bluuebunny/crossref_metadata_2025 huggingface dataset:
High prevalence of Cryptococcal antigenemia using a finger-prick lateral flow assay in individuals with advanced HIV disease in Santarém Municipality, Brazilian Amazon Basin
Authors: Assy João Guilherme Pontes Lima , Said Renato do Carmo , Pinheiro Olivia Campos , Brandão Alisson dos Santos , Boulware David R , França Francisco Oscar de Siqueira , Vidal José Ernesto
Published: March 2021

There is scarce information about HIV-related cryptococcosis in the Brazilian Amazon basin where laboratory infrastructure is limited. The serum cryptococcal antigen (CrAg) lateral flow assay (LFA) has simplified diagnosis of cryptococcosis and is recommended for screening in advanced HIV disease. We evaluated the prevalence of cryptococcal antigenemia using finger-prick CrAg LFA in the Brazilian Amazon basin. We enrolled a prospective cohort of outpatients and hospitalized individuals with advanced HIV disease at two centers in Santarém Municipality, Northern Brazil. All individuals were > 18 years old with advanced HIV disease, regardless of antiretroviral therapy (ART) status and with no prior or current history of confirmed cryptococcal meningitis. We tested CrAg LFA on finger-prick whole blood using an exact volume transfer pipette. From August 2018 to October 2019, 104 individuals were enrolled (outpatients 62 [60%] and hospitalized 42 [40%]). Median age was 38 years (interquartile range [IQR] 30–46), and 84 (81%) were male. Sixty-five (63%) individuals were ART-naïve. Prevalence of finger-prick CrAg LFA-positive was 10.6%; 95% CI, 5.4 to 18.1%. Prevalence of finger-prick CrAg LFA-positive among individuals without neurological symptoms was 6.0%; 95% CI, 1.7–14.6%. The number needed to test to detect one CrAg-positive individual was 9.4 persons (95% CI, 5.5–18.5). Prevalence of cryptococcal antigenemia using finger-prick whole blood CrAg LFA was high. Point-of-care approach was important for the diagnosis and screening of cryptococcosis in resource-limited settings. Screening and preemptive therapy strategy should be urgently implemented in individuals with advanced HIV disease in the Brazilian Amazon basin.
Blandford–Znajek jets in galaxy formation simulations: method and implementation
Authors: Talbot Rosie Y , Bourne Martin A , Sijacki Debora
Published: March 2021

Jets launched by active galactic nuclei (AGN) are believed to play a significant role in shaping the properties of galaxies and provide an energetically viable mechanism through which galaxies can become quenched. Here, we present a novel AGN feedback model, which we have incorporated into the arepo code, that evolves the black hole mass and spin as the accretion flow proceeds through a thin α-disc that we self-consistently couple to a Blandford–Znajek jet. We apply our model to the central region of a typical radio-loud Seyfert galaxy embedded in a hot circumgalactic medium (CGM). We find that jets launched into high-pressure environments thermalize efficiently due to the formation of recollimation shocks and the vigorous instabilities that these shocks excite increase the efficiency of the mixing of CGM and jet material. The beams of more overpressured jets, however, are not as readily disrupted by instabilities so the majority of the momentum flux at the jet base is retained out to the head, where the jet terminates in a reverse shock. All jets entrain a significant amount of cold circumnuclear disc material that, while energetically insignificant, dominates the lobe mass together with the hot, entrained CGM material. The jet power evolves significantly due to effective self-regulation by the black hole, fed by secularly driven, intermittent mass flows. The direction of jets launched directly into the circumnuclear disc changes considerably due to effective Bardeen–Petterson torquing. Interestingly, these jets obliterate the innermost regions of the disc and drive large-scale, multiphase, turbulent, bipolar outflows.
A purine loop and the primer binding site are critical for the selective encapsidation of mouse mammary tumor virus genomic RNA by Pr77Gag
Authors: Chameettachal Akhil , Vivet-Boudou Valérie , Pitchai Fathima Nuzra Nagoor , Pillai Vineeta N , Ali Lizna Mohamed , Krishnan Anjana , Bernacchi Serena , Mustafa Farah , Marquet Roland , Rizvi Tahir A
Published: March 2021

Retroviral RNA genome (gRNA) harbors cis-acting sequences that facilitate its specific packaging from a pool of other viral and cellular RNAs by binding with high-affinity to the viral Gag protein during virus assembly. However, the molecular intricacies involved during selective gRNA packaging are poorly understood. Binding and footprinting assays on mouse mammary tumor virus (MMTV) gRNA with purified Pr77Gag along with in cell gRNA packaging study identified two Pr77Gag binding sites constituting critical, non-redundant packaging signals. These included: a purine loop in a bifurcated stem-loop containing the gRNA dimerization initiation site, and the primer binding site (PBS). Despite these sites being present on both unspliced and spliced RNAs, Pr77Gag specifically bound to unspliced RNA, since only that could adopt the native bifurcated stem–loop structure containing looped purines. These results map minimum structural elements required to initiate MMTV gRNA packaging, distinguishing features that are conserved amongst divergent retroviruses from those perhaps unique to MMTV. Unlike purine-rich motifs frequently associated with packaging signals, direct involvement of PBS in gRNA packaging has not been documented in retroviruses. These results enhance our understanding of retroviral gRNA packaging/assembly, making it not only a target for novel therapeutic interventions, but also development of safer gene therapy vectors.
A ribonuclease III involved in virulence of Mucorales fungi has evolved to cut exclusively single-stranded RNA
Authors: Cánovas-Márquez José Tomás , Falk Sebastian , Nicolás Francisco E , Padmanabhan Subramanian , Zapata-Pérez Rubén , Sánchez-Ferrer Álvaro , Navarro Eusebio , Garre Victoriano
Published: March 2021

