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Frederick Lowe opublikował 5 miesięcy, 1 tydzień temu
The inflatable penile prosthesis was first implanted with a large vertical suprapubic incision. Nowadays, three surgical approaches are utilized penoscrotal, infrapubic, and subcoronal. Globally the penoscrotal approach is used most often. Our first author describes nuances of the high transverse scrotal incision technique gained over 48 years of experience. Many of these methods will interest the reader because they are divergent from the common practice of implanters across the world. These distinctions are designed to diminish the risk of infection, speed up the surgery, and improve outcomes for both the patient and his surgeon.Despite popularity, satisfaction rates of inflatable penile prosthesis (IPP) use can be improved by evaluating the ability to operate devices in the preoperative setting. The purpose of this study was to prospectively analyze the preference of three commonly available IPPs. In total, 125 IPP-naïve men 60 years of age or older were prospectively recruited from an outpatient Urology clinic from June 2019 to January 2020. A questionnaire standardized to all encounters was utilized to collect demographics, selected medical information, and key pinch strength. Participants were then asked to rank three models in terms of preference (from 1 to 3, 1 representing most preferred) for each inflation and deflation in a double-blinded manner. Statistical analysis was performed using ANOVA, a Chi-square test and multivariable logistical regression analysis. The results demonstrated preference for Coloplast Titan (44%) for inflation, and preference for AMS 700 (40%) for deflation. Men who preferred the Coloplast Titan inflation had a lower chance of preferring the AMS 700 MS deflation (OR = 0.29; p = 0.010) and Coloplast Titan Touch deflation (OR = 0.27; p = 0.012). Preference for Coloplast Titan was weakly associated with participant history of coronary artery disease (OR = 5.96, p = 0.006) and osteoarthritis (OR = 3.04, p = 0.044). Neither key pinch strength nor age was associated with preference for a particular model. IPP-naïve men over 60 years favor Coloplast Titan for inflation and AMS 700 for deflation, and men who preferred the Coloplast Titan for inflation were less likely to choose the AMS 700 MS or Coloplast Titan Touch for deflation. Further studies should aim to confirm these findings.Flexible cystoscopy under local anaesthesia is standard for the surveillance of bladder cancer. Frequently, several reusable cystoscopes fail to reprocess. With the new grasper incorporated single-use cystoscope for retrieval of ureteric stents, we explored the feasibility of using it off-label for diagnosis and the detection of bladder cancer. Consecutive diagnostic flexible cystoscopies between Mar 2016 and Nov 2018 were reviewed comparing the reusable versus the disposable cystoscopes. A total of 390 patients underwent 1211 cystoscopies. Median age was 61.5 years (SD 14.2, 18.8-91.4), males 331 (84.9%) and females 59 (15.1%). Indication for cystoscopy was prior malignancy in 1183 procedures (97.7%), haematuria 19 (1.6%) or bladder mass 7 (0.6%). There were 608 reusable and 603 disposable cystoscopies. There was no significant difference between groups at baseline in age, sex, BMI, smoking status, or prior tumor risk category. There was no significant difference in positive findings (123/608, 20.2% vs 111/603, 18.4%, p = 0.425) or cancer detection rates (95/608, 15.6% vs 88/603, 14.4%, p 0.574) among the two groups, respectively. We conclude that the disposable grasper integrated cystoscope is comparable to reusable cystoscope in the detection of bladder cancer.Circular RNAs (circRNAs) are involved in the regulation of many pathophysiological processes as non-coding RNAs. This study focuses on the role of circRACGAP1 in the development of non-small cell lung cancer (NSCLC). Expression patterns of circRACGAP1 and miR-144-5p in NSCLC tissues and cell lines were quantified by qRT-PCR analysis. Then, the function of circRACGAP1 on cell proliferation and tumorigenesis were confirmed in vitro and in vivo using CCK-8 assay, colony formation, EdU incorporation, and xenograft technique. The regulation of circRACGAP1 on Gefitinib resistance of NSCLC cells was evaluated by flow cytometry. The regulatory network of circRACGAP1/miR-144-5p/CDKL1 was verified by luciferase reporter assay and RNA pull-down. Western blotting analysis was performed to assess the biomarkers of cell cycle and apoptosis-associated proteins. CircRACGAP1 was highly expressed and miR-144-5p was inhibited both in NSCLC tissues and cell lines, suggesting their negative correlation in NSCLC. Knockdown of circRACGAP1 suppressed cell proliferation via arresting the cell cycle. miR-144-5p was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-144-5p directly targeted the 3′-UTR of CDKL1 to regulate cell cycle of NSCLC cells. circRACGAP1 knockdown dramatically inhibited the tumor growth and enhanced the sensitivity of NSCLC to Gefitinib in vitro and in vivo. In summary, our study revealed a novel machinery of circRACGAP1/miR-144-5p/CDKL1 for the NSCLC tumorigenesis and development, providing potential diagnostic and therapeutic targets for NSCLC.Metastatic breast cancer is characterized by high mortality and limited therapeutic target. During tumor metastasis, cytoskeletal reorganization is one of the key steps in the migration and invasion of breast cancer cells. Collapsin response mediator protein 2 (CRMP2) is a cytosolic phosphoprotein that plays an important role in regulating cytoskeletal dynamics. Previous researches have reported that altered CRMP2 expression is associated with breast cancer progression, but the underlying mechanism remains poorly understood. Here, we show that CRMP2 expression is reduced in various subtypes of breast cancers and negatively correlated with lymphatic metastasis. Overexpression of CRMP2 significantly inhibits invasion and stemness in breast cancer cells, while downregulation of CRMP2 promotes cell invasion, which is not required for tubulin polymerization. Mechanistic