FLASHlab@PITZ: New R&D platform with unique capabilities for electron FLASH and VHEE radiation therapy and radiation biology under preparation at PITZ.

At the Photo Injector Test facility at DESY in Zeuthen (PITZ), an R&D platform for electron FLASH and very high energy electron radiation therapy and radiation biology is being prepared (FLASHlab@PITZ). The beam parameters available at PITZ are worldwide unique. They are based on experiences from 20 + years of developing high brightness beam sources and an ultra-intensive THz light source demonstrator for ps scale electron bunches with up to 5 nC bunch charge at MHz repetition rate in bunch trains of up to 1 ms length, currently 22 MeV (upgrade to 250 MeV planned). Individual bunches can provide peak dose rates up to 1014 Gy/s, and 10 Gy can be delivered within picoseconds. Upon demand, each bunch of the bunch train can be guided to a different transverse location, so that either a "painting" with micro beams (comparable to pencil beam scanning in proton therapy) or a cumulative increase of absorbed dose, using a wide beam distribution, can be realized at the tumor. Full tumor treatment can hence be completed within 1 ms, mitigating organ movement issues. With extremely flexible beam manipulation capabilities, FLASHlab@PITZ will cover the current parameter range of successfully demonstrated FLASH effects and extend the parameter range towards yet unexploited short treatment times and high dose rates. A summary of the plans for FLASHlab@PITZ and the status of its realization will be presented.

Biological signalling supports biotechnology - Pulsed electric fields extract a cell-death inducing factor from Chlorella vulgaris.

Compared to mechanical extraction methods, pulsed electric field (PEF) treatment provides an energy-efficient and gentle alternative. However, the biological processes involved are poorly understood. The unicellular green microalga Chlorella vulgaris was used as model organism to investigate the effect of PEF treatment on biological cells. A viability assay using fluorescein diacetate measured by flow cytometry was established. The influence of developmental stage on viability could be shown in synchronised cultures when applying PEF treatment with very low specific energies where one part of cells undergoes cell death, and the other part stays viable after treatment. Reactive oxygen species generation after similar low-energy PEF treatment could be shown, indicating that PEFs could act as abiotic stress signal. Most importantly, a cell-death inducing factor could be extracted. A water-soluble extract derived from microalgae suspensions incubated for 24 h after PEF treatment caused the recipient microalgae to die, even though the recipient cells had not been subjected to PEF treatment directly. The working model assumes that low-energy PEF treatment induces programmed cell death in C.vulgaris while specifically releasing a cell-death inducing factor. Low-energy PEF treatment with subsequent incubation period could be a novel biotechnological strategy to extract soluble proteins and lipids in cascade process.

Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study.

Background: IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results: A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

Impact of incubation conditions on protein and C-Phycocyanin recovery from Arthrospira platensis post- pulsed electric field treatment.

Pulsed electric field (PEF) was conducted for the extraction of proteins/C-Phycocyanins from Arthrospira platensis. The cyanobacterial suspension was treated with 1 µs long pulses at an electric field strength of 40 kV·cm-1 and a treatment energy of 114 kJ·kgsus-1 and 56 kJ·kgsus-1. For benchmarking, additional biomass was processed by high pressure homogenization. Homogeneity of the suspension prior to PEF-treatment influenced the protein/C-phycocyanin extraction efficiency. Stability of C-Phycocyanin during post-PEF incubation time was affected by incubation temperature and pH of the external medium. Biomass concentration severely affect proteins/C-Phycocyanins extraction yield via PEF-treatment. The optimum conditions for extraction of proteins/C-Phycocyanin was obtained at 23 °C while incubating in pH 8-buffer. The energy demand for PEF-treatment amounts to 0.56 MJ·kgdw-1 when processing biomass at 100 gdw·kgsus-1. PEF treatment enhances the protein/C-Phycocyanin extraction yield, thus, it can be suggested as preferential downstream processing method for the production of C-Phycocyanin from A. platensis biomass.

Occurrence of Fungi and Fungal Toxins in Fish Feed During Storage.

