The difficult-to-treat, therapy-resistant cough: Why are current cough treatments not working and what can we do?

Cough can persist despite exhaustive diagnostic and therapeutic effort and has been termed 'idiopathic' or 'unexplained' but perhaps 'difficult to treat' cough is a more appropriate description. In this article the reasons for poor treatment response are discussed. These include a lack of physician fidelity to management guidelines, patient non-adherence and the lack of effective medicines. A number of randomized controlled trials have been undertaken including low dose opiate therapy, the use of a speech pathology intervention, oral antibiotics and antidepressants. The success or otherwise of such interventions will be discussed. A number of approaches to deal with the problem of 'difficult to treat cough' will be considered.

High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination

BACKGROUND: Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement.

METHODS: A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis.

RESULTS: In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations.

CONCLUSIONS: The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.

Testing preference formation in learning design contingent valuation (LDCV) using advanced information and repetitive treatments

Policymakers have largely replaced Single Bounded Discrete Choice (SBDC) valuation by the more statistically efficient repetitive methods; Double Bounded Discrete Choice (DBDC) and Discrete Choice Experiments (DCE) . Repetitive valuation permits classification into rational preferences: (i) a priori well-formed; (ii) consistent non-arbitrary values “discovered” through repetition and experience; (Plott, 1996; List 2003) and irrational preferences; (iii) consistent but arbitrary values as “shaped” by preceding bid level (Tufano, 2010; Ariely et al., 2003) and (iv) inconsistent and arbitrary values. Policy valuations should demonstrate behaviorally rational preferences. We outline novel methods for testing this in DBDC applied to renewable energy premiums in Chile.

Urinary thrombomodulin levels were significantly higher following occupational exposure to chemicals, in the presence of dipstick protein, but not in the presence of dipstick blood

Currently, there are no biomarkers which can identify patients with an increased risk of developing urothelial cancer as a result of occupational chemical exposure. The aim of this study was to evaluate the relationships between final diagnosis and 22 biomarkers measured in urine, serum and plasma collected from 156 hematuric patients. Fourteen of the 80 patients (17.5%) with urothelial cancer and 13/76 (17.1%) of the controls were deemed to have a history of chemical exposure. We applied Fisher's exact tests to explore associations between chemical exposure and final diagnosis, and tumor stage and grade, where applicable; ANOVA and t-test to compare age across patients with and without chemical exposure; and Zelen's exact test to evaluate relationships across final diagnosis, chemical exposure and smoking. Following pre-selection of biomarkers using Lasso, we identified biomarkers with differential levels across patients with and without chemical exposure using Welch's t-test. Using a one-sided t-test and considering multiple testing using FDR, we observed that TM levels in urine were significantly higher in samples from patients with a history of chemical exposure regardless of their diagnosis as control or urothelial cancer (one-sided t-test, p_UC = 0.014 and p_CTL = 0.043); in the presence of dipstick protein and when urinary pH levels ≤ 6 (p = 0.003), but not in the presence of dipstick blood (p = 0.115). Urothelial cancer patients with a history of chemical exposure were significantly younger (64.1 years) than those without chemical exposure (70.2 years) (one-sided t-test p-value = 0.012); and their tumors were higher grade (Fisher's exact test; p = 0.008). There was a strong association between a history of chemical exposure and smoking in urothelial cancer patients (Zelen's exact test; p = 0.025). Elevated urinary thrombomodulin levels could have the potential to identify chemical exposure in hematuric patients at high risk of developing urothelial cancer.

