Objective Brain mapping with direct electrical stimulation is considered the gold standard for maximum, safe resection of tumors affecting eloquent regions. However, no consensus exists in selection and interpretation of intraoperative testing for language and other cognitive domains. Our aim was to capture and statistically analyze variability in current practices in intraoperative language testing among neurosurgeons and neuropsychologists in the United States, Europe and rest of the world. https://www.selleckchem.com/products/d609.html Methods An electronic questionnaire was developed by a multidisciplinary team at Queen Square, London, and distributed internationally through selected organized societies. The survey included two domains terminology and common understanding of clinical deficits and selection of intraoperative tests used per specific brain region. Participants stratified by specialty, years of experience, and monthly caseload. Data were analyzed using Krippendorff's α, Wilcoxon rank sum test and Kruskal-Wallis analysis of variance. Results A total of 137 specialists participated. A low agreement was recorded for each of the 20 questions (Krippendorff's α=-0.023-0.312). Further subgroup analysis revealed low inter-rater reliability (IRR) independent of specialism, neurosurgeons (α=0.013-0.318) compared to non-neurosurgeons (α=-0.021-0.398; p=0.808) and years of experience, less then 1 years (α=-0.003-0.282), 2-5 years (α=0.009-0.327), 6-10 years (α=0.003-0.234) and over 10 years (α=-0.003-0.372; p=0.200). Conclusions The current study documents high interrater variability, regardless of specialism and years of experience in the cohort of neurosurgeons and language specialists surveyed, and may be applicable to much wider group of specialists, indicating the need to reduce inter-observer, inter-institutional and inter-specialty variability, reach consensus, and increase the validity, interpretation and predictive power of intraoperative mapping.Background Mechanical thrombectomy has become the standard treatment for acute ischemic stroke caused by large vessel occlusion; however, refractory occlusions still exist despite various thrombectomy procedures. The double stent-retriever (SR) technique, which utilizes not a single, but two SRs simultaneously at the occlusion, can be useful for such refractory occlusions. Methods We described two cases of refractory acute cerebral occlusion despite the use of conventional thrombectomy procedures, which were both treated with the double SR technique. To discuss the technical aspects of how this easy-to-perform technique facilitates the device-clot interaction, we also evaluated radiographic findings of the SR's strut during the procedure. Results In both cases, conventional thrombectomy procedures, including an SR alone, an aspiration catheter alone, and combined use of the SR and aspiration catheter failed to recanalize the occlusion. Then, the double SR technique was performed with the stent-in-stent method in one patient and the parallel stent method in the other patient. One pass of this technique retrieved hard clots and successfully recanalized the refractory occlusion in both cases. Intraprocedural radiographical images of these cases showed that the degree of stent expansion improved after deployment of the second SR compared with the first one. Conclusions Our radiographical findings suggested that adding one more SR facilitates the device-clot interaction at the occlusion site. The double SR technique may be an easy-to-perform thrombectomy technique to improve the clot-capturing ability for the management of refractory acute cerebral artery occlusions.Objective To evaluate the differences in surgical outcomes of patients with cervical spondylotic myelopathy with and without congenital cervical spinal stenosis (CCSS). Methods Institutional review board approval was obtained to conduct a retrospective chart review of patients with cervical spondylotic myelopathy who underwent decompression and fusion surgeries from 2010-2016 at a single institution. CCSS was identified using the Torg-Pavlov ratio on lateral cervical radiographs. Pre- and postoperative outcome measures were assessed using the modified Japanese Orthopedic Association (mJOA) and the EuroQol 5-dimension questionnaire (EQ-5D). Results Of 208 patients, Torg-Pavlov ratio identified 85 patients with CCSS. There were no significant differences between the CCSS patient and control patient groups in EuroQol 5-dimension questionnaire and mJOA scores at all 4 designated time points in the study (preoperative, earliest postoperative, 6 month postoperative, and 1 year postoperative). Although not statistically significantly, there was a notable trend for patients with CCSS to be less likely to have mJOA-defined severe myelopathy at the postoperative (odds ratio [OR], 0.75; P = 0.38), 6 month postoperative (OR, 0.66; P = 0.20), and 1 year postoperative (OR, 0.64; P = 0.14) time points. Conclusions Postoperatively, compared with non-CCSS patients, patients with congenital cervical stenosis reported equal quality of life for all markers. Our findings suggest that in patients with CCSS and relatively mild symptoms of myelopathy, equal consideration should be given for surgical intervention. The findings of this study warrant further large-scale, multi-institutional investigation to further understand the generalizability of these surgical outcome results.Purpose Lumbosacral lipomas (LSLs), one form of closed spinal dysraphism, are congenital disorders of the terminal spinal cord (sc). Delayed neurological deterioration often occurs in the subsequent developmental course of the patient. Identifying the cellular and molecular factors underlying the progressive damage to neural structures is a prerequisite for developing treatment strategies for LSLs. Methods Nine LSL specimens obtained from the sc/lipoma interface during surgical resection were examined. Normal sc tissue served as a control. Clinical characteristics were obtained, and spinal MRI was re-evaluated. Cellular marker profiles were established. Immunoreactivity (IR) of HIF-1a/-2a, EPO/EPOR, IL-1b/IL-1R1, and TNFa/TNF-R1 was analyzed qualitatively and semiquantitatively by densitometry. Colabeling with cellular markers was determined by multifluorescence labeling. Cytokines were further analyzed by real-time RT-PCR. Results LSL specimens exhibited significant gliosis. HIF-1a/-2a IR and EPO/EPR IR were found at significantly higher levels in the LSL specimens, as were IL-1b-/IL1-R1 IR and TNFa-/TNF-R IR (p less then 0.

