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Dodson McFarland opublikował 6 miesięcy temu
Shock waves associated with fast coronal mass ejections (CMEs) accelerate solar energetic particles (SEPs) in the long duration, gradual events that pose hazards to crewed spaceflight and near-Earth technological assets, but the source of the CME shock-accelerated plasma is still debated. Here, we use multi-messenger observations from the Heliophysics System Observatory to identify plasma confined at the footpoints of the hot, core loops of active region 11944 as the source of major gradual SEP events in January 2014. We show that the elemental composition signature detected spectroscopically at the footpoints explains the measurements made by particle counting techniques near Earth. Our results localize the elemental fractionation process to the top of the chromosphere. The plasma confined closest to that region, where the coronal magnetic field strength is high (a few hundred Gauss), develops the SEP composition signature. This source material is continually released from magnetic confinement and accelerated as SEPs following M-, C-, and X-class flares.The electric organs of electric eels are able to convert ionic gradients into high-efficiency electricity because their electrocytes contain numerous „subnanoscale” protein ion channels that can achieve highly selective and ultrafast ion transport. Despite increasing awareness of blue energy production through nanochannel membranes, achieving high-performance energy output remains considerably unexplored. Here, we report on a heterogeneous subnanochannel membrane, consisting of a continuous UiO-66-NH2 metal-organic framework (MOF) and a highly ordered alumina nanochannel membrane. In the positively charged membrane, the angstrom-scale windows function as ionic filters for screening anions with different hydrated sizes. Driven by osmosis, the subnanochannel membrane can produce an exceptionally high Br-/NO3 – selectivity of ~1240, hence yielding an unprecedented power of up to 26.8 W/m2 under a 100-fold KBr gradient. Achieving ultrahigh selective and ultrafast osmotic transport in ion channel-mimetic MOF-based membranes opens previously unexplored avenues toward advanced separation technologies and energy-harvesting devices.Broken symmetries induce strong even-order nonlinear optical responses in materials and at interfaces. Unlike conventional covalently bonded nonlinear crystals, van der Waals (vdW) heterostructures feature layers that can be stacked at arbitrary angles, giving complete control over the presence or lack of inversion symmetry at a crystal interface. Here, we report highly tunable second harmonic generation (SHG) from nanomechanically rotatable stacks of bulk hexagonal boron nitride (BN) crystals and introduce the term twistoptics to describe studies of optical properties in twistable vdW systems. By suppressing residual bulk effects, we observe SHG intensity modulated by a factor of more than 50, and polarization patterns determined by moiré interface symmetry. Last, we demonstrate greatly enhanced conversion efficiency in vdW vertical superlattice structures with multiple symmetry-broken interfaces. Our study paves the way for compact twistoptics architectures aimed at efficient tunable frequency conversion and demonstrates SHG as a robust probe of buried vdW interfaces.Basal-like breast cancer (BLBC) shows brain metastatic (BM) capability and overexpresses EGFR and death-receptors 4/5 (DR4/5); however, the anatomical location of BM prohibits efficient drug-delivery to these targetable markers. In this study, we developed BLBC-BM mouse models featuring different patterns of BMs and explored the versatility of estem cell (SC)-mediated bi-functional EGFR and DR4/5-targeted treatment in these models. Most BLBC lines demonstrated a high sensitivity to EGFR and DR4/5 bi-targeting therapeutic protein, EVDRL [anti-EGFR VHH (EV) fused to DR ligand (DRL)]. Functional analyses using inhibitors and CRISPR-Cas9 knockouts revealed that the EV domain facilitated in augmenting DR4/5-DRL binding and enhancing DRL-induced apoptosis. EVDRL secreting stem cells alleviated tumor-burden and significantly increased survival in mouse models of residual-tumor after macrometastasis resection, perivascular niche micrometastasis, and leptomeningeal metastasis. This study reports mechanism based simultaneous targeting of EGFR and DR4/5 in BLBC and defines a new treatment paradigm for treatment of BM.Endoplasmic reticulum-associated degradation (ERAD) is a process directing misfolded proteins from the ER lumen and membrane to the degradation machinery in the cytosol. A key step in ERAD is the translocation of ER proteins to the cytosol. Derlins are essential for protein translocation in ERAD, but the mechanism remains unclear. Here, we solved the structure of human Derlin-1 by cryo-electron microscopy. The structure shows that Derlin-1 forms a homotetramer that encircles a large tunnel traversing the ER membrane. The tunnel has a diameter of about 12 to 15 angstroms, large enough to allow an α helix to pass through. The structure also shows a lateral gate within the membrane, providing access of transmembrane proteins to the tunnel, and thus, human Derlin-1 forms a protein channel for translocation of misfolded proteins. Our structure is different from the monomeric yeast Derlin structure previously reported, which forms a semichannel with another protein.Perovskite-based electronic materials and devices such as perovskite solar cells (PSCs) have notoriously bad reproducibility, which greatly impedes both fundamental understanding of their intrinsic properties and real-world applications. Here, we report that organic iodide perovskite precursors can be oxidized to I2 even for carefully sealed precursor powders or solutions, which markedly deteriorates the performance and reproducibility of PSCs. Adding benzylhydrazine hydrochloride (BHC) as a reductant into degraded precursor solutions can effectively reduce the detrimental I2 back to I-, accompanied by a substantial reduction of I3 –induced charge traps in the films. BHC residuals in perovskite films further stabilize the PSCs under operation conditions. BHC improves the stabilized efficiency of the blade-coated p-i-n