Periods of unfavorable storing conditions can lead to changes in the quality of fish feeds, as well as the development of relevant mycotoxins. In the present study, a commercial fish feed was stored under defined conditions for four weeks. The main findings indicate that even storing fish feeds under unsuitable conditions for a short duration leads to a deterioration in quality. Mycotoxin and fungal contamination were subsequently analyzed. These investigations confirmed that different storage conditions can influence the presence of fungi and mycotoxins on fish feed. Notably, ochratoxin A (OTA) was found in samples after warm (25 °C) and humid (>60% relative humidity) treatment. This confirms the importance of this compound as a typical contaminant of fish feed and reveals how fast this mycotoxin can be formed in fish feed during storage.

Extraction of valuable compounds from Arthrospira platensis using pulsed electric field treatment.

Pulsed electric field (PEF) treatment was evaluated for phycocyanin and proteins extraction from Arthrospira platensis (Spirulina platensis). PEF extractions were performed using different specific energies (28, 56 and 122 J·ml-1 of suspension) and the results were compared to the extraction with bead milling. At highest PEF-treatment energies a damage of the cell morphology could be observed and the highest yields (up to 85.2 ±â€¯5.7 mg·g-1 and 48.4 ±â€¯4.4 g·100 g-1 of phycocyanins and proteins, respectively) could be obtained at 122 and 56 J·ml-1. The yields increased with incubation time after PEF-treatment. The antioxidant capacity of the extracts obtained after PEF-treatment was higher than of those obtained after bead milling. PEF treatment is a promising technology to obtain blue-green antioxidant extracts from A. platensis in an environmental friendly process.

In silico food allergenic risk evaluation of proteins extracted from macroalgae Ulva sp. with pulsed electric fields.

Extraction of protein from macroalgae, currently defined as "novel food", is challenging and limited information about the health impacts of these proteins is available. Here, we report on a non-thermal, chemical-free green macroalgae Ulva sp. protein extraction by osmotic shock combined with pulsed electric fields (PEF) followed by hydraulic pressure. The extracted proteins were identified and annotated to allergens using sequence similarity. The allergenicity potential of PEF extracted proteins was compared to osmotic shock extracts and complete Ulva sp. proteome, extracted with the thermochemical method. The PEF extracts contained 'superoxide dismutase' (SOD), a known food allergen, osmotic shock extract contained 'troponin C', and thermochemical extract contained two additional potential food allergens 'aldolase A' and 'thioredoxin h'. This study shows an importance and the need for deep investigation of algal proteins and protein extraction technology health impacts prior to large-scale release to the market of "novel food" derived proteins.

Deashing macroalgae biomass by pulsed electric field treatment.

Among all biomass constituents, the ashes are major hurdles for biomass processing. Ashes currently have low market value and can make a non-negligible fraction of the biomass dry weight significantly impacting its further processing by degrading equipment, lowering process yield, inhibiting reactions and decreasing products qualities. However, most of the current treatments for deashing biomass are of poor efficiency or industrial relevance. This work is the first report on the use of Pulsed Electric Field (PEF) to enhance deashing of biomass from a high ash content green marine macroalga, Ulva sp., using hydraulic pressing. By inducing cell permeabilization of the fresh biomass, PEF was able to enhance the ash extraction from 18.4% (non-treated control) to 37.4% of the total ash content in average, significantly enhancing the extraction of five of the major ash elements (K, Mg, Na, P and S) compared to pressing alone.

The 80-W KTP GreenLight laser vaporization of the prostate versus transurethral resection of the prostate (TURP): adjusted analysis of 5-year results of a prospective non-randomized bi-center study.