phyB-independent growth restriction of the jazD mutant was tightly correlated with upregulation of the tryptophan biosynthetic pathway but not changes in central carbon metabolism. Interestingly, jazD and jazD phyB plants were insensitive to a chemical inhibitor of tryptophan biosynthesis, which is a phenotype previously observed in plants expressing hyperactive MYC transcription factors that cannot bind JAZ repressors. These data provide evidence that the mechanisms underlying the JA-mediated growth-defense balance depend on the level of defense, and further establish an association between growth inhibition at high levels of defense and dysregulation of tryptophan biosynthesis. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.P granules are phase-separated liquid droplets that play important roles in the maintenance of germ cell fate in Caenorhabditis elegans Both the localization and formation of P granules are highly dynamic, but mechanisms that regulate such processes remain poorly understood. Here we show evidence that the VASA-like germline RNA helicase GLH-1 couples distinct steps of its ATPase hydrolysis cycle to control the formation and disassembly of P granules. In addition, we found that the FGG repeats in GLH-1 promote its localization at the perinucleus. Proteomic analyses of the GLH-1 complex with a GLH-1 mutation that interferes P granule disassembly revealed transient interactions of GLH-1 with several Argonautes and RNA binding proteins. https://www.selleckchem.com/products/sp-600125.html Finally, we found that defects in recruiting the P granule component PRG-1 to perinuclear foci in the adult germline correlate with the fertility defects observed in various GLH-1 mutants. Together, our results highlight the versatile roles of an RNA helicase in controlling the formation of liquid droplets in space and time. Copyright © 2020, Genetics.Emerging large-scale biobanks pairing genotype data with phenotype data present new opportunities to prioritize shared genetic associations across multiple phenotypes for molecular validation. Past research, by our group and others, has shown gene-level tests of association produce biologically interpretable characterization of the genetic architecture of a given phenotype. Here we present a new method, Ward clustering to identify Internal Node branch length outliers using Gene Scores (WINGS), for identifying shared genetic architecture among multiple phenotypes. The objective of WINGS is to identify groups of phenotypes, or "clusters," sharing a core set of genes enriched for mutations in cases. We validate WINGS using extensive simulation studies and then combine gene-level association tests with WINGS to identify shared genetic architecture among 81 case-control and seven quantitative phenotypes in 349,468 European-ancestry individuals from the UK Biobank. We identify eight prioritized phenotype clusters and recover multiple published gene-level associations within prioritized clusters. Copyright © 2020, Genetics.BACKGROUND Risk prediction models may be useful for precision breast-cancer screening. We aimed to evaluate the performance of breast cancer risk models developed in European-ancestry studies in a Korean population. METHODS We compared discrimination and calibration of three multivariable risk models in a cohort of 77,457 women from the Korean Cancer Prevention Study (KCPS)-II. The first incorporated US breast-cancer incidence and mortality rates, US risk-factor distributions, and relative risk (RR) estimates from European-ancestry studies. The second recalibrated the first by using Korean incidence and mortality rates and Korean risk factor distributions, while retaining the European-ancestry RR estimates. Finally, we derived a Korea-specific model incorporating the RR estimates from KCPS. RESULTS The US European-ancestry breast cancer risk model was well calibrated among Korean women less then 50 years (Expected/Observed=1.124 (0.989, 1.278)) but markedly overestimated the risk for those ≥50 years (E/O=2.472 (2.005, 3.049)). Recalibrating absolute risk estimates using Korean breast cancer rates and risk distributions markedly improved the calibration in women ≥50 (E/O=1.018 (0.825, 1.255)). The model incorporating Korean-based RRs had similar but not clearly improved performance relative to the recalibrated model. CONCLUSIONS The poor performance of the US European-ancestry breast cancer risk model among older Korean women highlights the importance of tailoring absolute risk models to specific populations. Recalibrating the model using Korean incidence and mortality rates and risk factor distributions greatly improved performance. IMPACT The data will provide valuable information to plan and evaluate actions against breast cancer focused on primary prevention and early detection in Korean women. Copyright ©2020, American Association for Cancer Research.BACKGROUND Synovial sarcoma is a rare cancer with peak incidence in the young adult period. Despite poor outcomes of this aggressive cancer, there is little epidemiologic research addressing its etiology. METHODS We collected birth characteristic data on synovial sarcoma cases born 1978-2015 and diagnosed 1988-2015 in California (n=244), and 12,200 controls frequency-matched on year of birth. We also constructed a dataset of cancer cases in siblings of sarcoma subjects to assess familial risk. RESULTS In multivariable logistic regression analyses, synovial sarcoma was more frequent in Hispanics compared to non-Hispanic whites [odds ratio (OR) = 1.48; 95% confidence interval (CI) 1.06-2.08]. Higher birthweight was a risk factor in Hispanics - each 500 g increase in birthweight was associated with a 22% increase in disease risk (OR = 1.22; 95% CI1.00- 1.48). Also, a strong role for birth order was suggested, with highest risk for the first born (second child compared to first OR = 0.61, 95% CI 0.44-0.84; third or later compared to first OR = 0.53, 95% CI 0.36-0.77). Siblings of synovial sarcoma patients did not display elevated cancer incidence, suggesting the low likelihood that strong familial predisposition alleles play a significant role in this disease. CONCLUSIONS The associations with birthweight and birth order suggest that nutritional, developmental, and environmental factors may play a role in the etiology of synovial sarcoma. IMPACT Further epidemiologic research on synovial sarcoma should evaluate epigenetic and developmental mechanisms and the formation of the archetypical t(X;18) translocation that defines this disease. Copyright ©2020, American Association for Cancer Research.