structure PSCs to a record value of 23.2% (22.62 ± 0.40% certified by National Renewable Energy Laboratory), and the high-efficiency devices have a very high yield. A stabilized aperture efficiency of 18.2% is also achieved on a 35.8-cm2 mini-module.Humans have a remarkable ability to understand what is and is not being said by conversational partners. It has been hypothesized that listeners decode the intended meaning of a communicative signal by assuming speakers speak cooperatively, rationally simulating the speaker’s choice process and inverting it to recover the speaker’s most probable meaning. We investigated whether and how rational simulations of speakers are represented in the listener’s brain, by combining referential communication games with functional neuroimaging. We show that listeners’ ventromedial prefrontal cortex encodes the probabilistic inference of what a cooperative speaker should say given a communicative goal and context, even when such inferences are irrelevant for reference resolution. The listener’s striatum encodes the amount of update on intended meaning, consistent with inverting a simulated mental model. These findings suggest a neural generative mechanism, subserved by the frontal-striatal circuits, that underlies our ability to understand communicative and, more generally, social actions.One of the ultimate goals of analytic chemistry is to efficiently discriminate between amino acids. Here we demonstrate this ability using a single-molecule electrical methodology based on molecular nanocircuits formed from stable graphene-molecule-graphene single-molecule junctions. These molecular junctions are fabricated by covalently bonding a molecular machine featuring a permethylated-β-cyclodextrin between a pair of graphene point contacts. Using pH to vary the type and charge of the amino acids, we find distinct multimodal current fluctuations originating from the different host-guest interactions, consistent with theoretical calculations. These conductance data produce characteristic dwell times and shuttling rates for each amino acid, and allow accurate, statistical real-time, in situ measurements. Testing four amino acids and their enantiomers shows the ability to distinguish between them within a few microseconds, thus paving a facile and precise way to amino acid identification and even single-molecule protein sequencing.Neonatal jaundice occurs in >80% of newborns in the first week of life owing to physiological hyperbilirubinemia. Severe hyperbilirubinemia could cause brain damage owing to its neurotoxicity, a state commonly known as kernicterus. Therefore, periodic bilirubin monitoring is essential to identify infants at-risk and to initiate treatment including phototherapy. However, devices for continuous measurements of bilirubin have not been developed yet. Here, we established a wearable transcutaneous bilirubinometer that also has oxygen saturation (SpO2) and heart rate (HR) sensing functionalities. Clinical experiments with neonates demonstrated the possibility of simultaneous detection of bilirubin, SpO2, and HR. Moreover, our device could consistently measure bilirubin during phototherapy. These results demonstrate the potential for development of a combined treatment approach with an automatic link via the wearable bilirubinometer and phototherapy device for optimization of the treatment of neonatal jaundice.Combining hyperspectral and polarimetric imaging provides a powerful sensing modality with broad applications from astronomy to biology. Existing methods rely on temporal data acquisition or snapshot imaging of spatially separated detectors. These approaches incur fundamental artifacts that degrade imaging performance. To overcome these limitations, we present a stomatopod-inspired sensor capable of snapshot hyperspectral and polarization sensing in a single pixel. The design consists of stacking polarization-sensitive organic photovoltaics (P-OPVs) and polymer retarders. Multiple spectral and polarization channels are obtained by exploiting the P-OPVs’ anisotropic response and the retarders’ dispersion. We show that the design can sense 15 spectral channels over a 350-nanometer bandwidth. A detector is also experimentally demonstrated, which simultaneously registers four spectral channels and three polarization channels. The sensor showcases the myriad degrees of freedom offered by organic semiconductors that are not available in inorganics and heralds a fundamentally unexplored route for simultaneous spectral and polarimetric imaging.The widely used quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases, resulting in irreversible topoisomerase cleavage complexes (TOPcc). Whereas the excision repair pathways of TOPcc in eukaryotes have been extensively studied, it is not known whether equivalent repair pathways for prokaryotic TOPcc exist. By combining genetic, biochemical, and molecular biology approaches, we demonstrate that exonuclease VII (ExoVII) excises quinolone-induced trapped DNA gyrase, an essential prokaryotic type IIA topoisomerase. We show that ExoVII repairs trapped type IIA TOPcc and that ExoVII displays tyrosyl nuclease activity for the tyrosyl-DNA linkage on the 5′-DNA overhangs corresponding to trapped type IIA TOPcc. ExoVII-deficient bacteria fail to remove trapped DNA gyrase, consistent with their hypersensitivity to quinolones. We also identify an ExoVII inhibitor that synergizes with the antimicrobial activity of quinolones, including in quinolone-resistant bacterial strains, further demonstrating the functional importance of ExoVII for the repair of type IIA TOPcc.Migratory marine species cross political borders and enter the high seas, where the lack of an effective global management framework for biodiversity leaves them vulnerable to threats. Here, we combine 10,108 tracks from 5775 individual birds at 87 sites with data on breeding population sizes to estimate the relative year-round importance of national jurisdictions and high seas areas for 39 species of albatrosses and large petrels. Populations from every country made extensive use of the high seas, indicating the stake each country has in the management of biodiversity in international waters. We quantified the links among national populations of these threatened