studies demonstrate that CRMP2 interacts with RECK, prevents RECK degradation, which, in turn, blocks NF-κB and Wnt signaling pathways. Furthermore, we find that phosphorylation of CRMP2 at T514 and S522 remarkably abolishes its functions to bind with RECK and to inhibit cell invasion. Pharmacologic rescue of CRMP2 expression suppressed breast cancer metastasis in vitro and in vivo and stimulated a synergetic effect with FN-1501 that induces CRMP2 dephosphorylation. Collectively, this study highlights the potential of CRMP2 as a therapeutic target in breast cancer metastasis and reveals a distinct mechanism of CRMP2.TMPRSS2 is an important membrane-anchored serine protease involved in human prostate cancer progression and metastasis. A serine protease physiologically often comes together with a cognate inhibitor for execution of proteolytically biologic function; however, TMPRSS2’s cognate inhibitor is still elusive. To identify the cognate inhibitor of TMPRSS2, in this study, we applied co-immunoprecipitation and LC/MS/MS analysis and isolated hepatocyte growth factor activator inhibitors (HAIs) to be potential inhibitor candidates for TMPRSS2. Moreover, the recombinant HAI-2 proteins exhibited a better inhibitory effect on TMPRSS2 proteolytic activity than HAI-1, and recombinant HAI-2 proteins had a high affinity to form a complex with TMPRSS2. The immunofluorescence images further showed that TMPRSS2 was co-localized to HAI-2. Both KD1 and KD2 domain of HAI-2 showed comparable inhibitory effects on TMPRSS2 proteolytic activity. In addition, HAI-2 overexpression could suppress the induction effect of TMPRSS2 on pro-HGF activation, extracellular matrix degradation and prostate cancer cell invasion. We further determined that the expression levels of TMPRSS2 were inversely correlated with HAI-2 levels during prostate cancer progression. In orthotopic xenograft animal model, TMPRSS2 overexpression promoted prostate cancer metastasis, and HAI-2 overexpression efficiently blocked TMPRSS2-induced metastasis. In summary, the results together indicate that HAI-2 can function as a cognate inhibitor for TMPRSS2 in human prostate cancer cells and may serve as a potential factor to suppress TMPRSS2-mediated malignancy.The excitation of surface plasma waves (SPW) by an intense short laser pulse is a useful tool to enhance the laser absorption and the electron heating in the target. In this work, the influence of the transverse laser profile and the pulse duration used to excited SPW is investigated from Fluid and 2D Particle-in-Cell simulations. We show the existence of a lobe of surface plasma wave modes. Our results highlight surface plasma waves excitation mechanism and define the laser parameters to optimise the SPW excitation and the kinetic energy of the associated electron trapped in the wave. It opens the door to monitor the spectral mode distribution and temporal shape of the excited surface waves in the high relativistic regime. The most important result of the study is that-at least in 2D-the charge and the energy of the electron bunches depend essentially on the laser energy rather than on temporal or spatial shape of the laser pulse.It is estimated that up to 10% of cancer incidents are attributed to inherited genetic alterations. Despite extensive research, there are still gaps in our understanding of genetic predisposition to cancer. It was theorized that ultra-rare variants partially account for the missing heritable component. We harness the UK BioBank dataset of ~ 500,000 individuals, 14% of which were diagnosed with cancer, to detect ultra-rare, possibly high-penetrance cancer predisposition variants. We report on 115 cancer-exclusive ultra-rare variations and nominate 26 variants with additional independent evidence as cancer predisposition variants. We conclude that population cohorts are valuable source for expanding the collection of novel cancer predisposition genes.Recurrent copy number variations (CNVs) are common causes of neurodevelopmental disorders (NDDs) and associated with a range of psychiatric traits. These CNVs occur at defined genomic regions that are particularly prone to recurrent deletions and duplications and often exhibit variable expressivity and incomplete penetrance. Robust estimates of the population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders (NDD CNVs) are lacking. Here we perform array-based CNV calling in 12,252 mother-father-child trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and analyse the inheritance pattern of 26 recurrent NDD CNVs in 13 genomic regions. We estimate the total prevalence of recurrent NDD CNVs (duplications and deletions) in live-born children to 0.48% (95% C.I. 0.37-0.62%), i.e., ~1 in 200 newborns has either a deletion or duplication in these NDDs associated regions. Approximately a third of the newborn recurrent NDD CNVs (34%, N = 20/59) are de novo variants. We provide prevalence estimates and inheritance information for each of the 26 NDD CNVs and find higher prevalence than previously reported for 1q21.1 deletions (~12000), 15q11.2 duplications (~14000), 15q13.3 microdeletions (~12500), 16p11.2 proximal microdeletions (~12000) and 17q12 deletions (~14000) and lower than previously reported prevalence for the 22q11.2 deletion (~112,000). In conclusion, our analysis of an unselected and representative population of newborns and their parents provides a clearer picture of the rate of recurrent microdeletions/duplications implicated in neurodevelopmental delay. These results will provide an important resource for genetic diagnostics and counseling.Although pathways controlling ribosome activity have been described to regulate chondrocyte homeostasis in osteoarthritis, ribosome biogenesis in osteoarthritis is unexplored. We hypothesized that U3 snoRNA, a non-coding RNA involved in ribosomal RNA maturation, is critical for chondrocyte protein translation capacity in osteoarthritis. U3 snoRNA was one of a number of snoRNAs with decreased expression in osteoarthritic cartilage and osteoarthritic chondrocytes. OA synovial fluid impacted U3 snoRNA expression by affecting U3 snoRNA gene