This review describes the application of peptide nucleic acids (PNAs) as clamps that prevent nucleic acid amplification of wild-type DNA so that DNA with mutations may be observed. These methods are useful to detect single-nucleotide polymorphisms (SNPs) in cases where there is a small amount of mutated DNA relative to the amount of normal (unmutated/wild-type) DNA. https://www.selleckchem.com/products/mki-1.html Detecting SNPs arising from mutated DNA can be useful to diagnose various genetic diseases, and is especially important in cancer diagnostics for early detection, proper diagnosis, and monitoring of disease progression. Most examples use PNA clamps to inhibit PCR amplification of wild-type DNA to identify the presence of mutated DNA associated with various types of cancer.Recent progress in the development of mobile Eye Tracking (ET) systems shows that there is a demand for modern flexible solutions that would allow for dynamic tracking of objects in the video stream. The paper describes a newly developed tool for work with ET glasses, and its advantages are outlined with the example of a pilot study. A flight task is performed on the FNTP II MCC simulator, and the pilots are equipped with the Mobile Tobii Glasses. The proposed Smart Trainer tool performs dynamic object tracking in a registered video stream, allowing for an interactive definition of Area of Interest (AOI) with blurred contours for the individual cockpit instruments and for the construction of corresponding histograms of pilot attention. The studies are carried out on a group of experienced pilots with a professional pilot CPL(A) license with instrumental flight (Instrument Rating (IR)) certification and a group of pilots without instrumental training. The experimental section shows the differences in the perception of the flight process between two distinct groups of pilots with varying levels in flight training for the ATPL(A) line pilot license. The proposed Smart Trainer tool might be exploited in order to assess and improve the process of training operators of advanced systems with human machine interfaces.Data gathering is an essential concern in Wireless Sensor Networks (WSNs). This paper proposes an efficient data gathering method in clustered WSNs based on sparse sampling to reduce energy consumption and prolong the network lifetime. For data gathering scheme, we propose a method that can collect sparse sampled data in each time slot with a fixed percent of nodes remaining in sleep mode. For data reconstruction, a subspace approach is proposed to enforce an explicit low-rank constraint for data reconstruction from sparse sampled data. Subspace representing spatial distributions of the WSNs data can be estimated from previous reconstructed data. Incorporating total variation constraint, the proposed reconstruction method reconstructs current time slot data efficiently. The results of experiments indicate that the proposed method can reduce the energy consumption and prolong the network lifetime with satisfying recovery accuracy.Near real time (NRT) remote sensing derived land surface temperature (Ts) data has an utmost importance in various applications of natural hazards and disasters. Space-based instrument MODIS (moderate resolution imaging spectroradiometer) acquired NRT data products of Ts are made available for the users by LANCE (Land, Atmosphere Near real-time Capability) for Earth Observing System (EOS) of NASA (National Aeronautics and Space Administration) free of cost. Such Ts products are swath data with 5 min temporal increments of satellite acquisition, and the average latency is 60-125 min to be available in public domain. The swath data of Ts requires a specialized tool, i.e., HEG (HDF-EOS to GeoTIFF conversion tool) to process and make the data useful for further analysis. However, the file naming convention of the available swath data files in LANCE is not appropriate to download for an area of interest (AOI) to be processed by HEG. In this study, we developed a method/algorithm to overcome such issues in identifying the appropriate swath data files for an AOI that would be able to further processes supported by the HEG. In this case, we used Terra MODIS acquired NRT swath data of Ts, and further applied it to an existing framework of forecasting forest fires (as a case study) for the performance evaluation of our processed Ts. We were successful in selecting appropriate swath data files of Ts for our study area that was further processed by HEG, and finally were able to generate fire danger map in the existing forecasting model. Our proposed method/algorithm could be applied on any swath data product available in LANCE for any location in the world.Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which significantly restricts is therapeutic activity. Therefore, this study assessed the metabolic stability of the 16 identified naphthoquinone derivatives 1-16 using hepatocarcinoma cells in combination with an optimized reverse-phase liquid chromatography (RP-LC) method. Most of the derivatives showed significantly better stability than idebenone over 6 h (p less then 0.001). By extending the side-chain of SCQs, increased stability for some compounds was observed. Metabolic conversion from the derivative 3 to 5 and reduced idebenone metabolism in the presence of 5 were also observed.

