bluuebunny/crossref_metadata_2025 huggingface dataset:
Durlobactam, a Broad-Spectrum Serine β-lactamase Inhibitor, Restores Sulbactam Activity AgainstAcinetobacterSpecies
Authors: Papp-Wallace Krisztina M , McLeod Sarah M , Miller Alita A
Published: May 2023

Sulbactam-durlobactam is a pathogen-targeted β-lactam/β-lactamase inhibitor combination in late-stage development for the treatment of Acinetobacter infections, including those caused by multidrug-resistant strains. Durlobactam is a member of the diazabicyclooctane class of β-lactamase inhibitors with broad-spectrum serine β-lactamase activity. Sulbactam is a first-generation, narrow-spectrum β-lactamase inhibitor that also has intrinsic antibacterial activity against Acinetobacter spp. due to its ability to inhibit penicillin-binding proteins 1 and 3. The clinical utility of sulbactam for the treatment of contemporary Acinetobacter infections has been eroded over the last decades due to its susceptibility to cleavage by numerous β-lactamases present in this species. However, when combined with durlobactam, the activity of sulbactam is restored against this problematic pathogen. The following summary describes what is known about the molecular drivers of activity and resistance as well as results from surveillance and in vivo efficacy studies for this novel combination.
Big tau aggregation disrupts microtubule tyrosination and causes myocardial diastolic dysfunction: from discovery to therapy
Authors: Luciani Marco , Montalbano Mauro , Troncone Luca , Bacchin Camilla , Uchida Keita , Daniele Gianlorenzo , Jacobs Wolf Bethany , Butler Helen M , Kiel Justin , Berto Stefano , Gensemer Cortney , Moore Kelsey , Morningstar Jordan , Diteepeng Thamonwan , Albayram Onder , Abisambra José F , Norris Russell A , Di Salvo Thomas G , Prosser Benjamin , Kayed Rakez , del Monte Federica
Published: May 2023

Background

Amyloid plaques and neurofibrillary tangles, the molecular lesions that characterize Alzheimer’s disease (AD) and other forms of dementia, are emerging as determinants of proteinopathies ‘beyond the brain’. This study aims to establish tau’s putative pathophysiological mechanistic roles and potential future therapeutic targeting of tau in heart failure (HF).

Methods and results

A mouse model of tauopathy and human myocardial and brain tissue from patients with HF, AD, and controls was employed in this study. Tau protein expression was examined together with its distribution, and in vitro tau-related pathophysiological mechanisms were identified using a variety of biochemical, imaging, and functional approaches. A novel tau-targeting immunotherapy was tested to explore tau-targeted therapeutic potential in HF. Tau is expressed in normal and diseased human hearts, in contradistinction to the current oft-cited observation that tau is expressed specifically in the brain. Notably, the main cardiac isoform is high-molecular-weight (HMW) tau (also known as big tau), and hyperphosphorylated tau segregates in aggregates in HF and AD hearts. As previously described for amyloid-beta, the tauopathy phenotype in human myocardium is of diastolic dysfunction. Perturbation in the tubulin code, specifically a loss of tyrosinated microtubules, emerged as a potential mechanism of myocardial tauopathy. Monoclonal anti-tau antibody therapy improved myocardial function and clearance of toxic aggregates in mice, supporting tau as a potential target for novel HF immunotherapy.

Conclusion

The study presents new mechanistic evidence and potential treatment for the brain–heart tauopathy axis in myocardial and brain degenerative diseases and ageing.
Personalized pulmonary vein antrum isolation guided by left atrial wall thickness for persistent atrial fibrillation
Authors: Falasconi Giulio , Penela Diego , Soto-Iglesias David , Francia Pietro , Teres Cheryl , Saglietto Andrea , Jauregui Beatriz , Viveros Daniel , Bellido Aldo , Alderete Jose , Meca-Santamaria Julia , Franco Paula , Gaspardone Carlo , San Antonio Rodolfo , Huguet Marina , Cámara Óscar , Ortiz-Pérez José-Tomás , Martí-Almor Julio , Berruezo Antonio
Published: May 2023

Aims

Pulmonary vein (PV) antrum isolation proved to be effective for treating persistent atrial fibrillation (PeAF). We sought to investigate the results of a personalized approach aimed at adapting the ablation index (AI) to the local left atrial wall thickness (LAWT) in a cohort of consecutive patients with PeAF.

Methods and results

Consecutive patients referred for PeAF first ablation were prospectively enrolled. The LAWT three-dimensional maps were obtained from pre-procedure multidetector computed tomography and integrated into the navigation system. Ablation index was titrated according to the local LAWT, and the ablation line was personalized to avoid the thickest regions while encircling the PV antrum. A total of 121 patients (69.4% male, age 64.5 ± 9.5 years) were included. Procedure time was 57 min (IQR 50–67), fluoroscopy time was 43 s (IQR 20–71), and radiofrequency (RF) time was 16.5 min (IQR 14.3–18.4). The median AI tailored to the local LAWT was 387 (IQR 360–410) for the anterior wall and 335 (IQR 300–375) for the posterior wall. First-pass PV antrum isolation was obtained in 103 (85%) of the right PVs and 103 (85%) of the left PVs. Median LAWT values were higher for PVs without first-pass isolation as compared to the whole cohort (P = 0.02 for left PVs and P = 0.03 for right PVs). Recurrence-free survival was 79% at 12 month follow-up.