Members of the ribonuclease III (RNase III) family regulate gene expression by processing double-stranded RNA (dsRNA). This family includes eukaryotic Dicer and Drosha enzymes that generate small dsRNAs in the RNA interference (RNAi) pathway. The fungus Mucor lusitanicus, which causes the deadly infection mucormycosis, has a complex RNAi system encompassing a non-canonical RNAi pathway (NCRIP) that regulates virulence by degrading specific mRNAs. In this pathway, Dicer function is replaced by R3B2, an atypical class I RNase III, and small single-stranded RNAs (ssRNAs) are produced instead of small dsRNA as Dicer-dependent RNAi pathways. Here, we show that R3B2 forms a homodimer that binds to ssRNA and dsRNA molecules, but exclusively cuts ssRNA, in contrast to all known RNase III. The dsRNA cleavage inability stems from its unusual RNase III domain (RIIID) because its replacement by a canonical RIIID allows dsRNA processing. A crystal structure of R3B2 RIIID resembles canonical RIIIDs, despite the low sequence conservation. However, the groove that accommodates dsRNA in canonical RNases III is narrower in the R3B2 homodimer, suggesting that this feature could be responsible for the cleavage specificity for ssRNA. Conservation of this activity in R3B2 proteins from other mucormycosis-causing Mucorales fungi indicates an early evolutionary acquisition.
Intraosseous Basivertebral Nerve Radiofrequency Ablation for the Treatment of Vertebral Body Endplate Low Back Pain: Current Evidence and Future Directions
Authors: Michalik Adam , Conger Aaron , Smuck Matthew , Maus Timothy P , McCormick Zachary L
Published: March 2021

Recently, basivertebral nerve (BVN) radiofrequency ablation has been developed for the treatment of chronic low back pain (CLBP) thought to arise from the vertebral body endplates (VEPs). This review describes the relevant neuroanatomy and pathobiology of VEP degeneration and injury, imaging correlates of presumed VEP pain, randomized controlled trials performed, appropriate patient selection, and safety. Anatomic, histological, and clinical evidence supports the concept of the VEP as a source of CLBP and the nociceptive role of the BVN. BVN radiofrequency ablation appears to be an effective treatment for a subset of patients with CLBP and evidence of Modic change types 1 and 2 in the L3 to S1 VEPs who have failed to respond to conservative treatment. However, all studies performed to date have been industry sponsored, and future non–industry-funded trials will be needed to confirm these results.
Quantum Gravity and Mereology: Not So Simple
Authors: Baron Sam , Le Bihan Baptiste
Published: March 2021

A number of philosophers have argued in favour of extended simples on the grounds that they are needed by fundamental physics. The arguments typically appeal to theories of quantum gravity. To date, the argument in favour of extended simples has ignored the fact that the very existence of spacetime is put under pressure by quantum gravity. We thus consider the case for extended simples in the context of different views on the existence of spacetime. We show that the case for extended simples based on physics is far more complex than has been previously thought. We present and then map this complexity, in order to present a much more textured picture of the argument for extended simples.
Exposure to mosquito coil and biomass fuel smoke and respiratory health in rural Tamil Nadu, India
Authors: Rao Sudha Ramachandra , Chitra Grace A , Elavarasu G , Kamaraj P , Kaliaperumal Kanagasabai , Kaur Prabhdeep
Published: March 2021

Background

Mosquito coil smoke, along with biomass fuel smoke, are sources of indoor air pollution. Biomass fuel smoke has been studied as a risk factor for poor respiratory outcomes. However, in an Indian context, few studies examine the effect of mosquito coil exposure on poor respiratory outcomes at the community level.

Objectives

To estimate the prevalence of the biomass fuel and mosquito coil use and to determine the association between the use of bio-mass fuel and mosquito coil and poor respiratory health.

Methods

A cross-sectional survey of 4662 individuals (above the age of 30 years) was conducted using a pre-tested questionnaire. Trained interviewers collected data on current and past use of biomass fuels and mosquito coils, usage practices and respiratory health. We computed proportions for exposure variables namely biomass fuel, mosquito coil use and other covariates. We conducted univariate analysis, followed by multivariate logistic regression.

Results

The prevalence of ever use of biomass fuels was high (wood: 97.9%; cow dung cake: 76.0% and crop residue: 54.4%). Current use of wood, cow dung cake and crop residue was prevalent among 75.7, 24.3 and 30.9% respondents, respectively. Almost 70% of respondents had ever used mosquito coils, whereas 54% were current users. Overall, 5.5% respondents had poor respiratory health either due to chronic bronchitis or asthma. In multivariate analysis, use of combination of all three biomass fuel types (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI]: 1.13–2.54) and use of mosquito coil more than or equal to 5 days per week (AOR 1.43, 95% CI: 1.04–1.99) were associated with poor respiratory health after adjusting for covariates age, gender, smoking, kitchen type and for each other.