Furthermore, its interaction with diacylglycerol kinase ζ (DGKζ), a negative regulator of DAG, sustains the precise modulation of this lipid and, thus, facilitates IS organization and signaling. Here, we review the role of SNX27, DAG metabolism, and their interplay in the control of T-cell activation and establishment of the IS.The measurement of handgrip strength (HGS) is an indicator of an individual's overall strength and can serve as a predictor of morbidity and mortality. This study aims to investigate whether HGS is associated with handedness in young adults and if it is influenced by anthropometric characteristics, body composition, and sport-related parameters. We conducted a cross-sectional study on a sample of 544 young Italian adults aged 18-30 years. We measured HGS using a dynamometer and collected data on handedness and physical activity, along with anthropometric measurements. In both sexes, the HGS of the dominant side was significantly greater than that of the non-dominant side. Furthermore, in ambidextrous individuals, the right hand was stronger than the left. A comparison between the lowest and the highest tercile of HGS highlighted its significant association with anthropometric and body composition parameters in both sexes. Moreover, sex, dominant upper arm muscle area, arm fat index, fat mass, and fat-free mass were found to be significant predictors of HGS by multiple regression analysis. Our findings suggest that HGS is especially influenced by body composition parameters and handedness category. Therefore, HGS can be used as a proxy for unhealthy conditions with impairment of muscle mass, provided that the dominance in the laterality of the subject under examination is taken into account.The importance of the maternal microbiota in terms of the initial bacterial seeding has previously been highlighted; however, little is currently known about the perinatal factors that could affect it. The aim of this study was to evaluate the effects of various delivery-related factors on the intestinal microbiome at delivery time and on post-partum weight retention. Data were collected from mothers (n = 167) during the first four months post-partum. A subset of 100 mothers were selected for the determination of the salivary cortisol concentration and microbiome composition at birth by 16S rRNA gene sequencing. The maternal microbiota was classified into two distinct clusters with significant differences in microbial composition and diversity. Maternal microbiota was also significantly influenced by the mode of delivery. https://www.selleckchem.com/products/skf-34288-hydrochloride.html Moreover, the salivary cortisol concentration was associated with some maternal microbiota genera and it was significantly higher in the vaginal delivery group (p = 0.003). The vaginal delivery group exhibited lower post-partum weight retention than the C-section (CS) mothers at four months post-partum (p less then 0.001). These results support the hypothesis that the mode of delivery as well as the codominant hormonal changes could influence the maternal microbiota and possibly impact maternal weight recovery during the post-partum period.High usage of emergency treatment and hospitalization has been reported among homeless individuals. Hence, this study aimed to identify the sociodemographic predictors associated with overnight and emergency hospital treatment among a sample of homeless adults. Participants were recruited from a shelter in Dallas, Texas (N = 354; Mage = 43.7 ± 11.7) and were predominantly uninsured, low-income men from various racial groups. The outcome variables were (a) stayed overnight for treatment in a hospital; and (b) treated in a hospital emergency room. In logistic regression models, sex emerged as the only predictor of overnight treatment in a hospital (OR = 2.68, 95% CI = 1.61-4.47), and treatment in an emergency room (OR = 2.21, 95% CI = 1.34-3.65), such that women were more likely than men to be treated overnight and use emergency care. Targeted interventions and policies are needed to address homeless women's primary care needs and reduce costlier treatment.β-Glucosidases and β-mannosidases hydrolyze substrates that differ only in the epimer of the nonreducing terminal sugar moiety, but most such enzymes show a strong preference for one activity or the other. Rice Os3BGlu7 and Os7BGlu26 β-glycosidases show a less strong preference, but Os3BGlu7 and Os7BGlu26 prefer glucosides and mannosides, respectively. Previous studies of crystal structures with glucoimidazole (GIm) and mannoimidazole (MIm) complexes and metadynamic simulations suggested that Os7BGlu26 hydrolyzes mannosides via the B2,5 transition state (TS) conformation preferred for mannosides and glucosides via their preferred 4H3/4E TS conformation. However, MIm is weakly bound by both enzymes. In the present study, we found that MIm was not bound in the active site of crystallized Os3BGlu7, but GIm was tightly bound in the -1 subsite in a 4H3/4E conformation via hydrogen bonds with the surrounding residues. One-microsecond molecular dynamics simulations showed that GIm was stably bound in the Os3BGlu7 active site and the glycone-binding site with little distortion. In contrast, MIm initialized in the B2,5 conformation rapidly relaxed to a E3/4H3 conformation and moved out into a position in the entrance of the active site, where it bound more stably despite making fewer interactions. The lack of MIm binding in the glycone site in protein crystals and simulations implies that the energy required to distort MIm to the B2,5 conformation for optimal active site residue interactions is sufficient to offset the energy of those interactions in Os3BGlu7. This balance between distortion and binding energy may also provide a rationale for glucosidase versus mannosidase specificity in plant β-glycosidases.The synthesis and structural characterization of 5,6'-dimethyl-2,2'-bipyridine (5,6'-Me2bpy) are reported, along with the preparations and characterizations of [Cu(POP)(5,6'-Me2bpy)][PF6] and [Cu(xantphos)(5,6'-Me2bpy)][PF6] (POP = bis(2-(diphenylphosphanyl)phenyl)ether, xantphos = 4,5-bis(diphenylphosphanyl)-9,9-dimethyl-9H-xanthene). Single-crystal X-ray structure determinations of [Cu(POP)(5,6'-Me2bpy)][PF6] and [Cu(xantphos)(5,6'-Me2bpy)][PF6] confirmed distorted tetrahedral copper(I) coordination environments with the 5-methylpyridine ring of 5,6'-Me2bpy directed towards the (C6H4)2O unit of POP or the xanthene unit of xantphos. In the xantphos case, this preference may be attributed to C-H…π interactions involving both the 6-CH unit and the 5-methyl substituent in the 5-methylpyridine ring and the arene rings of the xanthene unit. 1H NMR spectroscopic data indicate that this ligand orientation is also preferred in solution. In solution and the solid state, [Cu(POP)(5,6'-Me2bpy)][PF6] and [Cu(xantphos)(5,6'-Me2bpy)][PF6] are yellow emitters, and, for powdered samples, photoluminescence quantum yields (PLQYs) are 12 and 11%, respectively, and excited-state lifetimes are 5 and 6 μs, respectively.