Conclusion

In this prospective study, LAWT-guided PV antrum isolation for PeAF was effective and efficient, requiring low procedure, fluoroscopy, and RF time. A randomized trial comparing the LAWT-guided ablation with the standard of practice is in progress (ClinicalTrials.gov, NCT05396534).
RecF protein targeting to post-replication (daughter strand) gaps II: RecF interaction with replisomes
Authors: Henry Camille , Kaur Gurleen , Cherry Megan E , Henrikus Sarah S , Bonde Nina J , Sharma Nischal , Beyer Hope A , Wood Elizabeth A , Chitteni-Pattu Sindhu , van Oijen Antoine M , Robinson Andrew , Cox Michael M
Published: May 2023

The bacterial RecF, RecO, and RecR proteins are an epistasis group involved in loading RecA protein into post-replication gaps. However, the targeting mechanism that brings these proteins to appropriate gaps is unclear. Here, we propose that targeting may involve a direct interaction between RecF and DnaN. In vivo, RecF is commonly found at the replication fork. Over-expression of RecF, but not RecO or a RecF ATPase mutant, is extremely toxic to cells. We provide evidence that the molecular basis of the toxicity lies in replisome destabilization. RecF over-expression leads to loss of genomic replisomes, increased recombination associated with post-replication gaps, increased plasmid loss, and SOS induction. Using three different methods, we document direct interactions of RecF with the DnaN β-clamp and DnaG primase that may underlie the replisome effects. In a single-molecule rolling-circle replication system in vitro, physiological levels of RecF protein trigger post-replication gap formation. We suggest that the RecF interactions, particularly with DnaN, reflect a functional link between post-replication gap creation and gap processing by RecA. RecF’s varied interactions may begin to explain how the RecFOR system is targeted to rare lesion-containing post-replication gaps, avoiding the potentially deleterious RecA loading onto thousands of other gaps created during replication.
Therapeutic disruption of RAD52–ssDNA complexation via novel drug-like inhibitors
Authors: Bhat Divya S , Malacaria Eva , Biagi Ludovica Di , Razzaghi Mortezaali , Honda Masayoshi , Hobbs Kathryn F , Hengel Sarah R , Pichierri Pietro , Spies M Ashley , Spies Maria
Published: May 2023

RAD52 protein is a coveted target for anticancer drug discovery. Similar to poly-ADP-ribose polymerase (PARP) inhibitors, pharmacological inhibition of RAD52 is synthetically lethal with defects in genome caretakers BRCA1 and BRCA2 (∼25% of breast and ovarian cancers). Emerging structure activity relationships for RAD52 are complex, making it challenging to transform previously identified disruptors of the RAD52–ssDNA interaction into drug-like leads using traditional medicinal chemistry approaches. Using pharmacophoric informatics on the RAD52 complexation by epigallocatechin (EGC), and the Enamine in silico REAL database, we identified six distinct chemical scaffolds that occupy the same physical space on RAD52 as EGC. All six were RAD52 inhibitors (IC50 ∼23–1200 μM) with two of the compounds (Z56 and Z99) selectively killing BRCA-mutant cells and inhibiting cellular activities of RAD52 at micromolar inhibitor concentrations. While Z56 had no effect on the ssDNA-binding protein RPA and was toxic to BRCA-mutant cells only, Z99 inhibited both proteins and displayed toxicity towards BRCA-complemented cells. Optimization of the Z99 scaffold resulted in a set of more powerful and selective inhibitors (IC50 ∼1.3–8 μM), which were only toxic to BRCA-mutant cells. RAD52 complexation by Z56, Z99 and its more specific derivatives provide a roadmap for next generation of cancer therapeutics.
ADOPT: intrinsic protein disorder prediction through deep bidirectional transformers
Authors: Redl Istvan , Fisicaro Carlo , Dutton Oliver , Hoffmann Falk , Henderson Louie , Owens Benjamin M J , Heberling Matthew , Paci Emanuele , Tamiola Kamil
Published: May 2023

Intrinsically disordered proteins (IDPs) are important for a broad range of biological functions and are involved in many diseases. An understanding of intrinsic disorder is key to develop compounds that target IDPs. Experimental characterization of IDPs is hindered by the very fact that they are highly dynamic. Computational methods that predict disorder from the amino acid sequence have been proposed. Here, we present ADOPT (Attention DisOrder PredicTor), a new predictor of protein disorder. ADOPT is composed of a self-supervised encoder and a supervised disorder predictor. The former is based on a deep bidirectional transformer, which extracts dense residue-level representations from Facebook’s Evolutionary Scale Modeling library. The latter uses a database of nuclear magnetic resonance chemical shifts, constructed to ensure balanced amounts of disordered and ordered residues, as a training and a test dataset for protein disorder. ADOPT predicts whether a protein or a specific region is disordered with better performance than the best existing predictors and faster than most other proposed methods (a few seconds per sequence). We identify the features that are relevant for the prediction performance and show that good performance can already be gained with <100 features. ADOPT is available as a stand-alone package at https://github.com/PeptoneLtd/ADOPT and as a web server at https://adopt.peptone.io/.
DOSE ESTIMATION TO WILD MEDAKA AROUND FUKUSHIMA DAI-ICHI NUCLEAR POWER PLANT
Authors: Maruyama Kouichi , Wang Bing , Watanabe Yoshito
Published: May 2023