promoter activity, while BMP7 was able to increase its expression. Altering U3 snoRNA expression resulted in changes in chondrocyte phenotype. Interference with U3 snoRNA expression led to reduction of rRNA levels and translational capacity, whilst induced expression of U3 snoRNA was accompanied by increased 18S and 28S rRNA levels and elevated protein translation. Whole proteome analysis revealed a global impact of reduced U3 snoRNA expression on protein translational processes and inflammatory pathways. For the first time we demonstrate implications of a snoRNA in osteoarthritis chondrocyte biology and investigated its role in the chondrocyte differentiation status, rRNA levels and protein translational capacity.Gout is a complex inflammatory arthritis affecting ~20% of people with an elevated serum urate level (hyperuricemia). Gout and hyperuricemia are essentially specific to humans and other higher primates, with varied prevalence across ancestral groups. SLC2A9 and ABCG2 are major loci associated with both urate and gout in multiple ancestral groups. However, fine mapping has been challenging due to extensive linkage disequilibrium underlying the associated regions. We used trans-ancestral fine mapping integrated with primate-specific genomic information to address this challenge. Trans-ancestral meta-analyses of GWAS cohorts of either European (EUR) or East Asian (EAS) ancestry resulted in single-variant resolution mappings for SLC2A9 (rs3775948 for urate and rs4697701 for gout) and ABCG2 (rs2622621 for gout). Tests of colocalization of variants in both urate and gout suggested existence of a shared candidate causal variant for SLC2A9 only in EUR and for ABCG2 only in EAS. The fine-mapped gout variant rs4697701 was within an ancient enhancer, whereas rs2622621 was within a primate-specific transposable element, both supported by functional evidence from the Roadmap Epigenomics project in human primary tissues relevant to urate and gout. Additional primate-specific elements were found near both loci and those adjacent to SLC2A9 overlapped with known statistical epistatic interactions associated with urate as well as multiple super-enhancers identified in urate-relevant tissues. We conclude that by leveraging ancestral differences trans-ancestral fine mapping has identified ancestral and functional variants for SLC2A9 or ABCG2 with primate-specific regulatory effects on urate and gout.A null mutation in a patient can facilitate phenotype assignment and uncovers the function of that specific gene. We present five sibs of a consanguineous Pakistani family afflicted with a new syndrome with an unusual combination of skeletal anomalies including cranial asymmetry, fused sagittal sutures deviating from the medial axis, mandibular prognathia, maxillary hypoplasia, misaligned and crowded teeth, delayed bone age, multiple dislocations, hypoplastic and malpositioned patellae, humeral intracondylar fissures, scapular dyskinesis, long limbs, lumbar lordosis, protruding chest, prominent clavicles, short 5th digital rays, and ventral transverse digital creases plus features of cutis laxa. We mapped the disease gene locus to a 3.62-Mb region at 17q25.3 and identified a homozygous deletion of maximal 7.3 kb deduced to totally inactivate MYADML2 and downstream gene PYCR1, biallelic variants in which cause autosomal recessive cutis laxa (ARCL). All five affected sibs had the most common features of ARCL but not many of the less common ones. We attributed the anomalies not typical for ARCL to MYADML2 deficit, because no other genetic defect possibly a candidate to underlie the skeletal phenotype was found. MYADML2 is a gene of unknown function, has not been studied, and has not been associated with disease. Our findings present a possible phenotype for MYADML2 deficit that includes impaired bone patterning and maturation, definitely show that the gene is not essential for survival, and provide a start point for future studies on the function of MYADML2 protein. Detection of new patients is needed to confirm and delineate MYADML2-deficiency phenotype.The thermoelectric properties (TEPs), consisting of Seebeck coefficient, electrical resistivity and thermal conductivity, are infinite-dimensional vectors because they depend on temperature. Accordingly, a projection of them into a finite-dimensional space is inevitable for use in computers. In this paper, as a dimension reduction method, we validate the use of high-order polynomial interpolation of TEPs at Chebyshev nodes of the second kind. To avoid the numerical instability of high order Lagrange polynomial interpolation, we use the barycentric formula. The numerical tests on 276 sets of published TEPs show at least 8 nodes are recommended to preserve the positivity of electrical resistivity and thermal conductivity. With 11 nodes, the interpolation causes about 2% error in TEPs and only 0.4% error in thermoelectric generator module performance. The robustness of our method against noise in TEPs is also tested; as the relative error caused by the interpolation of TEPs is almost the same as the relative size of noise, the interpolation does not cause unnecessarily high oscillation at unsampled points. The accuracy and robustness of the interpolation indicate digitizing infinite-dimensional univariate material data is practicable with tens or less data points. Furthermore, since a large interpolation error comes from a drastic change of data, the interpolation can be used to detect an anomaly such as a phase transition.Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of IRAK2 Myddosome to mitochondria outer membranes via recognition by TOM20, followed by TIMM50-guided translocation of IRAK2 into mitochondria inner membranes, to suppress oxidative phosphorylation and fatty acid oxidation, thereby attenuating energy expenditure. Adipocyte-specific MyD88 or IRAK2 deficiency reduced high-fat-diet-induced weight gain, increased energy expenditure and ameliorated insulin resistance, associated with a smaller adipocyte size and increased cristae formation. IRAK2 kinase inactivation also reduced high-fat diet-induced metabolic diseases. Mechanistically, IRAK2 suppressed respiratory super-complex formation via interaction with PHB1 and OPA1 upon stimulation of IL-1. Taken together, our results suggest that the IRAK2 Myddosome functions as a critical link between inflammation and metabolism, representing a novel therapeutic target for patients with obesity.A large number of industries use heavy metal cations to fix dyes in fabrication processes. Malachite green (MG) is used in many factories and in aquaculture production to treat parasites, and it has genotoxic and carcinogenic effects. Chromium is used to fix the dyes and it is a global toxic heavy metal. Face centered central composite design (FCCCD) has been used to determine the most significant factors for enhanced simultaneous removal of MG and chromium ions from aqueous solutions using marine green alga Enteromorpha intestinalis biomass collected from Jeddah beach. The dry biomass of E. intestinalis samples were also examined using SEM and FTIR before and after MG and chromium biosoptions. The predicted results indicated that 4.3 g/L E. intestinalis biomass was simultaneously removed 99.63% of MG and 93.38% of chromium from aqueous solution using a MG concentration of 7.97 mg/L, the chromium concentration of 192.45 mg/L, pH 9.92, the contact time was 38.5 min with an agitation of 200 rpm. FTIR and SEM proved the change in characteristics of algal biomass after treatments. The dry biomass of E. intestinalis has the capacity to remove MG and chromium from aquatic effluents in a feasible and efficient manner.The magnetic tweezer technique has become a versatile tool for unfolding or folding of individual molecules, mainly DNA. In addition to single molecule analysis, the magnetic tweezer can be used to analyze the mechanical properties of cells and extracellular matrices. We have established a magnetic tweezer that is capable of measuring the linear and non-linear viscoelastic behavior of a wide range of soft matter in precisely controlled environmental conditions, such as temperature, CO2 and humidity. The magnetic tweezer presented in this study is suitable to detect specific differences in the mechanical properties of different cell lines, such as human breast cancer cells and mouse embryonic fibroblasts, as well as collagen matrices of distinct concentrations in the presence and absence of fibronectin crosslinks. The precise calibration and control mechanism employed in the presented magnetic tweezer setup provides the ability to apply physiological force up to 5 nN on 4.5 µm superparamagnetic beads coated with fibronectin and coupled to the cells or collagen matrices. These measurements reveal specific local linear and non-linear viscoelastic behavior of the investigated samples. The viscoelastic response of cells and collagen matrices to the force application is best described by a weak power law behavior. Our results demonstrate that the stress stiffening response and the fluidization of cells is cell type specific and varies largely between differently invasive and aggressive cancer cells. Finally, we showed that the viscoelastic behavior of collagen matrices with and without fibronectin crosslinks measured by the magnetic tweezer can be related to the microstructure of these matrices.A novel magnetic catalyst, (SGCN/Fe3O4/PVIs/Pd) was synthesized by growing of poly(1-vinylimidazole) on the surface of ionic liquid decorated magnetic S-doped graphitic carbon nitride, followed by stabilization of palladium nanoparticles. Catalytic activity of the prepared heterogeneous catalyst was explored for the catalytic reduction of hazardous dyes, methyl orange and Rhodamine B, in the presence of NaBH4. Besides, the effects of the reaction variables on the catalytic activity were investigated in detail. The kinetics study established that dye reduction was the first order reaction and the apparent activation energy was calculated to be 72.63 kJ/mol and 68.35 kJ/mol1 for methyl orange and Rhodamine B dyes, respectively. Moreover, ΔS# and ΔH# values for methyl orange were found to be – 33.67 J/mol K and 68.39 kJ/mol respectively. These values for Rhodamine B were – 45.62 J/mol K and 65.92 kJ/mol. The recycling test verified that the catalyst possessed good stability and reusability, thereby making it a good candidate for the catalytic purposes. Furthermore, a possible catalytic mechanism for dye catalytic reduction over SGCN/Fe3O4/PVIs/Pd was proposed.Multiproxy archaeobotanical analyses (starch granule, phytolith and microcharcoal) of an abandoned agricultural terrace at Wagadagam on Mabuyag Island, Torres Strait, Australia, document extensive, low-intensity forms of plant management from at least 2,145-1,930 cal yr BP and intensive forms of cultivation at 1,376-1,293 cal yr BP. The agricultural activities at 1,376-1,293 cal yr BP are evidenced from terrace construction, banana (Musa cultivars) cultivation and dramatic transformations to the local palaeoenvironment. The robust evidence for the antiquity of horticulture in western Torres Strait provides an historical basis for understanding the diffusion of cultivation practices and cultivars, most likely from New Guinea. This study also provides a methodological template for the investigation of plant management, potentially including forms of cultivation that were practiced in northern Australia before European colonization.In an era of pervasive anthropogenic ecological disturbances, there is a pressing need to understand the factors that constitute community response and resilience. A detailed understanding of disturbance response needs to go beyond associations and incorporate features of disturbances, species traits, rapid evolution and dispersal. Multispecies microbial communities that experience antibiotic perturbation represent a key system with important medical dimensions. However, previous microbiome studies on this theme have relied on high-throughput sequencing data from uncultured species without the ability to explicitly account for the role of species traits and immigration. Here, we serially passage a 34-species defined bacterial community through different levels of pulse antibiotic