Stable, long-term interactions between fungi and algae or cyanobacteria, collectively known as lichens, have repeatedly evolved complex architectures with little resemblance to their component parts. Lacking any central scaffold, the shapes they assume are casts of secreted polymers that cement cells into place, determine the angle of phototropic exposure and regulate water relations. A growing body of evidence suggests that many lichen extracellular polymer matrices harbour unicellular, non-photosynthesizing organisms (UNPOs) not traditionally recognized as lichen symbionts. Understanding organismal input and uptake in this layer is key to interpreting the role UNPOs play in lichen biology. Here we review both polysaccharide composition determined from whole, pulverized lichens and UNPOs reported from lichens to date. Most reported polysaccharides are thought to be structural cell wall components. The composition of the extracellular matrix is not definitively known. Several lines of evidence suggest some polysaccharides have evaded detection in routine analysis of neutral sugars and may be involved in the extracellular matrix. UNPOs reported from lichens include diverse bacteria and yeasts for which secreted polysaccharides play important biological roles. We conclude by proposing testable hypotheses on the role that symbiont give-and-take in this layer could play in determining or modifying lichen symbiotic outcomes. © FEMS 2020.Patients with ataxia-telangiectasia (A-T) lack a functional ATM kinase protein and exhibit defective repair of DNA double strand breaks (DSB) and response to oxidative stress. We show that CRISPR/Cas9-assisted gene correction combined with piggyBac transposon-mediated excision of the selection cassette enables seamless restoration of functional ATM alleles in induced pluripotent stem cells from an A-T patient carrying compound heterozygous exonic missense/frameshift mutations, and from a patient with a homozygous splicing acceptor mutation of an internal coding exon. We show that the correction of one allele restores expression of ~ 50% of full-length ATM protein and ameliorates DNA damage-induced activation (auto-phosphorylation) of ATM and phosphorylation of its downstream targets KAP-1 and H2AX. Restoration of ATM function also normalises radiosensitivity, mitochondrial ROS production, and oxidative stress-induced apoptosis levels in A-T iPSC lines, demonstrating that restoration of a single ATM allele is sufficient to rescue key ATM functions. Our data further show that, despite the absence of a functional ATM kinase, homology-directed repair and seamless correction of a pathogenic ATM mutation is possible. The isogenic pairs of A-T and gene-corrected iPSCs described here constitute valuable tools for elucidating the role of ATM in ageing and A-T pathogenesis. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND whether light-to-moderate alcohol intake is related to reduced mortality remains a subject of intense research and controversy. There are very few studies available on alcohol and reaching longevity. METHODS we investigated the relationship of alcohol drinking characteristics with the probability to reach 90 years of age. Analyses were conducted using data from the Netherlands Cohort Study. Participants born in 1916-1917 (n = 7,807) completed a questionnaire in 1986 (age 68-70 years) and were followed up for vital status until the age of 90 years (2006-07). Multivariable Cox regression analyses with fixed follow-up time were based on 5,479 participants with complete data to calculate risk ratios (RRs) of reaching longevity (age 90 years). RESULTS we found statistically significant positive associations between baseline alcohol intake and the probability of reaching 90 years in both men and women. Overall, the highest probability of reaching 90 was found in those consuming 5-  less then  15 g/d alcohol, with RR = 1.36 (95% CI, 1.20-1.55) when compared with abstainers. The exposure-response relationship was significantly non-linear in women, but not in men. Wine intake was positively associated with longevity (notably in women), whereas liquor was positively associated with longevity in men and inversely in women. Binge drinking pointed towards an inverse relationship with longevity. Alcohol intake was associated with longevity in those without and with a history of selected diseases. CONCLUSIONS the highest probability of reaching 90 years was found for those drinking 5-  less then  15 g alcohol/day. Although not significant, the risk estimates also indicate to avoid binge drinking. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society.Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from across 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. https://www.selleckchem.com/products/unc8153.html Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.The increasing availability and complexity of next generation sequencing (NGS) datasets make ongoing training an essential component of conservation and population genetics research. A workshop entitled "ConGen 2018" was recently held to train researchers in conceptual and practical aspects of NGS data production and analysis for conservation and ecological applications. Sixteen instructors provided helpful lectures, discussions, and hands-on exercises regarding how to plan, produce, and analyze data for many important research questions. Lecture topics ranged from understanding probabilistic (e.g. Bayesian) genotype calling to the detection of local adaptation signatures from genomic, transcriptomic, and epigenomic data. We report on progress in addressing central questions of conservation genomics, advances in NGS data analysis, the potential for genomic tools to assess adaptive capacity, and strategies for training the next generation of conservation genomicists. © The American Genetic Association 2020.

OBJECTIVE It is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population. METHODS Using a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes. RESULTS Of 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8-75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers (p less then 0.001 by log-rank test). https://www.selleckchem.com/products/mki-1.html The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31-0.48) for major vascular events, 0.81 (95% CI 0.57-1.16) for stroke recurrence, 0.28 (95% CI 0.21-0.36) for vascular death, and 0.53 (95% CI 0.45-0.61) for all-cause death. CONCLUSION Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin. © 2020 American Academy of Neurology.OBJECTIVE Medical students experience difficult conversations with patients during clinical clerkships. This study aimed to characterize barriers to and opportunities for learning in the setting of challenging conversations. METHODS Neurology clerkship medical students were enrolled prospectively in a concurrent nested mixed methods study. Qualitative data were collected using a postclerkship survey and semi-structured focus groups. Students were asked to reflect on challenging conversations they experienced with patients and to identify the top reasons why conversations were challenging. Responses were analyzed using directed content analysis. RESULTS A total of 159 medical students were enrolled (MS2 n = 35 [22%]; MS3 n = 97 [61%]; MS4 n = 27 [17%]). Three themes of difficulty were identified in survey and focus group data (1) tough clinical realities how the clinical environment makes conversations challenging; (2) communication skill needs the difficulty of finding the words to say; and (3) navigating emotions of patients, clinicians, and students themselves. Tough clinical realities were cited by over two-thirds of students in all years (MS2 n = 30 [86%]; MS3 n = 74 [76%]; MS4 n = 23 [85%]). Communication skills needs were cited most frequently by third-year students (MS2 n = 15 [43%]; MS3 n = 55 [57%]; MS4 n = 10 [37%]). Students early in training were more likely to cite difficulty navigating emotions (MS2 n = 28 [80%]; MS3 n = 71 [73%]; MS4 n = 19 [70%]). CONCLUSIONS Medical students frequently observe and participate in challenging