Tag: pubmed

Appl Environ Microbiol. 2022 May 24:e0046822. doi: 10.1128/aem.00468-22. Online ahead of print.

ABSTRACT

Marine cold seeps are natural sites of methane emission and harbor distinct microbial communities capable of oxidizing methane. The majority of known cold seeps are on tectonically active continental margins, but recent discoveries have revealed abundant seeps on passive margins as well, including on the U.S. Atlantic Margin (USAM). We sampled in and around four USAM seeps and combined pore water geochemistry measurements with amplicon sequencing of 16S rRNA and mcrA (DNA and RNA) to investigate the microbial communities present, their assembly processes, and how they compare to communities at previously studied sites. We found that the USAM seeps contained communities consistent with the canonical seep microbiome at the class and order levels but differed markedly at the sequence variant level, especially within the anaerobic methanotrophic (ANME) archaea. The ANME populations were highly uneven, with just a few dominant mcrA sequence variants at each seep. Interestingly, the USAM seeps did not form a distinct phylogenetic cluster when compared with other previously described seeps around the world. Consistent with this, we found only a very weak (though statistically significant) distance-decay trend in seep community similarity across a global data set. Ecological assembly indices suggest that the USAM seep communities were assembled primarily deterministically, in contrast to the surrounding nonseep sediments, where stochastic processes dominated. Together, our results suggest that the primary driver of seep microbial community composition is local geochemistry-specifically methane, sulfide, nitrate, acetate, and ammonium concentrations-rather than the geologic context, the composition of nearby seeps, or random events of dispersal. IMPORTANCE Cold seeps are now known to be widespread features of passive continental margins, including the northern U.S. Atlantic Margin (USAM). Methane seepage is expected to intensify at these relatively shallow seeps as bottom waters warm and underlying methane hydrates dissociate. While methanotrophic microbial communities might reduce or prevent methane release, microbial communities on passive margins have rarely been characterized. In this study, we investigated the Bacteria and Archaea at four cold seeps on the northern USAM and found that despite being colocated on the same continental slope, the communities significantly differ by site at the sequence variant level, particularly methane-cycling community members. Differentiation by site was not observed in similarly spaced background sediments, raising interesting questions about the dispersal pathways of cold seep microorganisms. Understanding the genetic makeup of these discrete seafloor ecosystems and how their microbial communities develop will be increasingly important as the climate changes.

PMID:35607968 | DOI:10.1128/aem.00468-22

Crit Care Med. 2022 May 16. doi: 10.1097/CCM.0000000000005579. Online ahead of print.

ABSTRACT

OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) in patients with COVID-19 has been supported by major healthcare organizations, yet the role of specific management strategies during ECMO requires further study. We sought to characterize tracheostomy practices, complications, and outcomes in ECMO-supported patients with acute respiratory failure related to COVID-19.

DESIGN: Retrospective cohort study.

SETTING: ECMO centers contributing to the Extracorporeal Life Support Organization Registry.

PATIENTS: Patients 16 years or older receiving venovenous ECMO for respiratory support for: 1) COVID-19 in 2020 and 2021 (through October 2021) and 2) pre-COVID-19 viral pneumonia in 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We identified 7,047 patients who received ECMO support for acute respiratory failure related to COVID-19. A total of 32% of patients were recorded as having a tracheostomy procedure during ECMO, and 51% had a tracheostomy at some point during hospitalization. The frequency of tracheostomy was similar in pre-COVID-19 viral pneumonia, but tracheostomies were performed 3 days earlier compared with patients with COVID-19 (median 6.7 d [interquartile range [IQR], 3.0-12.0 d] vs 10.0 d [IQR, 5.0-16.5 d]; p < 0.001). More patients were mobilized with pre-COVID-19 viral pneumonia, but receipt of a tracheostomy during ECMO was associated with increased mobilization in both cohorts. More bleeding complications occurred in patients who received a tracheostomy, with 9% of patients with COVID-19 who received a tracheostomy reported as having surgical site bleeding.

CONCLUSIONS: Tracheostomies are performed in COVID-19 patients receiving ECMO at rates similar to practices in pre-COVID-19 viral pneumonia, although later during the course of ECMO. Receipt of a tracheostomy was associated with increased patient mobilization. Overall mortality was similar between those who did and did not receive a tracheostomy.

PMID:35607973 | DOI:10.1097/CCM.0000000000005579

Ann Neurol. 2022 May 24. doi: 10.1002/ana.26411. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer’s disease (AD).

METHODS: In this randomized, double-blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre- and post- 60 minutes treatment with γ-tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ-tACS efficacy were evaluated.

RESULTS: We observed a significant improvement in the Rey auditory verbal learning (RAVL) test immediate recall (p<0.001) and delayed recall scores (p<0.001) after γ-tACS but not after sham tACS. Face-name associations scores improved with γ-tACS (p<0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ-tACS (p<0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ-tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus.