disturbance, manipulating the presence or absence of species immigration. To understand the ecological community response measured using amplicon sequencing, we combine initial trait data measured for each species separately and metagenome sequencing data revealing adaptive mutations during the experiment. We found that the ecological community response was highly repeatable within the experimental treatments, which could be attributed in part to key species traits (antibiotic susceptibility and growth rate). Increasing antibiotic levels were also coupled with an increasing probability of species extinction, making species immigration critical for community resilience. Moreover, we detected signals of antibiotic-resistance evolution occurring within species at the same time scale, leaving evolutionary changes in communities despite recovery at the species compositional level. Together, these observations reveal a disturbance response that presents as classic species sorting, but is nevertheless accompanied by rapid within-species evolution.The ability of DNA to produce a functional protein even after transfer to a foreign host is of fundamental importance in both evolutionary biology and biotechnology, enabling horizontal gene transfer in the wild and heterologous expression in the lab. However, the influence of genetic particulars on DNA functionality in a new host is poorly understood, as are the evolutionary mechanisms of assimilation and refinement. Here, we describe an automation-enabled large-scale experiment wherein Escherichia coli strains were evolved in parallel after replacement of the genes pgi or tpiA with orthologous DNA from donor species spanning all domains of life, from humans to hyperthermophilic archaea. Via analysis of hundreds of clones evolved for 50,000+ cumulative generations across dozens of independent lineages, we show that orthogene-upregulating mutations can completely mitigate fitness defects that result from initial non-functionality, with coding sequence changes unnecessary. Gene target, donor species and genomic location of the swap all influenced outcomes-both the nature of adaptive mutations (often synonymous) and the frequency with which strains successfully evolved to assimilate the foreign DNA. Additionally, time series DNA sequencing and replay evolution experiments revealed transient copy number expansions, the contingency of lineage outcome on first-step mutations and the ability for strains to escape from suboptimal local fitness maxima. Overall, this study establishes the influence of various DNA and protein features on cross-species genetic interchangeability and evolutionary outcomes, with implications for both horizontal gene transfer and rational strain design.Tropical forests vary in composition, structure and function such that not all forests have similar ecological value. This variability is caused by natural and anthropogenic disturbance regimes, which influence the ability of forests to support biodiversity, store carbon, mediate water yield and facilitate human well-being. While international environmental agreements mandate protecting and restoring forests, only forest extent is typically considered, while forest quality is ignored. Consequently, the locations and loss rates of forests of high ecological value are unknown and coordinated strategies for conserving these forests remain undeveloped. Here, we map locations high in forest structural integrity as a measure of ecological quality on the basis of recently developed fine-resolution maps of three-dimensional forest structure, integrated with human pressure across the global moist tropics. Our analyses reveal that tall forests with closed canopies and low human pressure typical of natural conditions comprise half of the global humid or moist tropical forest estate, largely limited to the Amazon and Congo basins. Most of these forests have no formal protection and, given recent rates of loss, are at substantial risk. With the rapid disappearance of these 'best of the last’ forests at stake, we provide a policy-driven framework for their conservation and restoration, and recommend locations to maintain protections, add new protections, mitigate deleterious human impacts and restore forest structure.Recent reports of dramatic declines in insect abundance suggest grave consequences for global ecosystems and human society. Most evidence comes from Europe, however, leaving uncertainty about insect population trends worldwide. We used >5,300 time series for insects and other arthropods, collected over 4-36 years at monitoring sites representing 68 different natural and managed areas, to search for evidence of declines across the United States. Some taxa and sites showed decreases in abundance and diversity while others increased or were unchanged, yielding net abundance and biodiversity trends generally indistinguishable from zero. This lack of overall increase or decline was consistent across arthropod feeding groups and was similar for heavily disturbed versus relatively natural sites. The apparent robustness of US arthropod populations is reassuring. Yet, this result does not diminish the need for continued monitoring and could mask subtler changes in species composition that nonetheless endanger insect-provided ecosystem services.