Abstract Hernia repair is one of the most common operations in general surgery, and its associated complications typically relate to infections, among others. The loading of antibiotics to surgical ...meshes to deliver them locally in the abdominal hernia repair site can be one way to manage infections associated with surgical implants. However, the amount of drug loaded is restricted by the low wettability of polypropylene (PP). In this work, plasma has been used to tailor the surface properties of PP meshes to obtain high loading of ampicillin while conserving the desired biological properties of the unmodified samples and conferring them with antibacterial activity. It was demonstrated that the new surface chemistry and improved wettability led to 3-fold higher antibiotic loading. Subsequently, a PEG-like dry coating was deposited from tetraglyme with low-pressure plasma which allowed maintaining the high drug loading and kept cell properties such as chemotaxis, adhesion and morphology to the same levels as the untreated ones which have shown long-standing clinical success.
Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences ...in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.
Abstract
Target of Rapamycin (TOR) is an evolutionarily conserved protein kinase that plays a central role in coordinating cell growth with light availability, the diurnal cycle, energy availability, ...and hormonal pathways. TOR Complex 1 (TORC1) controls cell proliferation, growth, metabolism, and defense in plants. Sugar availability is the main signal for activation of TOR in plants, as it also is in mammals and yeast. Specific regulators of the TOR kinase pathway in plants are inorganic compounds in the form of major nutrients in the soils, and light inputs via their impact on autotrophic metabolism. The lack of TOR is embryo-lethal in plants, whilst dysregulation of TOR signaling causes major alterations in growth and development. TOR exerts control as a regulator of protein translation via the action of proteins such as S6K, RPS6, and TAP46. Phytohormones are central players in the downstream systemic physiological TOR effects. TOR has recently been attributed to have roles in the control of DNA methylation, in the abundance of mRNA splicing variants, and in the variety of regulatory lncRNAs and miRNAs. In this review, we summarize recent discoveries in the plant TOR signaling pathway in the context of our current knowledge of mammalian and yeast cells, and highlight the most important gaps in our understanding of plants that need to be addressed in the future.
Target of Rapamycin Complex 1 (TORC1) is a central hub in the plant cell machinery throughout the plant life cycle, and it controls growth and development by regulating transcription and protein translation.
To determine the effects of 10 years of enzyme replacement therapy (ERT) in adult patients with Pompe disease, focusing on individual variability in treatment response.
In this prospective, ...multicenter cohort study, we studied 30 patients from the Netherlands and France who had started ERT during the only randomized placebo-controlled clinical trial with ERT in late-onset Pompe disease (NCT00158600) or its extension (NCT00455195) in 2005 to 2008. Main outcomes were walking ability (6-minute walk test 6MWT), muscle strength (manual muscle testing using Medical Research Council MRC grading), and pulmonary function (forced vital capacity FVC in the upright and supine positions), assessed at 3- to 6-month intervals before and after the start of ERT. Data were analyzed with linear mixed-effects models for repeated measurements.
Median follow-up duration on ERT was 9.8 years (interquartile range IQR 8.3-10.2 years). At the group level, baseline 6MWT was 49% of predicted (IQR 41%-60%) and had deteriorated by 22.2 percentage points (pp) at the 10-year treatment point (
< 0.001). Baseline FVC upright was 54% of predicted (IQR 47%-68%) and decreased by 11 pp over 10 years (
< 0.001). Effects of ERT on MRC sum score and FVC supine were similar. At the individual level, 93% of patients had initial benefit of ERT. Depending on the outcome measured, 35% to 63% of patients had a secondary decline after ≈3 to 5 years. Still, at 10 years of ERT, 52% had equal or better 6MWT and/or FVC upright compared to baseline.
The majority of patients with Pompe disease benefit from long-term ERT, but many patients experience some secondary decline after ≈3 to 5 years. Individual variation, however, is considerable.
This study provides Class IV evidence that for the majority of adults with Pompe disease, long-term ERT positively affects, or slows deterioration in, muscle strength, walking ability, and/or pulmonary function.
Background Minimally invasive techniques and even robotics in pancreaticobiliary surgery are being used increasingly. Cost-effectiveness is a practical burden associated with the introduction of ...surgical innovation. This study compares the costs and the outcomes of open, laparoscopic, and robotic distal pancreatectomies. We hypothesized that robotic distal pancreatectomy is cost-effective. Methods Between August 2008 and August 2009, 77 distal pancreatectomies were performed at a single academic medical center. A retrospective analysis of prospectively collected data on demographics, short-term outcomes, and direct cost was performed. Results Thirty-two open distal pancreatectomies, 28 laparoscopic distal pancreatectomies, and 17 robotic distal pancreatectomies were performed. Age, American Society of Anesthesia preoperative risk score, and specimen length were similar. Indications for laparoscopic distal pancreatectomies and robotic distal pancreatectomies included more cystic neoplasms (49%) and fewer malignancies (29%) versus open distal pancreatectomies (16% and 47%). Spleen preservation occurred in 65% robotic distal pancreatectomies versus 12% and 29% in open distal pancreatectomies and laparoscopic distal pancreatectomies ( P < .05). The operative time averaged 298 minutes in robotic distal pancreatectomies versus 245 and 222 minutes in open distal pancreatectomies and laparoscopic distal pancreatectomies ( P < .05). Blood loss and morbidity were similar with no mortality. The length of stay was 4 days in robotic distal pancreatectomies versus 8 and 6 in open distal pancreatectomies and laparoscopic distal pancreatectomies ( P < .05). The total cost was $10,588 in robotic distal pancreatectomies versus $16,059 and $12,986 in open distal pancreatectomies and laparoscopic distal pancreatectomies. Conclusion These data suggest direct hospital costs are comparable among all groups. They suggest a shorter length of stay in robotic versus laparoscopic or open approaches. Finally, spleen and vessel preservation rates may improve with a robotic approach at the expense of increased operative time. In summary, robotic distal pancreatectomy is safe and cost effective in selected cases.