INTERPRETATION: Precuneus γ-tACS, able to increase γ-power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ-tACS was dependent on genetic factors and disease stage. This article is protected by copyright. All rights reserved.

PMID:35607946 | DOI:10.1002/ana.26411

Phys Ther. 2022 May 23:pzac067. doi: 10.1093/ptj/pzac067. Online ahead of print.

ABSTRACT

OBJECTIVE: The “Benchmarking in Academic Physical Therapy” study uses the PT-Graduation Questionnaire (PT-GQ) survey to develop comprehensive performance benchmarks for physical therapist education. These benchmarks facilitate interprofessional comparisons and have application to accreditation self-study reporting. The purpose of this study is to report updated benchmarks from enrollment Wave 2 of the study, with an emphasis on curricular areas that align with accreditation standards.

METHODS: Seventy Doctor of Physical Therapy (DPT) programs (26.5% national sample) administered the survey to graduates during 2020-2021. Where possible, respondent data were contextualized by statistical comparison to published medical student data (Welch’s t-test, Hedges g).

RESULTS: There were 1894 respondents who participated in the study (response rate: 63.9%). Average survey duration was 32.9 minutes. White-only, non-Hispanic/Latino/a/x individuals (78.8%) exceeded the 2020 US Census prevalence (60.1%) and only half of respondents perceived a benefit to their training from the diversity present in their programs. Over 94% of respondents indicated that their curricula were characterized by “problem solving/critical thinking” and “clinical reasoning,” but nearly half indicated “busywork” was prevalent. High curricular satisfaction ratings clustered in content areas relating to profession-specific technical skills and low ratings clustered in foundational sciences. DPT respondents reported significantly lower tolerance for ambiguity, significantly more exhaustion, and significantly less disengagement than medical students. Respondents endorsed higher levels of “adaptive” perfectionism (striving for high performance) than “maladaptive” perfectionism (concern over negative evaluations). Respondents with loans (27.7%) had debt exceeding $150,000, the benchmark above which the DPT degree loses economic power.

CONCLUSIONS: PT-GQ benchmarks revealed strengths (eg, curricula emphasizing problem solving/critical thinking and clinical reasoning) and challenges (eg, low diversity, problematic student debt) in physical therapist education.

IMPACT: Programs can use benchmarking for quality-improvement efforts and as a data source for accreditation self-study reports. The ongoing study will refine national benchmarks and pilot items to address new research questions.

PMID:35607945 | DOI:10.1093/ptj/pzac067

Hosp Pediatr. 2022 May 24:e2021006417. doi: 10.1542/hpeds.2021-006417. Online ahead of print.

ABSTRACT

OBJECTIVES: Sources of variation within febrile infant management are incompletely described. In 2016, a national standardization quality improvement initiative, Reducing Excessive Variation in Infant Sepsis Evaluations (REVISE) was implemented. We sought to: (1) describe sociodemographic factors influencing laboratory obtainment and hospitalization among febrile infants and (2) examine the association of REVISE on any identified sources of practice variation.

METHODS: We included febrile infants ≤60 days of age evaluated between December 1, 2015 and November 30, 2018 at Pediatric Health Information System-reporting hospitals. Patient demographics and hospital characteristics, including participation in REVISE, were identified. Factors associated with variation in febrile infant management were described in relation to the timing of the REVISE initiative.

RESULTS: We identified 32 572 febrile infants in our study period. Pre-REVISE, payer-type was associated with variation in laboratory obtainment and hospitalization. Compared with those with private insurance, infants with self-pay (adjusted odds ratio [aOR] 0.43, 95% confidence interval [95% CI] 0.22-0.5) or government insurance (aOR 0.67, 95% CI 0.60-0.75) had lower odds of receiving laboratories, and self-pay infants had lower odds of hospitalization (aOR 0.38, 95% CI 0.28-0.51). Post-REVISE, payer-related disparities in care remained. Disparities in care were not associated with REVISE participation, as the interaction of time and payer was not statistically different between non-REVISE and REVISE centers for either laboratory obtainment (P = .09) or hospitalization (P = .67).

CONCLUSIONS: Payer-related care inequalities exist for febrile infants. Patterns in disparities were similar over time for both non-REVISE and REVISE-participating hospitals. Further work is needed to better understand the role of standardization projects in reducing health disparities.

PMID:35607933 | DOI:10.1542/hpeds.2021-006417

J Chem Inf Model. 2022 May 24. doi: 10.1021/acs.jcim.2c00297. Online ahead of print.