More than 10 y have passed since the Fukushima Dai-ichi Nuclear Power Plant (F1-NPP) accident, but there are still many areas with high levels of radioactive contamination, especially reservoirs and lakes, where the levels decrease slowly. The exposed dose to non-human biota is of great concern. In this work, the exposure dose to wild medaka (small aquarium fish) around F1-NPP was measured/estimated by two approaches: in situ measurement and with the ERICA assessment tool. S2 is a reservoir located 7.5 km from F1-NPP, and the ambient dose rate was 25.0 μSv per h in 2012, but decreased to 4.82 μSv per h in 2021. The external exposure dose rate to wild medaka living there was 0.8–11.8 μGy per h (2017–21) by in situ measurement, and the estimated dose rate with the ERICA assessment tool was 0.6–54.5 μGy per h (2012–21). The estimated and measured doses to wild medaka are not expected to cause any significant radiation effects.
Racialization and Reproduction: Asian Immigrants and California’s Twentieth-Century Eugenic Sterilization Program
Authors: Kaniecki Marie , Novak Nicole L , Gao Sarah , Lira Natalie , Treviño Toni Ann , O’Connor Kate , Stern Alexandra Minna
Published: May 2023

During the twentieth century, state health authorities in California recommended sterilization for over 20,000 individuals held in state institutions. Asian immigrants occupied a marginalized position in racial, gender, and class hierarchies in California at the height of its eugenic sterilization program. Scholars have documented the disproportionate sterilization of other racialized groups, but little research exists connecting the racist, gendered implementation of Asian immigration restriction to the racism and sexism inherent in eugenics. This study examines patterns of coercive sterilization in Asian immigrants in California, hypothesizing higher institutionalization and sterilization rates among Asian-born compared with other foreign- and US-born individuals. We used complete count census microdata from 1910 to 1940 and digitized sterilization recommendation forms from 1920 to 1945 to model relative institutionalization and sterilization rates of Asian-born, other foreign-born, and US-born populations, stratified by gender. Other foreign-born men and women had the highest institutionalization rates in all four census years. Sterilization rates were higher for Asian-born women compared with US-born [Incidence Rate Ratio (IRR) = 2.00 (95% CI: 1.61, 2.48)] and other foreign-born women (p < 0.001) across the entire study period. Sterilization rates for Asian-born men were not significantly higher than those of US-born men [IRR 0.95 (95% CI 0.83, 1.10). However, an inflection point model incorporating the year of sterilization found higher sterilization rates for Asian-born men than for US-born men prior to 1933 [IRR 1.31 (95% CI 1.09, 1.59)]. This original quantitative analysis contributes to the literature demonstrating the health impact of discrimination on Asian-Americans and the disproportionate sterilization of racial minorities under state eugenics programs.
Phytobiome Stampede: Bison as Potential Dispersal Agents for the Tallgrass Prairie Microbiome
Authors: Saleh Amgad A. , Kraisitudomsook Nattapol , Frank Erin E. , Dendy Shauna P. , Leslie John F. , Garrett Karen A.
Published: May 2023

Dispersal by grazing and browsing animals has the potential to structure plant-associated microbes in plant communities. Bison are one of the largest grazing animals in North America and charismatic symbols of the Great Plains. They have an important role in maintaining plant communities in tallgrass prairie and may have played a significant role in microbial dispersal across the Great Plains, along with other grazers and herbivores in general. To determine whether bison saliva could maintain viable fungal propagules, we sampled saliva from bison at Konza Prairie Biological Station. Fifty-nine internal transcribed spacer sequences were recovered from distinct fungal colonies on media selective for Fusarium species and Macrophomina phaseolina, representing at least 26 fungal species. Most sequences were identified as originating from potential plant pathogens, indicating that bison may play a role in spreading plant pathogens throughout the prairie. Given their historic numbers and extensive migration across North America, bison may have had a role in establishing the current structure of the prairie microbiome.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Efficacy and Effectiveness of Wireless Binaural Beamforming Technology of Hearing Aids in Improving Speech Perception in Noise: A Systematic Review
Authors: Kumar Sathish , Guruvayurappan Ankitha , Pitchaimuthu Arivudai Nambi , Nayak Srikanth
Published: May 2023

Objectives:

To conduct a systematic review to address the following research questions: Q1. Does wireless binaural beamforming technology perform better than conventional microphone technologies in improving the speech perception in noise abilities of individuals with hearing aids bilaterally? and Q2. Do the subjective rating scores of hearing aid benefits suggest that wireless binaural beamforming technology is better than other microphone technologies?

Design:

Two independent authors performed a comprehensive search utilizing electronic databases like PubMed, Embase, Web of Science, and Scopus. Aside from these databases, course transcripts, white papers, evidence, and field study articles from various manufacturer websites were also included. The certainty of the evidence for each outcome was determined using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines.

Results:

Eleven studies were included for the qualitative synthesis. The available data were categorized into three groups (bilateral omnidirectional, bilateral directional, and bilateral asymmetric directional microphone processing) and compared against wireless binaural beamformers. The results of the Sign test revealed that for Q1, the wireless binaural beamformer significantly outperformed the bilateral omnidirectional microphone processing. However, no significant differences were observed when compared with other groups. Results for Q2 showed no significant improvement in wireless binaural beamformers compared to other groups.