This study aims to compare long-term results of photoselective vaporization of the prostate (PVP) with an 80-W potassium titanyl phosphate (KTP) laser and monopolar transurethral resection of the prostate (TURP) in terms of efficacy, durability, and safety in an adjusted patient population. This prospective, non-randomized bi-center study included 120 (PVP) and 68 (TURP) patients in each arm. Patients were evaluated at 60 months of follow-up. Data from 30 (PVP) and 31 (TURP) patients were available for analysis. The primary outcome measurement was the International Prostate Symptom Score (IPSS) at 5 years. Secondary outcome measurements included voiding symptoms (quality of life (QoL) score), micturition parameters (maximal flow rate, Q max), post-void residual (PVR) volume, prostate-specific antigen (PSA) value, and reoperation rate. At study inclusion, voiding symptoms and micturition parameters were comparable between both groups. Age, prostate volume, and the proportion of patients with platelet aggregation inhibition or oral anticoagulation were significantly higher in the PVP group. No significant difference could be detected between patients available at 60 months and those lost to follow-up in terms of preoperative characteristics in either group. Sixty months postoperatively, the improvement of IPSS, QoL, Q max, and PVR volume showed no significant difference between both groups. PSA reduction was significantly higher after TURP. The reoperation rate due to urethral stricture (PVP, 13 %; TURP, none), bladder neck contracture (PVP, 3 %; TURP, none), and persisting or recurrent adenoma (PVP, 18 %; TURP, 3 %) was significantly higher after the 80-W PVP. Eighty-watt PVP leads to comparable functional outcomes to TURP. However, during a long-term follow-up, significantly more reoperations are necessary after PVP with the 80-W KTP laser, suggesting inferior tissue ablation capacity of the 80-W KTP laser.

GreenLight laser vs diode laser vaporization of the prostate: 3-year results of a prospective nonrandomized study.

BACKGROUND AND OBJECTIVE: Laser vaporization of the prostate is one of the alternatives to transurethral resection of the prostate. Short-term studies report a comparable outcome after laser vaporization with the 532 nm 120-W GreenLight high-performance system (HPS) laser and the 980 nm 200 W high-intensity diode (diode) laser. In this study, we analyzed the intermediate-term results of both techniques. MATERIALS AND METHODS: From January 2007 to January 2008, 112 consecutive patients with symptomatic benign prostate enlargement were nonrandomly assigned to treatment with the GreenLight laser or the diode laser. Perioperative parameters, postoperative functional outcome, complications, and the reoperation rate at 3 years were analyzed. RESULTS: Improvement of voiding symptoms (International Prostate Symptom Score, quality-of-life) and micturition parameters (maximum flow rate, postvoid residual volume) showed no significant difference between the HPS group and the diode group. A significantly higher reoperation rate was observed in the diode group in comparison to the HPS group (37.5% vs 8.9%, p=0.0003) due to obstructive necrotic tissue (16.1% vs 0%, p=0.0018), bladder neck stricture (16.1% vs 1.8%, p=0.008), and persisting or recurrent adenoma (5.4% vs 7.1%, p=0.70), respectively. CONCLUSIONS: Both lasers lead to comparable improvement of voiding parameters and micturition symptoms. Treatment with the 200 W diode laser led to a significantly higher reoperation rate, which might be attributed to a higher degree of coagulation necrosis. Thus, a careful clinical application of this diode laser type is warranted.

Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving µ-calpain activation.

Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved α-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9 cleavage, µ-calpain upregulation and cleaved α-spectrin 145/150kDa) cell death mechanisms were investigated by Western blot analysis. DPTI expedited CA1 neuronal death from day 4 to day 1 and increased the magnitude of CA1 neuronal death from 66.2% to 91.3% at day 7. Furthermore, DPTI decreased the overall (days 1-7) percentage of dying neurons displaying apoptosis-like morphology from 4.7% to 0.3% and, conversely, increased the percentage of neurons with necrosis-like morphology from 95.3% to 99.7%. In animals subjected to TFI without dexamethasone (ischemia-only), 7.4% of all dying CA1 neurons were casp-3-immunoreactive (IR), of which 3.1% co-localized with apoptosis-like and 4.3% with necrosis-like changes. By contrast, DPTI decreased the percentage of dying neurons with casp-3 IR to 1.4%, of which 0.3% co-localized with apoptosis-like changes and 1.1% with necrosis-like changes. Western blot analysis from DPTI animals showed a significant elevation of µ-calpain, a calpain-produced necrosis-related casp-9 fragment (25kDa) and cleavage of α-spectrin into 145/150kDa fragments at day 4, whereas in ischemia-only animals a significant increase of casp-3-cleaved PARP, cleavage of α-spectrin into 145/150 and 120kDa fragments was detected at day 7. We conclude that DPTI, in addition to augmenting and expediting CA1 neuronal death, causes a shift from apoptosis-like cell death to necrosis involving µ-calpain activation.

Maximum tumor diameter adjusted to the risk profile predicts biochemical recurrence after radical prostatectomy.

