COVID-19 infections caused by SARS-CoV-2 disseminated through human-to-human transmission can evoke severe inflammation. Treatments to reduce the SARS-CoV-2-associated inflammation are needed and are ...the focus of much research. In this study, we investigated the effect of N-ethyl-N'-(3β,5α)-17-oxoandrostan-3-yl urea (NEOU), a novel 17α-ketosteroid derivative, on the severity of COVID-19 infections.
Studies were conducted in SARS-CoV-2-infected K18-hACE2 mice.
SARS-CoV-2-infected K18-hACE2 mice developed severe inflammatory crises and immune responses along with up-regulation of genes in associated signalling pathways in male more than female mice. Notably, SARS-CoV-2 infection down-regulated genes encoding drug metabolizing cytochrome P450 enzymes in male but not female mice. Treatment with NEOU (1 mg·kg
·day
) 24 or 72 h post-viral infection alleviated lung injury by decreasing expression of genes encoding inflammatory cytokines and chemokines while increasing expression of genes encoding immunoglobins. In situ hybridization using RNA scope™ probes and immunohistochemical assays revealed that NEOU increased resident CD169
immunoregulatory macrophages and IBA-1 immunoreactive macrophage-dendritic cells within alveolar spaces in the lungs of infected mice. Consequentially, NEOU reduced morbidity more prominently in male than female mice. However, NEOU increased median survival time and accelerated recovery from infection by 6 days in both males and females.
These findings demonstrate that SARS-CoV-2 exhibits gender bias by differentially regulating genes encoding inflammatory cytokines, immunogenic factors and drug-metabolizing enzymes, in male versus female mice. Most importantly, we identified a novel 17α-ketosteroid that reduces the severity of COVID-19 infection and could be beneficial for reducing impact of COVID-19.
BACKGROUNDIodinated contrast media allergy is considered as a strong contra-indication for performing sialography. There is little evidence to support this approach. OBJECTIVETo evaluate the rate of ...iodinated contrast media (ICM) allergy in subjects undergoing sialography and to assess the risk for allergic responses in patients with a previous diagnosis of allergy. METHODSWe retrospectively reviewed sialo-CBCT studies performed from 2014 to 2019. During the study period we implemented a protocol for performing sialo-CBCT in patients with a prior diagnosis of allergy: 1) Clinical data were collected from a questionnaire and medical records. 2) No premedication was administered but, instead, oxygen, epinephrine and a resuscitation cart were accessible. 3) Following the procedure, each patient was observed for one hour and contacted by telephone 24 hrs later. RESULTSNo allergic responses were documented in the medical records of 1515 subjects following sialo-CBCT studies, including 13 individuals previously diagnosed with ICM allergy. Investigation of the subgroup with prior allergy disclosed that the range of injected volume was between 2 ml to 6.2 ml per patient and that complete secretion of ICM was detected in 7 of 13 patients. In the remainder of subjects, retention rates of 5-50% were observed. CONCLUSIONSAllergic reactions are exceedingly rare following sialo-CBCT studies regardless of a previous diagnosis of allergy. Pre-medication with corticosteroids and antihistamines is usually not warranted.
HVOO creates significant diagnostic and management dilemmas in pediatric liver transplant recipients, particularly with TVGs (split or reduced‐size grafts). Numerous technical variations for the ...hepatic vein to IVC anastomosis have been described to minimize the incidence of this complication, but no consensus for an optimal anastomotic technique exists. One hundred and thirty‐four liver transplants (70 TVGs) were performed in 124 patients between 1994 and 2011. These were divided into two cohorts. Group 1 (95 transplants, 41 TVGs) utilized a continuous running anastomosis. Group 2 (39 transplants, 29 TVGs) implemented a triangulated (three‐stitch) anastomosis. All were reviewed for demographics, diagnostics, interventions, and outcome. The overall HVOO incidence was seven of 134 transplants (5.2%) and six of 70 transplants utilizing TVGs (8.6%). Group 1 incidence was five of 41 (12.2%) compared with one of 29 (3.4%; p = 0.20, OR 3.89) in Group 2. Liver Doppler was employed in all patients, and only three suggested HVOO. All patients with HVOO underwent venogram, at a median of 81 days post‐transplant. All underwent percutaneous venoplasty and required 1–6 treatments, all resulting in HVOO resolution. Incidence of HVOO has improved since adopting the triangulated anastomosis, although not to a level of statistical significance. US is not adequately sensitive to exclude HVOO. Venogram is recommended in patients with prolonged ascites, and venoplasty has been highly successful in HVOO treatment.
Neurosurgery for psychiatric disorders (NPD), also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field ...have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law (what should be regulated), what types of regulations are required (eligibility criteria, approval procedures, data collection, and oversight mechanisms), and how to approach international harmonization given the potential migration of researchers and patients.
Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on ...type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.
We report the discovery of two ultra-faint stellar systems found in early data from the DECam Local Volume Exploration survey (DELVE). The first system, Centaurus I (DELVE J1238-4054), is identified ...as a resolved overdensity of old and metal-poor stars with a heliocentric distance of , a half-light radius of , an age of , a metallicity of , and an absolute magnitude of . This characterization is consistent with the population of ultra-faint satellites and confirmation of this system would make Centaurus I one of the brightest recently discovered ultra-faint dwarf galaxies. Centaurus I is detected in Gaia DR2 with a clear and distinct proper motion signal, confirming that it is a real association of stars distinct from the Milky Way foreground; this is further supported by the clustering of blue horizontal branch stars near the centroid of the system. The second system, DELVE 1 (DELVE J1630-0058), is identified as a resolved overdensity of stars with a heliocentric distance of , a half-light radius of , an age of , a metallicity of , and an absolute magnitude of , consistent with the known population of faint halo star clusters. Given the low number of probable member stars at magnitudes accessible with Gaia DR2, a proper motion signal for DELVE 1 is only marginally detected. We compare the spatial position and proper motion of both Centaurus I and DELVE 1 with simulations of the accreted satellite population of the Large Magellanic Cloud (LMC) and find that neither is likely to be associated with the LMC.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and ...therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used.