Conclusion:

The superior performance of the wireless binaural beamformers over conventional microphone technologies was demonstrated by the speech perception in noise tasks but not by the self-reported subjective ratings. Nevertheless, the evidence for both speech perception noise and subjective ratings was weak.
Vestibular Follow-up Program for Congenital Cytomegalovirus Based on 6 Years of Longitudinal Data Collection
Authors: Dhondt Cleo , Maes Leen , Van Acker Emmely , Martens Sarie , Vanaudenaerde Saartje , Rombaut Lotte , De Cuyper Elise , Van Hoecke Helen , De Leenheer Els , Dhooge Ingeborg
Published: May 2023

Objectives:

Congenital cytomegalovirus (cCMV), the leading nongenetic cause of pediatric sensorineural hearing loss, can also affect vestibular function. Literature findings suggest clinical presentation of vestibular loss in cCMV to be as variable as the hearing loss. Still, probably due to the considerable additional burden it entails for both patients and diagnostic centers, longitudinal vestibular follow-up in cCMV is not well-established in clinical practice. Therefore, this study aims to propose an evidence-based vestibular follow-up program with proper balance between its feasibility and sensitivity.

Design:

In this longitudinal cohort study, 185 cCMV-patients (mean age 3.2 years, SD 1.6 years, range 0.5–6.7 years) were included. Vestibular follow-up data were obtained through lateral video head impulse test (vHIT) and cervical vestibular evoked myogenic potential (cVEMP) evaluations around the ages of 6 months, 1 year, and 2 years. Around 3 and 4.5 years of age, data from vertical vHIT and ocular vestibular evoked myogenic potentials (oVEMP) were also collected.

Results:

At birth, 55.1% (102/185) of patients were asymptomatic and 44.9% (83/185) were symptomatic. The mean duration of follow-up for all patients was 20.8 (SD 16.3) months (mean number of follow-up assessments: 3.2, SD 1.5). Vestibular loss occurred at some point during follow-up in 16.8% (31/185) of all patients. Six percent (10/164) of patients with normal vestibular function at first assessment developed delayed-onset vestibular loss; 80.0% (8/10) of these within the first 2 years of life. Vestibular deterioration was reported both in patients who had been treated with postnatal antiviral therapy and untreated patients. At final evaluation, both the semicircular and the otolith system were impaired in the majority of vestibular-impaired ears (29/36, 80.6%). Dysfunctions limited to the semicircular system or the otolith system were reported in 4 (4/36, 11.1%) and 3 (3/36, 8.3%) ears, respectively. The occurrence of vestibular loss was highest in patients with first trimester seroconversion (16/59, 27.1%) or with an unknown timing of seroconversion (13/71, 18.3%), patients with sensorineural hearing loss (16/31, 51.6%), and patients with periventricular cysts on magnetic resonance imaging (MRI) (7/11, 63.6%).

Conclusions:

Longitudinal vestibular follow-up, most intensively during the first 2 years of life, is recommended in cCMV-patients with vestibular risk factors (first trimester or unknown timing of seroconversion; sensorineural hearing loss; periventricular cysts on MRI). If those risk factors can be ruled out, a single evaluation early in life (around 6 months of age) might be sufficient. Both semicircular and otolith system evaluation should be part of the follow-up program, as partial losses were reported.
Participation in an Attachment-Based Home Visiting Program Is Associated with Lower Child Salivary C-Reactive Protein Levels at Follow-Up
Authors: Londoño Tobón Amalia , Condon Eileen , Slade Arietta , Holland Margaret L. , Mayes Linda C. , Sadler Lois S.
Published: May 2023

Objective:

Exposure to early childhood adversity is associated with an increased risk for physiological disruption, including increased inflammation. Early interventions that support the mother-child relationship have been shown to potentially buffer negative psychosocial outcomes related to early adversity, but it is unclear whether these interventions have long-term biological effects. We evaluated whether prior participation in Minding the Baby® (MTB), an attachment-based home visiting intervention for young mother-infant dyads living in underserved communities, is associated with lower child salivary inflammatory biomarkers compared with controls at follow-up.

Methods:

Ninety-seven maternal-child dyads (n = 43 intervention and n = 54 controls) enrolled in a follow-up study of the MTB randomized controlled trial, an average of 4.6 years after RCT completion. Children provided salivary specimens. We used adjusted linear regression to examine the relationship between MTB participation and child salivary inflammatory biomarkers (C-reactive protein [CRP], interleukin [IL]-1β, IL-6, IL-8, and TNF-α).

Results:

Children were on average 6.6 years old, 48% female, and identified as non-Hispanic/Latino Black/African American (34%) and Hispanic/Latino (63%). Participation in MTB was associated with lower salivary CRP levels (β = −0.31, SE = 0.28, p = 0.003) compared with controls. Participation in MTB was not associated with salivary cytokine levels.