conversations with patients. Here, students identified what makes these conversations most difficult. Communication curricula should leverage clinical communication encounters, prepare students for inherent clinical realities, and help students navigate emotions in the health care setting. © 2020 American Academy of Neurology.in French OBJECTIF Offrir aux médecins de famille une approche diagnostique et thérapeutique actualisée de la pharyngite, en décrivant en détail les principaux symptômes, les méthodes d’investigation et un résumé des causes courantes. SOURCES D’INFORMATION L’approche décrite est basée sur la pratique clinique des auteurs et sur les publications revues par les pairs de 1989 à 2018. MESSAGE PRINCIPAL Le mal de gorge causé par la pharyngite est couramment observé dans les cliniques de médecine familiale; il est causé par l’inflammation du pharynx et des tissus environnants. La pharyngite est causée par une infection virale, bactérienne ou fongique. Les causes virales sont souvent spontanément résolutives, alors que les infections bactériennes et fongiques nécessitent habituellement l’antibiothérapie. Le test de détection rapide de l’antigène et la culture de gorge sont jumelés aux observations cliniques pour identifier l’organisme en cause. La pharyngite causée par streptococcus pyogenes fait partie des organismes les plus préoccupants en raison de ses complications graves, telles la fièvre rhumatismale aiguë et la glomérulonéphrite. Ainsi, il est nécessaire de poser un diagnostic attentif de pharyngite afin de pouvoir dispenser un traitement ciblé. CONCLUSION L’anamnèse détaillée est la clé du diagnostic de pharyngite. Le test de détection rapide de l’antigène doit être réservé aux cas où l’instauration de l’antibiothérapie est préoccupante. Les médecins doivent user de retenue lorsqu’ils instaurent l’antibiothérapie contre la pharyngite, puisque la retenue ne retarde pas le rétablissement ni n’augmente le risque d’infection à s. pyogenes.OBJECTIVE To examine how FP and practice characteristics relate to the provision of home visits. DESIGN Census survey linked to administrative billing data. SETTING Nova Scotia, 2014 to 2015. PARTICIPANTS Respondents to the family physician practice survey (N = 740; 84.5% response rate), the FP provider survey (N = 677; 56.7% response rate), and the nurse practitioner provider survey (N = 45; 68.9% response rate). MAIN OUTCOME MEASURES Provision of home visits. Family physician characteristics included age, sex, and proximity to retirement; practice characteristics included patient age and practice rurality. RESULTS Overall, 84.4% of surveyed FPs reported that they did home visits. In both survey data and billing data, older FPs were more likely to do home visits (P less then .01). In multivariate analyses, older FP age, older patient age, rural practice location, and male FP sex were all independently associated with provision of any home visits and with the number of home visits (all P less then .0001).

Introduction Effectiveness of e-learning diminishes without the support of a pedagogical model to guide its use. In minimally invasive surgery (MIS), this has been reported as a limitation when technology is used to deliver contents without a sound pedagogical background.Material and methods We describe how a generic pedagogical model, the 3D pedagogy framework, can be used for setting learning outcomes and activities in e-learning platforms focused on MIS cognitive skills. A demonstrator course on Nissen fundoplication was developed following the model step-by-step in the MISTELA learning platform. Course design was informed by Kolb's Experiential learning model. Content validation was performed by 13 MIS experts.Results Ten experts agreed on the suitability of content structuring done according to the pedagogical model. All experts agreed that the course provides means to assess the intended learning outcomes.Conclusions This work showcases how a general-purpose e-learning framework can be accommodated to the needs of MIS training without limiting the course designers' pedagogical approach. Key advances for its success include (1) proving the validity of the model in the wider scope of MIS skills and (2) raising awareness amongst stakeholders on the need of developing training plans with explicit, rather than assumed, pedagogical foundations. Abbreviations MIS minimally invasive surgery; TEL technology enhanced learning.A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (11) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients.The proliferation in the last few years of cannabidiol (CBD)-containing products in the U.S. markets has been greatly accelerated by changes in the regulatory environment, and by perceptions of their health benefits and presumed safety. The result has been aggressive marketing of many types of products, some of dubious quality, making or implying drug-type claims. The recent approval by the U.S. Food and Drug Administration (FDA) of CBD in the form of Epidiolex®, further complicates the regulatory picture. In addition, a number of studies suggest that, at least at high doses, there may be serious adverse effects or drug interactions associated with CBD. At present, CBD-containing products do not meet the strict definition of dietary supplements, but the FDA is continuing to consider some framework under which they might be allowed. Meanwhile, FDA has adopted a "risk-based" enforcement policy. Possible approaches to a new framework for regulation of CBD products as dietary supplements are discussed here, including expanded research emphasis, a robust corporate stewardship program, and a rigorous adverse event reporting program.Introduction Diffuse intrinsic pontine glioma (DIPG) is an almost universally fatal pediatric brain cancer. There has been no improvement in event-free survival (EFS) or overall survival (OS) despite immense effort through a multitude of clinical trials to find a cure. Recently, there has been a surge in the knowledge of DIPG biology, including the discovery of a recurrent H3F3A mutation in over 80% of these tumors. Areas covered The authors review the most recent approaches to diagnosis and treatment of DIPG including chemotherapy, biologics, surgical approaches, and immunotherapy. Expert opinion The authors propose four main opportunities to improve long-term survival. First, patients should be enrolled in scientifically sound clinical trials that include molecularly profiling either via stereotactic biopsy or liquid biopsy. Second, clinical trials should include more innovative endpoints other than traditional EFS and OS such as MRI/PET imaging findings combined with surrogates of activity (e.g. serial liquid biopsies) to better ascertain biologically active treatments. Third, innovative clinical trial approaches are needed to help allow for the rapid development of combination therapies to be tested. Finally, effort should be concentrated on reversing the effects of the histone mutation, as this malfunctioning development program seems to be key to DIPG relentlessness.Background Monitoring the impact of vaccine programs is necessary to identify changes in vaccine efficacy. https://www.selleckchem.com/products/vx-561.html We report the impact of the 12-year rotavirus vaccine program on diarrhea mortality and hospitalizations and their correlation to socioeconomic indicators. Methods this ecological study describes diarrhea hospitalizations and deaths from 2006 to 2018 in Brazil and correlates rotavirus vaccine coverage, hospitalizations and deaths to socioeconomic indicators and social vulnerability index (SVI) by state and region. Hospitalizations, deaths, and vaccine coverage trends were analyzed using Joinpoint regression models. Associations between hospitalizations, mortality and rotavirus vaccination coverage and socioeconomic and SVI indicators were established using Ordinary Least Square regressions. Results Rotavirus vaccine coverage remained stable between 2006 and 2018 (annual percentage changes (APC) [95%CI] 4.4% [-0.3%, 9.2%]). Diarrhea hospitalization rates decreased 52.5% (-5.7% [-7.5%, -3.8%]), from 68.4 to 32.