To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS.
Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo.
Urology outpatient clinics at 10 tertiary care medical centers in North America.
Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment.
The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events.
Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo.
The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes.
Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently.
Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.
In the western United States, prolonged drought, a warming climate, and historical fuel buildup have contributed to larger and more intense wildfires as well as to longer fire seasons. As these ...costly wildfires become more common, new tools and methods are essential for improving our understanding of the evolution of fires and how extreme weather conditions, including heat waves, windstorms, droughts, and varying levels of active-fire suppression, influence fire spread. Here, we develop the Geostationary Operational Environmental Satellites (GOES)-Observed Fire Event Representation (GOFER) algorithm to derive the hourly fire progression of large wildfires and create a product of hourly fire perimeters, active-fire lines, and fire spread rates. Using GOES-East and GOES-West geostationary satellite detections of active fires, we test the GOFER algorithm on 28 large wildfires in California from 2019 to 2021. The GOFER algorithm includes parameter optimizations for defining the burned-to-unburned boundary and correcting for the parallax effect from elevated terrain. We evaluate GOFER perimeters using 12 h data from the Visible Infrared Imaging Radiometer Suite (VIIRS)-derived Fire Event Data Suite (FEDS) and final fire perimeters from the California's Fire and Resource Assessment Program (FRAP). Although the GOES imagery used to derive GOFER has a coarser resolution (2 km at the Equator), the final fire perimeters from GOFER correspond reasonably well to those obtained from FRAP, with a mean Intersection-over-Union (IoU) of 0.77, in comparison to 0.83 between FEDS and FRAP; the IoU indicates the area of overlap over the area of the union relative to the reference perimeters, in which 0 is no agreement and 1 is perfect agreement. GOFER fills a key temporal gap present in other fire tracking products that rely on low-Earth-orbit imagery, where perimeters are available at intervals of 12 h or longer or at ad hoc intervals from aircraft overflights. This is particularly relevant when a fire spreads rapidly, such as at maximum hourly spread rates of over 5 km h−1. Our GOFER algorithm for deriving the hourly fire progression using GOES can be applied to large wildfires across North and South America and reveals considerable variability in the rates of fire spread on diurnal timescales. The resulting GOFER product has a broad set of potential applications, including the development of predictive models for fire spread and the improvement of atmospheric transport models for surface smoke estimates. The resulting GOFER product has a broad set of potential applications, including the development of predictive models for fire spread and the improvement of atmospheric transport models for surface smoke estimates (https://doi.org/10.5281/zenodo.8327264, Liu et al., 2023).
To compare the efficiency (stone fragmentation and removal time) and complications of three models of intracorporeal lithotripters in percutaneous nephrolithotomy (PCNL).
Prospective, randomized ...controlled trial at nine centers in North America from 2009 to 2016. Patients were randomized to one of three lithotripter devices: the Cyberwand, a dual-probe ultrasonic device; the Swiss Lithoclast Select, a combination pneumatic and ultrasonic device; and the StoneBreaker, a portable pneumatic device powered by CO
cartridges. Since the StoneBreaker lacks an ultrasonic component, it was used with the LUS-II ultrasonic lithotripter to allow fair comparison with combination devices.
Two hundred seventy patients were enrolled, 69 were excluded after randomization. Two hundred one patients completed the study: 71 in the Cyberwand group, 66 in the Lithoclast Select group, and 64 in the StoneBreaker group. The baseline patient characteristics of the three groups were similar. Mean stone surface area was smaller in the StoneBreaker group at 407.8 mm
vs 577.5 mm
(Lithoclast Select) and 627.9 mm
(Cyberwand). The stone clearance rate was slowest in the StoneBreaker group at 24.0 mm
/min vs 28.9 mm
/min and 32.3 mm
/min in the Lithoclast Select and Cyberwand groups, respectively. After statistically adjusting for the smaller mean stone in the StoneBreaker group, there was no difference in the stone clearance rate among the three groups (p = 0.249). Secondary outcomes, including complications and stone-free rates, were similar between the groups.
The Cyberwand, Lithoclast Select, and the StoneBreaker lithotripters have similar adjusted stone clearance rates in PCNL for stones >2 cm. The safety and efficacy of these devices are comparable.
A Decade of Advances in Military Trauma Care Glassberg, E.; Nadler, R.; Erlich, T. ...
Scandinavian Journal of Surgery,
06/2014, Letnik:
103, Številka:
2
Book Review, Journal Article
Recenzirano
Background:
While combat casualty care shares many key concepts with civilian trauma systems, its unique features mandate certain practices that are distinct from the civilian ones.
Methods:
This is ...a review of the most current literature on combat casualty care, based on computer database searches for studies on combat casualty care and military medicine. Studies were selected for inclusion in this review based on their relevance and contribution.
Results:
Over the last decade, meticulous, international data collection and research efforts have led to significant improvements in military trauma care. Combat medicine has focused on the causes of preventable deaths and targeted on bleeding control and resuscitation strategies, as well as improved evacuation. En route care and forward surgical interventions have resulted in unprecedented low fatality rates and the saving of more lives.
Conclusion:
This overview of the developments in combat casualty care in recent years emphasizes medical practices that are characteristic of combat medicine, yet with the potential to save lives in other scenarios, as well.
PDF
