Midazolam Infusion and Disease Severity Affect the Level of Sedation in Children: A Parametric Time-to-Event Analysis

Aim In critically ill mechanically ventilated children, midazolam is used first line for sedation, however its exact sedative effects have been difficult to quantify. In this analysis, we use parametric time-to-event (PTTE) analysis to quantify the effects of midazolam in critically ill children. Methods In the PTTE analysis, data was analyzed from a published study in mechanically ventilated children in which blinded midazolam or placebo infusions were administered during a sedation interruption phase until, based on COMFORT-B and NISS scores, patients became undersedated and unblinded midazolam was restarted. Using NONMEM® v.7.4.3., restart of unblinded midazolam was analysed as event. Patients in the trial were divided into internal and external validation cohorts prior to analysis. Results Data contained 138 events from 79 individuals (37 blinded midazolam; 42 blinded placebo). In the PTTE model, the baseline hazard was best described by a constant function. Midazolam reduced the hazard for restart of unblinded midazolam due to undersedation by 51%. In the blinded midazolam group, time to midazolam restart was 26 h versus 58 h in patients with low versus high disease severity upon admission (PRISM II < 10 versus > 21), respectively. For blinded placebo, these times were 14 h and 33 h, respectively. The model performed well in an external validation with 42 individuals. Conclusion The PTTE analysis effectively quantified the effect of midazolam in prolonging sedation and also the influence of disease severity on sedation in mechanically ventilated critically ill children, and provides a valuable tool to quantify the effect of sedatives. Clinical trial number and registry URL: Netherlands Trial Register, Trial NL1913 (NTR2030), date registered 28 September 2009 https://www.trialregister.nl/trial/1913.

Pain Changes Induced by Acupuncture in Single Body Areas in Fibromyalgia Syndrome: Results from an Open-Label Pragmatic Study

To date, there is considerable evidence of the effectiveness of acupuncture in fibromyalgia syndrome (FM). However, it is not known in which body areas acupuncture is more effective. The objective of this study was to assess the improvements of pain induced by acupuncture in single body areas in patients with FM. In this open-label pragmatic study, FM patients in a state of high disease severity were consecutively enrolled and treated with a course of 8 weekly sessions of manual acupuncture. Patients were assessed with the Self-Administered Pain Scale (SAPS) of the Fibromyalgia Assessment Status at baseline and at the end of eight acupuncture sessions. Acupuncture sessions were all conducted with the same acupuncture formula (LV3, SP6, ST36, LI4, CV6, CV12, Ex-HN-3, and GV20) in each session and in each patient. Ninety-six FM patients completed the course of treatment. All the 16 body areas assessed by SAPS showed improvement in pain. A statistically significant improvement was achieved in 12 of the 16 body areas investigated, with the best results in abdomen and forearms ( p = 0.001 ), while the worst results were registered for neck ( p = 0.058 ), chest ( p = 0.059 ), left buttock ( p = 0.065 ), and right thigh ( p = 0.052 ). The treatment has also shown significant effectiveness in improving fatigue and sleep quality ( p < 0.0001 ). Acupuncture has a beneficial effect on pain in all body areas in FM patients with high disease severity, with the greatest effects in the abdominal region and in the forearms, allowing a personalization of the treatment.

Co-Inoculation of Organic Potato with Fungi and Bacteria at High Disease Severity of Rhizoctonia solani and Streptomyces spp. Increases Beneficial Effects

Rhizobacteria-based technologies may constitute a viable option for biological fertilization and crop protection. The effects of two microbial inoculants (1) PPS: Pseudomonas protegens, P. jessenii and Stenotrophomonas maltophilia biocontrol bacterium strains and (2) TPB: Trichoderma atroviride, Pseudomonas putida, and Bacillus subtilis fungi, bacteria biocontrol, and biofertilizer combinations were examined on potato (Solanum tuberosum L. var. Demon) in three consecutive years in irrigated organic conditions. The number of tubers showing symptoms of Streptomyces sp. and Rhizoctonia sp. was recorded. The severity of symptoms was evaluated based on the damaged tuber surface. There was a large annual variability in both the symptoms caused by soil-borne pathogens, and the effect of bio-inoculants. In the first and second year, with a stronger Rhizoctonia and Streptomyces spp. incidence, the bacterial and fungal combination of TPB inoculums with both the potential plant nutrition and biocontrol ability of the strains seemed to have a better efficiency to control the diseases. This tendency was not supported in the third year, and this may be attributed to the relatively high natural precipitation. Further studies are required to investigate the agronomic benefits of these inoculants and to tailor their application to the soil microbial characteristics and weather conditions.