seabirds and the regional fisheries management organizations (RFMOs) which regulate fishing in the high seas. This work makes explicit the relative responsibilities that each country and RFMO has for the management of shared biodiversity, providing invaluable information for the conservation and management of migratory species in the marine realm.Organisms use l-amino acids (l-aa) for most physiological processes. Unlike other organisms, bacteria chiral-convert l-aa to d-configurations as essential components of their cell walls and as signaling molecules in their ecosystems. Mammals recognize microbe-associated molecules to initiate immune responses, but roles of bacterial d-amino acids (d-aa) in mammalian immune systems remain largely unknown. Here, we report that amino acid chirality balanced by bacteria-mammal cross-talk modulates intestinal B cell fate and immunoglobulin A (IgA) production. Bacterial d-aa stimulate M1 macrophages and promote survival of intestinal naïve B cells. Mammalian intestinal d-aa catabolism limits the number of B cells and restricts growth of symbiotic bacteria that activate T cell-dependent IgA class switching of the B cells. Loss of d-aa catabolism results in excessive IgA production and dysbiosis with altered IgA coating on bacteria. Thus, chiral conversion of amino acids is linked to bacterial recognition by mammals to control symbiosis with bacteria.Neurons synaptically interacting in a conductive medium generate extracellular endogenous electric fields (EFs) that reciprocally affect membrane potential. Exogenous EFs modulate neuronal activity, and their clinical applications are being profusely explored. However, whether endogenous EFs contribute to network synchronization remains unclear. We analyzed spontaneously generated slow-wave activity in the cerebral cortex network in vitro, which allowed us to distinguish synaptic from nonsynaptic mechanisms of activity propagation and synchronization. Slow oscillations generated EFs that propagated independently of synaptic transmission. We demonstrate that cortical oscillations modulate spontaneous rhythmic activity of neighboring synaptically disconnected cortical columns if layers are aligned. We provide experimental evidence that these EF-mediated effects are compatible with electric dipoles. With a model of interacting dipoles, we reproduce the experimental measurements and predict that endogenous EF-mediated synchronizing effects should be relevant in the brain. Thus, experiments and models suggest that electric-dipole interactions contribute to synchronization of neighboring cortical columns.Mnemonic techniques, such as the method of loci, can powerfully boost memory. We compared memory athletes ranked among the world’s top 50 in memory sports to mnemonics-naïve controls. In a second study, participants completed a 6-week memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. Functional magnetic resonance imaging during encoding and recognition revealed task-based activation decreases in lateral prefrontal, as well as in parahippocampal and retrosplenial cortices in both memory athletes and participants after memory training, partly associated with better performance after 4 months. This was complemented by hippocampal-neocortical coupling during consolidation, which was stronger the more durable memories participants formed. Our findings advance knowledge on how mnemonic training boosts durable memory formation through decreased task-based activation and increased consolidation thereafter. This is in line with conceptual accounts of neural efficiency and highlights a complex interplay of neural processes critical for extraordinary memory.Stress is a key risk factor for dystonia, a debilitating motor disorder characterized by cocontractions of muscles leading to abnormal body posture. While the serotonin (5HT) system is known to control emotional responses to stress, its role in dystonia remains unclear. Here, we reveal that 5HT neurons in the dorsal raphe nuclei (DRN) send projections to the fastigial deep cerebellar nuclei (fDCN) and that photostimulation of 5HT-fDCN induces dystonia in wild-type mice. Moreover, we report that photoinhibition of 5HT-fDCN reduces dystonia in a1A tot/tot mice, a genetic model of stress-induced dystonia, and administration of a 5HT-2A receptor inverse agonist (MDL100907; 0.1 to 1 mg/kg) or shRNA-mediated knockdown of the ht2ar gene in fDCN can notably reduce the onset of dystonia in a1A tot/tot mice. These results support the serotonin theory of dystonia and suggest strategies for alleviating symptoms in human patients by blocking 5HT-2A receptors.
To compare effect estimates of randomised clinical trials that use routinely collected data (RCD-RCT) for outcome ascertainment with traditional trials not using routinely collected data.
Meta-research study.
Studies included in the same meta-analysis in a Cochrane review.
Randomised clinical trials using any type of routinely collected data for outcome ascertainment, including from registries, electronic health records, and administrative databases, that were included in a meta-analysis of a Cochrane review on any clinical question and any health outcome together with traditional trials not using routinely collected data for outcome measurement.
Effect estimates from trials using or not using routinely collected data were summarised in random effects meta-analyses. Agreement of (summary) treatment effect estimates from trials using routinely collected data and those not using such data was expressed as the ratio of odds ratios. Subgroup analyses explored effects in trials based on different types oaking and the application of real world evidence.
Randomised clinical trials using routinely collected data for outcome ascertainment show smaller treatment benefits than traditional trials not using routinely collected data. These differences could have implications for healthcare decision making and the application of real world evidence.
To describe the injury and illness characteristics among participating athletes during the Lausanne 2020 Youth Olympic Winter Games (YOG 2020), 9-22 January 2020.
The daily number of athlete injuries and illnesses were recorded (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Lausanne 2020 medical staff.
