Pre-natal and post-natal exposure to respiratory infection and atopic diseases development: a historical cohort study

BACKGROUND: According to the hygiene hypothesis, infections in early life protect from allergic diseases. However, in earlier studies surrogate measures of infection rather than clinical infections were associated with decreased frequencies of atopic diseases. Exposure to infection indicating sub-clinical infection rather than clinical infection might protect from atopic diseases. Objective: to investigate whether exposure to acute respiratory infections within pregnancy and the first year of life is associated with atopic conditions at age 5–14 years and to explore when within pregnancy and the first year of life this exposure is most likely to be protective. METHODS: Historical cohort study: Population level data on acute respiratory infections from the routine reporting system of the former German Democratic Republic were linked with individual data from consecutive surveys on atopic diseases in the same region (n = 4672). Statistical analyses included multivariate logistic regression analysis and polynomial distributed lag models. RESULTS: High exposure to acute respiratory infection between pregnancy and age one year was associated with overall reduced odds of asthma, eczema, hay fever, atopic sensitization and total IgE. Exposure in the first 9 months of life showed the most pronounced effect. Adjusted odds ratio's for asthma, hay fever, inhalant sensitization and total IgE were statistical significantly reduced up to around half. CONCLUSION: Exposure to respiratory infection (most likely indicating sub-clinical infection) within pregnancy and the first year of life may be protective in atopic diseases development. The post-natal period thereby seems to be particularly important

The PlcR Virulence Regulon of Bacillus cereus

PlcR is a Bacillus cereus transcriptional regulator, which activates gene expression by binding to a nucleotidic sequence called the ‘PlcR box’. To build a list of all genes included in the PlcR regulon, a consensus sequence was identified by directed mutagenesis. The reference strain ATCC14579 sequenced genome was searched for occurrences of this consensus sequence to produce a virtual regulon. PlcR control of these genes was confirmed by comparing gene expression in the reference strain and its isogenic Δ-plcR strain using DNA microarrays, lacZ fusions and proteomics methods. The resulting list included 45 genes controlled by 28 PlcR boxes. Forty of the PlcR controlled proteins were exported, of which 22 were secreted in the extracellular medium and 18 were bound or attached to cell wall structures (membrane or peptidoglycan layer). The functions of these proteins were related to food supply (phospholipases, proteases, toxins), cell protection (bacteriocins, toxins, transporters, cell wall biogenesis) and environment-sensing (two-component sensors, chemotaxis proteins, GGDEF family regulators). Four genes coded for cytoplasmic regulators. The PlcR regulon appears to integrate a large range of environmental signals, including food deprivation and self cell-density, and regulate the transcription of genes designed to overcome obstacles that hinder B. cereus growth within the host: food supply, host barriers, host immune defenses, and competition with other bacterial species. PlcR appears to be a key component in the efficient adaptation of B. cereus to its host environment

Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation

Efficacy and tolerability in patients with chronic facial pain of two consecutive treatment periods of rTMS applied over the facial motor cortex, using protocols differing in stimulation frequency, duration, and train pattern

Abstract Objective: We conducted an open-label cross-over study assessing the global effect of two high-frequency protocols of electric-field navigated repetitive transcranial magnetic stimulation (rTMS) targeted to functional facial motor cortex and comparing their efficacy and tolerability in patients with chronic facial pain. Outcome predictors were also assessed. Methods: We randomized twenty consecutive patients with chronic facial pain (post-traumatic trigeminal neuropathic pain, n=14; persistent idiopathic facial pain, n=4; secondary trigeminal neuralgia, n=2) to receive two distinct 5-day rTMS interventions (10Hz, 2400 pulses and 20Hz, 3600 pulses) separated by six weeks. The target area was assessed by mapping of lower face representation. The primary endpoint was the change in weekly mean of pain intensity (numeric rating scale, NRS) between the baseline and therapy week (1st week), and follow-up weeks (2nd and 3rd weeks) for each rTMS intervention. Response was defined using a combination scale including the patient’s global impression of change and continuance with maintenance treatment. Results: Overall, pain intensity NRS decreased from 7.4 at baseline to 5.9 ten weeks later, after the second rTMS intervention (p=0.009). The repetition of the treatment had a significant effect (F=4.983, p=0.043) indicating that the NRS scores are lower during the second four weeks period. Eight (40%) patients were responders, 4 (20%) exhibited a modest effect, 4 (20%) displayed no effect, and 4 (20%) experienced worsening of pain. High disability and high pain intensity (>7) predicted a better outcome (p=0.043 and p=0.045). Female gender, shorter duration of pain and low Beck Anxiety Inventory scores showed a trend towards a better outcome (p=0.052, 0.060 and 0.055, respectively). Conclusions: High-frequency rTMS targeted to face M1 alleviates treatment resistant chronic facial pain. Repeated treatment improves the analgesic effect. A protocol with higher frequency (above 10Hz), longer session duration (more than 20 minutes) and higher number of pulses (above 2400 pulses/session) did not improve the outcome. The results support early consideration of rTMS