Conclusions

Use of biomass fuels and mosquito coils was high in the study population and was associated with poor respiratory health. Therefore, mosquito coil smoke should also be considered an important source of indoor air pollution, similar to biomass fuel exposure. Community education about these sources of indoor air pollution and increased coverage of cleaner fuels and alternative mosquito control methods should be the way forward in the rural areas.
Forced vital capacity predicts the survival of interstitial lung disease in anti-MDA5 positive dermatomyositis: a multi-centre cohort study
Authors: Wu Wanlong , Xu Wenwen , Sun Wenjia , Zhang Danting , Zhao Jiangfeng , Luo Qun , Wang Xiaodong , Zhu Feng , Zheng Yu , Xue Yu , Wan Weiguo , Wu Huaxiang , Han Qian , Ye Shuang
Published: March 2021

Objectives

Anti-melanoma differentiation-associated gene 5 (MDA5) positive DM is a life-threatening disease often complicated with rapidly progressive interstitial lung disease (ILD). This study aimed to establish and validate a clinical prediction model for 6-month all-cause mortality in Chinese patients with anti-MDA5 positive DM-ILD.

Methods

We conducted a retrospective observational study using a single-centre derivation cohort and a multicentre validation cohort. Hospitalized DM patients with positive anti-MDA5 antibody and ILD course ≤3 months on admission were included. Patients’ baseline characteristics were described and compared between the deceased and survivors by univariable Cox regression. Optimal cut-off values were defined by the ‘survminer’ R package for significant continuous variables. Independent prognostic factors were determined by the final multivariable Cox regression model chosen by backward stepwise algorithm, which could be reproduced in both cohorts. The Kaplan–Meier survival analyses based on the derived predictor were conducted.

Results

A total of 184 and 81 eligible patients were included with a cumulative 40.8 and 40.7% 6-month mortality in the derivation and validation cohorts, respectively. Based on multivariable Cox regression, the prognostic factor at baseline was identified and validated as three-category forced vital capacity (FVC)%: FVC% ≥50%, FVC% <50%, unable to perform. This significantly distinguishes three risk stages with mortalities of 15.3, 46.8, 97.4% in the derivation cohort, and 14.9, 58.3, 86.4 in the validation cohort, respectively (all P <0.05).

Conclusion

The validated FVC%-based categorical predictor in anti-MDA5 positive DM-ILD is helpful for risk stratification in clinical practice and might facilitate cohort enrichment for future trials.
Isolation, Characterization, and Genomic Investigation of a Phytopathogenic Strain ofStenotrophomonas maltophilia
Authors: Hu Ming , Li Chuhao , Xue Yang , Hu Anqun , Chen Shanshan , Chen Yufan , Lu Guangtao , Zhou Xiaofan , Zhou Jianuan
Published: March 2021

Stenotrophomonas maltophilia is ubiquitous in diverse environmental habitats. It merits significant concern because of its increasing incidence of nosocomial and community-acquired infection in immunocompromised patients and multiple drug resistance. It is rarely reported as a phytopathogen except in causing white stripe disease of rice in India and postharvest fruit rot of Lanzhou lily. For this study, Dickeya zeae and S. maltophilia strains were simultaneously isolated from soft rot leaves of Clivia miniata in Guangzhou, China, and were both demonstrated to be pathogenic to the host. Compared with the D. zeae strains, S. maltophilia strains propagated faster for greater growth in lysogeny broth medium and produced no cellulases or polygalacturonases, but did produce more proteases and fewer extracellular polysaccharides. Furthermore, S. maltophilia strains swam and swarmed dramatically less on semisolid media, but formed a great many more biofilms. Both D. zeae and S. maltophilia strains isolated from clivia caused rot symptoms on other monocot hosts, but not on dicots. Similar to previously reported S. maltophilia strains isolated from other sources, the strain JZL8 survived under many antibiotic stresses. The complete genome sequence of S. maltophilia strain JZL8 consists of a chromosome of 4,635,432 bp without a plasmid. Pan-genome analysis of JZL8 and 180 other S. maltophilia strains identified 50 genes that are unique to JZL8, seven of which implicate JZL8 as the potential pathogen contributor in plants. JZL8 also contains three copies of Type I Secretion System machinery; this is likely responsible for its greater production of proteases. Findings from this study extend our knowledge on the host range of S. maltophilia and provide insight into the phenotypic and genetic features underlying the plant pathogenicity of JZL8.
Recognizing the importance of whistleblowers in healthcare
Authors: O'Neill Nicolle
Published: March 2021

Healthcare professionals who raise concerns about workplace safety or other problems should be praised as heroes and changemakers. However, some whistleblowers face retaliation for speaking out, and the incidence of retaliation cases against these employees has spiked during the COVID-19 pandemic. This article reflects on the role of whistleblowers and their importance to public accountability.
Educational Studies Examining Knowledge of Substance Use Disorders and Career Aspirations Among Medical Trainees in an Inner-City Hospital
Authors: Gooding Luke , Hamilton Michee-Ana , Dong Huiru , Wood Evan , Cullen Walter , Fairbairn Nadia , Nolan Seonaid , Klimas Jan
Published: March 2021

Objectives:

Gaps in addiction medicine training are a reason for poor substance use care in North America. Hospital addiction medicine consult services (AMCS) provide critical medical services, including screening and treatment of substance use disorders. Although these programs often feature an educational component for medical learners, the impact of AMCS teaching on objective knowledge and career aspirations in addiction medicine has not been well described.