Discussion:

Participation in an intensive two-generation home visiting intervention such as MTB may reduce salivary inflammatory biomarkers associated with early childhood adversity. Replication and further research are needed to improve the understanding of the potential for early childhood interventions to buffer the biological embedding of early adversity.
Stellate Multiform Amelanotic Choroidopathy (SMACH). Clinical and Multimodal Imaging Features.
Authors: Ramtohul Prithvi , Pellegrini Marco , Pichi Francesco , Preziosa Chiara , Marchese Alessandro , Cicinelli Maria Vittoria , Miserocchi Elisabetta , Mundae Rusdeep , Mrejen Sarah , Rofagha Soraya , Mein Calvin E. , Mein Luke , Ober Michael D. , Cunha de Souza Eduardo , Cohen Salomon Yves , van Dijk Elon H. C. , Jampol Lee , Boon Camiel J. F. , Freund K. Bailey
Published: May 2023

Purpose:

To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy).

Methods:

Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT-angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed.

Results:

Eighteen eyes from 18 patients (mean age: 28±19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish-orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10/18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth.

Conclusions:

SMACH appears to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, we propose renaming this entity “stellate multiform amelanotic choroidopathy”, a name which retains its prior abbreviation “SMACH”.
Characteristics and Related Parameters of Quick Contrast Sensitivity Function in Chinese Ametropia Children
Authors: Ye Yuhao , Xian Yiyong , Liu Fang , Lu Zhong-Lin , Zhou Xingtao , Zhao Jing
Published: May 2023

Purpose:

To investigate the characteristics of quick contrast sensitivity function (qCSF) and its related parameters in Chinese ametropia children.

Methods:

This case series study enrolled 106 eyes of 53 children (male/female=29/24, age: 9.04±2.06 years). Examinations included manifest refraction, axial length, corneal curvature, and monocular and binocular qCSF readings without refractive correction (area under log CSF [AULCSF], CSF acuity, and contrast sensitivity [CS] at 1.0 to 18.0 cpd). The subjects were divided into groups according to age and refractive parameters for analysis.

Results:

The mean spherical equivalent (SE), AULCSF, and CSF acuity of the test eyes were −0.94±1.53 D, 0.44±0.33, and 8.50±5.97 cpd, respectively. In the monocular qCSF comparison, the refraction sphere (RS) was the major factor correlated with qCSF readings (B=0.186, P=0.009 for AULCSF; B=0.543, P=0.019 for CSF acuity; generalized linear model). The three groups stratified by RS/SE (<−1.00D, −1.00D to 0D, and >0D) showed significant differences in CS at medium spatial frequencies (3.0 and 6.0 cpd; all P<0.05). In the low RS/SE group (within −1 to 0 D), the CS at 12.0 cpd was significantly lower than that in the hyperopia group (all P<0.05). Binocular qCSF readings were significantly correlated with those of the eyes with lower RS (all P<0.05).

Conclusion:

RS and SE are the major contributing factors of qCSF without refractive correction in children. The CS at medium spatial frequencies decrease significantly as the RS/SE increase. In low myopia children, the CS at medium and high spatial frequencies are significantly decreased, providing practical value in visual function screening in children.
Comparison of Deep Anterior Lamellar Keratoplasty and Penetrating Keratoplasty in Keratoconic Eyes With Previous Hydrops-Related Corneal Scar
Authors: Kemer Atik Burcu , Emul Merve , Kirgiz Ahmet , Cubuk Mehmet Ozgur , Ahmet Sibel , Kandemir Besek Nilay
Published: May 2023

Purpose:

This study aimed to compare the outcomes of deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) procedures in keratoconic eyes with a previous hydrops-related corneal scar.

Methods:

In this retrospective study, the medical records of patients who had hydrops-related corneal scarring and underwent keratoplasty surgery were reviewed. Patients treated with DALK were classified as group 1, and patients treated with PK as group 2. Preoperative and postoperative best-corrected visual acuity, central corneal thickness, keratometry (K), and refractive error values of each group were recorded and compared.

Results:

Seventy-eight eyes (41 in group 1 and 37 in group 2) were included in this study. The mean follow-up period of the patients was 37.7 ± 30.0 months in group 1 and 51.2 ± 29.4 months in group 2 (P = 0.06). The preoperative and postoperative best-corrected visual acuity and central corneal thickness values were statistically similar in both groups (each P value >0.05). Keratometry values (K1 and mean keratometry) were significantly steeper in group 1 (P
1 = 0.02 and P
2 = 0.03, respectively). Descemet membrane perforation was experienced in 7 (4 macroperforation and 3 microperforation; 15.6%) of 45 eyes that planned to perform DALK. These 4 eyes with macroperforation underwent PK and were excluded from the study. When all postoperative complications were assessed, although the total complication rate was 21% after DALK, it was 43% after PK (P = 0.04).

Conclusions:

DALK with a big-bubble technique is a feasible surgery in eyes with corneal scarring due to previous hydrops and is comparable with PK in terms of visual and refractive outcomes. This study suggests that DALK, which is safer than PK with less postoperative complication rates, should be the primary surgical option to avoid serious complications in keratoconic eyes with hydrops-related corneal scarring.
High Astigmatism After Conventional Diameter Deep Anterior Lamellar Keratoplasty in Keratoconus Can Be Successfully Managed With Repeat Wide Diameter Deep Anterior Lamellar Keratoplasty
Authors: Panthagani Jesse , Law Elizabeth M. , Chipeta Chimwemwe , Roberts Harry , Myerscough James
Published: May 2023

Purpose:

The aim of this study was to describe a new surgical technique to replace a conventional diameter (≤8 mm) deep anterior lamellar keratoplasty (DALK) graft with associated high astigmatism refractory to corneal-based astigmatic procedure/intolerance to contact lenses with a larger diameter (≥9 mm) DALK graft to improve best spectacle–corrected visual acuity (BSCVA).