In total, 1783 athletes from 79 NOCs were observed. NOC and Lausanne 2020 medical staff reported 228 injuries and 167 illnesses, equating 11.7 injuries and 8.6 illnesses per 100 athletes over the 14-day period. Injury incidence was highest for snowboard slopestyle (39%), bobsleigh (36%), snowboard big air (29%), ski slopestyle (29%), snowboard cross (24%) and ski cross (21%), and lowest for speed skating, snowboard halfpipe and curling (2%-4%). The highest incidence of illness was recorded for curling (21%), ski mountaineering (15%), snowboard halfpipe (13%), bobsleigh (11%), cross-country skiing (10%) and figure skating (10%). Almost one-third of injuries were expected to result in time loss and 17% of illnesses. Most injuries occurred to the knee (12%) and head (11%), and 64% of illnesses affected the respiratory system. Overall, women suffered more injuries and illness than males.
Overall, injury and illness rates were similar compared with recent YOG. While the rate and characteristics of injury and illness varied between sports, consistent patterns across YOG are emerging. If addressed, changes in highlighted areas of risk could have a positive impact on the health and well-being of these young athletes.
Overall, injury and illness rates were similar compared with recent YOG. While the rate and characteristics of injury and illness varied between sports, consistent patterns across YOG are emerging. If addressed, changes in highlighted areas of risk could have a positive impact on the health and well-being of these young athletes.The deuterosome is a non-membranous organelle involved in large-scale centriole amplification during multiciliogenesis. Deuterosomes are specifically assembled during the process of multiciliogenesis. However, the molecular mechanisms underlying deuterosome formation are poorly understood. In this study, we investigated the molecular properties of deuterosome protein 1 (Deup1), an essential protein involved in deuterosome assembly. We found that Deup1 has the ability to self-assemble into macromolecular condensates both in vitro and in cells. The Deup1-containing structures formed in multiciliogenesis and the Deup1 condensates self-assembled in vitro showed low turnover of Deup1, suggesting that Deup1 forms highly stable structures. Our biochemical analyses revealed that an increase of the concentration of Deup1 and a crowded molecular environment both facilitate Deup1 self-assembly. The self-assembly of Deup1 relies on its N-terminal region, which contains multiple coiled coil domains. Using an optogenetic approach, we demonstrated that self-assembly and the C-terminal half of Deup1 were sufficient to spatially compartmentalize centrosomal protein 152 (Cep152) and polo like kinase 4 (Plk4), master components for centriole biogenesis, in the cytoplasm. Collectively, the present data suggest that Deup1 forms the structural core of the deuterosome through self-assembly into stable macromolecular condensates.This article has an associated First Person interview with the first author of the paper.
Chronic and mental health conditions are increasingly prevalent worldwide. As devices in our everyday lives offer more and more voice-based self-service, voice-based conversational agents (VCAs) have the potential to support the prevention and management of these conditions in a scalable manner. However, evidence on VCAs dedicated to the prevention and management of chronic and mental health conditions is unclear.
This study provides a better understanding of the current methods used in the evaluation of health interventions for the prevention and management of chronic and mental health conditions delivered through VCAs.
We conducted a systematic literature review using PubMed MEDLINE, Embase, PsycINFO, Scopus, and Web of Science databases. We included primary research involving the prevention or management of chronic or mental health conditions through a VCA and reporting an empirical evaluation of the system either in terms of system accuracy, technology acceptance, or both. A total of 2 independent rare encouraging, there is still a need to establish more conclusive evidence on the efficacy of VCAs for the prevention and management of chronic and mental health conditions, both in absolute terms and in comparison with standard health care.
An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools.
This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model.
The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling.
A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.
Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.
Attention deficit-hyperactivity disorder is a behavioral disorder characterized by a lack of focus, impulsive behavior, and or excessive activity. This research aimed to evaluate the association between signs of attention deficit-hyperactivity disorder and malocclusion in schoolchildren.
A cross-sectional study was conducted with a representative sample of 633 children aged 7-12years. The children were clinically examined for malocclusion using the Dental Aesthetic Index. The predominant breathing pattern was also determined. Parents answered a questionnaire addressing socioeconomic characteristics and the presence of nonnutritive sucking habits. The Swanson, Nolan, and Pelham Scale-IV was filled out by both parents and teachers to compare behavioral patterns. The children were submitted to a neuropsychological evaluation using the Raven’s Colored Progressive Matrix Test. Data analysis involved the chi-square test and Poisson regression analysis.
The prevalence of malocclusion was 42% higher among children with signs of hyperactivity reported by both parents and teachers (prevalence ratio [PR], 1.42; 95% confidence interval [CI], 1.11-1.81; P=0.004). In the final Poisson regression model, the prevalence of malocclusion was lower among schoolchildren aged 11 and 12years (PR, 0.62; 95% CI. 0.52-0.73; P<0.001) and higher among those who used a pacifier for at least 4years (PR, 1.25; 95% CI, 1.02-1.54; P=0.029) as well as those classified as mouth breathers (PR, 1.28; 95% CI, 1.09-1.51; P=0.003).
The prevalence of malocclusion was higher among children with signs of hyperactivity independently of age, pacifier use, and mouth breathing.