•Detecting M. bovis antibodies in cattle sera after a tuberculin skin test (TST) may improve bovine tuberculosis control.•Used as an anamnestic test, the ELISA reported herein had high levels of ...specificity and positive predictive value.•The ELISA fulfilled the World Organization for Animal Health criteria.•This serological ELISA used 15–17 days after a negative TST could be used on dairy farms to improve livestock health.
Programs for the eradication of bovine tuberculosis (bTB) focus on the tuberculin skin test (TST) and slaughter of reactor cattle. However, the disease remains an animal health concern in several countries and improving the efficiency of the TST has become a critical issue. The detection of Mycobacterium bovis antibodies in serum, within weeks after the TST, may be a rapid and inexpensive way to improve bTB control. This study reports the validation of an enzyme-linked immunosorbent assay (ELISA) to detect bovine tuberculosis as an ancillary test to TST in dairy farms in Argentina.
The estimated validation parameters were within the established requirements of the World Organization for Animal Health (OIE). The test demonstrated high repeatability, with coefficients of variation <25%. High test reproducibility through interlaboratory testing was also found, with an estimated Pearson coefficient of 0.9648 (95% confidence intervals 0.9315–0.9820). The ELISA detected tuberculous cattle unidentified by the TST. Of 43 animals sent to slaughterhouses that were ELISA positive 15–17 days after a negative TST, 36 were confirmed as infected with M. bovis by histopathology and IS6110 PCR. According to ROC curve analysis of results of 145 cattle from M. bovis-free herds and the 36 M. bovis-infected cattle, at a corrected optical density cut-off point of 0.3853, specificity was 95.95% and the positive predictive value at this cut-off was 83.72%. The ELISA detection test validated in this study could be readily applied in dairy farms, to complement a prior TST and improve livestock health.
The timing and extent of the morphological changes that occurred in the last 200years in a large gravel bed river (the Piave River, eastern Italian Alps) that was heavily impacted by human activities ...(training structures, hydropower schemes, and gravel mining) have been analyzed by historical maps, aerial photos, repeated topographic measurements, and geomorphological surveys. Results show that the channel underwent a strong narrowing during the twentieth century, but with a faster pace during the 1970s–1990s and with an associated shift from a dominant braided pattern to a wandering morphology. Bed incision up to 2m — mostly from gravel mining — has been documented for this period. Large areas of the former active channel were colonized by riparian forests, both as islands and as marginal woodlands. The ceasing of gravel extraction in the late 1990s seems to have determined a reversal in the evolutionary trend, with evidence of vegetation erosion/channel widening even though a significant aggradation phase is not present. We conclude that alteration of sediment regime has played a major role on the long-term channel evolution. However, only relevant flood events (RI>10–15years) appear to determine substantial island erosion, and therefore the proportion of island vs. channel area fluctuates depending on flood history.
Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as ...other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RARbeta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers. Our results show that singly retained alleles of germline mutated genes are never hypermethylated in inherited tumors. However, this epigenetic change is a frequent second "hit", associated with the wild-type copy of these genes in inherited tumors where both alleles are retained. Global hypomethylation was similar between sporadic and hereditary cases, but distinct differences existed in patterns of methylation at non-familial genes. This study demonstrates that hereditary cancers "mimic" the DNA methylation patterns present in the sporadic tumors.
Aims: To determine whether Ha‐AP10, a member of the plant lipid transfer proteins (LTPs) family produces a direct cytotoxic effect on fungal cells mediated by membrane permeabilization. LTPs can ...inhibit fungal growth and are considered members of the ubiquitous class of antimicrobial peptides. However, the way they exert their effects on target cells is not yet understood.
Methods and Results: Viability assays demonstrate that Ha‐AP10 acts as a fungicidal compound but no harmful effect is observed on plant cells. Liposome leakage assays show that the protein induces a moderate release of fluorescent probes encapsulated in model membranes, indicating its ability to interact with phospholipids. Using a fluorescent indicator of damage at the membrane level, we demonstrate that Ha‐AP10 is able to induce the permeabilization of intact fungal spores in a dose‐dependent manner.
Conclusion: The results presented here demonstrate the permeabilization of fungal spores caused by Ha‐AP10.
Significance and Impact of the Study: To our knowledge, this is the first demonstration of fungal membrane damage by an LTP, giving a clue to elucidate the basis of its antimicrobial properties.
Recent developments in Geant4 Allison, J.; Amako, K.; Apostolakis, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2016, Letnik:
835, Številka:
C
Journal Article
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Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including ...high energy physics, astrophysics and space science, medical physics and radiation protection. Over the past several years, major changes have been made to the toolkit in order to accommodate the needs of these user communities, and to efficiently exploit the growth of computing power made available by advances in technology. The adaptation of Geant4 to multithreading, advances in physics, detector modeling and visualization, extensions to the toolkit, including biasing and reverse Monte Carlo, and tools for physics and release validation are discussed here.
•Multithreading resulted in a smaller memory footprint and nearly linear speed-up.•Scoring options, faster geometry primitives, more versatile visualization were added.•Improved electromagnetic and hadronic models and cross sections were developed.•Reverse Monte Carlo and general biasing methods were added.•Physics validation efforts were expanded and new validation tools were added.
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