively. Preoperative atorvastatin treatment had no statistically significant effect on erectile function after prostatectomy as compared with placebo, although IIEF-5 scores were higher at all time points in the statin arm. Furthermore, atorvastatin treatment compared with placebo improved IIEF-5 scores at 12 months after surgery when the cavernous nerves were at least partially intact bilaterally (P < .04, n = 65); however, after full bilateral or unilateral nerve-sparing, the difference was not statistically significant.Clinical ImplicationShort-term statin treatment did not improve recovery of erectile function after prostatectomy; however, further studies are needed before final conclusions.Strengths & LimitationsThis was a randomized placebo-controlled study. Original ESTO1 study was designed to detect a difference in prostate cancer biomarkers.ConclusionShort-term atorvastatin treatment before radical prostatectomy had no statistically significant effect on the recovery of erectile functions in a non-selected cohort of patients undergoing radical prostatectomy. Further studies will be needed to clarify the role of long-term atorvastatin use before and after prostatectomy.Siltari A, Riikonen J, Fode M, et al. Effects of Preoperative Atorvastatin Treatment On Erectile Function After Radical Prostatectomy: Results From a Subgroup of ESTO1, a Randomized, Double-Blind, Placebo-Controlled Study. J Sex Med 2019;16:1597–1605.     

Results from a randomized clinical trial of coadministration of RotaTeq, a pentavalent rotavirus vaccine, and NeisVac-C, a meningococcal serogroup C conjugate vaccine

RotaTeq (Merck & Co. Inc./Sanofi Pasteur MSD) is a three-dose, oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis. The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine (MenCC; NeisVac-C; Baxter Healthcare) to healthy infants without impairing the protective immune responses to MenCC. This was an open-label, randomized, comparative study conducted in Finland. The study was designed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines. Healthy infants (n = 247), aged 6 to 7 weeks, were recruited. Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C (the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ≥ 8 was 100% in both groups). The other responses to MenCC (titer of ≥ 1:128, ≥ 4-fold increase in titer, and geometric mean titers [GMTs]) and the responses to RotaTeq (IgA and SNA response to G1 to G4 and P1A[8], GMTs, and ≥ 3-fold increase in titer) were comparable between groups, including a ≥ 3-fold IgA increase in >96% of the infants in both groups. Concomitant administration of the first doses of MenCC, diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib), and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib, but that was not observed after the second concomitant administration. The convenience of concomitant administration of RotaTeq and MenCC may, however, outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine. These results support the coadministration of RotaTeq and MenCC.     

Immunogenicity and safety of the human rotavirus vaccine Rotarix™ co-administered with routine infant vaccines following the vaccination schedules in Europe

This study assessed the immunogenicity and safety of a human rotavirus vaccine RIX4414; the effect of co-administration of childhood vaccines on the immune responses was also assessed.     

Annual injection of vitamin D and fractures of aged bones

Summary In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people, an annual intramuscular injection of ergocalciferol (150,000–300,000 IU) was given to two series of aged subjects: first to 199 (45 male) of 479 subjects (110 male) aged more than 85 years who were living in their own home, and second to 142 (29 male) of 320 (58 male) subjects aged 75–84 and living in a home for aged people. This prospective series was divided into treatment groups according to month of birth. These injections were given annually from September to December in the years 1985–1989, two to five times to each participant. The fracture rates, laboratory values, vitamin D levels, possible side effects, and mortality were followed until October 1990. A total of 56 fractures occurred in the 341 vitamin D recipients (16.4%) and 100 in 458 controls (21.8%) (P=0.034). The fracture rate was about the same in both outpatient and municipal home series. Fractures of the upper limb were fewer in the vitamin D recipients, 10/341=2.9% (P=0.025), than in the controls, 28/458=6.1%, during the follow-up. A similar result was obtained in fractures of ribs, 3/341=0.9% and 12/458=2.6%, respectively. Fractures of the lower limbs occurred almost as frequently, 31/341=9.1%, among the vitamin D recipients as among the controls, 49/458=10.7%. The fracture rate was higher in females (22.2%) than in males (9.5%). The fractures were fewer in the vitamin D recipients only in females. No significant differences were found in total mortality, or due to any group of diseases, between the two treatment groups. No deleterious effects of the vitamin D injections were seen. The authors recommend the supplementation of vitamin D in aged people, at least in northernmost latitudes (e.g., as an annual intramuscular injection).