Methods:

Two eyes from 2 keratoconic patients at Southend University Hospital between December 2019 and June 2021 with a minimum follow-up of 17 months were evaluated. The primary outcome of interest was Snellen BSCVA with a secondary outcome of topographic cylinder.

Results:

Patient 1 had undergone initial 8 mm diameter DALK, with residual keratometric astigmatism of nearly 12 diopters (D) postoperatively despite numerous astigmatic interventions, with a BSCVA of 6/60, before undergoing 9 mm diameter repeat modified DALK. After suture removal and subsequent in-the-wound blunt manual relaxing incisions, the patient had a final keratometric astigmatism of 3.5 D, manifest refraction of plano/−3.50 × 175, and a BSCVA of 6/9. Patient 2 had undergone initial 7.75 mm diameter DALK, with residual keratometric astigmatism of 10.5 D with a BSCVA of counting fingers. The patient underwent 9 mm repeat modified DALK with final residual keratometric astigmatism of 3.1 D after suture removal, manifest refraction of −1.00/−2.75 × 25, and BSCVA of 6/9.

Conclusions:

Wide diameter DALK (>9 mm) is effective in the management of conventional diameter DALK (≤8 mm) associated high astigmatism in keratoconus. Creation of a peripheral posterior stromal shoulder also allows safe further titration of residual astigmatism if needed.
National Early Warning Score Deployment in a Veterans Affairs Facility: A Quality Improvement Initiative and Analysis
Authors: Al-Kofahi Mejalli , Spicer Alexandra , Schaefer Richard S. , Uhl Andrea , Churpek Matthew , Govindan Sushant
Published: May 2023

Early warning scores are algorithms designed to identify clinical deterioration. Current literature is predominantly in non-Veteran populations. Studies in Veterans are lacking. This study was a prospective quality improvement project deploying and assessing the National Early Warning Score (NEWS) at Kansas City VA Medical Center. Performance of NEWS was assessed as follows: discrimination for predicting a composite outcome of intensive care unit transfer or mortality within 24 hours via area under the receiver operating curve. A total of 4781 Veterans with 142 375 NEWS values were included. The NEWS area under the receiver operating curve for the composite outcome was 0.72 (95% CI, 0.71-0.74), indicating acceptable predictive accuracy. A NEWS of ≥7 was more likely associated with the composite outcome versus <7 (13.6% vs 0.8%; P < 0.001). This is one of the first studies to demonstrate successful deployment of NEWS in a Veteran population, with resultant important implications across the Veterans Health Administration.
The Relationship Between Job Satisfaction and Faculty Turnover Among Physician Assistant Educators During the COVID-19 Pandemic
Authors: Lynch Shaun
Published: May 2023

Introduction

This research explored the relationship between job satisfaction and intent to leave among physician assistant (PA) educators during the COVID-19 pandemic. Additionally, the study aimed to identify differences in PA educators' job satisfaction within gender and their intention to stay at their current employment.

Methods

A nonexperimental, cross-sectional survey was conducted with 1788 PA educators at 232 accredited programs nationally. A Web-based survey was employed to measure job satisfaction and intent to leave and to collect demographic information. Descriptive statistics were used to describe the study population, and logistic regression was used to analyze the independent variables predicting faculty turnover.

Results

PA educators were generally satisfied with their jobs (51.2%, n = 251), with the nature of the work, quality of supervision, and collegial relationships contributing the most to job satisfaction. Males were generally more satisfied with their jobs than females. More than half of the PA educators (52.4%, n = 257) considered leaving academia in the past year. Job satisfaction (odds ratio [OR] = .945, 95% confidence interval [CI] = .936-.956) and individual facets—including the nature of the work (OR = .806, 95% CI = .731-.888); communication (OR = .926, 95% CI = .860-.997); and quality of supervision (OR = .904, 95% CI = .850-.960)—were predictive of intent to leave. Gender was not found to significantly affect the relationship between job satisfaction and intent to leave.

Discussion

The findings from the study suggest the need for faculty retention to be prioritized among program and institutional leadership. PA programs need experienced leadership to develop, guide, and mentor faculty. Lastly, program and institutional leadership should create a supportive work environment that communicates clear expectations.
Thinking Outside the Box: Advancing Clinical Education in an Era of Preceptor Shortage
Authors: Kayingo Gerald , Gordes Karen L. , Fleming Shani , Cawley James F.
Published: May 2023

The expansion of health professions educational programs has led to an acute shortage of available clinical training sites. Rapid growth in the number of medical schools, physician assistant (PA) programs, and advanced nurse practitioner (APRN) programs, all of which share a need for similar types of clinical training experiences, has increased competition for clinical training sites and placed new challenges on educational institutions. Solutions are urgently needed to increase the quantity and quality of supervised clinical practice experiences as well as to ensure diversity among preceptors and geographical clinical sites. This article identifies key barriers to securing sufficient clinical training sites, notes emerging trends, and presents potential innovations through stakeholder collaboration for enhancing clinical training across health professions.
Foundational Skill-Building in a Novel Well-being Curriculum
Authors: Neary Stephanie , Ruggeri Mary , Roman Christopher , Hoover Eve , Butaney Bhupin , Weller Indigo
Published: May 2023

Introduction

Mental illness and decreased well-being are pervasive throughout physician assistant (PA) training, and the accreditation standards require a wellness curriculum. The purpose of this study was to determine if a mandatory, multifaceted virtual wellness curriculum can mitigate the decline in well-being experienced by first-year PA students.