Locust bean gum-based microparticles for pulmonary delivery of antibiotics

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Cinnamaldehyde increases the susceptibility of quorum-sensing-mediated biofilms to conventional antibiotics

The role of bacterial communication, also known as quorum sensing is an important mechanism in biofilm formation which is fundamental to the development of anti-biofilm strategies. In this current study, the synergy between a quorum sensing inhibitor (cinnamaldehyde) and two antibiotics (ceftazidime and levofloxacin) was evaluated in an attempt to develop a strategy for biofilm disruption using the high-throughput minimum biofilm eliminating concentration (MBEC) assay. Klebsiella pneumoniae and Proteus mirabilis biofilms of initial broth suspensions of 108 colony forming units (CFU) per mL, cultivated on the pegs of the MBEC device were challenged with 5120 µg/ml of ceftazidime and levofloxacin in a double dilution assay in the presence of 500 µM cinnamaldehyde. The minimum inhibitory concentrations (MIC) in the presence of cinnamaldehyde for ceftazidime and levofloxacin were 0.125% (640 µg/mL) and 0.0625% (320 µg/mL) respectively with no significant bacterial growth on LB agar. The MBECs for ceftazidime and levofloxacin were above 5120 and 2560 µg/mL respectively which yielded over 70% reduction in both Klebsiella pneumoniae and Proteus mirabilis biofilms. The above results indicate the possibility that the synergy between antimicrobial agents may lead to biofilm eradication.

In Vitro Assessment of the Synergy between Polymyxin B (PMB) and Polymyxin B Nonapeptide (PMBN) and Antibiotics on Biofilms from Diabetic Foot Infections

Background: The increasing resistance of Gram-negative bacteria isolated from nosocomial infections and chronic wounds, such as diabetic foot ulcers has renewed research interests in the use of polymyxins in the treatment of multidrug resistant infections. The added resistance conferred by biofilm development in such infections and the absence of novel antibiotics presuppose that polymyxins are the likely drugs of choice in spite of their nephrotoxicity. The effects of PMB and PMBN have been previously assessed on planktonic bacteria isolated from various infections. Methods: This current study assessed the synergy between a PMB/PMBN and two antibiotics (ceftazidime and levofloxacin) in an attempt to develop a strategy for biofilm disruption using the Minimum Biofilm Eradication Concentration Physiology and Genetic assay (MBEC™ P & G, Innovotech Inc, Edmonton, Alberta, Canada) according to manufacturer’s instructions. Klebsiella pneumoniae (K. pneumoniae) and Proteus mirabilis (P. mirabilis) biofilms of initial broth suspensions of 108 colony forming units per mL, cultivated on the pegs of the MBEC device were challenged with 5120 µg/mL of both ceftazidime and levofloxacin in a ten-fold dilution assay and in the presence of 100 and 500 µg/mL PMB and PMBN. Results: From table of results (Table 1), it can be deduced that both ceftazidime and levofloxacin are very effective in inhibiting biofilm development (as shown by percentage inhibition (PI)) when augmented with PMB and PMBN. This is about 100-fold increase in efficacy when compared to the antibiotics used on their own. The percentage reduction (PR) in biofilm was also increased considerably when PMB and PMBN concentrations were increased to 500 µg/mL. PMB was more effective than its less antibacterial derivative PMBN. Levofloxacin was also found to be more effective than ceftazidime when combined with both PMB and PMBN due to its enhanced cell-membrane permeability and as an anti-DNA replication uncoupling agent. Conclusion: The above results indicate that the synergy between antibiotics and cell membrane permeabilising agents may provide alternate strategies towards biofilm eradication

The Swiss Systemic lupus erythematosus Cohort Study (SSCS) - cross-sectional analysis of clinical characteristics and treatments across different medical disciplines in Switzerland.