Methods:

The authors report findings from two sequential studies conducted at a large academic hospital in Vancouver, Canada. The first study assessed the impact of an AMCS clinical rotation on medical trainee addiction medicine objective knowledge using an online survey of 6 true/false questions before and after the rotation. The second study examined the impact of an AMCS rotation on career aspirations using 4 seven-point Likert-type questions. One-sample t tests on mean differences (MD) with Benjamini-Hochberg adjustment for multiple comparisons were employed for statistical analyses.

Results:

Between May 2017 and June 2018, knowledge scores were significantly higher postrotation (MD = 4.78, standard deviation [SD] = 19.5, P = 0.034) among 115 medical trainees. Between July 2018 and July 2019, aspirations to practice addiction medicine were significantly more favorable postrotation (MD = 3.48, SD = 3.15, P < 0.001) among 101 medical trainees.

Conclusions:

AMCS rotations appear to improve addiction medicine knowledge and aspirations to practice addiction medicine among medical trainees. Larger-scale evaluations and outcomes research on integrating substance use disorders teaching in these settings will help move the discipline forward.
The Effects of Early Onset Tranquilizers, Sedatives, and Sleeping Pills Use on Recent Consumption Among Adolescents
Authors: Cobo Beatriz , Pulido José , Pascual Sara , Sáiz Ana , Carrasco-Garrido Pilar , Carabantes-Alarcón David , Sordo Luis
Published: March 2021

Background:

Adolescents’ consumption of tranquilizers, sedatives, and sleeping pills (TSSp) has increased during the last few decades, and TSSp are currently among the substances with the lowest age-of-onset. We characterized current-use patterns of TSSp consumers by age when first taken.

Methods:

This study used individualized secondary data retrieved from the 2016 Spanish State Survey on Drug Use in Secondary Education (16–18-year-olds), and included all subjects who reported having taken TSSp at any point, but excluded those who had started during the previous year (n = 1502). Logistic regression models were used to obtain adjusted odds ratios (aOR) for associations between early TSSp consumption (<14 years) and current TSSp use patterns, adjusted for sociodemographic factors.

Results:

About 17.9% of respondents had taken TSSp (average age-of-onset = 13.7) and 45% of these without a prescription. TSSp consumption at <14 years was higher for males and nonrepeaters. Having begun to use TSSp < 14 years was associated with both higher probability of consumption in the last month (aOR = 1.41; 95%CI:1.12–1.77) and daily/almost daily consumption in the last month (aOR = 1.56; 95CI%:1.16–2.08).

Conclusions:

The results of this study show there is a high proportion of 16 to 18 TSSp student consumers – both prescribed and nonprescribed; it also establishes that early onset-of-use is associated with higher levels of intensive use later on.
Immune Checkpoint Inhibitor–related Guillain-Barré Syndrome: A Case Series and Review of the Literature
Authors: Janssen Jorien B.E. , Leow Theresa Y.S. , Herbschleb Karin H. , Gijtenbeek Johanna M.M. , Boers-Sonderen Marye J. , Gerritsen Winald R. , Westdorp Harm
Published: March 2021

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of various malignancies with promising clinical outcomes. Treatment can, however, be accompanied by serious immune-related adverse events. Neurological adverse events like Guillain-Barré syndrome (GBS) are rare but potentially life-threatening. We present 3 cases of ICI-related GBS; review cases described in current literature, and discuss treatment strategies. Three patients developed GBS after ICI treatment. The first case with pembrolizumab had a fatal outcome despite treatment with multiple regimens, including steroids and intravenous immunoglobulin (IVIg). The other 2 cases with nivolumab-induced and pembrolizumab-induced GBS, respectively, responded well to treatment with IVIg and steroids. In the current literature, a total of 31 other cases were found. Treatment for ICI-related GBS mostly consisted of concurrent IVIg and steroids (44%), which led to clinical improvement in 73%. Most patients recovered with remaining symptoms (68%), while 10 patients developed respiratory failure (29%) and 6 patients (18%) died. ICI-related GBS should be suspected in patients on ICI treatment who develop subacute progressive weakness of the limbs, sensory loss, and areflexia. On the basis of the guidelines recommendations and our review of the literature, we advise first-line therapy with concurrent IVIg 0.4 g/kg/d for 5 days and prednisolone 1–2 mg/kg/d. Discontinuation of immunotherapy after ICI-related GBS is advised.
Mitochondrial Disruption Is Involved in the Effect of Nuclear Factor of Activated T cells, Cytoplasmic 4 on Aggravating Cardiomyocyte Hypertrophy
Authors: Liu Xueping , Gao Si , Gao Hui , Jiang Xudong , Wei Qiqiu
Published: March 2021

Nuclear factor of activated T cells, cytoplasmic 4 (NFATc4), a nuclear transcription factor, has been implicated in cardiac hypertrophy through the enhancement of hypertrophic gene expression. However, the role of NFATc4 in mitochondrial modulation is mostly unknown. The current study aimed to investigate the role of NFATc4 in regulating mitochondrial function during phenylephrine (PE)-induced cardiac hypertrophy. Our results showed that overexpression of NFATc4 aggravated the PE-induced decrease in mitochondrial genesis, membrane potential, and mitochondrial gene expression as well as impaired mitochondrial respiration. However, knockdown of NFATc4 relieved PE-induced perturbations in mitochondria and cardiomyocyte hypertrophy. Mechanistically, by activating phosphoinositide-dependent kinase 1 and promoting a combination of AKT and phosphoinositide-dependent kinase 1, phosphorylation and sequential acetylation of PGC-1α were aggravated by NFATc4 and suppressed the activity of PGC-1α. In conclusion, NFATc4-regulated factors were shown to be associated with mitochondrial function and exacerbated PE-induced mitochondrial dysfunction. These findings revealed new roles of NFATc4 in cardiac hypertrophy.
Influence of Lipid Excipients on Platelet Function and the Pharmacodynamic Effects of Aspirin
Authors: Schneider David J. , Taatjes-Sommer Heidi S. , Prats Jayne , Deliargyris Efthymios N.
Published: March 2021