Currently, no consensus exists on the best method for tumor quantification in prostate cancer (PCA), and its prognostic value remains controversial. We evaluated how a newly defined maximum tumor diameter (MTD) might contribute to the prediction of biochemical recurrence (BCR) in a consecutive series of PCA patients treated with radical prostatectomy (RP). Patients with PCA who underwent RP without neoadjuvant therapy at a single center were included for analysis. MTD was defined as the largest diameter of all identified tumors in all three dimensions (i.e., length, width, or depth) of the prostate ("Basel technique"). Cox regression models addressed the association of MTD with BCR in three risk groups (low risk-prostate-specific antigen (PSA) < 10 ng/ml, pT2, and Gleason score (GS) ≤ 6; intermediate risk-PSA ≥ 10 and <20 ng/ml and/or pT2 and GS = 7; high risk-PSA > 20 ng/ml or pT3 or GS ≥ 8) and whole cohort. Within a median follow-up of 44 months (interquartile range (IQR) 23-66), 48 patients (9.4 %) in the intermediate-risk and high-risk groups experienced BCR. In multivariate Cox regression analysis, PSA, pathological stage (pT stage), GS, positive surgical margins (PSMs), and MTD > 19.5 mm were independent predictors for BCR (p < 0.05). In subgroup analysis, MTD as a nominal variable (<24.5 and >24.5 mm) was the only independent predictor of BCR in the intermediate-risk group (hazard ratio (HR) 9.933, 95 % confidence interval (CI) 2.070-47.665; p < 0.05). MTD is an independent risk factor of BCR in PC patients after RP. The combination of the MTD with other well-known prognostic factors after RP may improve decision-making concerning follow-up intensity or adjuvant treatment.

Seven hours to adequate antimicrobial therapy in urosepsis using isothermal microcalorimetry.

Urosepsis can progress toward severe sepsis, septic shock, and, ultimately, death. Rapid antimicrobial susceptibility testing is crucial to decrease mortality and morbidity. This report shows that isothermal microcalorimetry can provide an antibiogram within 7 h with a sensitivity of 95% and specificity of 91% using Vitek-2 system as a reference.

Vaporization techniques for benign prostatic obstruction: GreenLight all the way?

PURPOSE OF REVIEW: To give an overview and discuss the recent literature of different vaporization techniques of the prostate using laser energy or high-frequency current. RECENT FINDINGS: Ten studies covering GreenLight vaporization of the prostate with its evolution from 80 W KTP to 120 W HPS to 180 W XPS system were identified. Only one study had a randomized design comparing HPS to transurethral resection of the prostate. The diode laser is discussed with its results after recent modification with quartz head fiber. Although complication rates are low, the comparison to transurethral resection of the prostate is lacking. Current data on established vapoenucleation and promising vaporesection of thulium:YAG lasers are presented. Further, recent studies on plasmakinetic vaporization are discussed. SUMMARY: At present, high evidence data on vaporization techniques of the prostate are lacking. The data on GreenLight vaporization of the prostate are the most convincing.

Potential consequences of low biopsy core number in selection of patients with prostate cancer for current active surveillance protocols.

OBJECTIVE: To compare the performance of the Epstein criteria and the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria in the identification of patients eligible for active surveillance (AS) but treated with radical prostatectomy. MATERIALS AND METHODS: We evaluated the baseline characteristics, final pathologic examination, and prostate-specific antigen follow-up (median 43 months, range 1-118) in a series of 492 consecutive patients with prostate cancer managed by radical prostatectomy without AS from 2001 to 2011 at a single institution. Using the postoperative histologic findings, multivariate analysis was used to identify the preoperative predictors of unfavorable AS selection (Gleason score >6 and/or greater than stage pT2c on the final pathologic examination). Biochemical recurrence-free survival was compared between favorably and unfavorably selected patients. RESULTS: Applying the Epstein and PRIAS criteria, 29.2% and 32.2% of the patients had Gleason score >6 or stage pT3 on final pathologic examination, respectively. After a median follow-up of 35.5 and 38 months, 4.2% and 4.3% of patients developed biochemical recurrence in the Epstein and PRIAS criteria groups, respectively. Patients with unfavorable selection had significantly worse biochemical recurrence-free survival than patients with favorable selection (P <.05). Although the median biopsy core number was 8, a biopsy core number <9 was a significant and independent predictor for unfavorable preoperative AS selection in the PRIAS group. CONCLUSION: We found a non-negligible risk of underestimating unfavorable cancer in patients theoretically qualifying for AS in our cohort. The current use of a sufficient number of biopsy cores might improve the selection process for AS.