ABSTRACT

The prediction and optimization of pharmacokinetic properties are essential in lead optimization. Traditional strategies mainly depend on the empirical chemical rules from medicinal chemists. However, with the rising amount of data, it is getting more difficult to manually extract useful medicinal chemistry knowledge. To this end, we introduced IDL-PPBopt, a computational strategy for predicting and optimizing the plasma protein binding (PPB) property based on an interpretable deep learning method. At first, a curated PPB data set was used to construct an interpretable deep learning model, which showed excellent predictive performance with a root mean squared error of 0.112 for the entire test set. Then, we designed a detection protocol based on the model and Wilcoxon test to identify the PPB-related substructures (named privileged substructures, PSubs) for each molecule. In total, 22 general privileged substructures (GPSubs) were identified, which shared some common features such as nitrogen-containing groups, diamines with two carbon units, and azetidine. Furthermore, a series of second-level chemical rules for each GPSub were derived through a statistical test and then summarized into substructure pairs. We demonstrated that these substructure pairs were equally applicable outside the training set and accordingly customized the structural modification schemes for each GPSub, which provided alternatives for the optimization of the PPB property. Therefore, IDL-PPBopt provides a promising scheme for the prediction and optimization of the PPB property and would be helpful for lead optimization of other pharmacokinetic properties.

PMID:35607907 | DOI:10.1021/acs.jcim.2c00297

Worldviews Evid Based Nurs. 2022 May 24. doi: 10.1111/wvn.12589. Online ahead of print.

ABSTRACT

BACKGROUND: Quality cancer care necessitates opportunities for patient participation, supposedly recognizing the individual’s preferences and experiences for being involved in their health and healthcare issues. Previous research shows that surgical cancer patients wish to be more involved, requiring professionals to be sensitive of patients’ needs.

AIMS: To explore preference-based patient participation in surgical cancer care.

METHODS: A cross-sectional study was conducted. The Patient Preferences for Patient Participation tool (4Ps) was used, which includes 12 attributes of preferences for and experiences of patient participation. Data were analyzed with descriptive and comparative statistical methods.

RESULTS: The results are based on a total of 101 questionnaires. Having reciprocal communication and being listened to by healthcare staff were commonly deemed crucial for patient participation. While 60% of the patients suggested that taking part in planning was crucial for their participation, they had experienced this only to some extent. Learning to manage symptoms and phrasing personal goals were items most often representing insufficient conditions for preference-based patient participation.

LINKING EVIDENCE TO ACTION: To support person-centered surgical care, further efforts to suffice preference-based participation are needed, including opportunities for patients to share their experiences and engage in the planning of healthcare activities.

PMID:35607906 | DOI:10.1111/wvn.12589

J Endourol. 2022 May 24. doi: 10.1089/end.2022.0103. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the oncological outcomes and recurrence patterns of clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after a template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU).

METHODS: A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template of RPLND included the renal hilar and paraaortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses.

RESULTS: Compared to the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated five-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared to the group without RPLND (64.2%) (p = 0.014). The estimated five-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while a significant difference was not observed in the rate of regional LN recurrence.

CONCLUSION: This study suggests that a template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves the recurrence-free survival by reducing distant recurrences.

PMID:35607848 | DOI:10.1089/end.2022.0103

Neurol Neurochir Pol. 2022 May 24. doi: 10.5603/PJNNS.a2022.0036. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy.

CLINICAL RATIONALE: Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV’s effect on nocturnal sleep architecture.

MATERIAL AND METHODS: The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy.

RESULTS: Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance.

CONCLUSIONS: Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug.

PMID:35607879 | DOI:10.5603/PJNNS.a2022.0036

Stat Med. 2022 May 24. doi: 10.1002/sim.9446. Online ahead of print.

ABSTRACT

Are weak associations between a treatment and a binary outcome always sensitive to small unmeasured biases in observational studies? This possibility is often discussed in epidemiology. The familiar Mantel-Haenszel test for a 2×2×S$$ 2times 2times S $$ contingency table exaggerates sensitivity to unmeasured biases when the population odds ratios vary among the S$$ S $$ strata. A statistic built from several components, here from the S$$ S $$ strata, is said to have demonstrated insensitivity to bias if it uses only those components that provide indications of insensitivity to bias. Briefly, such a statistic is a d$$ d $$ -statistic. There are 2S–1$$ {2}^S-1 $$ candidate statistics with S$$ S $$ strata, and a d$$ d $$ -statistic considers them all. To have level α$$ alpha $$ , a test based on a d$$ d $$ -statistic must pay a price for its double use of the data, but as the sample size increases, that price becomes small, while the gain may be large. The price is paid by conditioning on the limited information used to identify components that are insensitive to a bias of specified magnitude, basing the test result on the information that remains after conditioning. In large samples, the d$$ d $$ -statistic achieves the largest possible design sensitivity, so it does not exaggerate sensitivity to unmeasured bias. A simulation verifies that the large sample result has traction in samples of practical size. A study of sunlight as a cause of cataract is used to illustrate issues and methods. Several extensions of the method are discussed. An R package dstat2x2xk implements the method.

PMID:35607846 | DOI:10.1002/sim.9446