The combination of pharmaceutical lipid excipients with aspirin in a novel liquid oral formulation (Vazalore) limits gastrointestinal toxicity of aspirin. This study was performed to determine whether the lipid excipients influence the pharmacodynamic effects of aspirin and whether the excipients directly affect platelet function. The pharmacodynamic effects of aspirin were assessed over a range of concentrations designed to exert limited to maximal inhibition of cyclooxygenase-1 (COX1) necessary for thromboxane A2 production. Platelet aggregation induced by arachidonic acid and assessed with the use of light transmission aggregometry was used as a direct measure of the inhibition of COX1 by aspirin. Flow cytometry was used to assess the direct effect of excipients on platelet function. Twice the ratio of lipid excipient to aspirin used in the formulation of the novel oral agent was used. Blood was taken from 20 healthy subjects and anticoagulated with trisodium citrate (3.2%, 1:10 vol/vol). Aspirin and excipients were added in vitro and incubated for 10 minutes before performance of light transmission aggregometry and flow cytometry. The excipients did not limit the pharmacodynamic effects of aspirin. When the extent of inhibition of platelet aggregation was limited, the excipients tended to enhance pharmacodynamic effects. The excipients did not activate platelets in the absence of agonist and did not alter activation of platelets in response to adenosine diphosphate, arachidonic acid, thrombin, or convulxin (a collagen mimetic). Lipid excipients used in an oral formulation of aspirin do not impair the pharmacodynamic effects of aspirin and do not alter platelet function.
Integrated metagenome and metabolome analyses of blood pressure studies in early postmenopausal Chinese women
Authors: Liu Hui-Min , Lin Xu , Meng Xiang-He , Zhao Qi , Shen Jie , Xiao Hong-Mei , Deng Hong-Wen
Published: March 2021

Objective:

We carried out sensitivity analyses on gut microbiota metagenomic sequencing, untargeted metabolome, targeted metabolome for short-chain fatty acids (SCFAs) and human whole genome sequencing from 402 early postmenopausal Chinese women to search for early omics-biomarkers and gain novel insights into the potential mechanisms of BP regulation in postmenopausal women.

Methods:

Clusters of co-abundant gut bacterial species and serum untargeted metabolites were identified by weighted gene co-expression network analysis (WGCNA). Partial least square analysis and joint analysis were performed to detect BP-associated omics-variables. Partial Pearson correlation was conducted to identify the interactions of microbe--host for host BP variation. Mendelian randomization analysis and causal inference test were used to examine causal relationships among gut microbiota, metabolites and BP variation.

Results:

In the present study, 651 bacterial species and 296 metabolites were binned into 53 and 26 co-abundance clusters by WGCNA, respectively. Then, we totally identified four gut bacterial species, one host metabolites and two SCFAs that were significantly associated with both SBP and DBP. Moreover, we found that gut microbiota would play important roles in host metabolic activity. Finally, our results revealed that increased Bacteroides fragilis could elevate BP via decreased caproic acid, and phenylacetylglutamine mediated the causal relationships of both B. fragilis and Clostridium sp.CAG.226 on DBP variation.

Conclusion:

Multi-omics datasets integration has the potential to capture complementary effect and their interactions for BP variation, revealed the potential pathogenesis of BP variation and may be useful for studying other complex diseases/traits.
SUCCESSFUL INTERVENTIONS TO IMPROVE EFFICIENCY AND REDUCE PATIENT VISIT DURATION IN A RETINA PRACTICE
Authors: Lin Charles C. , Li Angela S. , Ma Hung , Lin Xiao Mei , Olivares Montserrat Z. , Haubrich Anna , Sanislo Steven , Do Diana V.
Published: March 2021

Purpose:

To reduce the total clinic visit duration among retina providers in an academic ophthalmology department.

Methods:

All patient encounters across all providers in the department were analyzed to determine baseline clinic visit duration time, defined as the elapsed time between appointment time and checkout. To increase photography capacity, a major bottleneck identified through root cause analysis, four interventions were implemented: training ophthalmic technicians to perform fundus photography in addition to optical coherence tomographies, relocating photography equipment to be adjacent to examination rooms, procuring three additional Optos widefield retinal photography units, and shifting staff schedules to better align with that of the providers. These interventions were implemented in the clinics of two retina providers.

Results:

The average baseline visit duration for all patients across all providers was 87 minutes (19,550 patient visits). The previous average visit duration was 80 minutes for Provider 1 (557 patient visits) and 81 minutes for Provider 2 (1,246 patient visits). In the 4 weeks after interventions were implemented, the average visit duration decreased to 60 minutes for Provider 1 and 57 minutes for Provider 2.