The prevalence of malocclusion was higher among children with signs of hyperactivity independently of age, pacifier use, and mouth breathing.Local debridement or decompression of the posterior heel in Haglund’s syndrome yields variable results. This condition is sometimes due to an excessively long calcaneus rather than simply a large posterosuperior bony prominence. Failure to address this abnormality may explain the poor results in some series. We recently published a new measurement (the X/Y ratio) which, combined with the calcaneal pitch angle, assesses the abnormality of the shape of the calcaneus. The Zadek osteotomy strongly modifies that shape. We retrospectively reviewed 50 patients treated by a Zadek osteotomy at a mean 7 years follow-up using the AOFAS ankle-hindfoot score, the VISA-A score and Tegner scale. We measured only the X/Y ratio and the calcaneal inclination angle, as the classically described radiographic measurements in Haglund’s syndrome are unreliable. We then assessed the condition of the distal end of the Achilles tendon with an MRI. Our results demonstrate excellent outcomes(40/50, 80%) following Zadek osteotomy and correspond to the change in pre- and post-operative measurements, especially the X/Y ratio. An algorithm using those geometrical measurements of the calcaneus is proposed for decision making in Haglund’s syndrome. Level of clinical evidence Level 3.
Chronic kidney disease (CKD) is common in patients with multiple myeloma (MM) and is associated with a poor prognosis. We assessed CKD-associated clinical outcomes among elderly patients with MM initiating chemotherapy in the United States.
We identified elderly Medicare beneficiaries (≥66 years) diagnosed with MM who initiated first-line therapy from 2008 to 2014. We identified CKD using diagnosis codes. We followed patients for death, time to next treatment (TTNT), and myeloma-defining events (anemia, hypercalcemia, skeletal-related events, progression to/of CKD) until September 30, 2015. We estimated overall survival, TTNT, and cumulative incidence of myeloma-defining events using the Kaplan-Meier method and risk of CKD-associated outcomes using Cox proportional hazards models, adjusting for demographics and comorbid conditions.
Of 22,484 included patients, 8704 (39%) had CKD at first-line therapy initiation. Compared with patients without CKD, patients with CKD had shorter median overall survival (2.1 vs. 3.6 years) and median TTNT (10.0 vs. 12.4, 9.7 vs. 11.2, 8.3 vs. 9.2, and 6.9 vs. 8.3 months at first- to fourth-line therapy). Probability of CKD progression for patients at stages 1 to 5 was higher than the probability of developing CKD for patients without CKD (3-year cumulative incidence [95% confidence interval, CI], 47% [45-48%] vs. 27% [24-26%]). Adjusted hazard ratios for CKD versus non-CKD were all-cause death, 1.23 (95% CI, 1.18-1.28); anemia, 1.34 (95% CI, 1.24-1.45); hypercalcemia, 1.23 (95% CI, 1.09-1.38); skeletal-related events, 0.85 (95% CI, 0.90-0.91); and TTNT, from 1.03 (95% CI, 0.96-1.10) at third-line therapy to 1.15 (95% CI, 1.04-1.27) at fourth-line therapy.
Data from the study suggest that CKD-associated clinical burden is substantial in elderly patients with MM.
Data from the study suggest that CKD-associated clinical burden is substantial in elderly patients with MM.
Total knee arthroplasty (TKA) is a frequent intervention that can associate significant blood loss. There are several methods to avoid transfusions. One of the most relevant is tranexamic acid (TXA). Our purpose is to analyse the efficacy in terms of blood savings, transfusion needs, functional results, and cost-effectiveness of intra-articular (IA) administration in TKA.
We conducted a retrospective analysis of historical cohorts (75 patients each) between January 2015 and December 2016. We included 150 patients (59.3% women) with a mean age of 73.58 years. The intervention consisted of administering 2 g of IA TXA with a contact time of 30 minutes. Demographic data, preoperative haematological status, surgery data, estimated total blood loss (ETBL), need for transfusion, functional results, and cost analysis were collected. The level of statistical significance was p ≤ 0,05.
The incidence of transfusion was 17.33% in the control group and 5.33% in the TXA group (p = 0.039), with a relative risk reduction of 78.3%. The TXA cohort showed a reduction in ETBL (p < 0.0005), units transfused (p = 0.019) and length of stay (p = 0.004). All early functional parameters also improved, including a 10° improvement in both flexion and extension (p < 0.0005). The use of IA TXA resulted in savings of 337.78 € per patient.
In our experience, the administration of IA TXA in TKA is a cost-effective and efficient measure in terms of blood savings and immediate postoperative functional improvement.
In our experience, the administration of IA TXA in TKA is a cost-effective and efficient measure in terms of blood savings and immediate postoperative functional improvement.
This study aims to investigate the association between epi- and pericardial adipose tissue deposits around the heart against patient body habitus when using cardiac computed tomography (CT).
Ninety-two consecutive patients with suspected coronary artery disease underwent coronary CT angiography with quantitative cardiac and adipose tissue volume measurements. Body mass index (BMI), body surface area (BSA), thoracic circumference, anteroposterior diameter, cardiac and adipose tissue volumes were compared between genders by employing Pearson’s correlation and results were considered statistically significant if p≤0.05.