Identification of non-ribosomal peptide synthetase in Ganoderma boninense Pat. that was expressed during the interaction with oil palm

Basal stem rot (BSR) of oil palm is a disastrous disease caused by a white-rot fungus Ganoderma boninense Pat. Non-ribosomal peptides (NRPs) synthesized by non-ribosomal peptide synthetases (NRPSs) are a group of secondary metabolites that act as fungal virulent factors during pathogenesis in the host. In this study, we aimed to isolate NRPS gene of G. boninense strain UPMGB001 and investigate the role of this gene during G. boninense-oil palm interaction. The isolated NRPS DNA fragment of 8322 bp was used to predict the putative peptide sequence of different domains and showed similarity with G. sinense (85%) at conserved motifs of three main NRPS domains. Phylogenetic analysis of NRPS peptide sequences demonstrated that NRPS of G. boninense belongs to the type VI siderophore family. The roots of 6-month-old oil palm seedlings were artificially inoculated for studying NRPS gene expression and disease severity in the greenhouse. The correlation between high disease severity (50%) and high expression (67-fold) of G. boninense NRPS gene at 4 months after inoculation and above indicated that this gene played a significant role in the advancement of BSR disease. Overall, these findings increase our knowledge on the gene structure of NRPS in G. boninense and its involvement in BSR pathogenesis as an effector gene.

Temperature and incubation period affect Septoria pistaciarum conidium germination: disease forecasting and validation

Septoria leaf spot is an important disease of pistachio trees in Greece. This study aimed to determine effects of temperature and the incubation period on germination of conidia of Septoria pistaciarum, and to evaluate a generic model to forecast pistachio leaf spot under the field conditions of Aegina Island, Greece. The optimum temperature for conidium germination was 23°C, and germination was inhibited at 35 and 4°C. At constant temperature of 23°C, conidia commenced germination after 9 h. The predictive model indexed disease risk close to 100 at 10 May at two locations (Rachi Moschona and Vigla) in 2017, and first leaf spot symptoms were observed on 17 May. Moderate to high disease severity (>25% leaves infected) were observed in unsprayed trees at the end of May. In 2018, the model indexed risk close to 100 on 9 May at Rachi Moschona, and first symptoms were observed on 18 May. Moderate to high disease severity (>25% leaves infected) were observed in unsprayed trees on 25th of May. This study has shown that the forecasting model can be used in Aegina Island, Greece, to predict the severity of Septoria leaf spot of pistachio.

Pathogenicity of Gaeumannomyces Tritici (J. Walker) Hern.-Restr. & Crous, The Take-All Fungus and efficacy of Bacillus strains against disease

Isolates of Gaeumannomyces spp. obtained from diseased roots of winter wheat showing take-all symptoms were characterized by pathogenicity. All isolates were more pathogenic on wheat and barley than on oat, and were identified as Gaeumannomyces tritici. Most isolates of G. tritici were characterized as middle pathogenic, the pathogenicity of one isolate was higher than those of others, and two isolates showed the lowest pathogenicity. In growth chamber assay, the effect of two Bacillus strains, B. subtilis 16 and B. pumilus 11, on take-all of wheat was studied. Pathogen inoculation was made by isolates of G. tritici of different pathogenicity. It was found that effective biological control depends on take-all severity, which, in turn, co-ordinates with the pathogenicity of fungal isolate. Applying the bacterial cells into the plant growth substrate stimulated the seedling growth when artificial inoculation was performed with a middle pathogenic isolate of G. tritici, and the disease severity was middle. There was no growth promotion by bacterial inoculant at slight disease severity. No stimulating effect was also observed at the high disease severity, where pathogen inoculation was performed with a highly pathogenic isolate of G. tritici.

Perfectionism and Pain Intensity in Women with Fibromyalgia: Its Influence on Activity Avoidance from The Contextual Perspective

Given the scarcity of studies regarding perfectionism from a contextual perspective, this study aims to analyze its role in the relationship between pain and activity avoidance and its differential effect among patients with different fibromyalgia severity. A cross-sectional study with 228 women with fibromyalgia classified into two disease severity groups (low/moderate vs. high) was carried out. Moderation analyses were conducted; perfectionism was used as moderator, pain (in high and low pain situations) as independent variable, and activity avoidance as the outcome. Among the high disease severity group, analyses showed direct contributions of perfectionism (p < 0.001) but not of pain (p > 0.05); moderation effects were found in high pain situations (p = 0.002) (for low levels of perfectionism, a positive association was found between pain intensity and avoidance). Among the low severity group, direct effects of perfectionism (p < 0.05) and pain intensity (p = 0.04) were found (although the latter only for high pain situations); moderation effects were found in high pain situations (p = 0.018) (for high levels of perfectionism a positive and significant association was found between pain intensity and avoidance). Perfectionism has been found to be a key variable in the differential relationship between pain intensity (in high pain situations) and activity avoidance in groups with high and low disease severity.