Conclusion:

A systematic approach and a multidisciplinary team resulted in targeted, cost-effective interventions that reduced total visit durations.
Spontaneous Deflation of the Big Bubble: A New Complication in Big Bubble Deep Anterior Lamellar Keratoplasty
Authors: Fogla Rajesh , Gujar Prateek
Published: March 2021

Purpose:

To report a new complication of spontaneous deflation of type 1 big bubble (BB) in deep anterior lamellar keratoplasty (DALK).

Methods:

This is a retrospective review of the surgical videos of BB DALK in 2 cases of advanced keratoconus, wherein spontaneous deflation of type 1 big bubble was noted after removal of air injection cannula. Surgical management and visual outcomes were noted.

Results:

After spontaneous deflation of the BB, the first case was managed using a layer-by-layer dissection of the residual posterior stroma to expose pre-Descemet layer. In the second case, a paracentesis was performed to lower intraocular pressure along with reinflation of the type 1 BB, which was followed by standard surgical steps of BB DALK. Both cases accomplished good visual outcome in the postoperative period. Retrospective analysis of the surgical videos revealed possible mechanism of spontaneous deflation.

Conclusions:

Spontaneous deflation of type 1 BB can occur after removal of the air injection cannula during DALK, especially in eyes with advanced keratoconus and thin corneas. This complication can be successfully managed without compromising the final visual outcome.
Rapid Expansion of the Airway Response Team to Meet the Needs of the COVID-19 Pandemic
Authors: Walsh Elisa C. , Kwo Jean , Chang Marvin G. , Pino Richard M. , Bittner Edward A.
Published: March 2021

Introduction:

The COVID-19 pandemic has brought unprecedented numbers of patients with acute respiratory distress to medical centers. Hospital systems require rapid adaptation to respond to the increased demand for airway management while ensuring high quality patient care and provider safety. There is limited literature detailing successful system-level approaches to adapt to the surge of COVID-19 patients requiring airway management.

Methods:

A deliberate system-level approach was used to expand a preexisting airway response service. Through a needs analysis (taking into account both existing resources and anticipated demands), we established priorities and solutions for the airway management challenges encountered during the pandemic.

Results:

During our COVID-19 surge (March 10, 2020, through May 26, 2020), there were 619 airway consults, and the COVID airway response team (CART) performed 341 intubations. Despite a 4-fold increase in intubations during the surge, there was no increase in cardiac arrests or surgical airways and no documented COVID-19 infections among the CART.

Conclusions:

Our system-level approach successfully met the sudden escalation in demand in airway management incurred by the COVID-19 surge. The approach that addressed staffing needs prioritized provider protection and enhanced quality and safety monitoring may be adaptable to other institutions.
The Impact of Organizational Support on Practice Outcomes in Nurse Practitioners in Taiwan
Authors: HO Li-Hui , CHANG Shu-Chen , KAU Kevin , SHIU Shu-Ying , HUANG Sheng-Shiung , WANG Ya-Jung , TSAY Shiow-Luan
Published: March 2021

Background

Nurse practitioners (NPs) in Taiwan have practiced mainly in acute care hospitals since 2006. Although organizational support and level of support have been associated with the successful integration of NP roles and effective practice outcomes, organizational support in the context of NPs in inpatient settings is an area that has been rarely explored in the literature.

Purpose

The purpose of this study was to investigate the relationship between organizational support and the practice outcomes of job satisfaction, care effectiveness, and intention to leave in NPs.

Methods

A national survey of 512 NPs was conducted that included a demographic characteristics datasheet, the Nurse Practitioner Primary Care Organizational Climate Questionnaire, the Misener Nurse Practitioner Job Satisfaction Scale, and the Nurse Practitioner Care Effectiveness Scale. Multiple regression analysis was applied to explore the specific factors associated with job satisfaction. The statistical significance level was set at .05 with a two-tailed test. All statistical analyses were conducted using SPSS Statistics Version 22.0 software.

Results

More than half of the participants were found to be dissatisfied with their hospital managers (54.8%) and with each dimension of organizational support. Overall, 82.1% of the participants were satisfied with their current practice. A multiple regression analysis showed that the participants who perceived higher levels of organizational support in the workplace (β = .53, p < .001), expressed satisfaction with working with their managers (β = .25, p < .001), or perceived better care outcomes (β = .10, p < .001) reported higher job satisfaction. In addition, the participants who expressed intention to leave within 1 year (β = −.09, p < .001) and those with higher patient loads (β = −.09, p < .001) reported lower job satisfaction. Organizational support was found to explain 50% of the variance in job satisfaction.

Conclusions/Implications for Practice

The results of this study highlight organizational support as the most important factor affecting job satisfaction in NPs. Therefore, administrators work to promote organizational support and improve the work environment to enhance the job satisfaction, increase the clinical practice retention, and improve the care outcomes of NPs.
The role of bariatric surgery in the management of nonalcoholic steatohepatitis
Authors: Seymour Keri A. , Abdelmalek Manal F.
Published: March 2021

Purpose of review

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States and increasing globally. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), can lead to cirrhosis and complications of end-stage liver disease. No FDA-approved therapy for NAFLD/NASH exists. Treatment of NAFLD/NASH includes effective and sustained life-style modification and weight loss. This review reports on the recent findings of bariatric surgery in the management of NASH.

Recent findings

NAFLD, at all stages, is common in those who meet indication for bariatric surgery. Bariatric surgery resolves NAFLD/NASH and reverses early stages of fibrosis. Although randomized controlled trials of bariatric surgery in NASH are infeasible, studies defining the metabolic changes induced by bariatric surgery, and their effect on NASH, provide insight for plausible pharmacologic targets for the nonsurgical treatment of NASH.