Statistically significant differences between genders were observed with males having a greater height (males 1.72±0.11), BMI (30.76±7.87kg/m
), BSA (2.06±0.21m
), thoracic circumference (1022.12±97.90mm
), and pericardial adipose tissue volume (46.72±36.62mm
) (p<0.05). For men, for Group 1 (BMI ≤ 27) each of the measured volumes showed moderate correlation between pericardial adipose tissue and AP chest-diameter (r=0.429, p <0.05), whereas in Group 2 (27 < BMI ≤ 31.1), coronary artery volume had a strong association with the AP chest-diameter (r=0.453, p<0.05).
BMI and thoracic circumference are closely related to variable epi- and pericardial adipose tissue volumes in both males and females during cardiac CT.
Quantification of epi- and pericardial adipose tissue deposits between males and females during cardiac CT may help further categorise coronary artery disease risk when including BMI and thoracic circumference for males and females.
Quantification of epi- and pericardial adipose tissue deposits between males and females during cardiac CT may help further categorise coronary artery disease risk when including BMI and thoracic circumference for males and females.
Ultrasound is one of many areas of specialism for radiographers to develop their skills in. As part of a wider suite of surveys, the European Federation of Radiographer Societies (EFRS) wanted to investigate the extent and scope of practice for radiographers practising ultrasound across Europe. This report details the results of the initial survey, exploring the views of the EFRS countries’ National Radiographer Societies.
An electronic survey was sent to representatives of the 43 national radiographer societies who were members of the EFRS. Questions asked about radiographer practice in ultrasound within individual countries, scope of the role, particularly report writing, in addition to investigating current ultrasound education, barriers and opinions on priorities for radiographer ultrasound practice.
Forty individual responses were received, from a total of 27 countries, covering 62.8% of the EFRS member societies invited to participate. Radiologists or specialised medical practitioners performed ulltrasound as a pathway for radiographer progression in countries, where it is not yet available, include education programmes, acceptance by medical professionals and changes to legislation.Functional impairment is a defining feature of psychotic disorders. The Functional Assessment Short Test (FAST) is one of the most widely used instruments to measure psychosocial functioning. However, cut-offs of impairment have been well-established for bipolar disorders, but not for other clinical populations. This study aims to analyse psychometric properties of the FAST and establish their corresponding cut-off values for the different severity gradations in a first-episode of non-affective psychosis (FEP) patients. Global Assessment Functioning (GAF) and FAST ratings from 212 non-affective FEP and 204 healthy controls were analyzed. The psychometric properties of FAST (internal consistency, concurrent validity, discriminant validity, factorial analyses and sensitivity to change) were analyzed. The severity gradations of the FAST were defined by the congruence between two grading methods linear regression analysis (LRA) and percentiles. The FAST showed strong psychometric properties. LRA with the GAF scores yielded the following equation GAFscore= 80.83 – 0.639*FASTscore. The FAST ranges in non-affective FEP patients derived from LRA and percentiles, were as follows 0-9 (No impairment); 10-19 (Minimal impairment); 20-34 (Mild impairment); 35-45 (Moderate impairment); 46-72 (Severe impairment). Patients with no functional impairment had a higher socioeconomic status, fewer depressive and negative symptoms, lower severity of illness and higher cognitive reserve level than the others groups. In conclusion, the FAST shows optimal psychometric properties which corroborate its applicability in FEP populations. It is a well-demonstrated valid instrument and the present cut-off scores could be implemented in clinical and research practice to assess properly the psychosocial functional outcome of non-affective FEP populations.
Hip motion in the transverse plane is coupled with foot motion in the frontal plane during closed kinematic activities, such as gait. Considering that movement patterns and bone alignment might influence passive mechanical properties of joints in the long term, it is possible that hip passive stiffness and foot complex stiffness and alignment are related to each other.
To investigate whether hip passive stiffness, midfoot passive stiffness and shank-forefoot alignment are related to each other.
Thirty healthy adult individuals with a mean age of 25.4 years participated (18 women and 12 men). The Foot Torsimeter was used to measure midfoot stiffness, and hip stiffness and foot alignment were measured using clinical measures. Pearson and Spearman correlation coefficients were calculated to test the associations between each pair of variables, with α = 0.05.
Hip stiffness was positively correlated with midfoot absolute stiffness (r = 0.41, p = 0.02), indicating that increased hip stiffness is associated with increased midfoot stiffness. There were no associations between shank-forefoot alignment and the other variables.
In clinical settings, individuals with reduced hip passive stiffness may also have reduced midfoot passive stiffness, and vice versa. Shank-forefoot alignment is not linearly associated with hip or midfoot passive stiffness.
In clinical settings, individuals with reduced hip passive stiffness may also have reduced midfoot passive stiffness, and vice versa. Shank-forefoot alignment is not linearly associated with hip or midfoot passive stiffness.
Alfaxalone is a popular veterinary anesthetic; however, research on this anesthetic in snakes has been limited to ball pythons, garter snakes and several Australian species. The objective was to evaluate the anesthetic effects of alfaxalone in corn snakes (Pantherophis guttatus), a popular pet snake.
Prospective, randomized crossover study.
A total of eight corn snakes.