Methods

First-year PA students from 5 programs (n = 259) participated in a 16-week asynchronous virtual course. The course integrated evidence-based content on vulnerability and stigma, mindfulness and decentering, and reflective writing. Total weekly content averaged 30-60 minutes and was presented in multiple formats including recorded lectures and panels, readings, and discussion forums. Students completed anonymous pre- and postsurveys, and ordinary least squares (OLS) regression with a fixed effect for each school was used for data analysis.

Results

In total, 157 of 259 (60.6%) students completed both surveys with matching unique identifiers. The majority of students (73.6%; 134/182) thought this course had a positive impact on their training as a PA student. Baseline scores were significantly predictive of end-point scores for the PHLMS, OMS-HC-15, SSOSH, RPQ, and UCLA-3 (see Methods section for full names of surveys). Race was significantly predictive of PHLMS and OMS-HC-15 scores; age was significantly predictive of SSOSH scores; and gender was significantly predictive of RPQ scores.

Discussion

For a student with low baseline well-being who is entering a PA program, dedicated curricula focusing on foundational wellness skills can be successful in improving well-being. Future work is needed to more fully characterize the scope and extent of this program’s impact on PA learners. Additional efforts are also necessary to optimize the delivery and provide access to PA students nationwide.
Fall Prevention Care Management
Authors: Yoder Claire L. McKinley , Kyoshi-Teo Hiroko , Ochoa-Cosler Olivia
Published: May 2023

Background:

Accidental falls are common among older adults and may lead to devastating consequences. One promising approach to reduce falls is to engage older adults in fall risk reduction through care management.

Purpose:

This article describes the implementation by undergraduate nursing students of a 6-week interdisciplinary Fall Prevention Care Management (FPCM) intervention to improve the safety of older adults living in assisted living facilities.

Methods:

A secondary qualitative descriptive analysis of narrative visit notes was conducted using the Meyer et al taxonomy to characterize fall prevention interventions with older adults.

Results:

Individualized fall prevention interventions including motivational interviewing and care management supported clients' engagement with fall prevention by facilitating behavior change related to fall prevention, helping clients identify and reflect on meaning and/or perceptions related to fall prevention.

Conclusion:

The FPCM project was acceptable, facilitated high fall risk older adults' engagement with fall prevention, and yielded many positive outcomes.
Hyperferritinemia in Severe Dengue Infection: Single-Center Retrospective Cohort Study
Authors: Lakshmanan Chidhambharam , Ranjit Suchitra , Natraj Rajeswari , Venkatachalapathy Priyavarthini , Kumar Vasanth S. , Lum Lucy Chai See
Published: May 2023

OBJECTIVES:

Hyperferritinemia in the critical phase of dengue infections may correlate with severe dengue (sd) disease, and our primary objective was to examine the association between ferritin level on day 1 of PICU admission and 2009 World Health Organization (WHO) criteria for sd. Our secondary objective was outcome in relation to care. It is unclear whether immunomodulatory therapy during the critical phase may restore immune homeostasis and mitigate disease severity.

DESIGN, SETTING, AND PATIENTS:

Retrospective cohort study of children with dengue 1 month to 16 years old with admission ferritin greater than or equal to 500 ng/mL requiring PICU admission. Demographics, clinical, and laboratory parameters, presence of the 2009 WHO sd criteria and outcomes were analyzed. Immunomodulatory therapy was used when there was persistent hyperinflammation beyond the critical phase of plasma leakage.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Fifty-five patients were admitted in the critical phase of dengue with median (interquartile range) ferritin levels of 8,105 ng/mL (2,350–15,765 ng/mL). Patients with at least one WHO sd category had higher ferritin levels compared to those without any sd criteria, with the highest levels in eight patients with all three sd categories. In our cohort of 55, 52 patients (94%) recovered with standard supportive therapy. Recovery was associated with decreased ferritin levels that occurred in parallel with improved circulation and platelet counts; this included 22 of 24 patients with admission ferritin levels greater than or equal to 10,000 ng/mL and two with ferritin greater than 1,00,000 ng/mL. Immunomodulation was used in three patients with unremitting fever, persistent hyperferritinemia, and progressive multiple organ dysfunction beyond the critical phase, of whom two died.

CONCLUSIONS:

Hyperferritinemia in the critical phase of sd is associated with the number of 2009 WHO sd criteria present. Our data also indicate that many patients with sd recover well with supportive care.
Socioeconomic Inequalities and Predictors of Cardiac Rehabilitation Referral
Authors: Rocha José Afonso , Azevedo Luís F. , Freitas Alberto , Cardoso José Carlos S.
Published: May 2023

Objective

The aim of the study is to identify factors associated with cardiac rehabilitation referral after an acute coronary syndrome at a university hospital.