Resolution of NASH and fibrosis regression can occur after bariatric surgery. Although the exact mechanism(s) underlying the improvement of NASH and hepatic fibrosis following bariatric surgery is not fully elucidated, emerging data on this topic is vitally important for lending insight into the pharmacotherapies for NASH for patients who are not otherwise suitable candidates for bariatric surgery.
Advances in cirrhotic cardiomyopathy
Authors: Liu Hongqun , Yoon Ki Tae , Zhang Jing , Lee Samuel S.
Published: March 2021

Purpose of review

Cirrhotic cardiomyopathy (CCM) is a well-recognized entity. When patients with CCM encounter challenges such as liver transplantation, overt cardiac dysfunction manifests, leading to morbidity and mortality. Although revised diagnostic criteria for CCM have recently been proposed, these still need to be validated.

Recent findings

Previous reviews have summarized the mechanisms of CCM, such as abnormalities of the β-adrenergic pathway, cardiac plasma membrane biophysical and biochemical properties, and electrophysiological changes. Cardiomyocyte apoptosis, inflammation, and oxidative stress also play important roles. The present review details further mechanisms of CCM, which include myosin heavy chain isoform shifts and abnormalities in cellular calcium transients. Additionally, we review recent studies on therapeutic strategies. Recent work underscores the importance of CCM in the natural history of the immediate and medium-term postoperative period after liver transplantation. Appropriate management strategies for CCM remain the area of greatest unmet need, requiring much further research.

CCM is a clinically relevant syndrome affecting patients with cirrhosis, leading to increased morbidity and mortality. New diagnostic criteria have been recently proposed by an expert working group. The pathogenic mechanisms remain incompletely clarified and optimal management strategies need much further study.
Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST)
Authors: Castillon Marine , Kammerer-Jacquet Solène-Florence , Cariou Mélanie , Costa Sebastian , Conq Gwenael , Samaison Laura , Douet-Guilbert Nathalie , Marcorelles Pascale , Doucet Laurent , Uguen Arnaud
Published: March 2021

Tyrosine kinase inhibitors have revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Nevertheless, some GISTs do not contain any targetable KIT or PDGFRA mutations classically encountered in this field. Novel approved therapies targeting TRK chimeric proteins products of NTRK genes fusions consist in a promising approach to treat some patients with GISTs lacking any identified driver oncogenic mutation in KIT, PDGFRA or BRAF genes. Thus, an adequate testing strategy permitting to diagnose the rare NTRK-rearranged GISTs is required. In this work, we studied about the performances of pan-TRK immunohistochemistry (IHC) and NTRK1/2/3 fluorescent in situ hybridization in a series of 39 GISTs samples. Among 22 patients with GISTs lacking KIT or PDGFRA mutations, BRAFV600E IHC permitted to diagnose 2/22 (9%) BRAFV600E-mutated GISTs and, among the 20 KIT, PDGFRA, and BRAF wild type tumors, 1/20 (5%), NTRK3-rearranged tumor was diagnosed using NTRK3 fluorescent in situ hybridization. Pan-TRK IHC using EPR17341 and A7H6R clones was negative in this NTRK3-rearranged sample. Pan-TRK IHC was frequently positive in NTRK not rearranged tumors without (24 samples analyzed) or with (15 samples analyzed) KIT or PDGFRA mutations with major discrepancies between the 2 IHC clones (intraclass correlation coefficient of 0.3042). Given the new therapeutic opportunity offered by anti-TRK targeted therapies to treat patients with advanced cancers including GISTs, it is worth to extend molecular analysis to NTRK fusions testing in KIT, PDGFRA, and BRAF wild type GISTs. Pan-TRK IHC appears not relevant in this field but performing a simple NTRK3 fluorescent in situ hybridization test consists in a valuable approach to identify the rare NTRK3-rearranged GISTs treatable using anti-TRK therapies.
Atypical Endometrial Hyperplasia, Low-grade
Authors: D’Angelo Emanuela , Espinosa Iñigo , Cipriani Valentina , Szafranska Justyna , Barbareschi Mattia , Prat Jaime
Published: March 2021

Atypical endometrial hyperplasia (AEH) is considered a precursor of endometrioid carcinoma. The 2020 World Health Organization (WHO) classification divides endometrial hyperplasia into 2 categories: hyperplasia without atypia and atypical hyperplasia/endometrioid intraepithelial neoplasia (EIN); however, this classification does not consider the degree of nuclear atypia. We graded nuclear atypia for estimating the risk of finding carcinoma at hysterectomy. Also, we investigated genes involved in endometrial carcinogenesis including mismatch repair (MMR) genes and ARID1A, PIK3CA, PTEN, KRAS, and CTNNB1. We reviewed 79 biopsies of AEH from 79 patients who underwent hysterectomy within a 1-year interval. Intraobserver and interobserver agreement of grading nuclear atypia and the relationship between the grade of nuclear atypia at biopsy and the findings at hysterectomy were evaluated. Immunohistochemistry for MMR status was performed in all cases and targeted sequencing in 11. Using low-grade versus high-grade nuclear atypia, κ values ranged from 0.74 to 0.91 (89% to 96%) and from 0.72 to 0.81 (87% to 91%) for the intraobserver and the interobserver agreement, respectively. The degree of nuclear atypia at biopsy was highly predictive of the findings at hysterectomy (P=1.6×10−15). Of 53 patients with low-grade AEH, none had carcinoma at hysterectomy, whereas 6 (6/26; 23%) with high-grade AEH in the biopsy also had high-grade AEH in the uterus and 16 (16/26; 61%) had FIGO grade 1 carcinoma. MMR deficiency was found in 3 of the 79 patients. None of the genes showed a mutational load significantly associated with the degree of nuclear atypia. In summary, our data show high reproducibility within and between observers for the diagnosis of low-grade and high-grade AEH. Most cases of AEH had low-grade nuclear atypia and neither high-grade AEH nor carcinoma was encountered in the corresponding hysterectomy specimens.
Sir Thomas Walter Bannerman Kibble. 23 December 1932—2 June 2016
Authors: Duff M. J. , Stelle K. S.
Published: March 2021