The effect of increased maximum power output on perioperative and early postoperative outcome in photoselective vaporization of the prostate.

BACKGROUND AND OBJECTIVE: Preclinical studies suggest an increased vaporization rate and speed of the 532 nm 180-W XPS GreenLight laser (180-W) compared with the 120-W HPS GreenLight laser (120-W) and the 80-W PV GreenLight laser (80-W). To test the clinical relevance of this observation we analyzed intraoperative data and early postoperative results after photoselective vaporization of the prostate (PVP) with the 180-W, 120-W, and 80-W laser. STUDY DESIGN/MATERIALS AND METHODS: A retrospective pair-to-pair comparison was performed including 80 consecutive patients who underwent PVP for the treatment of benign prostate enlargement with the 180-W, 120-W, and 80-W laser. The groups matched concerning age, prostate volume, PSA-value, and preoperative catheterization. Primary study outcome measurement was PSA-value reduction at 3 months; intraoperative data, perioperative complications, and early postoperative functional course were secondary study outcome measurements. RESULTS: Energy application per case (kJ), preoperative prostate volume (kJ/ml) operating time (kJ/minute), and lasing time (kJ/minute) was significantly higher with the 180-W laser. Prevalence of impaired visibility due to bleeding was comparable between the 180-W and the 120-W laser but significantly lower with 80-W. Duration of hospitalization was shorter with the 180-W laser compared to the former laser systems. During the postoperative course of 3 months voiding parameters and micturition symptoms significantly improved in all groups, the incidence of postoperative dysuria was comparable. Postoperative PSA-value reduction was significantly higher after treatment with the 180-W laser. CONCLUSIONS: With the 180-W laser, higher energy application and higher speed of tissue vaporization leads to increased tissue vaporization compared to the former 120-W and 80-W laser systems. Clinical efficacy and perioperative safety are maintained with the higher powered laser.

Microbial biofilm formation and catheter-associated bacteriuria in patients with suprapubic catheterisation.

PURPOSE: Catheter-associated bacteriuria (CAB) with transurethral catheters is almost inevitable. Suprapubic catheters (SPCs) are widely considered to decrease the risk of CAB. However, SPCs are implants similarly prone to microbial biofilm formation. The spectrum of colonising pathogens has not been investigated. The aim of this prospective study was: (1) to assess the diversity of microbial suprapubic catheter colonisation (MSPCC), (2) to identify risk factors and (3) to investigate its association with CAB and catheter-associated urinary tract infection (CA-UTI). METHODS: A total of 218 SPCs from 112 patients were studied. Urine specimens were obtained after device replacement or removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex, age, indwelling time, and underlying disease were recorded. RESULTS: Sonicate-fluid culture (SFC) detected MSPCC in 95 %. Increasing indwelling time correlated with MSPCC (p < 0.05). Negative SFC was more frequent when antibiotic prophylaxis was applied at time of catheter placement (15 vs. 2 %, p < 0.05). Most commonly isolated were Enterobacteriaceae (45.8 %), followed by Enterococcus spp. (25.7 %) and Pseudomonas aeruginosa (10.3 %). CAB and CA-UTI were observed in 95 and 11 %, respectively. CONCLUSIONS: This study provides the first analysis of MSPCC. Indwelling time increases, whereas antibiotic prophylaxis decreases the risk of MSPCC. The spectrum of pathogens is comparable to the one obtained from urethral catheter biofilms. Urine specimens could not demonstrate the microbial diversity of MSPCC. SPCs are not preferable to urethral catheters to reduce CAB. Whether the risk of CA-UTI could be minimised by SPCs remains to be clarified.

Microbial colonization and ureteral stent-associated storage lower urinary tract symptoms: the forgotten piece of the puzzle?