Design

We analyzed 2814 hospitalizations due to acute coronary syndrome between 2017 and 2019 in Centro Hospitalar São João. The hospital’s morbidity database was used to retrieve patient information. Cardiac rehabilitation referral and participation were identified from administrative databases and clinical records. Socioeconomic data were obtained from municipality of residence-level data rather than patient-specific data.

Results

Of 2814 hospitalizations, 72% (2028 cases) were eligible for cardiac rehabilitation. Mean age was 65.2 ± 13.4 yrs; 72% men, 33% diabetic, 57.1% hypertensive, and 63.6% dyslipidemic. Cardiac rehabilitation referral rate was low, at 18.8%, with 42 (11.0%) not attending cardiac rehabilitation and 39 (10.2%) dropping out. Females (odds ratio = 0.72 [95% confidence interval = 0.52–1.00]), older patients (odds ratio = 0.57 [0.42–0.77]; 55–64 vs. <55 yrs), and those coming from lower-income municipalities (odds ratio = 0.53 [0.41–0.69], below median vs. above median) with lower education level (odds ratio = 0.70 [0.54–0.92]; ≤4 vs. >4 yrs) were less likely to be referred to cardiac rehabilitation.

Conclusions

There is a need for new strategies to promote cardiac rehabilitation in disadvantaged groups, as sex, age, and socioeconomic inequities in access to cardiac rehabilitation remain unresolved.
Craniofacial Microsomia: New Updates in Spinal Anomalies
Authors: Gonçalves Ferraz Beatriz , Vendramini-Pittoli Siulan , Gomes Luiz Paulo , Madeira Brandão Michele , Alonso Nivaldo , Tonello Cristiano
Published: May 2023

Introduction:

Craniofacial microsomia (CFM) involves anomalies of the first and second pharyngeal arches, mainly of the mandible, maxilla, ears, and vertebral spine. This study aimed to identify the frequency and morphology of spinal anomalies of individuals with clinical diagnoses of CFM. In addition, the correlation between spinal anomalies and craniofacial involvement was performed.

Materials and Methods:

This study was a retrospective review of individuals with a clinical diagnosis of craniofacial microsomia. The inclusion criteria were a clinical diagnosis of CFM with no overlap with any other syndromes of first and second pharyngeal arches and radiograph availability in the hospital’s database. Prevalence and morphology of spinal anomalies were calculated and clinical details were recorded: types of spinal anomalies and correlations according to OMENS score.

Results:

The sample consisted of 46 individuals with a clinical diagnosis of CFM, 24 (52,2%) female and 22 (47,8%) male (1M:1F). Twenty-one (45,7%) had unilateral craniofacial involvement and 25 (54,3%), bilateral. Twenty-eight (60,9%) individuals presented spinal anomalies. Those with unaltered spinal morphology showed a slight preference toward OMENS scores under 5: 7 patients did, only one of which had spinal alterations (14,3%); 68,8% (22) in the group with scores 5 to 9 (n=32) and 71,4% (5) in the 10 to 15 group (n=7) did as well.

Discussion and conclusions:

Spinal anomalies in individuals with CFM are more common than usually reported in medical literature, mainly when associated with radial anomalies and correlate with statistical significance to facial features, mainly the OMENS score.
Current use and utility of magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, and pancreatic duct stents: A secondary analysis from the Western Trauma Association multicenter trials group on pancreatic injuries
Authors: Biffl Walter L. , Ball Chad G. , Moore Ernest E. , West Michaela , Russo Rachel M. , Balogh Zsolt J. , Kornblith Lucy , Castelo Matthew ,   the WTA Multicenter Trials Group on Pancreatic Injuries
Published: May 2023

INTRODUCTION

The single most important predictor of pancreas-specific complications (PSCs) after pancreatic trauma is injury to the main pancreatic duct (MPD). Pancreatography has been recommended to evaluate the integrity of the MPD. In addition, pancreatic duct stents have been proposed to prevent or treat PSC. The primary purpose of this study was to determine the accuracy of magnetic resonance cholangiopancreatography (MRCP) in diagnosing MPD injury. We further sought to determine whether stents were effective in preventing PSC or facilitated the resolution of pancreatic leaks or fistulae.

METHODS

A secondary analysis of a multicenter retrospective review of pancreatic injuries in patients 15 years and older from 2010 to 2018, focusing on patients who underwent MRCP or endoscopic retrograde cholangiopancreatography (ERCP), was performed. Final pancreatic injury grade was determined based on all available assessments, ultimately adjudicated by the site principal investigator. Data were analyzed using various statistical tests where appropriate.

RESULTS

Thirty-three centers reported on 1,243 patients. A total of 216 underwent pancreatography—137 had MRCP and 115 ERCP, with 36 having both. The sensitivity of MRCP for MPD injury was 37%, the specificity was 94%, the positive predictive value was 77%, and the negative predictive value was 73%. When compared with ERCP, MRCP findings were discordant in 64% of cases. Pancreatic stents were placed in 77 patients; 48 (62%) were to treat PSC, with no clear benefit. Twenty-nine had prophylactic stents placed. There did not appear to be benefit in reduced PSC compared with the entire study group or among patients with high-grade pancreatic injuries.

CONCLUSION

The accuracy of MRCP to evaluate the integrity of the MPD does not appear to be superior to computed tomography scan. Consequently, the results of MRCP should be interpreted with caution. The current data do not support prophylactic use of pancreatic stents; they should be studied in a prospective trial.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.