OBJECTIVES: To describe disease characteristics and treatment modalities in a multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in Switzerland. METHODS: Cross-sectional analysis of 255 patients included in the Swiss SLE Cohort and coming from centres specialised in Clinical Immunology, Internal Medicine, Nephrology and Rheumatology. Clinical data were collected with a standardised form. Disease activity was assessed using the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), an integer physician's global assessment score (PGA) ranging from 0 (inactive) to 3 (very active disease) and the erythrocyte sedimentation rate (ESR). The relationship between SLE treatment and activity was assessed by propensity score methods using a mixed-effect logistic regression with a random effect on the contributing centre. RESULTS: Of the 255 patients, 82% were women and 82% were of European ancestry. The mean age at enrolment was 44.8 years and the median SLE duration was 5.2 years. Patients from Rheumatology had a significantly later disease onset. Renal disease was reported in 44% of patients. PGA showed active disease in 49% of patients, median SLEDAI was 4 and median ESR was 14 millimetre/first hour. Prescription rates of anti-malarial drugs ranged from 3% by nephrologists to 76% by rheumatologists. Patients regularly using anti-malarial drugs had significantly lower SELENA-SLEDAI scores and ESR values. CONCLUSION: In our cohort, patients in Rheumatology had a significantly later SLE onset than those in Nephrology. Anti-malarial drugs were mostly prescribed by rheumatologists and internists and less frequently by nephrologists, and appeared to be associated with less active SLE.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Disassembly of a Medial Transenvelope Structure by Antibiotics during Intracellular Division.

Chlamydiales possess a minimal but functional peptidoglycan precursor biosynthetic and remodeling pathway involved in the assembly of the division septum by an atypical cytokinetic machine and cryptic or modified peptidoglycan-like structure (PGLS). How this reduced cytokinetic machine collectively coordinates the invagination of the envelope has not yet been explored in Chlamydiales. In other Gram-negative bacteria, peptidoglycan provides anchor points that connect the outer membrane to the peptidoglycan during constriction using the Pal-Tol complex. Purifying PGLS and associated proteins from the chlamydial pathogen Waddlia chondrophila, we unearthed the Pal protein as a peptidoglycan-binding protein that localizes to the chlamydial division septum along with other components of the Pal-Tol complex. Together, our PGLS characterization and peptidoglycan-binding assays support the notion that diaminopimelic acid is an important determinant recruiting Pal to the division plane to coordinate the invagination of all envelope layers with the conserved Pal-Tol complex, even during osmotically protected intracellular growth.

Stress parental et lien mère-enfant: impact sur le développement de l’enfant âgé d’un an.