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Chronic kidney disease (CKD) is a major public health issue and an independent risk factor for cardiovascular and all-cause mortality. Diabetic kidney disease develops in 30-50% of diabetic patients and it is the leading cause of end-stage renal disease in the Western world. Strict blood pressure control and renin-angiotensin system (RAS) blocker use are the cornerstones of CKD treatment; however, their application in everyday clinical practice is not always ideal and in many patients CKD progression still occurs. Accumulated evidence in the past few years clearly suggests that sodium-glucose co-transporter-2 (SGLT-2) inhibitors present potent nephroprotective properties. In clinical trials in patients with type 2 diabetes mellitus, these agents were shown to reduce albuminuria and proteinuria by 30-50% and the incidence of composite hard renal outcomes by 40-50%. Furthermore, their mechanism of action appears rather solid, as they interfere with the major mechanism of proteinuric CKD progression, i.e., glomerular hypertension and hyperfiltration. The present review summarizes the current evidence from human trials on the effects of SGLT-2 inhibitors on nephroprotection and discusses their position in everyday clinical practice.The understanding of water adsorption and desorption behavior in the shale rocks is of great significance in the reserve estimation, wellbore stability and hydrocarbon extraction in the shale gas reservoirs. However, the water sorption behavior in the shales remains unclear. In this study, water vapor adsorption/desorption isotherms of the Longmaxi shale in the Sichuan Basin, China were conducted at various temperatures (30 °C, 60 °C) and a relative pressure up to 0.97 to understand the water sorption behavior. Then the effects of temperature and shale properties were analyzed, and the water adsorption, hysteresis, saturation and capillary pressure were discussed. The results indicate that water adsorption isotherms of the Longmaxi shale exhibit the type II characteristics. The water molecules initially adsorb on the shale particle/pore surfaces at low relative pressure while the capillary condensation dominates at high relative pressure. Temperature favors the water sorption in the shales at high relative prshale gas reservoirs.Dialkylresorcinols are a class of antimicrobial natural products produced by a range of bacterial species. Semi-synthetic derivatization of two microbial dialkylresorcinols isolated from a Pseudomonas aurantiaca strain has yielded 21 derivatives, which were tested for antimicrobial activity, revealing several trends in their activity. The presence of aromatic and phenolic hydrogen atoms was crucial for activity, with all derivatives lacking these features possessing greatly reduced activity. On the other hand, derivatives with shorter alkyl chains at C-5 possessed lower MIC values, while one mono-fluorosulfated derivative showed significantly improved activity against several of the test strains.To reduce the view-flipping effect and enhance the viewing resolution, the modulation characteristics of the hogel based holographic stereogram is constructed and validated. The performance of the view-flipping effect is analyzed, and the results indicate that decreasing the size of hogel is beneficial to the reduction of the view flipping, however, which will result in significant diffraction effect which can degrade the reconstruction quality. Furthermore, a diffraction-limited imaging model of the hogel based holographic stereogram is established, where both the limited aperture of the hogel and the defocused aberration of the object point are introduced, and the effective resolvable size of the reconstructed image point is simulated. The theory shows that there is an optimal hogel size existed for the certain depth of scene. Both the numerical and optical experiments are implemented, and the results are well agreed with the theoretical prediction, which demonstrates that the view-flipping reduction and reconstruction visualization enhancement for EPISM based holographic stereogram can be achieved when the proper size of hogel is utilized.This study aimed to evaluate the effects of stellate ganglion block (SGB) on postoperative trigeminal neuropathy (TNP) after dental surgery. This was a retrospective study based on the medical records of all patients with postoperative TNP at Kyushu Dental University Hospital from 2014 to 2019. Patients were divided into the SGB group (received SGB) and non-SGB group (did not receive SGB). We evaluated the severity of TNP at 3 months after surgery and the incidence rate of abnormal sensations. Abnormal sensations were counted using patients’ reports of uncomfortable symptoms during the treatment, including dysaesthesia, allodynia, and hyperalgesia. A propensity score (PS) matching analysis was performed to evaluate these data. After PS matching, amongst others, the force equivalent values of the Semmes-Weinstein test at 3-months post-treatment were significantly lower in the SGB group than in the non-SGB group (2.00 ± 0.44 vs 2.30 ± 0.48; p less then 0.05). In addition, after PS matching, the incidence rate of abnormal sensations during the treatment was significantly lower in the SGB group than in the non-SGB group (10 cases [4.7%] vs 22 cases [10.3%]; p less then 0.05). Collectively, the findings support that SGB may improve the recovery from postoperative TNP and reduce the incidence rate of abnormal sensations after dental surgery.
To assess the exclusive role and outcomes of Crigler’s lacrimal sac compression in the management of congenital nasolacrimal duct obstruction (CNLDO).
Retrospective interventional case-series was performed on patients diagnosed with CNLDO and who were advised Crigler’s lacrimal sac compression (CLSC) at a tertiary care Dacryology Institute from Jan 2016 to June 2019. CNLDO patients who were practicing incorrect techniques of lacrimal sac compression at presentation were separately assessed. All the patients were assigned to four groups (Gr 1 0-3 months, Gr 2 >3 & <6 months, Gr 3 >6 & <9 months and Gr 4 >9 and <12 months) based on the age at which the CLSC was initiated and followed up quarterly or as needed till at least1 year of age. The parameters studied include patient demographics, clinical presentation, age of initiation of CLSC, success rate with CLSC, and need for additional interventions. Success was defined as the subjective resolution of epiphora and discharge with obje outcomes. Significantly high resolution was noted even beyond nine months of ageand encouraging results beyond 12 months of age.
It is crucial to initiate the correct techniques of Crigler’s lacrimal sac compression to achieve favourable outcomes. Age of initiation of CLSC in infancy does not appear to influence the outcomes.The resolution rate continued to be significantly high up to 1 year of age. There is a need to assess the role of CLSC beyond 12 months of age.