In recent literature, there is a growing interest for the high ankle sprain with emerging evidence on biomechanical behavior, function, injury, and treatment. Interpretation of emerging publications on the distal tibiofibular syndesmosis may raise questions about striking similarities with the anterior cruciate ligament function and pivot-shift mechanism of injury in the knee. This editorial note puts to question whether identical entities, a continuum or separate injuries are faced by contemplating on the mechanism of injury, diagnostics, treatment, and outcome.PURPOSE Clinical examination is an important part in the diagnosis of femoroacetabular impingement (FAI) syndrome. However, knowledge on reliability and validity of clinical diagnostic tests is scarce. The aims were to evaluate the inter-rater agreement and diagnostic accuracy of clinical tests to detect patients with FAI syndrome. METHODS Eighty-one patients (49% women) were recruited. Two experienced raters performed impingement and range of motion (ROM) tests. Three criteria had to be fulfilled for the diagnosis of FAI syndrome (1) symptoms; (2) CAM and/or Pincer morphology; and (3) being responder to intra-articular block injection. For inter-rater agreement, the Cohen's kappa statistics were used (0.41-0.60 = moderate, 0.61-0.80 = substantial agreement). For diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were calculated. RESULTS Anterior impingement test (AIMT), FADIR test and FABER test showed kappa values above 0.6. All passive hip ROM, except extension, had kappa values above 0.4. AIMT and FADIR showed the highest sensitivity, i.e., 80%, with a specificity of 26% and 25%, respectively. Passive hip ROM in internal rotation with neutral hip position had a sensitivity of 29% and a specificity of 94%. CONCLUSION The AIMT, FADIR and FABER tests were reliable between two experienced raters, while results from different raters for hip ROM should be interpreted with caution. The AIMT and FADIR test can only be used to rule out patients with FAI syndrome, while evaluation of ROM in internal rotation with neutral position may be more suitable to rule in patients with FAI syndrome. LEVEL OF EVIDENCE II.PURPOSE This study investigated the relationship between femoral shaft bowing and the orientation of the surgical transepicondylar axis (TEA) in the coronal plane in varus knee osteoarthritis (OA). METHODS A total of 82 knees scheduled to undergo total knee arthroplasty (TKA) for the treatment of varus knee OA were enrolled. The hip-knee-ankle angle (HKA) was measured preoperatively on anteroposterior whole-leg standing radiographs. The lateral angle between the TEA and the mechanical axis of the femur (MA-TEA) was measured in the coronal plane from preoperative computed tomography (CT) images. https://www.selleckchem.com/products/d609.html Femoral shaft bowing was measured on CT images. Pearson's correlation coefficient was used to examine the correlation of the MA-TEA with the HKA and femoral shaft bowing. RESULTS The MA-TEA correlated negatively with the HKA (r = - 0.321, P  less then  0.01) and positively with femoral shaft bowing (r = 0.415, P  less then  0.01). CONCLUSIONS The TEA changed to varus as femoral shaft bowing increased in patients with varus knee OA. This suggests that the TEA is not always the centre of the rotational axis of the femur after TKA. In addition, the TEA may not be useful as a consistent parameter in the coronal plane in patients with increasing femoral shaft bowing. LEVEL OF EVIDENCE III.PURPOSE This article aims to share northern Italy's experience in hospital re-organization and management of clinical pathways for traumatic and orthopaedic patients in the early stages of the COVID-19 pandemic. METHODS Authors collected regional recommendations to re-organize the healthcare system during the initial weeks of the COVID-19 pandemic in March, 2020. The specific protocols implemented in an orthopaedic hospital, selected as a regional hub for minor trauma, are analyzed and described in this article. RESULTS Two referral centres were identified as the hubs for minor trauma to reduce the risk of overload in general hospitals. These two centres have specific features an emergency room, specialized orthopaedic surgeons for joint diseases and trauma surgeons on-call 24/7. Patients with trauma without the need for a multi-disciplinary approach or needing non-deferrable elective orthopaedic surgery were moved to these hospitals. Authors report the internal protocols of one of these centres. All elective surgery was stopped, outpatient clinics limited to emergencies and specific pathways, ward and operating theatre dedicated to COVID-19-positive patients were implemented. An oropharyngeal swab was performed in the emergency room for all patients needing to be admitted, and patients were moved to a specific ward with single rooms to wait for the results. Specific courses were organized to demonstrate the correct use of personal protection equipment (PPE). CONCLUSION The structure of the orthopaedic hubs, and the internal protocols proposed, could help to improve the quality of assistance for patients with musculoskeletal disorders and reduce the risk of overload in general hospitals during the COVID-19 pandemic.PURPOSE Although many open techniques have been developed, no all-arthroscopic technique has been introduced to reduce acute acromioclavicular joint dislocation (ACJD) and augment both coracoclavicular (CC) ligaments. The Kite technique is the first all arthroscopic technique with this aim. METHODS Forty-one consecutive patients [35M-6F; median 29.2 years (range 23-36)] with acute type III and V acromioclavicular joint dislocation were treated with the Kite technique it consists of positioning three titanium buttons connected by heavy sutures in an 8-strand configuration between clavicle and coracoid to restore the anatomy of CC ligaments. Patients were followed up for a median of 35 months (range 30-43 months). RESULTS Median operation time was 70.6 min (range 58-82), with no cases of intra-operative complications. At the final follow-up, the median post-operative Constant Score and SST were 94.1 (range 89-98) and 11.6 (range 10-12), respectively. At the final follow-up reduction maintenance was present in 39 patients; in one patient, signs of acromioclavicular joint dislocation recurrence were present 3 months post-op.