Au cours de la grossesse et dans les premières années de vie de l’enfant, plusieurs facteurs externes, tels que le stress maternel ou le lien maternel, peuvent interférer avec son développement et avoir des conséquences à court et à long terme. Bien que le stress maternel périnatal ait souvent été étudié, plusieurs facteurs pré et postnataux potentiellement confondants (comme le stress paternel, la dépression, la prise d’antidépresseurs, etc.) n’ont pas systématiquement été pris en compte. Comparativement à l’attachement de l’enfant (à sa mère), moins de recherches se sont intéressées au lien maternel, en particulier chez des femmes ayant un diagnostic de dépression et/ou d’anxiété et exposées à des antidépresseurs. Notre thèse visait donc à étudier ces deux facteurs et leur association avec le développement du jeune enfant âgé d’un an, dans un contexte où la santé mentale maternelle (présence ou non de troubles psychologiques) et de traitements pharmacologiques associés étaient aussi considérés. Afin d’améliorer le dépistage de retards développementaux, nous avons également évalué l’administration au téléphone de deux instruments de pré-dépistage et dépistage actuellement utilisés. Notre thèse était constituée de quatre phases dont les objectifs étaient: la détermination des propriétés psychométriques de l’échelle de stress perçu de quatre items (en français et en anglais) au sein de la population de femmes enceintes (première étude); évaluer l’effet du stress maternel prénatal et parental postnatal sur le développement de l’enfant âgé d’un an (deuxième étude); estimer l’association entre le lien maternel et le développement de l’enfant âgé d’un an, en stratifiant sur la prise maternelle d’antidépresseurs (troisième étude); et évaluer l’administration au téléphone du ″Ages and Stages Questionnaire″ (ASQ, version de 12 mois) et du ″Revised Pre-screening Denver Questionnaire″(R-PDQ, version de 9-24 mois),deux questionnaires utilisés pour le pré-dépistage et le dépistage du développement infantile (quatrième étude). Ce projet faisait partie d’une plus grande étude, nommée le projet OTIS (The″Organization of Teratology Information Specialists″ Antidepressant in Pregnancy cohort study), qui visait à évaluer l’impact de l’arrêt versus la continuation de la prise d’antidépresseurs au cours de la grossesse sur les comportements maternels et sur le développement de l’enfant âgé de un à trois ans. Ainsi, entre 2006 et 2010, la cohorte prospective OTIS de femmes enceintes a été construite et suivie jusqu’à trois ans postpartum. À partir de 2008, l’évaluation du stress et du lien maternel (thématiques de ce projet de thèse) a été incorporée au projet initial. Aussi, à partir de là, toute femme nouvellement recrutée pour la cohorte OTIS pouvait faire partie des études de cette thèse. Notre population source était composée des femmes enceintes ayant eu recours à un service nord-américain d’information sur les tératogènes ou ayant été suivies à la clinique d'obstétrique et de gynécologie du CHU Ste Justine. Pour être admissibles, les femmes devaient 1) être âgées d’au moins 18 ans, 2) être enceinte d’au maximum 14 semaines (le début de la grossesse étant défini comme étant le premier jour des dernières règles); 3) être exposées à un antidépresseur depuis au moins le premier jour de grossesse (pour le groupe exposé à un antidépresseur), 4) savoir lire et comprendre l’anglais ou le français. Pour les études deux, trois et quatre, les femmes devaient habiter dans un rayon de 250 km autour de Montréal pour recevoir notre visite à domicile, nécessaire à l’évaluation psychométrique du développement infantile. Les pères des enfants ont été recrutés à deux mois postpartum pour évaluer leur stress. Les données ont été collectées par entrevue téléphonique, auto-administration de questionnaires, et évaluation psychométrique du développement infantile. Dans le cadre de cette thèse, les femmes étaient suivies depuis le premier trimestre de grossesse jusqu’à un an postpartum. Les résultats de nos travaux démontrent que le recours à l’échelle de stress perçu de quatre items est une mesure fiable et valide pour mesurer le stress au cours de la grossesse (en recherche ou en clinique). Ensuite, le stress postnatal maternel et paternel serait défavorable au développement moteur et socio-émotionnel de l’enfant d’un an, respectivement. Par contre le stress maternel prénatal favoriserait le développement moteur. Un lien maternel optimal est associé à un meilleur développement socio-émotionnel à un an chez l’enfant, en particulier pour les femmes exposées à des antidépresseurs. Enfin, l’administration au téléphone de l’ASQ et des sous-échelles de langage, de motricité fine et motricité globale du R-PDQ serait une alternative possible au mode auto-administré pour dépister et pré-dépister les retards de développement chez les enfants.

Biochemical and molecular characterization of pathogenic vibrios from hatcheries and aquaculture farms

