Among critically ill patients undergoing orotracheal intubation in the emergency department (ED) or intensive care unit (ICU), failure to visualise the vocal cords and intubate the trachea on the ...first attempt is associated with an increased risk of complications. Two types of laryngoscopes are commonly available: direct laryngoscopes and video laryngoscopes. For critically ill adults undergoing emergency tracheal intubation, it remains uncertain whether the use of a video laryngoscope increases the incidence of successful intubation on the first attempt compared with the use of a direct laryngoscope.
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(DEVICE) trial is a prospective, multicentre, non-blinded, randomised trial being conducted in 7 EDs and 10 ICUs in the USA. The trial plans to enrol up to 2000 critically ill adults undergoing orotracheal intubation with a laryngoscope. Eligible patients are randomised 1:1 to the use of a video laryngoscope or a direct laryngoscope for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is the incidence of severe complications between induction and 2 min after intubation, defined as the occurrence of one or more of the following: severe hypoxaemia (lowest oxygen saturation <80%); severe hypotension (systolic blood pressure <65 mm Hg or new or increased vasopressor administration); cardiac arrest or death. Enrolment began on 19 March 2022 and is expected to be completed in 2023.
The trial protocol was approved with waiver of informed consent by the single institutional review board at Vanderbilt University Medical Center and the Human Research Protection Office of the Department of Defense. The results will be presented at scientific conferences and submitted for publication in a peer-reviewed journal.
ClinicalTrials.gov Registry (NCT05239195).
Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood ...lead levels prevents or reduces such impairment.
We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months.
During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter 0.2 to 0.3 micromol per liter). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant.
Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels.
Protoplasts of complementing auxotrophs of Candida albicans can fuse in the presence of polyethylene glycol and generate prototrophic cells. The yields of prototrophs from fusion mixtures depend ...greatly on the particular combinations of auxotrophies involved but not on other features of the strain backgrounds of protoplasts. The initial cellular products of fusions isolated on selective media are heterokaryons which replicate slowly but also segregate single parental nuclei into blastospores in high frequency. Karyogamy within heterokaryons produces hybrid nuclei which, on segregation, give rise to rapidly growing, uninucleate substrains. Analyses of the substrains show that hybrid nuclei either stabilize as diploid or undergo random loss of chromosomes to stabilize at various levels of aneuploidy prior to segregation. Chromosome losses and radiation induced mitotic crossing-over can effect recombination for parental auxotrophic markers in hybrids; patterns of recombination for ader and arg markers provide the first documented example of chromosomal linkage in C. albicans. Thus, protoplast fusions offer opportunities otherwise unavailable for applying the incisive tools of genetic recombination to analysis of this important, asexual yeast.
Introduction: Telemicrobiology is a growing component of clinical microbiology informatics. However, few studies have been performed to assess the diagnostic utility of telemicroscopy systems in ...evaluating infectious agents. Objective: Evaluate multiple contemporary digital pathology platforms for use in diagnostic telemicrobiology. Materials and Methods: A mix of thirty cases that included viral, bacterial, fungal, and parasitological findings were evaluated by four experts using ×40 whole slide imaging (WSI) scans, ×83 oil-immersion WSI scans, ×100 oil-immersion WSI scans, digital photomicrographs, and glass slides. Results: The ×83 WSI, ×100 WSI, and photomicrograph interpretations were not significantly different in quality and accuracy when compared to glass slide interpretations. The ×40 WSI interpretations were of lower quality and were more likely to be incorrect when compared to glass slide interpretations. Conclusions: In this study, high magnification, oil-immersion digital pathology platforms are better suited to support telemicrobiology applications and yield interpretations on par with glass slide evaluations.
Prototrophic aneuploid and euploid derivatives of wild type Candida albicans strains 207 were produced by fusing protoplasts of complementing auxotrophs obtained from strain 207. Comparisons of cell ...survivals and incidences of mitotic recombinants occurring after ultraviolet irradiation (UV) of these strains indicate that (i) aneuploids are categorically less efficient than euploids for repair of pyrimidine dimers induced in DNA by UV and that (ii) such repair is enhanced by growing irradiated cells at 25 degrees C, on minimal medium or in the presence of ergosterol rather than at 37 degrees C, on amino acid enriched medium or medium unsupplemented with ergosterol. In addition, the comparisons establish than one cannot discriminate between strains of C. albicans which differ in cellular DNA contents or genomic constitutions on the basis of their UV survival curves.