It is crucial to initiate the correct techniques of Crigler’s lacrimal sac compression to achieve favourable outcomes. Age of initiation of CLSC in infancy does not appear to influence the outcomes. The resolution rate continued to be significantly high up to 1 year of age. There is a need to assess the role of CLSC beyond 12 months of age.The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionised imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardised and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The second part of this imaging review will deal with invasive imaging methods and in particular ocular angiography.Congenital and childhood cataracts are uncommon but regularly seen in the clinics of most paediatric ophthalmology teams in the UK. They are often associated with profound visual loss and a large proportion have a genetic aetiology, some with significant extra-ocular comorbidities. Optimal diagnosis and treatment typically require close collaboration within multidisciplinary teams. Surgery remains the mainstay of treatment. A variety of surgical techniques, timings of intervention and options for optical correction have been advocated making management seem complex for those seeing affected children infrequently. This paper summarises the proceedings of two recent RCOphth paediatric cataract study days, provides a literature review and describes the current UK 'state of play’ in the management of paediatric cataracts.
The purpose of this retrospective case-control study was to evaluate the relationship between foveal structure, function, microvascular morphology and visual acuity in school-age children with laser-treated retinopathy of prematurity (ROP).
Foveal structural parameters, including the central foveal thickness (CFT), inner retinal thickness (IRT) and outer retinal thickness (ORT), were measured on B-scans using an Optovue XR Avanti optical coherence tomography device. Foveal microvascular parameters, including the foveal avascular zone (FAZ), superficial capillary plexus-vessel density (SCP-VD) and deep capillary plexus-vessel density (DCP-VD), were measured on optical coherence tomography angiography with a scan size of 3 × 3. The P1 amplitudes and P1 implicit times were recorded by a multifocal electroretinogram with 61 elements.
Fifty-five eyes (26 eyes of school-age ROP children and 29 eyes of full-term controls) were analysed. The ROP children manifested a significantly smaller FAZ, higher SCP-VD and higher DCP-VD than the controls (p < 0.001). The CFT (p < 0.001), IRT (p < 0.001) and ORT (p = 0.001) were significantly increased in the ROP group. The P1 amplitudes in all five-ring retinal regions were significantly smaller in the ROP group (p < 0.001). Multivariable analysis indicated that best-corrected visual acuity was positively correlated with post-menstrual age (PMA) and negatively correlated with SCP-VD and CFT (R
= 0.529, p < 0.001, 0.043 and 0.020, respectively).
The foveal structure, function and microvascular morphology are affected in school-age children with laser-treated ROP. PMA, foveal structural anomalies and microvascular changes in ROP children were associated with impaired visual function.
The foveal structure, function and microvascular morphology are affected in school-age children with laser-treated ROP. PMA, foveal structural anomalies and microvascular changes in ROP children were associated with impaired visual function.Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM) is a promising drug candidate with excellent antibacterial activity against Gram-positive bacteria. The present study was designed to characterize its Cytochrome P450 (CYP) enzymes inhibition activities and the genotoxicity with the standard Ames test. We determined the inhibitory effects of DPTM on CYP1A2, CYP2D1/6, CYP2E1, CYP2C11/9 and CYP3A/4 in rat liver microsomes (RLMs) and in human liver microsomes (HLMs). The mRNA expressions of the above CYP isoforms and their transcriptional regulators were also evaluated using the Hep G2 cell model. The results showed DPTM exhibited a moderate inhibitory potential against CYP3A/4 (IC50 values of 10 ± 2 and 8 ± 2 μM, respectively) and weak against the other CYP enzymes based on their IC50 values. Compared to the control, CYP isoforms and their transcriptional regulators mRNA expressions significantly increased when the Hep G2 cells were treated with DPTM for a certain period of time. In the Ames test, Salmonella strains TA97, TA98, TA100, TA102 and TA1535 were treated with or without the metabolic activation (S9). Analysis showed the average number of revertant colonies per plate was less in double in the groups treated with DPTM than that in the negative control plate and showed no dose-related increase.As defined by the World Health Organization, an endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, its progeny, or (sub)populations. Traditional experimental testing regimens to identify toxicants that induce endocrine disruption can be expensive and time-consuming. Computational modeling has emerged as a promising and cost-effective alternative method for screening and prioritizing potentially endocrine-active compounds. The efficient identification of suitable chemical descriptors and machine-learning algorithms, including deep learning, is a considerable challenge for computational toxicology studies. Here, we sought to apply classic machine-learning algorithms and deep-learning approaches to a panel of over 7500 compounds tested against 18 Toxicity Forecaster assays related to nuclear estrogen receptor (ERα and ERβ) activity. Three binary fingerprints (Extended Connectivity FingerPriistically related endpoints. Consensus predictions based on the average values of individual models remain the best modeling strategy for computational toxicity evaluations.In this study, we propose a contagion model as a simple and powerful mathematical approach for predicting the spatial spread and temporal evolution of the onset and recession of floodwaters in urban road networks. A network of urban roads resilient to flooding events is essential for the provision of public services and for emergency