Vibrio are important during hatchery rearing. aquaculture phase and post-harvest quality of shrimps. Vibrio spp are of concern to shrimp farmers and hatchery operators because certain species can cause Vibriosis. Vibrio species are of concern to humans because certain species cause serious diseases.With the progress in aquaculture, intensive systems used for shrimp aquaculture create an artificial environment that increases bacterial growth. To maintain the productivity of such an intensive aquaculture, high inputs of fish protein have to be employed for feeding together with high levels of water exchange and the massive use of antibiotics/ probiotics / chemicals. It seems that the combination of these conditions favours the proliferation of vibrios and enhances their virulence and disease prevalence. The risk of a microbial infection is high, mainly at larval stages. The effect and severity are related to Vibrio species and dose, water, feed, shrimp quality and aquaculture management.Consumption of seafood can occasionally result in food-bome illnesses due to the proliferation of indigenous pathogens like Vibrio.Of the l2 pathogenic Vibrio species, 8 species are known to be directly food associated. Strict quality guidelines have been laid by the importing nations, for the food products that enter their markets. The microbiological quality requirement for export of frozen shrimp products is that V.cholerae, V.parahaemolyticus and V. vulnificus should be absent in 25g of the processed shrimp (Export Inspection Council of India, 1995). The mere presence of these pathogenic Vibrios is sufficient for the rejection of the exported product.The export rejections cause serious economic loss to the shrimp industry and might harm the brand image of the shrimp products from the countiy.There is a need for an independent study on the incidence of different pathogenic vibrios in shrimp aquaculture and investigate their biochemical characteristics to have a better understanding about the growth and survival of these organisms in the shrimp aquaculture niche. PCR based methods (conventional PCR, duplex PCR, multiplex-PCR and Real Time PCR) for the detection of the pathogenic Vibrios is important for rapid post-harvest quality assessment. Studies on the genetic heterogeneity among the specific pathogenic vibrio species isolated from shrimp aquaculture system provide; valuable information on the extent of genetic diversity of the pathogenic vibrios, the shrimp aquaculture system.So the present study was undertaken to study the incidence of pathogenic Vibrio spp. in Penaeus monodon shrimp hatcheries and aquaculture farms, to carry out biochemical investigations of the pathogenic Vibrio spp isolated from P. monodon hatchery and. aquaculture environments, to assess the effect of salt (NaCl) on the growth and enzymatic activities of pathogenic Vibrio spp., to study the effect of preservatives, and chemicals on the growth of pathogenic Vibrio spp. and to employ polymerase chain reaction (PCR) methods for the detection of pathogenic V ibrio spp.Samples of water (n=7) and post-larvae (n=7) were obtained from seven Penaeus monodon hatcheries and samples of water (n=5), sediment (n=5) and shrimp (n=5) were obtained from five P. monodon aquaculture farms located on the East Coast of lndia. The microbiological examination of water, sediment, post-larvae and shrimp samples was carried out employing standard methods and by using standard media.The higher bacterial loads were obtained in pond sediments which can be attributed to the accumulation of organic matter at the pond bottom which stimulated bacterial growth.Shrimp head. (4.78 x 105 +/- 3.0 x 104 cfu/g) had relatively higher bacterial load when compared to shrimp muscle 2.7 x 105 +/- 1.95 x 104 cfu/g). ln shrimp hatchery samples, the post-larvae (2.2 x 106 +/- 1.9 x 106 cfu/g) had higher bacterial load than water (5.6 x 103 +/- 3890 cfu/ml).The mean E.coli counts were higher in aquaculture pond sediment (204+/-13 cfu/g) and pond water (124+/-88 cfu/ml). Relatively lower Escherichia coli counts were obtained from shrimp samples (12+/-11 to 16+/-16.7 cfu/g). The presence of E.coli in aquaculture environment might have been from the source water. E.coli was not detected in hatchery waters and post-larvae.

Effects of different tillage treatments on labile soil organic matter pools and stabilization processes