During the Atlanta Supersite Project, four particle mass spectrometers were operated together for the first time: NOAA's Particle Analysis by Laser Mass Spectrometer (PALMS), University of California ...at Riverside's Aerosol Time‐of‐Flight Mass Spectrometer (ATOFMS), University of Delaware's Rapid Single‐Particle Mass Spectrometer II (RSMS‐II), and Aerodyne's Aerosol Mass Spectrometer (AMS). Although these mass spectrometers are generally classified as similar instruments, they clearly have different characteristics due to their unique designs. One primary difference is related to the volatilization/ionization method: PALMS, ATOFMS, and RSMS‐II utilize laser desorption/ionization, whereas particles in the AMS instrument are volatilized by impaction onto a heated surface with the resulting components ionized by electron impact. Thus mass spectral data from the AMS are representative of the ensemble of particles sampled, and those from the laser‐based instruments are representative of individual particles. In addition, the AMS instrument cannot analyze refractory material such as soot, sodium chloride, and crustal elements, and some sulfate or water‐rich particles may not always be analyzed with every laser‐based instrument. A main difference among the laser‐based mass spectrometers is that the RSMS‐II instrument can obtain size‐resolved single particle composition information for particles with aerodynamic diameters as small as 15 nm. The minimum sizes analyzed by ATOFMS and PALMS are 0.2 and about 0.35 μm, respectively, in aerodynamic diameter. Furthermore, PALMS, ATOFMS, and RSMS‐II use different laser ionization conditions. Despite these differences the laser‐based instruments found similar individual particle classifications, and their relative fractions among comparable sized particles from Atlanta were broadly consistent. Finally, the AMS measurements of the nitrate/sulfate mole ratio were highly correlated with composite measurements (r2 = 0.93). In contrast, the PALMS nitrate/sulfate ion ratios were only moderately correlated (r2 ∼ 0.7).
Heterokaryons (hets) of Candida albicans constructed by fusing protoplasts of complementing auxotrophs produce heterogeneous clones on minimal medium consisting of (i) a minority of slow-growing ...hets, (ii) a preponderance of non-growing, parental-type auxotrophic monokaryons, and (iii) some prototrophic monokaryons bearing hybrid nuclei. Hets grown at a given temperature within the range 25 degrees C to 41 degrees C replate with higher efficiencies at any lower temperature and exhibit progressively declining plating efficiencies as plate temperatures increase beyond that at which they were initially grown. Neither auxotrophic nor prototrophic monokaryons show such responses. Growth of colonies produced by hets, wild-type strains or prototrophic hybrid monokaryons is stimulated by temperatures in the order, 37 degrees C greater than 30 degrees C greater than 41 degrees C greater than 25 degrees C. However, the proportion of hets to auxotrophic monokaryons within individual het clones increases directly from 25 degrees C to 41 degrees C. Though this pattern obtains whether colonies are compared at equivalent sizes or ages, het frequencies decline as colonies age at all temperatures. Appearance of hybrid monokaryons within het clones is unaffected by growth temperature. The relationships of temperatures to plating efficiencies and stabilities of hets are independent of the natures of their complementing auxotrophies or the wild-type backgrounds of their nuclear components and are, therefore, functions of heterokaryosis per se. Modifications of these relationships by selective metabolic antagonists or by growth of hets on different pre- and post-plating carbon sources indicate that they reflect temperature-dependent properties of mitochondria which are peculiar to hets.
The Chinese hamster ovary (CHO) cell 40S ribosomal subunit protein S14 provides a unique opportunity to investigate an important mammalian housekeeping gene and its mRNA and protein products. The S14 ...gene appears to be single copy, and CHO cell S14 mutants have been isolated as emetine-resistant (emtB) clones in tissue culture. Thus, S14 is the only mammalian ribosomal protein whose gene structure and function are amenable to straightforward genetic and biochemical analysis. Recently, we isolated a wild-type Chinese hamster lung cell cDNA clone, pCS14-1, including an almost complete copy of the ribosomal protein S14 message (N. Nakamichi, D. D. Rhoads, and D. J. Roufa, J. Biol. Chem. 258: 13236-13242, 1983). Here we describe comparable cDNAs from wild-type and emtB CHO cells. We report both mRNA and polypeptide sequences of the wild-type and mutant ribosomal protein transcripts. As a consequence of the genetic methods used to obtain our emetine-resistant mutants, the emtB S14 cDNAs differ from wild-type cDNA by single-base changes. Physical and chemical features of polypeptides encoded by the cDNAs are consistent with well-characterized S14 protein polymorphisms. The three emtB mutations analyzed affect two adjacent arginine codons within the very basic S14 carboxyl region, indicating a significant role for this portion of the protein in the function and architecture of the mammalian 40S ribosomal subunit.
Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. ...Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.
To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.
In this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)-based executive functioning tasks and an associative memory task 3 times over 2 weeks. Observational research participants were enrolled through 18 centers of a North American FTLD research consortium (ALLFTD) and were asked to complete the tests remotely using their own smartphones. Of 1163 eligible individuals (enrolled in parent studies), 360 were enrolled in the present study; 364 refused and 439 were excluded. Participants were divided into discovery (n = 258) and validation (n = 102) cohorts. Among 329 participants with data available on disease stage, 195 were asymptomatic or had preclinical FTLD (59.3%), 66 had prodromal FTLD (20.1%), and 68 had symptomatic FTLD (20.7%) with a range of clinical syndromes.
Participants completed standard in-clinic measures and remotely administered ALLFTD mobile app (app) smartphone tests.
Internal consistency, test-retest reliability, association of smartphone tests with criterion standard clinical measures, and diagnostic accuracy.
In the 360 participants (mean SD age, 54.0 15.4 years; 209 58.1% women), smartphone tests showed moderate-to-excellent reliability (intraclass correlation coefficients, 0.77-0.95). Validity was supported by association of smartphones tests with disease severity (r range, 0.38-0.59), criterion-standard neuropsychological tests (r range, 0.40-0.66), and brain volume (standardized β range, 0.34-0.50). Smartphone tests accurately differentiated individuals with dementia from controls (area under the curve AUC, 0.93 95% CI, 0.90-0.96) and were more sensitive to early symptoms (AUC, 0.82 95% CI, 0.76-0.88) than the Montreal Cognitive Assessment (AUC, 0.68 95% CI, 0.59-0.78) (z of comparison, -2.49 95% CI, -0.19 to -0.02; P = .01). Reliability and validity findings were highly similar in the discovery and validation cohorts. Preclinical participants who carried pathogenic variants performed significantly worse than noncarrier family controls on 3 app tasks (eg, 2-back β = -0.49 95% CI, -0.72 to -0.25; P < .001) but not a composite of traditional neuropsychological measures (β = -0.14 95% CI, -0.42 to 0.14; P = .32).
The findings of this cohort study suggest that smartphones could offer a feasible, reliable, valid, and scalable solution for remote evaluations of FTLD and may improve early detection. Smartphone assessments should be considered as a complementary approach to traditional in-person trial designs. Future research should validate these results in diverse populations and evaluate the utility of these tests for longitudinal monitoring.
Chinese hamster ribosomal protein S14 cDNA was used to recognize homologous human cDNA and genomic clones. Human and Chinese hamster S14 protein sequences deduced from the cDNAs are identical. Two ...overlapping human genomic S14 DNA clones were isolated from a Charon 28 placental DNA library. A fragment of single-copy DNA derived from an intron region of one clone was mapped to the functional RPS14 locus on human chromosome 5q by using a panel of human X Chinese hamster hybrid cell DNAs. The human S14 gene consists of five exons and four introns spanning 5.9 kilobase pairs of DNA. Polyadenylated S14 transcripts purified from HeLa cell cytoplasma display heterogeneous 5′ ends that map within noncoding RPS14 exon 1. This precludes assignment of a unique 5′ boundary of RPS14 transcripts with respect to the cloned human genomic DNA. Apparently HeLa cells either initiate transcription at multiple sites within RPS14 exon 1, or capped 5′ oligonucleotides are removed from most S14 mRNAs posttranscription. In contrast to the few murine ribosomal protein and several other mammalian housekeeping genes whose structures are known, human RPS14 contains a TATA sequence (TATACTT) upstream from exon 1. Three related short sequence motifs, also observed in murine and yeast ribosomal protein genes, occur in this region of the RPS14 gene. RPS14 introns 3 and 4 both contain Alu sequences. Interestingly, the Alu sequence in intron 3 is located slightly downstream from a chromosome 5 deletion breakpoint in one human X hamster hybrid clone analyzed.
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