In phase I, snakes were subcutaneously administered three doses of alfaxalone (5, 10 and 15 mg kg
) in the cranial third of the body to determine the most effective dose. In phase II, a dose of 15 mg kg
was administered in the cranial and caudal thirds of the snakes to determine if injection site affected anesthesia duration. Heart rate (HR), respiratory rate (f
), righting reflex, escape response, tail pinch, needle prick and tongue flick were monitored at baseline and 5 minute intervals until the snakes fully recovered.
Duration of anesthesia differed significantly, with higher doses lasting longer than lower doses 5 mg kg
[23.8 ± 4.4 (15-30) minutes]; 10 mg kg
[40.6 ± 9.4 (25-55) minutes]; and 15 mg kg
[56.9 ± 8.4 (50-70) minutes], mean ± standard deviation (range). The tail pinch reflex was not completely lost in phase 1. There was a significant change in f
over time, but this was not related to dose. HR was not different by time or dose. Duration of anesthesia was not different after administration of alfaxalone (15 mg kg
) in the cranial third versus the caudal third of the body; however, there was a significant decrease in HR and f
at this dose, regardless of injection site.
Based on these results, alfaxalone (15 mg kg
) provides adequate anesthesia for brief procedures or intubation; however, additional analgesia is required for painful procedures.
Based on these results, alfaxalone (15 mg kg-1) provides adequate anesthesia for brief procedures or intubation; however, additional analgesia is required for painful procedures.The aim of the study was to re-assess neuropsychological profile in a group of boys with Duchenne muscular dystrophy without intellectual disability and neuropsychiatric disorder three years apart from a previous evaluation, to establish possible changes over time. We were also interested in defining more in detail correlation between genotype and neuropsychological phenotype. Thirty-three of the previous 40 subjects (mean age at follow up 10 years and 7 months) agreed to participate in the follow up study and to perform the new assessment. The results confirm a typical neuropsychological profile, with difficulty in the manipulation of stored information, poor abstract reasoning and planning capacity and impulsiveness, supporting the involvement of a cerebellar striatal cortical network for these children. The more detailed description of subgroups of subjects, according to the real expression of Dp140, let to reveal possible genotype-neuropsychological phenotype correlations, and a more general neuropsychological impairment emerged in boys without Dp140 expression.Immunotherapy based on immune checkpoint inhibitors (ICIs) either alone or in combination with platinum-based chemotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer. However, only a subset of patients derives clinical benefits. Although programmed death-ligand 1 (PD-L1) and tumor mutational burden (TMB) are known to be prognostic and demonstrated utility in selecting patients for immunotherapy response, they are imperfect biomarkers. Recent evidence demonstrates that AT-rich interaction domain 1A (ARID1A) deficiency is associated with high antitumor immunity, mismatch repair and TMB, and thus may potentially contribute as a predictive biomarker for ICIs. We herein describe a 60-year-old woman, former smoker, who was diagnosed with lung adenocarcinoma metastatic to the left adrenal gland, with a PD-L1 expression of 60%. Next-generation sequencing test revealed an ARID1A mutation (F2141fs*59, variant allele frequency = 22.5%), TMB of 92 mut/Mb and stable microsatellite status. Given the high PD-L1 expression, elevated TMB, and ARID1A mutation, the patient started on first-line treatment with pembrolizumab monotherapy, and, 5 months after initiating treatment, presented an expressive reduction of lung lesion and a complete response of the adrenal gland. This case illustrates a dramatic response to ICI monotherapy in a lung cancer patient with ARID1A mutation. Predictive biomarkers for immune checkpoint blockade are of the utmost importance to select the patients who truly benefit from immunotherapy. The combination of biomarkers may be the most effective strategy to improve outcomes with ICIs, and ARID1A status should definitely be taken into account when present.
Radiation pneumonitis (RP) is a dose-limiting and potentially fatal toxicity of thoracic radiotherapy most often seen in patients treated for primary lung cancer. The purpose of this study was to identify predictors of in-hospital death among lung cancer patients admitted for acute RP in the Healthcare Cost and Utilization Project (HCUP) database.
The HCUP National Inpatient Sample database was queried from 2012 through 2016 to capture adult lung cancer patients admitted to the hospital with a principal diagnosis of acute RP. Multivariate logistic regression modeling and χ
tests were used to determine predictors of in-hospital death.
Of the 882 patients with lung cancer admitted for RP, 67 patients (7.6%) died during the hospitalization and 90 patients (10.2%) required mechanical ventilation. Of those requiring mechanical ventilation, 38 patients (42.2%) died. The average age at hospitalization was 70.4 years (range, 35-90). Of those factors associated with death on univariate analysis, interstitial lents with RP.
The COVID-19 pandemic has resulted in significant changes in pharmacy graduate students’ (PhGS) lives. While pharmacy graduate programs across the U.S. have reported adjustments due to the pandemic, there is currently no data on the PhGS’ wellness, and the impact on and extent to which offered supports and guidance has met PhGS needs.
This study’s objectives were 1) to explore PhGS’ perspectives on their challenges and the impact of these challenges on their wellness, and 2) to identify PhGS’ suggestions for pharmacy graduate programs to improve guidance and support offered during the COVID-19 pandemic.
This study conducted semi-structured interviews based on the Objective, Reflective, Interpretative, Decisional (ORID) methodology. Pharmacy students working on completing a PhD in programs across the United States were invited to participate. All interviews were conducted using the Zoom platform between May and June 2020. Digital audio recordings were auto transcribed using the Trint platform. Thematic asition graduate program success post-pandemic.