An improved understanding of soil organic carbon (Corg) dynamics in interaction with the mechanisms of soil structure formation is important in terms of sustainable agriculture and reduction of environmental costs of agricultural ecosystems. However, information on physical and chemical processes influencing formation and stabilization of water stable aggregates in association with Corg sequestration is scarce. Long term soil experiments are important in evaluating open questions about management induced effects on soil Corg dynamics in interaction with soil structure formation. The objectives of the present thesis were: (i) to determine the long term impacts of different tillage treatments on the interaction between macro aggregation (>250 µm) and light fraction (LF) distribution and on C sequestration in plots differing in soil texture and climatic conditions. (ii) to determine the impact of different tillage treatments on temporal changes in the size distribution of water stable aggregates and on macro aggregate turnover. (iii) to evaluate the macro aggregate rebuilding in soils with varying initial Corg contents, organic matter (OM) amendments and clay contents in a short term incubation experiment. Soil samples were taken in 0-5 cm, 5-25 cm and 25-40 cm depth from up to four commercially used fields located in arable loess regions of eastern and southern Germany after 18-25 years of different tillage treatments with almost identical experimental setups per site. At each site, one large field with spatially homogenous soil properties was divided into three plots. One of the following three tillage treatments was carried in each plot: (i) Conventional tillage (CT) with annual mouldboard ploughing to 25-30 cm (ii) mulch tillage (MT) with a cultivator or disc harrow 10-15 cm deep, and (iii) no tillage (NT) with direct drilling. The crop rotation at each site consisted of sugar beet (Beta vulgaris L.) - winter wheat (Triticum aestivum L.) - winter wheat. Crop residues were left on the field and crop management was carried out following the regional standards of agricultural practice. To investigate the above mentioned research objectives, three experiments were conducted: Experiment (i) was performed with soils sampled from four sites in April 2010 (wheat stand). Experiment (ii) was conducted with soils sampled from three sites in April 2010, September 2011 (after harvest or sugar beet stand), November 2011 (after tillage) and April 2012 (bare soil or wheat stand). An incubation study (experiment (iii)) was performed with soil sampled from one site in April 2010. Based on the aforementioned research objectives and experiments the main findings were: (i) Consistent results were found between the four long term tillage fields, varying in texture and climatic conditions. Correlation analysis of the yields of macro aggregate against the yields of free LF ( ≤1.8 g cm-3) and occluded LF, respectively, suggested that the effective litter translocation in higher soil depths and higher litter input under CT and MT compensated in the long term the higher physical impact by tillage equipment than under NT. The Corg stocks (kg Corg m−2) in 522 kg soil, based on the equivalent soil mass approach (CT: 0–40 cm, MT: 0–38 cm, NT: 0–36 cm) increased in the order CT (5.2) = NT (5.2) < MT (5.7). Significantly (p ≤ 0.05) highest Corg stocks under MT were probably a result of high crop yields in combination with reduced physical tillage impact and effective litter incorporation, resulting in a Corg sequestration rate of 31 g C-2 m-2 yr-1. (ii) Significantly higher yields of macro aggregates (g kg-2 soil) under NT (732-777) and MT (680-726) than under CT (542-631) were generally restricted to the 0-5 cm sampling depth for all sampling dates. Temporal changes on aggregate size distribution were only small and no tillage induced net effect was detectable. Thus, we assume that the physical impact by tillage equipment was only small or the impact was compensated by a higher soil mixing and effective litter translocation into higher soil depths under CT, which probably resulted in a high re aggregation. (iii) The short term incubation study showed that macro aggregate yields (g kg-2 soil) were higher after 28 days in soils receiving OM (121.4-363.0) than in the control soils (22.0-52.0), accompanied by higher contents of microbial biomass carbon and ergosterol. Highest soil respiration rates after OM amendments within the first three days of incubation indicated that macro aggregate formation is a fast process. Most of the rebuilt macro aggregates were formed within the first seven days of incubation (42-75%). Nevertheless, it was ongoing throughout the entire 28 days of incubation, which was indicated by higher soil respiration rates at the end of the incubation period in OM amended soils than in the control soils. At the same time, decreasing carbon contents within macro aggregates over time indicated that newly occluded OM within the rebuilt macro aggregates served as Corg source for microbial biomass. The different clay contents played only minor role in macro aggregate formation under the particular conditions of the incubation study. Overall, no net changes on macro aggregation were identified in the short term. Furthermore, no indications for an effective Corg sequestration on the long term under NT in comparison to CT were found. The interaction of soil disturbance, litter distribution and the fast re aggregation suggested that a distinct steady state per tillage treatment in terms of soil aggregation was established. However, continuous application of MT with a combination of reduced physical tillage impact and effective litter incorporation may offer some potential in improving the soil structure and may therefore prevent incorporated LF from rapid decomposition and result in a higher C sequestration on the long term.