response. The spread of floodwaters in urban networks is a complex spatial-temporal phenomenon. This study presents a mathematical contagion model to describe the spatial-temporal spread and recession process of floodwaters in urban road networks. The evolution of floods within networks can be captured based on three macroscopic characteristics-flood propagation rate ([Formula see text]), flood incubation rate ([Formula see text]), and recovery rate ([Formula see text])-in a system of ordinary differential equations analogous to the Susceptible-Exposed-Infected-Recovered (SEIR) model. We integrated the flood contagion model with the network percolation process in which the probability of flooding of a road segment depends on the degree to which the nearby road segments are flooded. The application of the proposed model is verified using high-resolution historical data of road flooding in Harris County during Hurricane Harvey in 2017. The results show that the model can monitor and predict the fraction of flooded roads over time. Additionally, the proposed model can achieve 90% precision and recall for the spatial spread of the flooded roads at the majority of tested time intervals. The findings suggest that the proposed mathematical contagion model offers great potential to support emergency managers, public officials, citizens, first responders, and other decision-makers for flood forecast in road networks.Duck meat enjoys growing popularity among consumers. Alternative protein sources to soybean are being investigated to eliminate genetically modified components from the poultry’ diet. The aim of this study was to compare growth performance, quality of meat, and fatty acid composition in subcutaneous and abdominal fat from ducks fed a diet based on yellow lupin and rapeseed meal, sources of protein alternative to soybean meal (SBM). Ducks were allocated to different dietary treatment groups and reared for 8 weeks (N = 102 per group). Group A received a diet based on SBM, while group B was fed a diet based on yellow lupin with the addition of rapeseed meal. Both groups were divided into two subgroups, of male and female birds. Growth performance parameters and zoometric traits of ducks were monitored during the growth period. After 8 weeks selected birds were slaughtered and dissected (N = 10 per group). Carcass composition was calculated and selected traits of meat quality important for further processing were analysed. Subcutaneous and abdominal fat were collected to analyse fatty acid composition. The alternative diet had no negative effect on ducks’ growth performance parameters and dressing percentage. The replacement of SBM with yellow lupin and rapeseed meal increased n-3 fatty acid content, which is important for consumers. In conclusion, SBM can be replaced with feed containing 60.10% of yellow lupin and 14.00% of rapeseed meal in concentrate. These sources of protein are mainly recommended for small poultry farms, which do not always have access to SBM and prepare poultry feed from their own crops.Tick cell lines are an easy-to-handle system for the study of viral and bacterial infections and other aspects of tick cellular processes. Tick cell cultures are often continuously cultivated, as freezing can affect their viability. However, the long-term cultivation of tick cells can influence their genome stability. In the present study, we investigated karyotype and genome size of tick cell lines. Though 16S rDNA sequencing showed the similarity between Ixodes spp. cell lines at different passages, their karyotypes differed from 2n = 28 chromosomes for parental Ixodes spp. ticks, and both increase and decrease in chromosome numbers were observed. For example, the highly passaged Ixodes scapularis cell line ISE18 and Ixodes ricinus cell lines IRE/CTVM19 and IRE/CTVM20 had modal chromosome numbers 48, 23 and 48, respectively. Also, the Ornithodoros moubata cell line OME/CTVM22 had the modal chromosome number 33 instead of 2n = 20 chromosomes for Ornithodoros spp. ticks. All studied tick cell lines had a larger genome size in comparison to the genomes of the parental ticks. Thus, highly passaged tick cell lines can be used for research purposes, but possible differences in encoded genetic information and downstream cellular processes, between different cell populations, should be taken into account.Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses, here we investigate PD-1 function in pulmonary ILC2s during IL-33-induced airway inflammation. PD-1 limits the viability of ILC2s and downregulates their effector functions. Additionally, PD-1 deficiency shifts ILC2 metabolism toward glycolysis, glutaminolysis and methionine catabolism. PD-1 thus acts as a metabolic checkpoint in ILC2s, affecting cellular activation and proliferation. As the blockade of PD-1 exacerbates AHR, we also develop a human PD-1 agonist and show that it can ameliorate AHR and suppresses lung inflammation in a humanized mouse model. Together, these results highlight the importance of PD-1 agonistic treatment in allergic asthma and underscore its therapeutic potential.Individuals found at bars in slums have several risk factors for HIV and tuberculosis (TB). To determine the prevalence of HIV and TB among individuals found at bars in slums of Kampala, Uganda, we enrolled adults found at bars that provided written informed consent. Individuals with alcohol intoxication were excluded. We performed HIV testing using immunochromatographic antibody tests (Alere Determine HIV-1/2 and Chembio HIV 1/2 STAT-PAK). TB was confirmed using the Xpert MTB/RIF Ultra assay, performed on single spot sputum samples. We enrolled 272 participants from 42 bars in 5 slums. The prevalence of HIV and TB was 11.4% (95% CI 8.1-15.8) and 15 (95% CI 6-39) per 1,000 population respectively. Predictors of HIV were female sex (aOR 5.87, 95% CI 2.05-16.83), current cigarette smoking (aOR 3.23, 95% CI 1.02-10.26), history of TB treatment (aOR 10.19, 95% CI 3.17-32.82) and CAGE scores of 2-3 (aOR 3.90, 95% CI 1.11-13.70) and 4 (aOR 4.77, 95% CI 1.07-21.35). The prevalence of HIV and TB was twice and four times the national averages respectively.