Results The principles of design that underpin the EAT-HC were highly accepted by participants and provided a framework for a systematic exploration of Singaporean residential care for people with dementia. Some topics of particular relevance to Singapore were identified. These can be subsumed by the principles without the need for the principles to be changed. Conclusion The results support the use of the design principles underpinning the EAT-HC as the foundation of a tool for the evaluation of Singaporean dementia facilities.Objective The aim of this study was to evaluate the role of cerebroplacental ratio (CPR) in term pregnancies with reduced fetal movements (RFM) and appropriate for gestational age (AGA)fetuses to predict poor neonatal outcomes.Methods A prospective cohort study was performed on 150 singleton pregnancies with gestational age of 37-41 weeks and multiple episodes of RFM (case group) and 150 pregnancies within the same criteria only without RFM (control group). Both groups had appropriate for gestational age (AGA)fetuses. Umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI) were measured, and MCA to UA ratio (CPR) was calculated. Doppler indices and neonatal outcomes were compared between the two groups. https://www.selleckchem.com/products/ono-ae3-208.html Independent prediction role of CPR MoM was evaluated through a binary logistic regression method.Results The RFM group had significantly higher UA- PI MoM (1.01 ± 0.19 versus 0.86 ± 0.05, p less then .001), lower MCA MoM (1.28 ± 0.20 versus 1.40 ± 0.13, (p less then .001)) and lowerlogistic regression analysis included parity, history of abortion and ART, AFI, BPP and CPR MoM; the AFI (OR 0.976; 95% CI 0.957-0.995, p = .014), BPP (OR 0.306; 95% CI 0.172-0.545, p less then .001) and CPR MoM (OR 0.00005 95% CI 0.000003-0.00061, p less then .001) were the significant predictor of RFM. Area under the curve in receiver operating characteristics (ROC) curve was calculated as 0.828 for CPR MoM as a predictor of RFM (SE 0.024, p less then .001), yielding sensitivity and specificity estimates of 80.0% and 65.0%, respectively, using an optimal cutoff level of = less then 1.19.Conclusion This study concluded that reduced fetal movement was significantly related to low CPR MOM. Also, it showed the independent role of CPR MoM for prediction of lower neonatal umbilical artery pH, lower Apgar score minute 1 and higher rate of NICU admission in AGA term fetuses without considering NST results. Also, AFI, BPP and CPR MoM are significant predictors of RFM.Purpose Our objective was to determine significant predictors of spinal cord ischemia (SCI) following Thoracic Endovascular Aortic Repair (TEVAR) and to further develop a simple and clinically orientated risk score model. Methods A retrospective review of data from the Society of Vascular Surgery/Vascular Quality Initiative national data set was performed for all patients undergoing TEVAR from January, 2014 to June 2018. Preoperative demographics, procedure-related variables, and clinical details related to SCI were examined. A SCI risk score was developed utilizing a multivariable logistic regression model. Results For the 7889 patients in the final analysis who underwent TEVAR during the study period, the mean age was 67.6 ± 13.9, range 18 to 90 years, and the majority was male (65%). Postoperative outcomes included stroke (3.0%), myocardial infarction (2.9%), inhospital mortality (5.4%), transient SCI (1.5%), and permanent SCI (2.1%). Nearly half of the overall cases were performed in high volume centers. decisions, patient consent process, risk-assessment, and procedural strategy.Objective To determine if there is a difference in the maternal and perinatal characteristics and outcomes of women undergoing a medically indicated labor induction and delivering vaginally compared to women in spontaneous labor delivering vaginally.Methods This is a planned secondary analysis of previously published data with additional data collected for a case-control design. Maternal and perinatal characteristics and outcomes of women undergoing a medically indicated labor induction of labor and delivering vaginally were compared with the next woman who went into labor spontaneously and delivered vaginally.Results There were 1097 women in the medically indicated labor group and 1096 women in the spontaneous labor group. The medically indicated induction group was younger (p less then .0001), had less women of "other" race (p = .004), were of a lower gravidity and parity (p less then .0001), had a lower Bishops' score on admission (p less then .0001), had a greater proportion of umbilical arterial cord pH values less then 7.1 and less then 7.0 (p less then .0001). Additionally, the induction group had longer first and second stages of labor (p less then .0001). While the unadjusted rates of post-partum complications and NICU admission were higher in the medically indicated labor induction group, only cord gas pH less then 7.1 remained statistically significant after adjustment.Conclusion Even with successful vaginal delivery of a medically indicated induction of labor, the risk for adverse outcomes remains elevated.Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Salmonella spp. are part of a group of pathogens that pose a major threat to human health due to the emergence of multidrug-resistant strains. Moreover, these bacteria have several virulence factors that allow them to successfully colonize their hosts, such as toxins and the ability to produce biofilms, resulting in an urgent need to develop new strategies to fight these pathogens. In this review, we compile the most up-to-date information on the epidemiology, virulence and resistance of these clinically important microorganisms. Additionally, we address new therapeutic alternatives, with a focus on molecules with antivirulence activity, which are considered promising to combat multidrug-resistant bacteria.Asthma, a chronic respiratory disease characterized by chronic airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction, poses a substantial economic burden on patients and caregivers alike. Moreover, the heterogeneous nature of the disease and the presence of various phenotypes make the treatment of asthma challenging and nuanced. Despite the availability of several approved pharmacological treatments, approximately half of patients with asthma in the United States experienced exacerbations in 2016, highlighting the need for effective add-on treatments. Furthermore, asthma control remains suboptimal due to low adherence to medications, poor inhaler technique, and several patient-related factors. Importantly, the primary care setting, in which pharmacists play an integral role, represents a critical environment for providing long-term follow-up care for the effective management of chronic diseases, such as asthma. Pharmacists are uniquely positioned to ensure optimal clinical outcomes in patients with asthma since they have the clinical expertise to educate patients on their disease state and the role of asthma medications, provide training on inhalation technique, address patients' concerns about potential side effects of medications, and improve adherence to therapy.