Despite the COVID-19 pandemic, graduate programs should continue developing a robust and tailored system to encourage and maintain mentorship programs to facilitate graduate students’ successful path through their doctoral studies. Moreover, the suggestions offered by the PhGS participants in this study, when appropriately implemented, can also position graduate program success post-pandemic.
Human Immunodeficiency Virus (HIV) Pre-exposure prophylaxis (PrEP) helps to decrease HIV acquisition and transmission rates. The purpose of this study was to assess awareness of HIV PrEP and willingness to use it, if available, among individuals residing in Buea, Cameroon.
Residents in different communities throughout Buea, Cameroon participated in the study through survey completion with their responses assessed by age, marital status, highest level of education completed, profession, and health area (urban or rural).
421 participants completed the survey with the majority being 20-29 years of age, single, having secondary or tertiary education, residing in rural Cameroonian areas. Eighty percent of respondents had not previously heard of HIV PrEP. Ninety-five percent of the study sample expressed willingness to use HIV PrEP, if available. Participants ages 40 years old and above were less aware of HIV PrEP than those 39 years old and younger. Primary education, serving in the role of a nurse, doctor, or scientist, along with hospital affiliations were characteristics closely associated with HIV PrEP awareness. Participants younger than 20 years old were less likely to report willingness to use HIV PrEP whereas married participants found HIV PrEP to be a more favorable option.
Awareness of HIV PrEP was minimal with healthcare personnel having more familiarity. Willingness to use HIV PrEP decreased by age but higher among married participants. Further promotion of HIV PrEP and facilitating its accessibility can lead to less transmissions of HIV worldwide.
Awareness of HIV PrEP was minimal with healthcare personnel having more familiarity. Willingness to use HIV PrEP decreased by age but higher among married participants. Further promotion of HIV PrEP and facilitating its accessibility can lead to less transmissions of HIV worldwide.
It has been established that radiotherapy can increase the risk of adverse pregnancy outcomes. However, there is currently no consensus on the effective sterilizing dose of adulthood uterine radiotherapy.
This is a case report of a 36-year-old women with three different cancer types who received repeated high-dose radiotherapy of 66Gy and 50Gy to the pelvis. The study used a dose-volume histogram, the most widely used tool to calculate the radiation distribution within a volume of interest in a patient during radiotherapy. It was determined that the current patient’s uterus might have received the highest uterine radiation dosage for full-term live birth that has been reported in the current literature.
Due to iatrogenic ovarian failure, the woman was only able to use donor eggs. After preparation of the endometrium for 18 days, it had reached 8.7mm in thickness with a triple-line appearance. Two cleavage-stage embryos were transferred, one of which implanted successfully. The course of the pregnancy was uneventful. Finally, the patient gave birth to a healthy baby via Caesarean section at 38
weeks of gestation.
The uterus may be more resistant to radiotherapy than previously understood. Uterine fertility preservation methods should be guided by the age of the patient receiving radiotherapy and the actual dose of radiation exposure of the uterus. Future studies should implement a dose-volume histogram to calculate the radiation exposure of the reproductive organs.
The uterus may be more resistant to radiotherapy than previously understood. Uterine fertility preservation methods should be guided by the age of the patient receiving radiotherapy and the actual dose of radiation exposure of the uterus. Future studies should implement a dose-volume histogram to calculate the radiation exposure of the reproductive organs.
Are there genetic determinants shared by unrelated women with unexplained recurrent early miscarriage (REM)?
Thirty REM cases and 30 controls were selected with extreme phenotype among women from Eastern Brittany (France), previously enrolled in an incident case-control study on thrombophilic mutations. Cases and controls were selected based on the number of early miscarriages or live births, respectively. Peripheral blood was collected for DNA extraction at initial visit. The burden of low-frequency variants in the coding part of the genes was compared using whole exome sequencing (WES).
Cases had 3 to 17 early miscarriages (20 cases ≥5 previous losses). Controls had 1 to 4 live births (20 controls ≥3 previous live births) and no miscarriages. WES data were available for 29 cases and 30 controls. A total of 209,387 variants were found (mean variant per patient 59,073.05) with no difference between groups (P = 0.68). The top five most significantly associated genes were ABCA4, NFAM1, TCN2, AL078585.1 and EPS15. Previous studies suggest the involvement of vitamin B12 deficiency in REM. TCN2 encodes for vitamin B12 transporter into cells. Therefore, holotranscobalamin (active vitamin B12) was measured for both cases and controls (81.2±32.1 versus 92.9±34.3pmol/l, respectively, P=0.186). Five cases but no controls were below 50pmol/l (P=0.052).
This study highlights four new genes of interest in REM, some of which belong to known networks of genes involved in embryonic development (clathrin-mediated endocytosis and ciliary pathway). The study also confirms the involvement of TCN2 (vitamin B12 pathway) in the early first trimester of pregnancy.
This study highlights four new genes of interest in REM, some of which belong to known networks of genes involved in embryonic development (clathrin-mediated endocytosis and ciliary pathway). The study also confirms the involvement of TCN2 (vitamin B12 pathway) in the early first trimester of pregnancy.