Professor Tom Kibble was an internationally-renowned theoretical physicist whose contributions to theoretical physics range from the theory of elementary particles to modern early-Universe cosmology. The unifying theme behind all his work is the theory of non-abelian gauge theories, the Yang–Mills extension of electromagnetism. One of Kibble's most important pieces of work in this area was his study of the symmetry-breaking mechanism whereby the force-carrying vector particles in the theory can acquire a mass accompanied by the appearance of a massive scalar boson. This idea, put forward independently by Brout and Englert, by Higgs, and by Guralnik, Hagen and Kibble in 1964, and generalized by Kibble in 1967, lies at the heart of the Standard Model and all modern unified theories of fundamental particles. It was vindicated in 2012 by the discovery of the Higgs boson at CERN. According to Nobel Laureate Steven Weinberg: ‘Tom Kibble showed us why light is massless’; this is the fundamental basis of electromagnetism.
Evaluating the clinical performance of a novel dual-target stool DNA test for colorectal cancer detection
Authors: Wang Zhongxin , shang Jian , Zhang Guannan , Kong Lingjun , Zhang Feng , Guo Ye , Dou Yaling , Lin Jun
Published: March 2021

BACKGROUND AND AIMS

Methylation-based stool DNA test showed a promising application for colorectal cancer (CRC) detection. This study aimed to evaluate the performance of a novel dual-target stool DNA test (DT-sDNA), composed of SDC2 and TFPI2, for the detection of CRC in clinical practice by using large-scale data from a multicenter clinical trial.

METHODS

We enrolled 1,164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases and 300 healthy controls. Their stool samples were collected and tested paralleled by DT-sDNA test under the guidance of standard operating procedure. All participants were dichotomized as positive and negative according to the cycling threshold (Ct) values measured by quantitative methylation-specific PCR (MSP). The diagnostic performance of DT-sDNA test was assessed by calculating indexes of sensitivity, specificity, and overall coincidence rate. Sanger sequencing and retesting of resected participants were performed to verify the accuracy and effectiveness of the test.

RESULTS

Overall, the sensitivity, specificity, and total coincidence rate of DT-sDNA test for CRC detection were 95.31%, 88.39%, and 90.29%, respectively, with the kappa value of 0.775 (P < 0.05) when comparing to non-CRCs. The sensitivities for the detection of advanced adenomas (n=38) and non-advanced adenomas (n=110) were 63.16% and 33.64%, and the specificity was 96.67% for healthy normal controls. The methylation status of SDC2 and TFPI2 in 375 samples were verified by Sanger sequencing and the average coincidence rate reached 99.62%. The coincidence rate was 94.12% (n=32) for 34 participants that undertook DT-sDNA test again after surgical resection. These results demonstrated high accuracy of the DT-sDNA test in discriminating CRCs from other diseases and healthy controls.

CONCLUSIONS

The novel DT-sDNA test showed good performance for the diagnosis of colorectal cancer in clinical practice; fda.hubei.gov.cn number; 20190020787.
Past SARS-CoV-2 infection elicits a strong immune response after a single vaccine dose
Authors: Chahla Rossana Elena , Hernán Tomas-Grau Rodrigo , Inés Cazorla Silvia , Ploper Diego , Pingitore Esteban Vera , López Mónica Aguilar , Aznar Patricia , Alcorta Malena , del Mar Vélez Eva María , Stagnetto Agustín , Ávila César Luís , Maldonado-Galdeano Carolina , Benjamín Socias Sergio , Heinze Dar , Navarro Silvia Adriana , Llapur Conrado , Costas Dardo , Flores Isolina , Apfelbaum Gabriela , Mostoslavsky Raúl , Mostoslavsky Gustavo , Perdigón Gabriela , Chehín Rosana Nieves
Published: March 2021

We hypothesized that in individuals with previous SARS-CoV-2 infection, the first vaccine dose would work as a booster, eliciting a faster and more intense immune response. We herein describe antibody responses to the first and second doses of Gam-COVID-Vac (SPUTNIK V) vaccine in health personnel of Tucumán, Argentina, with previous COVID-19 and compared it with uninfected personnel. Individuals with anti-SARS-CoV-2 titers at baseline showed significantly higher responses to the first dose than people with no prior history of disease (p <0.0001), with titers higher to those registered after the second dose in the control group, representing a clear secondary antibody response. This suggests that a single dose of SPUTNIK V for people with previous SARS-CoV-2 infection could contribute to a better use of available doses.

One-Sentence Summary

First vaccine dose in subjects with prior COVID19 elicits a higher antibody response than two doses in uninfected individuals