PURPOSE: Ureteral stents are frequently associated with side effects. Most patients suffer from storage lower urinary tract symptoms (LUTS). Storage LUTS are commonly attributed to the irritation of the trigone, smooth muscle spasm or a combination of factors. The relationship between microbial ureteral stent colonization (MUSC) and de novo or worsening storage LUTS has not been investigated yet. METHODS: Five hundred ninety-one polyurethane ureteral stents from 275 male and 153 female patients were prospectively evaluated. The removed stents were sonicated to dislodge adherent microorganisms. Urine flow cytometry was performed to detect pyuria. A standardized urinary symptom questionnaire was given to all patients. RESULTS: Thirty-five per cent of male and 28% of female cases showed de novo or worsened storage LUTS. MUSC was more common in patients with storage LUTS compared to patients without storage LUTS (men: 26 vs. 13%, respectively, P < 0.05; women: 63 vs. 48%, respectively, P = 0.13). Pyuria was significantly more common in patients with storage LUTS compared to patients without storage LUTS (men: 55 vs. 40%, respectively, P < 0.05; women: 70 vs. 45%, respectively, P < 0.05). No significant correlation was observed between the detected genera of microorganisms and storage LUTS. CONCLUSIONS: Our data show a significant association between MUSC- and stent-related de novo experienced or worsened storage LUTS in men. The incidence of MUSC is most common in both female and male patients with storage LUTS and accompanying pyuria. In these patients, a combination of antibiotics and anti-inflammatory drugs may be regarded as treatment option.

A cluster randomised controlled trial of an adolescent smoking cessation intervention: short and long-term effects.

BACKGROUND: There is a lack of effective smoking cessation interventions which have a high reach among adolescent smokers. METHOD: We conducted a randomised controlled trial of an adolescent smoking cessation intervention for students aged 15-21 at 22 continuation schools in Denmark. The intervention was a minimal intervention based on events with short counselling and a range of self-help materials. Our 1-month follow up consisted of 514 baseline daily smokers and the 14-month follow up of 369 daily smokers. RESULTS: We found positive short-term effects regarding smoking cessation (adjusted OR 4.50, 95% CI 1.20-16.86), self-efficacy (p=0.01), and intentions to quit (p=0.004). However, none of these effects were maintained at 1-year follow up. The intervention was successful in reaching more than half of all daily smokers in the target group with more than 30% receiving counselling at least once in the intervention period. CONCLUSIONS: This trial shows that a "minimal" intervention can produce short-term effects but that this approach is insufficient in producing long-term effects.

Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age.

BACKGROUND: Changes in the human microbiome have been suggested as a risk factor for a number of lifestyle-related disorders, such as atopic diseases, possibly through a modifying influence on immune maturation in infancy. OBJECTIVES: We aimed to explore the association between neonatal fecal flora and the development of atopic disorders until age 6 years, hypothesizing that the diversity of the intestinal microbiota influences disease development. METHODS: We studied the intestinal microbiota in infants in the Copenhagen Prospective Study on Asthma in Childhood, a clinical study of a birth cohort of 411 high-risk children followed for 6 years by clinical assessments at 6-month intervals, as well as at acute symptom exacerbations. Bacterial flora was analyzed at 1 and 12 months of age by using molecular techniques based on 16S rRNA PCR combined with denaturing gradient gel electrophoresis, as well as conventional culturing. The main outcome measures were the development of allergic sensitization (skin test and specific serum IgE), allergic rhinitis, peripheral blood eosinophil counts, asthma, and atopic dermatitis during the first 6 years of life. RESULTS: We found that bacterial diversity in the early intestinal flora 1 and 12 months after birth was inversely associated with the risk of allergic sensitization (serum specific IgE P = .003; skin prick test P = .017), peripheral blood eosinophils (P = .034), and allergic rhinitis (P = .007). There was no association with the development of asthma or atopic dermatitis. CONCLUSIONS: Reduced bacterial diversity of the infant's intestinal flora was associated with increased risk of allergic sensitization, allergic rhinitis, and peripheral blood eosinophilia, but not asthma or atopic dermatitis, in the first 6 years of life. These results support the general hypothesis that an imbalance in the intestinal microbiome is influencing the development of lifestyle-related disorders, such as allergic disease.